Patent application title: ANTISENSE COMPOUNDS TARGETING GENES ASSOCIATED WITH FIBRONECTIN
Inventors:
IPC8 Class: AC12N15113FI
USPC Class:
1 1
Class name:
Publication date: 2018-05-10
Patent application number: 20180127751
Abstract:
The present invention provides compounds comprising oligonucleotides
complementary to a fibronectin transcript. Certain such compounds are
useful for hybridizing to a fibronectin transcript, including but not
limited to a fibronectin transcript in a cell. In certain embodiments,
such hybridization results in modulation of splicing of the fibronectin
transcript. In certain embodiments, such compounds are used to treat one
or more symptoms associated with fibrosis. In certain embodiments, such
compounds are used to treat one or more symptoms associated with renal
fibrosis.Claims:
1. A compound comprising a modified oligonucleotide consisting of 18 to
20 linked nucleosides and having a nucleobase sequence comprising a
complementary region comprising at least 8 contiguous nucleobases
complementary to a target region of equal length of a fibronectin
transcript, wherein the target region is within nucleobase 55441 and
nucleobase 55790 of SEQ ID NO: 1.
2. The compound of claim 1, wherein the complementary region of the modified oligonucleotide is 100% complementary to the target region.
3-118. (canceled)
119. The compound of claim 1, wherein the modified oligonucleotide comprises at least one modified internucleoside linkage.
120. The compound of claim 119, comprising at least one phosphorothioate internucleoside linkage.
121. The compound of claim 1, wherein the modified oligonucleotide comprises at least one 2'-substituted sugar moiety.
122. The compound of claim 121, wherein the 2'-substituted sugar moiety is selected from a group consisting of 2'-MOE, 2'-OMe, and 2'-F.
123. The compound of claim 121, wherein the 2'-substituted sugar moiety is a 2'-MOE.
124. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier or diluent.
Description:
SEQUENCE LISTING
[0001] The present application is being filed along with a Sequence Listing in electronic format. The Sequence Listing is provided as a file entitled BIOL0197USC1SEQ.txt, created Oct. 18, 2017, which is 264 Kb in size. The information in the electronic format of the sequence listing is incorporated herein by reference in its entirety.
BACKGROUND OF THE INVENTION
[0002] Fibronectin is a high-molecular weight glycoprotein of the extracellular matrix that binds to membrane-spanning receptor integrin proteins. Fibronectin has been implicated in a number of fibrotic disorders, including renal fibrosis. Alternative splicing of fibronectin pre-mRNA leads to the creation of fibronectin mRNA having a different combination of exons, which in turn leads to the creation of several isoforms of fibronectin protein. In certain instances, alternative splicing of the fibronectin gene results in a fibronectin protein isoform containing the extra type III domain A (EDA). Fibronectin containing extra type III domain A (EDA) is implicated in the formation of fibrosis. See, e.g., Muro et al., An Essential Role for Fibronectin Extra Type III Domain A in Pulmonary Fibrosis, American Journal of Respitory and Critical Care Medicine, Vol. 177, 638 (2008).
[0003] Antisense compounds have been used to modulate target nucleic acids. Antisense compounds comprising a variety of chemical modifications and motifs have been reported. In certain instances, such compounds are useful as research tools, diagnostic reagents, and as therapeutic agents. In certain instances antisense compounds have been shown to modulate protein expression by binding to a target messenger RNA (mRNA) encoding the protein. In certain instances, such binding of an antisense compound to its target mRNA results in cleavage of the mRNA. Antisense compounds that modulate processing of a pre-mRNA have also been reported. Such antisense compounds alter splicing, interfere with polyadenylation or prevent formation of the 5'-cap of a pre-mRNA.
[0004] Certain antisense compounds have been described previously. See for example U.S. Pat. No. 7,399,845 and published International Patent Application No. WO 2008/049085, which are hereby incorporated by reference herein in their entirety.
SUMMARY OF THE INVENTION
[0005] In certain embodiments, the present invention provides compounds comprising oligonucleotides. In certain embodiments, such oligonucleotides are complementary to a fibronectin transcript. In certain such embodiments, oligonucleotides are complementary to a target region of the fibronectin transcript comprising the EDA exon. In certain such embodiments, oligonucleotides are complementary to a target region of the fibronectin transcript comprising an intron adjacent to the EDA exon. In certain such embodiments, oligonucleotides are complementary to a target region of the fibronectin transcript comprising an intron adjacent to the EDA exon and downstream of the EDA exon. In certain such embodiments, oligonucleotides are complementary to a target region of the fibronectin transcript comprising an intron adjacent to the EDA exon and upstream of the EDA exon. In certain embodiments, the fibronectin transcript comprises an exonic splice enhancer for the EDA exon. In certain embodiments, the fibronectin transcript comprises an exonic splice silencer for the EDA exon. In certain embodiments, oligonucleotides inhibit inclusion of the EDA exon. In certain embodiments, oligonucleotides promote skipping of the of the EDA exon. In certain such embodiments, fibronectin mRNA without EDA mRNA is increased. In certain such embodiments, fibronectin protein without EDA is increased.
[0006] The present disclosure provides the following non-limiting numbered embodiments:
Embodiment 1
[0007] A compound comprising a modified oligonucleotide consisting of 8 to 30 linked nucleosides and having a nucleobase sequence comprising a complementary region comprising at least 8 contiguous nucleobases complementary to a target region of equal length of a fibronectin transcript.
Embodiment 2
[0008] The compound of embodiment 1, wherein the complementary region of the modified oligonucleotide is 100% complementary to the target region.
Embodiment 3
[0009] The compound of embodiment 1 or 2, wherein the complementary region of the modified oligonucleotide comprises at least 10 contiguous nucleobases.
Embodiment 4
[0010] The compound of embodiment 1 or 2, wherein the complementary region of the modified oligonucleotide comprises at least 12 contiguous nucleobases.
Embodiment 5
[0011] The compound of embodiment 1 or 2, wherein the complementary region of the modified oligonucleotide comprises at least 15 contiguous nucleobases.
Embodiment 6
[0012] The compound of embodiment 1 or 2, wherein the complementary region of the modified oligonucleotide comprises at least 18 contiguous nucleobases.
Embodiment 7
[0013] The compound of embodiment 1 or 2, wherein the complementary region of the modified oligonucleotide comprises at least 20 contiguous nucleobases.
Embodiment 8
[0014] The compound of any of embodiments 1-5, wherein the nucleobase sequence of the oligonucleotide is at least 80% complementary to an equal-length region of the fibronectin transcript, as measured over the entire length of the oligonucleotide.
Embodiment 9
[0015] The compound of any of embodiments 1-5, wherein the nucleobase sequence of the oligonucleotide is at least 90% complementary to an equal-length region of the fibronectin transcript, as measured over the entire length of the oligonucleotide.
Embodiment 10
[0016] The compound of any of embodiments 1-5, wherein the nucleobase sequence of the oligonucleotide is 100% complementary to an equal-length region of the fibronectin transcript, as measured over the entire length of the oligonucleotide.
Embodiment 11
[0017] The compound of any of embodiments 1-10, wherein the target region is within nucleobase 55469 and nucleobase 55790 of SEQ ID NO.: 1.
Embodiment 12
[0018] The compound of any of embodiments 1-10, wherein the target region is within nucleobase 55469 and nucleobase 55511 of SEQ ID NO.: 1.
Embodiment 13
[0019] The compound of any of embodiments 1-10, wherein the target region is within nucleobase 55511 and nucleobase 55732 of SEQ ID NO.: 1.
Embodiment 14
[0020] The compound of any of embodiments 1-10, wherein the target region is within nucleobase 55732 and nucleobase 55790 of SEQ ID NO.: 1.
Embodiment 15
[0021] The compound of any of embodiments 1-10, wherein the target region is within nucleobase 55491 and nucleobase 55511 of SEQ ID NO.: 1.
Embodiment 16
[0022] The compound of any of embodiments 1-10, wherein the target region is within nucleobase 55490 and nucleobase 55510 of SEQ ID NO.: 1.
Embodiment 17
[0023] The compound of any of embodiments 1-10, wherein the target region is within nucleobase 55491 and nucleobase 55513 of SEQ ID NO.: 1.
Embodiment 18
[0024] The compound of any of embodiments 1-10, wherein the target region is within nucleobase 55536 and nucleobase 55555 of SEQ ID NO.: 1.
Embodiment 19
[0025] The compound of any of embodiments 1-10, wherein the target region is within nucleobase 55576 and nucleobase 55600 of SEQ ID NO.: 1.
Embodiment 20
[0026] The compound of any of embodiments 1-10, wherein the target region is within nucleobase 55604 and nucleobase 55623 of SEQ ID NO.: 1.
Embodiment 21
[0027] The compound of any of embodiments 1-10, wherein the target region is within nucleobase 55610 and nucleobase 55697 of SEQ ID NO.: 1.
Embodiment 22
[0028] The compound of any of embodiments 1-10, wherein the target region is within nucleobase 55701 and nucleobase 55737 of SEQ ID NO.: 1.
Embodiment 23
[0029] The compound of any of embodiments 1-10, wherein the target region is within nucleobase 55738 and nucleobase 55757 of SEQ ID NO.: 1.
Embodiment 24
[0030] The compound of any of embodiments 1-10, wherein the target region is within nucleobase 55753 and nucleobase 55781 of SEQ ID NO.: 1.
Embodiment 25
[0031] The compound of any of embodiments 1-24, wherein the antisense oligonucleotide comprises SEQ ID NO: 5.
Embodiment 26
[0032] The compound of any of embodiments 1-24, wherein the antisense oligonucleotide comprises SEQ ID NO: 9.
Embodiment 27
[0033] The compound of any of embodiments 1-24, wherein the antisense oligonucleotide comprises SEQ ID NO: 13.
Embodiment 28
[0034] The compound of any of embodiments 1-24, wherein the antisense oligonucleotide comprises SEQ ID NO: 14.
Embodiment 29
[0035] The compound of any of embodiments 1-24, wherein the antisense oligonucleotide comprises SEQ ID NO: 15.
Embodiment 30
[0036] The compound of any of embodiments 1-24, wherein the antisense oligonucleotide comprises SEQ ID NO: 18.
Embodiment 31
[0037] The compound of any of embodiments 1-24, wherein the antisense oligonucleotide comprises SEQ ID NO: 22.
Embodiment 32
[0038] The compound of any of embodiments 1-24, wherein the antisense oligonucleotide comprises SEQ ID NO: 66.
Embodiment 33
[0039] The compound of any of embodiments 1-24, wherein the antisense oligonucleotide comprises SEQ ID NO: 67.
Embodiment 34
[0040] The compound of any of embodiments 1-24, wherein the antisense oligonucleotide comprises any of SEQ ID NOs: 5 to 24.
Embodiment 35
[0041] The compound of any of embodiments 1-24, wherein the antisense oligonucleotide comprises any of SEQ ID NOs: 30 to 90.
Embodiment 36
[0042] The compound of any of embodiments 1-24, wherein the antisense oligonucleotide comprises SEQ ID NO: 413.
Embodiment 37
[0043] The compound of any of embodiments 1-24, wherein the antisense oligonucleotide comprises SEQ ID NO: 346.
Embodiment 38
[0044] The compound of any of embodiments 1-24, wherein the antisense oligonucleotide comprises any of SEQ ID NOs: 104 to 176.
Embodiment 39
[0045] The compound of any of embodiments 1-24, wherein the antisense oligonucleotide comprises any of SEQ ID NOs: 177 to 329.
Embodiment 40
[0046] The compound of any of embodiments 1-24, wherein the antisense oligonucleotide comprises any of SEQ ID NOs: 403 to 435.
Embodiment 41
[0047] The compound of any of embodiments 1-24, wherein the antisense oligonucleotide comprises any of SEQ ID NOs: 105, 87, 126, 133, 134, 140, 141, 147, 149, 157, 159, 190, 223, 238, 244, 268, 285, 300, 302, 303, 308, 319, 327, 381, 382, 339, 346, 348, 364, 365, 367, 368, 369, 370, 268, 276, 280, 406, 407, 412, 413, and 324.
Embodiment 42
[0048] The compound of any of embodiments 1-24, wherein the antisense oligonucleotide has a nucleobase sequence comprising CTTCTTCT.
Embodiment 43
[0049] The compound of any of embodiments 1-24, wherein the antisense oligonucleotide has a nucleobase sequence comprising GTTCC.
Embodiment 44
[0050] The compound of any of embodiments 1-24, wherein the antisense oligonucleotide has a nucleobase sequence comprising GTCCC.
Embodiment 45
[0051] The compound of any of embodiments 1-24, wherein the antisense oligonucleotide comprises a sugar motif described by Formula I as follows:
[(A)-(B).sub.2-(A)].sub.n
[0052] wherein:
[0053] each A is independently a bicyclic nucleoside;
[0054] each B is independently a 2'-substituted nucleoside or a 2'-deoxynucleoside; and
[0055] n is an integer from 3-6.
Embodiment 46
[0056] The compound of any of embodiments 1-24, wherein the antisense oligonucleotide comprises a sugar motif described by Formula II as follows:
(A).sub.2-[(B).sub.2-(A)].sub.n-(A)
[0057] wherein:
[0058] each A is independently a bicyclic nucleoside;
[0059] each B is independently a 2'-substituted nucleoside or a 2'-deoxynucleoside; and
[0060] n is an integer from 3-6.
Embodiment 47
[0061] The compound of any of embodiments 1-24, wherein the antisense oligonucleotide comprises a sugar motif described by Formula III as follows:
(A).sub.2-[(B).sub.2-(A)].sub.n
[0062] wherein:
[0063] each A is independently a bicyclic nucleoside;
[0064] each B is independently a 2'-substituted nucleoside or a 2'-deoxynucleoside; and
[0065] n is an integer from 3-6.
Embodiment 48
[0066] The compound of any of embodiments 45 to 47, wherein each A comprises a bicyclic nucleoside selected from among LNA and cEt.
Embodiment 49
[0067] The compound of any of embodiments 45 to 47, wherein each A comprises a cEt modification.
Embodiment 50
[0068] The compound of any of embodiments 45 to 47, wherein each A comprises an LNA modification.
Embodiment 51
[0069] The compound of any of embodiments 45 to 50, wherein each B comprises a 2'-substituted nucleoside having a 2'-modification selected from among 2'-OMe, 2'-F, and 2'-MOE.
Embodiment 52
[0070] The compound embodiment 51, wherein the 2'-modification is a 2'-MOE modification.
Embodiment 53
[0071] The compound of any of embodiments 45 to 50, wherein each B comprises a 2'-deoxynucleoside.
Embodiment 54
[0072] The compound of any of embodiments 1-44, wherein the modified oligonucleotide comprises at least one modified nucleoside.
Embodiment 55
[0073] The compound of embodiment 54, wherein at least one modified nucleoside comprises a modified sugar moiety.
Embodiment 56
[0074] The compound of embodiment 55, wherein at least one modified sugar moiety is a 2'-substituted sugar moiety.
Embodiment 57
[0075] The compound of embodiment 56, wherein the 2'-substituent of at least one 2'-substituted sugar moiety is selected from among: 2'-OMe, 2'-F, and 2'-MOE.
Embodiment 58
[0076] The compound of embodiment 57, wherein the 2'-substituent of at least one 2'-substituted sugar moiety is a 2'-MOE.
Embodiment 59
[0077] The compound of any of embodiments 54-56, wherein at least one modified sugar moiety is a bicyclic sugar moiety.
Embodiment 60
[0078] The compound of embodiment 59, wherein at least one bicyclic sugar moiety is LNA or cEt.
Embodiment 61
[0079] The compound of any of embodiments 54-60, wherein at least one sugar moiety is a sugar surrogate.
Embodiment 62
[0080] The compound of embodiment 61, wherein at least one sugar surrogate is a morpholino.
Embodiment 63
[0081] The compound of embodiment 61, wherein at least one sugar surrogate is a modified morpholino.
Embodiment 64
[0082] The compound of any of embodiment 1-63, wherein the modified oligonucleotide comprises at least 5 modified nucleosides, each independently comprising a modified sugar moiety.
Embodiment 65
[0083] The compound of embodiment 64, wherein the modified oligonucleotide comprises at least 10 modified nucleosides, each independently comprising a modified sugar moiety.
Embodiment 66
[0084] The compound of embodiment 64, wherein the modified oligonucleotide comprises at least 15 modified nucleosides, each independently comprising a modified sugar moiety.
Embodiment 67
[0085] The compound of any of embodiments 1 to 44 or 54 to 66, wherein each nucleoside of the modified oligonucleotide is a modified nucleoside, each independently comprising a modified sugar moiety Embodiment 68. The compound of any of embodiments 1-67, wherein the modified oligonucleotide comprises at least two modified nucleosides comprising modified sugar moieties that are the same as one another.
Embodiment 69
[0086] The compound of any of embodiments 1-68, wherein the modified oligonucleotide comprises at least two modified nucleosides comprising modified sugar moieties that are different from one another.
Embodiment 70
[0087] The compound of any of embodiments 1-69, wherein the modified oligonucleotide comprises a modified region of at least 5 contiguous modified nucleosides.
Embodiment 71
[0088] The compound of any of embodiments 1 to 44 or 54 to 70, wherein the modified oligonucleotide comprises a modified region of at least 10 contiguous modified nucleosides.
Embodiment 72
[0089] The compound of any of embodiments 1 to 44 or 54 to 70, wherein the modified oligonucleotide comprises a modified region of at least 15 contiguous modified nucleosides.
Embodiment 73
[0090] The compound of any of embodiments 1 to 44 or 54 to 70, wherein the modified oligonucleotide comprises a modified region of at least 20 contiguous modified nucleosides.
Embodiment 74
[0091] The compound of any of embodiments 70-73, wherein each modified nucleoside of the modified region has a modified sugar moiety independently selected from among: 2'-F, 2'-OMe, 2'-MOE, cEt, LNA, morpholino, and modified morpholino.
Embodiment 75
[0092] The compound of any of embodiments 70-73, wherein the modified nucleosides of the modified region each comprise the same modification as one another.
Embodiment 76
[0093] The compound of embodiment 75, wherein the modified nucleosides of the modified region each comprise the same 2'-substituted sugar moiety.
Embodiment 77
[0094] The compound of embodiment 75, wherein the 2'-substituted sugar moiety of the modified nucleosides of the region of modified nucleosides is selected from 2'-F, 2'-OMe, and 2'-MOE.
Embodiment 78
[0095] The compound of embodiment 77, wherein the 2'-substituted sugar moiety of the modified nucleosides of the region of modified nucleosides is 2'-MOE.
Embodiment 79
[0096] The compound of embodiment 75, wherein the modified nucleosides of the region of modified nucleosides each comprise the same bicyclic sugar moiety.
Embodiment 80
[0097] The compound of embodiment 79, wherein the bicyclic sugar moiety of the modified nucleosides of the region of modified nucleosides is selected from LNA and cEt.
Embodiment 81
[0098] The compound of embodiment 75, wherein the modified nucleosides of the region of modified nucleosides each comprises a sugar surrogate.
Embodiment 82
[0099] The compound of embodiment 81, wherein the sugar surrogate of the modified nucleosides of the region of modified nucleosides is a morpholino.
Embodiment 83
[0100] The compound of embodiment 81, wherein the sugar surrogate of the modified nucleosides of the region of modified nucleosides is a modified morpholino.
Embodiment 84
[0101] The compound of any of embodiments 1-83, wherein the modified nucleotide comprises no more than 4 contiguous naturally occurring nucleosides.
Embodiment 85
[0102] The compound of any of embodiments 1 to 44 or 54 to 85, wherein each nucleoside of the modified oligonucleotide is a modified nucleoside.
Embodiment 86
[0103] The compound of embodiment 85 wherein each modified nucleoside comprises a modified sugar moiety.
Embodiment 87
[0104] The compound of embodiment 86, wherein the modified nucleosides of the modified oligonucleotide comprise the same modification as one another.
Embodiment 88
[0105] The compound of embodiment 87, wherein the modified nucleosides of the modified oligonucleotide each comprise the same 2'-substituted sugar moiety.
Embodiment 89
[0106] The compound of embodiment 88, wherein the 2'-substituted sugar moiety of the modified oligonucleotide is selected from 2'-F, 2'-OMe, and 2'-MOE.
Embodiment 90
[0107] The compound of embodiment 89, wherein the 2'-substituted sugar moiety of the modified oligonucleotide is 2'-MOE.
Embodiment 91
[0108] The compound of embodiment 87, wherein the modified nucleosides of the modified oligonucleotide each comprise the same bicyclic sugar moiety.
Embodiment 92
[0109] The compound of embodiment 91, wherein the bicyclic sugar moiety of the modified oligonucleotide is selected from LNA and cEt.
Embodiment 93
[0110] The compound of embodiment 87, wherein the modified nucleosides of the modified oligonucleotide each comprises a sugar surrogate.
Embodiment 94
[0111] The compound of embodiment 93, wherein the sugar surrogate of the modified oligonucleotide is a morpholino.
Embodiment 95
[0112] The compound of embodiment 93, wherein the sugar surrogate of the modified oligonucleotide is a modified morpholino.
Embodiment 96
[0113] The compound of any of embodiments 1-95, wherein the modified oligonucleotide comprises at least one modified internucleoside linkage.
Embodiment 97
[0114] The compound of embodiment 96, wherein each internucleoside linkage is a modified internucleoside linkage.
Embodiment 98
[0115] The compound of embodiment 96 or 97, comprising at least one phosphorothioate internucleoside linkage.
Embodiment 99
[0116] The compound of embodiment 77, wherein each internucleoside linkage is a modified internucleoside linkage and wherein each internucleoside linkage comprises the same modification.
Embodiment 100
[0117] The compound of embodiment 99, wherein each internucleoside linkage is a phosphorothioate internucleoside linkage.
Embodiment 101
[0118] The compound of any of embodiments 1-100 comprising at least one conjugate.
Embodiment 102
[0119] The compound of any of embodiments 1-101 consisting of the modified oligonucleotide.
Embodiment 103
[0120] The compound of any of embodiments 1-102, wherein the compound modulates splicing of the fibronectin transcript.
Embodiment 104
[0121] The compound of any of embodiments 1-103, having a nucleobase sequence comprising any of the sequences as set forth in SEQ ID NOs. 5 to 25 or 30 to 90.
Embodiment 105
[0122] The compound of any of embodiments 1-103, having a nucleobase sequence comprising the sequence as set forth in SEQ ID NO: 5.
Embodiment 106
[0123] The compound of any of embodiments 1-103, having a nucleobase sequence comprising the sequence as set forth in SEQ ID NO: 9.
Embodiment 107
[0124] The compound of any of embodiments 1-103, having a nucleobase sequence comprising the sequence as set forth in SEQ ID NO: 13.
Embodiment 108
[0125] The compound of any of embodiments 1-103, having a nucleobase sequence comprising the sequence as set forth in SEQ ID NO: 14.
Embodiment 109
[0126] The compound of any of embodiments 1-103, having a nucleobase sequence comprising the sequence as set forth in SEQ ID NO: 15.
Embodiment 110
[0127] The compound of any of embodiments 1-103, having a nucleobase sequence comprising the sequence as set forth in SEQ ID NO: 18.
Embodiment 111
[0128] The compound of any of embodiments 1-103, having a nucleobase sequence comprising the sequence as set forth in SEQ ID NO: 22.
Embodiment 112
[0129] The compound of any of embodiments 1-103, having a nucleobase sequence comprising the sequence as set forth in SEQ ID NO: 66.
Embodiment 113
[0130] The compound of any of embodiments 1-103, having a nucleobase sequence comprising the sequence as set forth in SEQ ID NO: 67.
Embodiment 114
[0131] The compound of any of embodiments 1-103, wherein the antisense oligonucleotide has a nucleobase sequence comprising CTTCTTCT.
Embodiment 115
[0132] The compound of any of embodiments 1-103, wherein the antisense oligonucleotide has a nucleobase sequence comprising GTTCC.
Embodiment 116
[0133] The compound of any of embodiments 1-103, wherein the antisense oligonucleotide has a nucleobase sequence comprising GTCCC.
Embodiment 117
[0134] A pharmaceutical composition comprising a compound according to any of embodiments 1-116 and a pharmaceutically acceptable carrier or diluent.
Embodiment 118
[0135] The pharmaceutical composition of embodiment 117, wherein the pharmaceutically acceptable carrier or diluent is sterile saline.
Embodiment 119
[0136] A method of decreasing the amount of EDA+ fibronectin protein in a cell, comprising contacting the cell with a compound according to any of embodiments 1-117.
Embodiment 120
[0137] A method of increasing the amount of EDA- fibronectin protein in a cell, comprising contacting the cell with a compound according to any of embodiments 1-117.
Embodiment 121
[0138] A method of reducing fibrosis, comprising contacting the cell with a compound according to any of embodiments 1-117.
Embodiment 122
[0139] A method of reversing fibrosis, comprising contacting the cell with a compound according to any of embodiments 1-117.
Embodiment 123
[0140] A method of reducing changes in cell phenotype due to fibrosis, comprising contacting the cell with a compound according to any of embodiments 1-117.
Embodiment 124
[0141] A method of reversing changes in cell phenotype due to fibrosis, comprising contacting the cell with a compound according to any of embodiments 1-117.
Embodiment 125
[0142] The method of embodiments 123-124, wherein the change in cell phenotype due to fibrosis is the modulation of cadherin expression.
Embodiment 126
[0143] The method of embodiments 123-124, wherein the change in cell phenotype due to fibrosis is the induction of .alpha. Smooth Muscle Actin (.alpha.SMA).
Embodiment 127
[0144] The method of embodiments 123-124, wherein the change in cell phenotype due to fibrosis is the alteration of cortical f-actin localization.
Embodiment 128
[0145] The method of embodiments 123-124, wherein the change in cell phenotype due to fibrosis is the induction of connexin 43 (Cx 43) expression.
Embodiment 129
[0146] The method of embodiments 123-124, wherein the change in cell phenotype due to fibrosis is the increased secretion of MMP2 & MMP9.
Embodiment 130
[0147] The method of embodiments 123-124, wherein the change in cell phenotype due to fibrosis is the alteration of the amount vimentin or the arrangement of vimentin within a cell.
Embodiment 131
[0148] The method of embodiments 123-124, wherein the change in cell phenotype due to fibrosis is the alteration of the amount tight junction protein ZO-1 or the arrangement of tight junction protein ZO-1 within a cell.
Embodiment 132
[0149] A method of reducing loss of cell phenotype due to fibrosis, comprising contacting the cell with a compound according to any of embodiments 1-117.
Embodiment 133
[0150] A method of reversing the loss of cell phenotype due to fibrosis, comprising contacting the cell with a compound according to any of embodiments 1-117.
Embodiment 134
[0151] A method of increasing the ratio of EDA+/EDA- fibronectin in a cell, comprising contacting the cell with a compound according to any of embodiments 1-117.
Embodiment 135
[0152] A method of decreasing the ratio of EDA+/EDA- fibronectin in a cell, comprising contacting the cell with a compound according to any of embodiments 1-117.
Embodiment 136
[0153] A method of increasing the ratio of EDA-/EDA+ fibronectin in a cell, comprising contacting the cell with a compound according to any of embodiments 1-117.
Embodiment 137
[0154] A method of decreasing the ratio of EDA-/EDA+ fibronectin in a cell, comprising contacting the cell with a compound according to any of embodiments 1-117.
Embodiment 138
[0155] A method of increasing the ratio of EDA+/EDA- fibronectin protein in a cell, comprising contacting the cell with a compound according to any of embodiments 1-117.
Embodiment 139
[0156] A method of decreasing the ratio of EDA+/EDA- fibronectin protein in a cell, comprising contacting the cell with a compound according to any of embodiments 1-117.
Embodiment 140
[0157] A method of increasing the ratio of EDA-/EDA+ fibronectin protein in a cell, comprising contacting the cell with a compound according to any of embodiments 1-117.
Embodiment 141
[0158] A method of decreasing the ratio of EDA-/EDA+ fibronectin protein in a cell, comprising contacting the cell with a compound according to any of embodiments 1-117.
Embodiment 142
[0159] The method of any of embodiments 119-142, wherein the cell is in vitro.
Embodiment 143
[0160] The method of embodiments 119-142, wherein the cell is in an animal.
Embodiment 144
[0161] The method of embodiments 119-142, wherein the animal is a mouse.
Embodiment 145
[0162] The method of embodiments 119-142, wherein the animal is a human.
Embodiment 146
[0163] The method of any of embodiments 119-145, wherein TGF.beta.1 is present in the cell.
Embodiment 147
[0164] The method of any of embodiments 119-146, wherein the healing and/or restoration functions of the cell are not substantially affected.
Embodiment 148
[0165] A pharmaceutical composition comprising a compound according to any of embodiments 1-117 and a pharmaceutically acceptable carrier or diluent.
Embodiment 149
[0166] The pharmaceutical composition of embodiment 148, wherein the pharmaceutically acceptable carrier or diluent is sterile saline.
Embodiment 150
[0167] A method comprising administering the pharmaceutical composition of embodiments 148 or 149 to an animal.
Embodiment 151
[0168] The method of embodiment 150, wherein the animal is a mouse.
Embodiment 152
[0169] The method of embodiment 150, wherein the animal is a human.
Embodiment 153
[0170] The method of embodiment 150, wherein the administration is by injection.
Embodiment 154
[0171] The method of embodiment 150, wherein the administration is systemic.
Embodiment 155
[0172] The method of embodiment 150 wherein the administration is local.
Embodiment 156
[0173] The method of any of embodiments 150-155, wherein the animal has one or more symptom associated with fibrosis.
Embodiment 157
[0174] The method of embodiment 156, wherein the administration results in amelioration of at least one symptom associated with fibrosis.
Embodiment 158
[0175] The method of embodiment 156-157, wherein the fibrosis is renal fibrosis.
Embodiment 159
[0176] The method of embodiment 156-157, wherein the fibrosis is lung fibrosis.
Embodiment 160
[0177] The method of embodiment 156-157, wherein the fibrosis is liver fibrosis.
Embodiment 161
[0178] The method of embodiment 156-157, wherein the fibrosis is brain fibrosis.
Embodiment 162
[0179] The method of embodiment 156-157, wherein the fibrosis is muscular fibrosis.
Embodiment 163
[0180] The method of embodiment 156-157, wherein the fibrosis is cardiovascular fibrosis.
Embodiment 164
[0181] The method of embodiment 156-157, wherein the fibrosis is in the bone or the bone marrow.
Embodiment 165
[0182] The method of embodiment 156-157, wherein the fibrosis is intestinal fibrosis.
Embodiment 166
[0183] The method of embodiment 156-157, wherein the fibrosis is epidural fibrosis.
Embodiment 167
[0184] The method of any of embodiments 156-167, wherein the animal is a mouse.
Embodiment 168
[0185] The method of any of embodiments 156-167, wherein the animal is a human.
Embodiment 169
[0186] Use of the compound of any of embodiments 1 to 117 or the composition of embodiments 148-149 for the preparation of a medicament for use in the treatment of at least one symptom associated with fibrosis.
Embodiment 170
[0187] Use of the compound of any of embodiments 1 to 117 or the composition of embodiments 148-149 for the preparation of a medicament for use in the amelioration of one or more symptoms associated with fibrosis.
Embodiment 171
[0188] The use of any of embodiment 169-170, wherein the fibrosis is selected from among renal, lung, liver, brain, muscular, cardiovascular, bone or bone marrow, intestinal, and/or epidural fibrosis.
Embodiment 172
[0189] A compound comprising a modified oligonucleotide consisting of 8 to 30 linked nucleosides and having a nucleobase sequence comprising a complementary region comprising at least 8 contiguous nucleobases complementary to a target region of equal length of a target nucleic acid, wherein the modified oligonucleotide comprises a sugar motif described by Formula I as follows:
[(A)-(B).sub.2-(A)].sub.n
[0190] wherein:
[0191] each A is independently a bicyclic nucleoside;
[0192] each B is independently a 2'-substituted nucleoside or a 2'-deoxynucleoside; and
[0193] n is an integer from 3-6.
Embodiment 173
[0194] A compound comprising a modified oligonucleotide consisting of 8 to 30 linked nucleosides and having a nucleobase sequence comprising a complementary region comprising at least 8 contiguous nucleobases complementary to a target region of equal length of a target nucleic acid, wherein the modified oligonucleotide comprises a sugar motif described by Formula II as follows:
(A).sub.2-[(B).sub.2-(A)]n-(A)
[0195] wherein:
[0196] each A is independently a bicyclic nucleoside;
[0197] each B is independently a 2'-substituted nucleoside or a 2'-deoxynucleoside; and
[0198] n is an integer from 3-6.
Embodiment 174
[0199] A compound comprising a modified oligonucleotide consisting of 8 to 30 linked nucleosides and having a nucleobase sequence comprising a complementary region comprising at least 8 contiguous nucleobases complementary to a target region of equal length of a target nucleic acid, wherein the modified oligonucleotide comprises a sugar motif described by Formula III as follows:
(A).sub.2-[(B).sub.2-(A)].sub.n
[0200] wherein:
[0201] each A is independently a bicyclic nucleoside;
[0202] each B is independently a 2'-substituted nucleoside or a 2'-deoxynucleoside; and
[0203] n is an integer from 3-6.
Embodiment 175
[0204] The compound of any of embodiments 172 to 174, wherein each A comprises a bicyclic nucleoside selected from among LNA and cEt.
Embodiment 176
[0205] The compound of any of embodiments 172 to 174, wherein each A comprises a cEt modification.
Embodiment 177
[0206] The compound of any of embodiments 172 to 174, wherein each A comprises an LNA modification.
Embodiment 178
[0207] The compound of any of embodiments 172 to 177, wherein each B comprises a 2'-substituted nucleoside having a 2'-modification selected from among 2'-OMe, 2'-F, and 2'-MOE.
Embodiment 179
[0208] The compound embodiments 178, wherein the 2'-modification is a 2'-MOE modification.
Embodiment 180
[0209] The compound of any of embodiments 172 to 179, wherein each B comprises a 2'-deoxynucleoside.
Embodiment 181
[0210] A compound comprising a modified oligonucleotide consisting of 8 to 30 linked nucleosides and having a nucleobase sequence comprising a complementary region comprising at least 8 contiguous nucleobases complementary to a target region of equal length of a target nucleic acid, wherein the modified oligonucleotide comprises a kd.sub.2kd.sub.2kd.sub.2kd.sub.2kd.sub.2k motif, wherein each k comprises a cEt modification and each d comprises a 2'-deoxynucleoside.
Embodiment 182
[0211] A compound comprising a modified oligonucleotide consisting of 8 to 30 linked nucleosides and having a nucleobase sequence comprising a complementary region comprising at least 8 contiguous nucleobases complementary to a target region of equal length of a target nucleic acid, wherein the modified oligonucleotide comprises a kkddkddkddkddkddkk motif, wherein each k comprises a cEt modification and each d comprises a 2'-deoxynucleoside.
Embodiment 183
[0212] A compound comprising a modified oligonucleotide consisting of 8 to 30 linked nucleosides and having a nucleobase sequence comprising a complementary region comprising at least 8 contiguous nucleobases complementary to a target region of equal length of a target nucleic acid, wherein the modified oligonucleotide comprises a kkeekeekeekeekeeke motif, wherein each k comprises a cEt modification and each e comprises a 2'-MOE modification.
Embodiment 184
[0213] A compound comprising a modified oligonucleotide consisting of 8 to 30 linked nucleosides and having a nucleobase sequence comprising a complementary region comprising at least 8 contiguous nucleobases complementary to a target region of equal length of a target nucleic acid, wherein the modified oligonucleotide comprises a kddkddkddkddkddk motif wherein each k comprises a cEt modification and each d comprises a 2'-deoxynucleoside.
Embodiment 185
[0214] A compound comprising a modified oligonucleotide consisting of 8 to 30 linked nucleosides and having a nucleobase sequence comprising a complementary region comprising at least 8 contiguous nucleobases complementary to a target region of equal length of a target nucleic acid, wherein the modified oligonucleotide comprises a keekeekeekeekeek motif, wherein each k comprises a cEt modification and each e comprises a 2'-MOE modification.
[0215] In certain embodiments, including, but not limited to any of the above numbered embodiments, the fibronectin transcript is in a human. In certain embodiments, including, but not limited to any of the above numbered embodiments, the fibronectin transcript is in a mouse.
BRIEF DESCRIPTION OF THE FIGURES
[0216] FIG. 1 shows a schematic of fibronectin splicing. Exons are represented as boxes and introns are represented as lines. Diagonal lines indicate splicing pathways. As illustrated by the schematic, alternative splicing produces two different mRNA products. Inclusion of the EDA exon results in mRNA containing the EDA exon (EDA+) which results in fibronectin protein having EDA. Alternatively, exclusion of the EDA exon results in mRNA without the EDA exon (EDA-) and results in fibronectin protein without EDA.
DETAILED DESCRIPTION OF THE INVENTION
[0217] Unless specific definitions are provided, the nomenclature used in connection with, and the procedures and techniques of, analytical chemistry, synthetic organic chemistry, and medicinal and pharmaceutical chemistry described herein are those well known and commonly used in the art. Standard techniques may be used for chemical synthesis, and chemical analysis. Certain such techniques and procedures may be found for example in "Carbohydrate Modifications in Antisense Research" Edited by Sangvi and Cook, American Chemical Society, Washington D.C., 1994; "Remington's Pharmaceutical Sciences," Mack Publishing Co., Easton, Pa., 21.sup.st edition, 2005; and "Antisense Drug Technology, Principles, Strategies, and Applications" Edited by Stanley T. Crooke, CRC Press, Boca Raton, Fla.; and Sambrook et al., "Molecular Cloning, A laboratory Manual," 2nd Edition, Cold Spring Harbor Laboratory Press, 1989, which are hereby incorporated by reference for any purpose. Where permitted, all patents, applications, published applications and other publications and other data referred to throughout in the disclosure are incorporated by reference herein in their entirety.
[0218] Unless otherwise indicated, the following terms have the following meanings:
[0219] As used herein, "nucleoside" means a compound comprising a nucleobase moiety and a sugar moiety. Nucleosides include, but are not limited to, naturally occurring nucleosides (as found in DNA and RNA) and modified nucleosides. Nucleosides may be linked to a phosphate moiety.
[0220] As used herein, "chemical modification" means a chemical difference in a compound when compared to a naturally occurring counterpart. In reference to an oligonucleotide, chemical modification does not include differences only in nucleobase sequence. Chemical modifications of oligonucleotides include nucleoside modifications (including sugar moiety modifications and nucleobase modifications) and internucleoside linkage modifications.
[0221] As used herein, "furanosyl" means a structure comprising a 5-membered ring comprising four carbon atoms and one oxygen atom.
[0222] As used herein, "naturally occurring sugar moiety" means a ribofuranosyl as found in naturally occurring RNA or a deoxyribofuranosyl as found in naturally occurring DNA.
[0223] As used herein, "sugar moiety" means a naturally occurring sugar moiety or a modified sugar moiety of a nucleoside.
[0224] As used herein, "modified sugar moiety" means a substituted sugar moiety, a bicyclic or tricyclic sugar moiety, or a sugar surrogate.
[0225] As used herein, "substituted sugar moiety" means a furanosyl comprising at least one substituent group that differs from that of a naturally occurring sugar moiety. Substituted sugar moieties include, but are not limited to furanosyls comprising substituents at the 2'-position, the 3'-position, the 5'-position and/or the 4'-position.
[0226] As used herein, "2'-substituted sugar moiety" means a furanosyl comprising a substituent at the 2'-position other than H or OH. Unless otherwise indicated, a 2'-substituted sugar moiety is not a bicyclic sugar moiety (i.e., the 2'-substituent of a 2'-substituted sugar moiety does not form a bridge to another atom of the furanosyl ring.
[0227] As used herein, "MOE" means --OCH.sub.2CH.sub.2OCH.sub.3.
[0228] As used herein, "bicyclic sugar moiety" means a modified sugar moiety comprising a 4 to 7 membered ring (including but not limited to a furanosyl) comprising a bridge connecting two atoms of the 4 to 7 membered ring to form a second ring, resulting in a bicyclic structure. In certain embodiments, the 4 to 7 membered ring is a sugar ring. In certain embodiments the 4 to 7 membered ring is a furanosyl. In certain such embodiments, the bridge connects the 2'-carbon and the 4'-carbon of the furanosyl.
[0229] As used herein the term "sugar surrogate" means a structure that does not comprise a furanosyl and that is capable of replacing the naturally occurring sugar moiety of a nucleoside, such that the resulting nucleoside is capable of (1) incorporation into an oligonucleotide and (2) hybridization to a complementary nucleoside. Such structures include rings comprising a different number of atoms than furanosyl (e.g., 4, 6, or 7-membered rings); replacement of the oxygen of a furanosyl with a non-oxygen atom (e.g., carbon, sulfur, or nitrogen); or both a change in the number of atoms and a replacement of the oxygen. Such structures may also comprise substitutions corresponding to those described for substituted sugar moieties (e.g., 6-membered carbocyclic bicyclic sugar surrogates optionally comprising additional substituents). Sugar surrogates also include more complex sugar replacements (e.g., the non-ring systems of peptide nucleic acid). Sugar surrogates include without limitation morpholino, modified morpholinos, cyclohexenyls and cyclohexitols.
[0230] As used herein, "nucleotide" means a nucleoside further comprising a phosphate linking group. As used herein, "linked nucleosides" may or may not be linked by phosphate linkages and thus includes, but is not limited to "linked nucleotides." As used herein, "linked nucleosides" are nucleosides that are connected in a continuous sequence (i.e. no additional nucleosides are present between those that are linked).
[0231] As used herein, "nucleobase" means a group of atoms that can be linked to a sugar moiety to create a nucleoside that is capable of incorporation into an oligonucleotide, and wherein the group of atoms is capable of bonding with a complementary naturally occurring nucleobase of another oligonucleotide or nucleic acid. Nucleobases may be naturally occurring or may be modified.
[0232] As used herein, "heterocyclic base" or "heterocyclic nucleobase" means a nucleobase comprising a heterocyclic structure.
[0233] As used herein the terms, "unmodified nucleobase" or "naturally occurring nucleobase" means the naturally occurring heterocyclic nucleobases of RNA or DNA: the purine bases adenine (A) and guanine (G), and the pyrimidine bases thymine (T), cytosine (C) (including 5-methyl C), and uracil (U).
[0234] As used herein, "modified nucleobase" means any nucleobase that is not a naturally occurring nucleobase.
[0235] As used herein, "modified nucleoside" means a nucleoside comprising at least one chemical modification compared to naturally occurring RNA or DNA nucleosides. Modified nucleosides comprise a modified sugar moiety and/or a modified nucleobase.
[0236] As used herein, "bicyclic nucleoside" or "BNA" means a nucleoside comprising a bicyclic sugar moiety.
[0237] As used herein, "constrained ethyl nucleoside" or "cEt" means a nucleoside comprising a bicyclic sugar moiety comprising a 4'-CH(CH.sub.3)--O-2' bridge.
[0238] As used herein, "locked nucleic acid nucleoside" or "LNA" means a nucleoside comprising a bicyclic sugar moiety comprising a 4'-CH.sub.2--O-2' bridge.
[0239] As used herein, "2'-substituted nucleoside" means a nucleoside comprising a substituent at the 2'-position other than H or OH. Unless otherwise indicated, a 2'-substituted nucleoside is not a bicyclic nucleoside.
[0240] As used herein, "2'-deoxynucleoside" means a nucleoside comprising 2'-H furanosyl sugar moiety, as found in naturally occurring deoxyribonucleosides (DNA). In certain embodiments, a 2'-deoxynucleoside may comprise a modified nucleobase or may comprise an RNA nucleobase (e.g., uracil).
[0241] As used herein, "oligonucleotide" means a compound comprising a plurality of linked nucleosides. In certain embodiments, an oligonucleotide comprises one or more unmodified ribonucleosides (RNA) and/or unmodified deoxyribonucleosides (DNA) and/or one or more modified nucleosides.
[0242] As used herein "oligonucleoside" means an oligonucleotide in which none of the internucleoside linkages contains a phosphorus atom. As used herein, oligonucleotides include oligonucleosides.
[0243] As used herein, "modified oligonucleotide" means an oligonucleotide comprising at least one modified nucleoside and/or at least one modified internucleoside linkage.
[0244] As used herein "internucleoside linkage" means a covalent linkage between adjacent nucleosides in an oligonucleotide.
[0245] As used herein "naturally occurring internucleoside linkage" means a 3' to 5' phosphodiester linkage.
[0246] As used herein, "modified internucleoside linkage" means any internucleoside linkage other than a naturally occurring internucleoside linkage.
[0247] As used herein, "oligomeric compound" means a polymeric structure comprising two or more sub-structures. In certain embodiments, an oligomeric compound comprises an oligonucleotide. In certain embodiments, an oligomeric compound comprises one or more conjugate groups and/or terminal groups. In certain embodiments, an oligomeric compound consists of an oligonucleotide.
[0248] As used herein, "terminal group" means one or more atom attached to either, or both, the 3' end or the 5' end of an oligonucleotide. In certain embodiments a terminal group is a conjugate group. In certain embodiments, a terminal group comprises one or more terminal group nucleosides.
[0249] As used herein, "conjugate" means an atom or group of atoms bound to an oligonucleotide or oligomeric compound. In general, conjugate groups modify one or more properties of the compound to which they are attached, including, but not limited to pharmacodynamic, pharmacokinetic, binding, absorption, cellular distribution, cellular uptake, charge and/or clearance properties.
[0250] As used herein, "conjugate linking group" means any atom or group of atoms used to attach a conjugate to an oligonucleotide or oligomeric compound.
[0251] As used herein, "antisense compound" means a compound comprising or consisting of an oligonucleotide at least a portion of which is complementary to a target nucleic acid to which it is capable of hybridizing, resulting in at least one antisense activity.
[0252] As used herein, "antisense activity" means any detectable and/or measurable change attributable to the hybridization of an antisense compound to its target nucleic acid.
[0253] As used herein, "detecting" or "measuring" means that a test or assay for detecting or measuring is performed. Such detection and/or measuring may result in a value of zero. Thus, if a test for detection or measuring results in a finding of no activity (activity of zero), the step of detecting or measuring the activity has nevertheless been performed.
[0254] As used herein, "detectable and/or measurable activity" means a statistically significant activity that is not zero.
[0255] As used herein, "essentially unchanged" means little or no change in a particular parameter, particularly relative to another parameter which changes much more. In certain embodiments, a parameter is essentially unchanged when it changes less than 5%. In certain embodiments, a parameter is essentially unchanged if it changes less than two-fold while another parameter changes at least ten-fold. For example, in certain embodiments, an antisense activity is a change in the amount of a target nucleic acid. In certain such embodiments, the amount of a non-target nucleic acid is essentially unchanged if it changes much less than the target nucleic acid does, but the change need not be zero.
[0256] As used herein, "expression" means the process by which a gene ultimately results in a protein. Expression includes, but is not limited to, transcription, post-transcriptional modification (e.g., splicing, polyadenlyation, addition of 5'-cap), and translation.
[0257] As used herein, "target nucleic acid" means a nucleic acid molecule to which an antisense compound hybridizes.
[0258] As used herein, "mRNA" means an RNA molecule that encodes a protein.
[0259] As used herein, "pre-mRNA" means an RNA transcript that has not been fully processed into mRNA. Pre-RNA includes one or more intron.
[0260] As used herein, "transcript" means an RNA molecule transcribed from DNA. Transcripts include, but are not limited to mRNA, pre-mRNA, and partially processed RNA.
[0261] As used herein, "fibronectin transcript" means a transcript transcribed from a fibronectin gene. In certain embodiments, a fibronectin transcript comprises SEQ ID NO: 1: the complement of GENBANK Accession No. NT_005403.14 truncated from nucleotides 66434501 to 66510708.
[0262] As used herein, "fibronectin gene" means a gene that encodes a fibronectin protein and any fibronectin protein isoforms. In certain embodiments, a fibronectin gene is represented by GENBANK Accession No. NT_005403.14 truncated from nucleotides 66434501 to 66510708, or a variant thereof. In certain embodiments, a fibronectin gene is at least 95% identical to GENBANK Accession No. NT_005403.14 truncated from nucleotides 66434501 to 66510708. In certain embodiments, a fibronectin gene is at least 90% identical to GENBANK Accession No. NT_005403.14 truncated from nucleotides 66434501 to 66510708.
[0263] As used herein, "EDA- fibronectin protein" means a fibronectin protein isoform that does not contain extra type III domain A.
[0264] As used herein, "EDA+ fibronectin protein" means a fibronectin protein isoform that contains extra type III domain A.
[0265] As used herein, "EDA- fibronectin mRNA" means a fibronectin transcript that does not contain the extra type III domain A exon.
[0266] As used herein, "EDA+ fibronectin mRNA" means a fibronectin transcript that contains the extra type III domain A exon.
[0267] As used herein, "targeting" or "targeted to" means the association of an antisense compound to a particular target nucleic acid molecule or a particular region of a target nucleic acid molecule. An antisense compound targets a target nucleic acid if it is sufficiently complementary to the target nucleic acid to allow hybridization under physiological conditions.
[0268] As used herein, "nucleobase complementarity" or "complementarity" when in reference to nucleobases means a nucleobase that is capable of base pairing with another nucleobase. For example, in DNA, adenine (A) is complementary to thymine (T). For example, in RNA, adenine (A) is complementary to uracil (U). In certain embodiments, complementary nucleobase means a nucleobase of an antisense compound that is capable of base pairing with a nucleobase of its target nucleic acid. For example, if a nucleobase at a certain position of an antisense compound is capable of hydrogen bonding with a nucleobase at a certain position of a target nucleic acid, then the position of hydrogen bonding between the oligonucleotide and the target nucleic acid is considered to be complementary at that nucleobase pair. Nucleobases comprising certain modifications may maintain the ability to pair with a counterpart nucleobase and thus, are still capable of nucleobase complementarity.
[0269] As used herein, "non-complementary" in reference to nucleobases means a pair of nucleobases that do not form hydrogen bonds with one another.
[0270] As used herein, "complementary" in reference to oligomeric compounds (e.g., linked nucleosides, oligonucleotides, or nucleic acids) means the capacity of such oligomeric compounds or regions thereof to hybridize to another oligomeric compound or region thereof through nucleobase complementarity under stringent conditions. Complementary oligomeric compounds need not have nucleobase complementarity at each nucleoside. Rather, some mismatches are tolerated. In certain embodiments, complementary oligomeric compounds or regions are complementary at 70% of the nucleobases (70% complementary). In certain embodiments, complementary oligomeric compounds or regions are 80% complementary. In certain embodiments, complementary oligomeric compounds or regions are 90% complementary. In certain embodiments, complementary oligomeric compounds or regions are 95% complementary. In certain embodiments, complementary oligomeric compounds or regions are 100% complementary.
[0271] As used herein, "hybridization" means the pairing of complementary oligomeric compounds (e.g., an antisense compound and its target nucleic acid). While not limited to a particular mechanism, the most common mechanism of pairing involves hydrogen bonding, which may be Watson-Crick, Hoogsteen or reversed Hoogsteen hydrogen bonding, between complementary nucleobases.
[0272] As used herein, "specifically hybridizes" means the ability of an oligomeric compound to hybridize to one nucleic acid site with greater affinity than it hybridizes to another nucleic acid site. In certain embodiments, an antisense oligonucleotide specifically hybridizes to more than one target site.
[0273] As used herein, "percent complementarity" means the percentage of nucleobases of an oligomeric compound that are complementary to an equal-length portion of a target nucleic acid. Percent complementarity is calculated by dividing the number of nucleobases of the oligomeric compound that are complementary to nucleobases at corresponding positions in the target nucleic acid by the total length of the oligomeric compound.
[0274] As used herein, "percent identity" means the number of nucleobases in a first nucleic acid that are the same type (independent of chemical modification) as nucleobases at corresponding positions in a second nucleic acid, divided by the total number of nucleobases in the first nucleic acid.
[0275] As used herein, "modulation" means a change of amount or quality of a molecule, function, or activity when compared to the amount or quality of a molecule, function, or activity prior to modulation. For example, modulation includes the change, either an increase (stimulation or induction) or a decrease (inhibition or reduction) in gene expression. As a further example, modulation of expression can include a change in splice site selection of pre-mRNA processing, resulting in a change in the absolute or relative amount of a particular splice-variant compared to the amount in the absence of modulation.
[0276] As used herein, "motif" means a pattern of chemical modifications in an oligomeric compound or a region thereof. Motifs may be defined by modifications at certain nucleosides and/or at certain linking groups of an oligomeric compound.
[0277] As used herein, "nucleoside motif" means a pattern of nucleoside modifications in an oligomeric compound or a region thereof. The linkages of such an oligomeric compound may be modified or unmodified. Unless otherwise indicated, motifs herein describing only nucleosides are intended to be nucleoside motifs. Thus, in such instances, the linkages are not limited.
[0278] As used herein, "sugar motif" means a pattern of sugar modifications in an oligomeric compound or a region thereof.
[0279] As used herein, "linkage motif" means a pattern of linkage modifications in an oligomeric compound or region thereof. The nucleosides of such an oligomeric compound may be modified or unmodified. Unless otherwise indicated, motifs herein describing only linkages are intended to be linkage motifs. Thus, in such instances, the nucleosides are not limited.
[0280] As used herein, "nucleobase modification motif" means a pattern of modifications to nucleobases along an oligonucleotide. Unless otherwise indicated, a nucleobase modification motif is independent of the nucleobase sequence.
[0281] As used herein, "sequence motif" means a pattern of nucleobases arranged along an oligonucleotide or portion thereof. Unless otherwise indicated, a sequence motif is independent of chemical modifications and thus may have any combination of chemical modifications, including no chemical modifications.
[0282] As used herein, "type of modification" in reference to a nucleoside or a nucleoside of a "type" means the chemical modification of a nucleoside and includes modified and unmodified nucleosides. Accordingly, unless otherwise indicated, a "nucleoside having a modification of a first type" may be an unmodified nucleoside.
[0283] As used herein, "differently modified" mean chemical modifications or chemical substituents that are different from one another, including absence of modifications. Thus, for example, a MOE nucleoside and an unmodified DNA nucleoside are "differently modified," even though the DNA nucleoside is unmodified. Likewise, DNA and RNA are "differently modified," even though both are naturally-occurring unmodified nucleosides. Nucleosides that are the same but for comprising different nucleobases are not differently modified. For example, a nucleoside comprising a 2'-OMe modified sugar and an unmodified adenine nucleobase and a nucleoside comprising a 2'-OMe modified sugar and an unmodified thymine nucleobase are not differently modified.
[0284] As used herein, "the same type of modifications" refers to modifications that are the same as one another, including absence of modifications. Thus, for example, two unmodified DNA nucleoside have "the same type of modification," even though the DNA nucleoside is unmodified. Such nucleosides having the same type modification may comprise different nucleobases.
[0285] As used herein, "pharmaceutically acceptable carrier or diluent" means any substance suitable for use in administering to an animal. In certain embodiments, a pharmaceutically acceptable carrier or diluent is sterile saline. In certain embodiments, such sterile saline is pharmaceutical grade saline.
[0286] As used herein, "substituent" and "substituent group," means an atom or group that replaces the atom or group of a named parent compound. For example a substituent of a modified nucleoside is any atom or group that differs from the atom or group found in a naturally occurring nucleoside (e.g., a modified 2'-substituent is any atom or group at the 2'-position of a nucleoside other than H or OH). Substituent groups can be protected or unprotected. In certain embodiments, compounds of the present invention have substituents at one or at more than one position of the parent compound. Substituents may also be further substituted with other substituent groups and may be attached directly or via a linking group such as an alkyl or hydrocarbyl group to a parent compound.
[0287] Likewise, as used herein, "substituent" in reference to a chemical functional group means an atom or group of atoms differs from the atom or a group of atoms normally present in the named functional group. In certain embodiments, a substituent replaces a hydrogen atom of the functional group (e.g., in certain embodiments, the substituent of a substituted methyl group is an atom or group other than hydrogen which replaces one of the hydrogen atoms of an unsubstituted methyl group). Unless otherwise indicated, groups amenable for use as substituents include without limitation, halogen, hydroxyl, alkyl, alkenyl, alkynyl, acyl (--C(O)R.sub.aa), carboxyl (--C(O)O--R.sub.aa), aliphatic groups, alicyclic groups, alkoxy, substituted oxy (--O--R.sub.aa), aryl, aralkyl, heterocyclic radical, heteroaryl, heteroarylalkyl, amino (--N(R.sub.bb)(R.sub.cc)), imino(.dbd.NR.sub.bb), amido (--C(O)N(R.sub.bb)(R.sub.cc) or --N(R.sub.bb)C(O)R.sub.aa), azido (--N.sub.3), nitro (--NO.sub.2), cyano (--CN), carbamido (--OC(O)N(R.sub.bb)(R.sub.cc) or --N(R.sub.bb)C(O)OR.sub.aa), ureido (--N(R.sub.bb)C(O)N(R.sub.bb)(R.sub.cc)), thioureido (--N(R.sub.bb)C(S)N(R.sub.bb)--(R.sub.cc)), guanidinyl (--N(R.sub.bb)C(.dbd.NR.sub.bb)N(R.sub.bb)(R.sub.cc)), amidinyl (--C(.dbd.NR.sub.bb)N(R.sub.bb)(R.sub.cc) or --N(R.sub.bb)C(.dbd.NR.sub.bb)(R.sub.aa)), thiol (--SR.sub.bb), sulfinyl (--S(O)R.sub.bb), sulfonyl (--S(O).sub.2R.sub.bb) and sulfonamidyl (--S(O).sub.2N(R.sub.bb)(R.sub.cc) or --N(R.sub.bb)S--(O).sub.2R.sub.bb). Wherein each R.sub.aa, R.sub.bb and R.sub.cc is, independently, H, an optionally linked chemical functional group or a further substituent group with a preferred list including without limitation, alkyl, alkenyl, alkynyl, aliphatic, alkoxy, acyl, aryl, aralkyl, heteroaryl, alicyclic, heterocyclic and heteroarylalkyl. Selected substituents within the compounds described herein are present to a recursive degree.
[0288] As used herein, "alkyl," as used herein, means a saturated straight or branched hydrocarbon radical containing up to twenty four carbon atoms. Examples of alkyl groups include without limitation, methyl, ethyl, propyl, butyl, isopropyl, n-hexyl, octyl, decyl, dodecyl and the like. Alkyl groups typically include from 1 to about 24 carbon atoms, more typically from 1 to about 12 carbon atoms (C.sub.1-C.sub.12 alkyl) with from 1 to about 6 carbon atoms being more preferred.
[0289] As used herein, "alkenyl," means a straight or branched hydrocarbon chain radical containing up to twenty four carbon atoms and having at least one carbon-carbon double bond. Examples of alkenyl groups include without limitation, ethenyl, propenyl, butenyl, 1-methyl-2-buten-1-yl, dienes such as 1,3-butadiene and the like. Alkenyl groups typically include from 2 to about 24 carbon atoms, more typically from 2 to about 12 carbon atoms with from 2 to about 6 carbon atoms being more preferred. Alkenyl groups as used herein may optionally include one or more further substituent groups.
[0290] As used herein, "alkynyl," means a straight or branched hydrocarbon radical containing up to twenty four carbon atoms and having at least one carbon-carbon triple bond. Examples of alkynyl groups include, without limitation, ethynyl, 1-propynyl, 1-butynyl, and the like. Alkynyl groups typically include from 2 to about 24 carbon atoms, more typically from 2 to about 12 carbon atoms with from 2 to about 6 carbon atoms being more preferred. Alkynyl groups as used herein may optionally include one or more further substituent groups.
[0291] As used herein, "acyl," means a radical formed by removal of a hydroxyl group from an organic acid and has the general Formula --C(O)--X where X is typically aliphatic, alicyclic or aromatic. Examples include aliphatic carbonyls, aromatic carbonyls, aliphatic sulfonyls, aromatic sulfinyls, aliphatic sulfinyls, aromatic phosphates, aliphatic phosphates and the like. Acyl groups as used herein may optionally include further substituent groups.
[0292] As used herein, "alicyclic" means a cyclic ring system wherein the ring is aliphatic. The ring system can comprise one or more rings wherein at least one ring is aliphatic. Preferred alicyclics include rings having from about 5 to about 9 carbon atoms in the ring. Alicyclic as used herein may optionally include further substituent groups.
[0293] As used herein, "aliphatic" means a straight or branched hydrocarbon radical containing up to twenty four carbon atoms wherein the saturation between any two carbon atoms is a single, double or triple bond. An aliphatic group preferably contains from 1 to about 24 carbon atoms, more typically from 1 to about 12 carbon atoms with from 1 to about 6 carbon atoms being more preferred. The straight or branched chain of an aliphatic group may be interrupted with one or more heteroatoms that include nitrogen, oxygen, sulfur and phosphorus. Such aliphatic groups interrupted by heteroatoms include without limitation, polyalkoxys, such as polyalkylene glycols, polyamines, and polyimines. Aliphatic groups as used herein may optionally include further substituent groups.
[0294] As used herein, "alkoxy" means a radical formed between an alkyl group and an oxygen atom wherein the oxygen atom is used to attach the alkoxy group to a parent molecule. Examples of alkoxy groups include without limitation, methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, sec-butoxy, tert-butoxy, n-pentoxy, neopentoxy, n-hexoxy and the like. Alkoxy groups as used herein may optionally include further substituent groups.
[0295] As used herein, "aminoalkyl" means an amino substituted C.sub.1-C.sub.12 alkyl radical. The alkyl portion of the radical forms a covalent bond with a parent molecule. The amino group can be located at any position and the aminoalkyl group can be substituted with a further substituent group at the alkyl and/or amino portions.
[0296] As used herein, "aralkyl" and "arylalkyl" mean an aromatic group that is covalently linked to a C.sub.1-C.sub.12 alkyl radical. The alkyl radical portion of the resulting aralkyl (or arylalkyl) group forms a covalent bond with a parent molecule. Examples include without limitation, benzyl, phenethyl and the like. Aralkyl groups as used herein may optionally include further substituent groups attached to the alkyl, the aryl or both groups that form the radical group.
[0297] As used herein, "aryl" and "aromatic" mean a mono- or polycyclic carbocyclic ring system radicals having one or more aromatic rings. Examples of aryl groups include without limitation, phenyl, naphthyl, tetrahydronaphthyl, indanyl, idenyl and the like. Preferred aryl ring systems have from about 5 to about 20 carbon atoms in one or more rings. Aryl groups as used herein may optionally include further substituent groups.
[0298] As used herein, "halo" and "halogen," mean an atom selected from fluorine, chlorine, bromine and iodine.
[0299] As used herein, "heteroaryl," and "heteroaromatic," mean a radical comprising a mono- or polycyclic aromatic ring, ring system or fused ring system wherein at least one of the rings is aromatic and includes one or more heteroatoms. Heteroaryl is also meant to include fused ring systems including systems where one or more of the fused rings contain no heteroatoms. Heteroaryl groups typically include one ring atom selected from sulfur, nitrogen or oxygen. Examples of heteroaryl groups include without limitation, pyridinyl, pyrazinyl, pyrimidinyl, pyrrolyl, pyrazolyl, imidazolyl, thiazolyl, oxazolyl, isooxazolyl, thiadiazolyl, oxadiazolyl, thiophenyl, furanyl, quinolinyl, isoquinolinyl, benzimidazolyl, benzooxazolyl, quinoxalinyl and the like. Heteroaryl radicals can be attached to a parent molecule directly or through a linking moiety such as an aliphatic group or hetero atom. Heteroaryl groups as used herein may optionally include further substituent groups.
Oligomeric Compounds
[0300] In certain embodiments, the present invention provides oligomeric compounds. In certain embodiments, such oligomeric compounds comprise oligonucleotides optionally comprising one or more conjugate and/or terminal groups. In certain embodiments, an oligomeric compound consists of an oligonucleotide. In certain embodiments, oligonucleotides comprise one or more chemical modifications. Such chemical modifications include modifications one or more nucleoside (including modifications to the sugar moiety and/or the nucleobase) and/or modifications to one or more internucleoside linkage.
[0301] Certain Sugar Moieties
[0302] In certain embodiments, oligomeric compounds of the invention comprise one or more modified nucleosides comprising a modified sugar moiety. Such oligomeric compounds comprising one or more sugar-modified nucleosides may have desirable properties, such as enhanced nuclease stability or increased binding affinity with a target nucleic acid relative to oligomeric compounds comprising only nucleosides comprising naturally occurring sugar moieties. In certain embodiments, modified sugar moieties are substituted sugar moieties. In certain embodiments, modified sugar moieties are bicyclic or tricyclic sugar moieties. In certain embodiments, modified sugar moieties are sugar surrogates. Such sugar surrogates may comprise one or more substitutions corresponding to those of substituted sugar moieties.
[0303] In certain embodiments, modified sugar moieties are substituted sugar moieties comprising one or more substituent, including but not limited to substituents at the 2' and/or 5' positions. Examples of sugar substituents suitable for the 2'-position, include, but are not limited to: 2'-F, 2'-OCH.sub.3 ("OMe" or "O-methyl"), and 2'-O(CH.sub.2).sub.2OCH.sub.3 ("MOE"). In certain embodiments, sugar substituents at the 2' position is selected from allyl, amino, azido, thio, O-allyl, O--C.sub.1-C.sub.10 alkyl, O--C.sub.1-C.sub.10 substituted alkyl; I--C.sub.1-C.sub.10 alkoxy; O--C.sub.1-C.sub.10 substituted alkoxy, OCF.sub.3, O(CH.sub.2).sub.2SCH.sub.3, O(CH.sub.2).sub.2--O--N(Rm)(Rn), and O--CH.sub.2--C(.dbd.O)--N(Rm)(Rn), where each Rm and Rn is, independently, H or substituted or unsubstituted C.sub.1-C.sub.10 alkyl. Examples of sugar substituents at the 5'-position, include, but are not limited to: 5'-methyl (R or S); 5'-vinyl, and 5'-methoxy. In certain embodiments, substituted sugars comprise more than one non-bridging sugar substituent, for example, 2'-F-5'-methyl sugar moieties (see, e.g., PCT International Application WO 2008/101157, for additional 5', 2'-bis substituted sugar moieties and nucleosides).
[0304] Nucleosides comprising 2'-substituted sugar moieties are referred to as 2'-substituted nucleosides. In certain embodiments, a 2'-substituted nucleoside comprises a 2'-substituent group selected from halo, allyl, amino, azido, O--C.sub.1-C.sub.10 alkoxy; O--C.sub.1-C.sub.10 substituted alkoxy, SH, CN, OCN, CF.sub.3, OCF.sub.3, O-alkyl, S-alkyl, N(R.sub.m)-alkyl; O-alkenyl, S-alkenyl, or N(R.sub.m)-alkenyl; O-alkynyl, S-alkynyl, N(R.sub.m)-alkynyl; O-alkylenyl-O-alkyl, alkynyl, alkaryl, aralkyl, O-alkaryl, O-aralkyl, O(CH.sub.2).sub.2SCH.sub.3, O--(CH.sub.2).sub.2--O--N(R.sub.m)(R.sub.n) or O--CH.sub.2--C(.dbd.O)--N(R.sub.m)(R.sub.n), where each R.sub.m and R.sub.n is, independently, H, an amino protecting group or substituted or unsubstituted C.sub.1-C.sub.10 alkyl. These 2'-substituent groups can be further substituted with one or more substituent groups independently selected from hydroxyl, amino, alkoxy, carboxy, benzyl, phenyl, nitro (NO.sub.2), thiol, thioalkoxy (S-alkyl), halogen, alkyl, aryl, alkenyl and alkynyl.
[0305] In certain embodiments, a 2'-substituted nucleoside comprises a 2'-substituent group selected from F, NH.sub.2, N.sub.3, OCF.sub.3, O--CH.sub.3, O(CH.sub.2).sub.3NH.sub.2, CH.sub.2--CH.dbd.CH.sub.2, O--CH.sub.2--CH.dbd.CH.sub.2, OCH.sub.2CH.sub.2OCH.sub.3, O(CH.sub.2).sub.2SCH.sub.3, O--(CH.sub.2).sub.2--O--N(R.sub.m)(R.sub.n), O(CH.sub.2).sub.2O(CH.sub.2).sub.2N(CH.sub.3).sub.2, and N-substituted acetamide (O--CH.sub.2--C(.dbd.O)--N(R.sub.m)(R.sub.n) where each R.sub.m and R.sub.n is, independently, H, an amino protecting group or substituted or unsubstituted C.sub.1-C.sub.10 alkyl.
[0306] In certain embodiments, a 2'-substituted nucleoside comprises a sugar moiety comprising a 2'-substituent group selected from F, OCF.sub.3, O--CH.sub.3, OCH.sub.2CH.sub.2OCH.sub.3, O(CH.sub.2).sub.2SCH.sub.3, O--(CH.sub.2).sub.2--O--N(CH.sub.3).sub.2, --O(CH.sub.2).sub.2O(CH.sub.2).sub.2N(CH.sub.3).sub.2, and O--CH.sub.2--C(.dbd.O)--N(H)CH.sub.3.
[0307] In certain embodiments, a 2'-substituted nucleoside comprises a sugar moiety comprising a 2'-substituent group selected from F, O--CH.sub.3, and OCH.sub.2CH.sub.2OCH.sub.3.
[0308] Certain modified sugar moieties comprise a bridging sugar substituent that forms a second ring resulting in a bicyclic sugar moiety. In certain such embodiments, the bicyclic sugar moiety comprises a bridge between the 4' and the 2' furanose ring atoms. Examples of such 4' to 2' sugar substituents, include, but are not limited to: --[C(R.sub.a)(R.sub.b)].sub.n--, --[C(R.sub.a)(R.sub.b)].sub.n--O--, --C(R.sub.aR.sub.b)--N(R)--O-- or, --C(R.sub.aR.sub.b)--O--N(R)--; 4'- CH.sub.2-2', 4'-(CH.sub.2).sub.2-2', 4'-(CH.sub.2).sub.3-2'; 4'-(CH.sub.2)--O-2' (LNA); 4'-(CH.sub.2)--S-2'; 4'-(CH.sub.2).sub.2--O-2' (ENA); 4'-CH(CH.sub.3)--O-2' (cEt) and 4'-CH(CH.sub.2OCH.sub.3)--O-2', and analogs thereof (see, e.g., U.S. Pat. No. 7,399,845, issued on Jul. 15, 2008); 4'-C(CH.sub.3)(CH.sub.3)--O-2' and analogs thereof, (see, e.g., WO2009/006478, published Jan. 8, 2009); 4'-CH.sub.2--N(OCH.sub.3)-2' and analogs thereof (see, e.g., WO2008/150729, published Dec. 11, 2008); 4'-CH.sub.2--O--N(CH.sub.3)-2' (see, e.g., US2004/0171570, published Sep. 2, 2004); 4'-CH.sub.2--O--N(R)-2', and 4'-CH.sub.2--N(R)-0-2'-, wherein each R is, independently, H, a protecting group, or C.sub.1-C.sub.12 alkyl; 4'-CH.sub.2--N(R)--O-2', wherein R is H, C.sub.1-C.sub.12 alkyl, or a protecting group (see, U.S. Pat. No. 7,427,672, issued on Sep. 23, 2008); 4'-CH.sub.2--C(H)(CH.sub.3)-2' (see, e.g., Chattopadhyaya, et al., J. Org. Chem., 2009, 74, 118-134); and 4'-CH.sub.2--C(.dbd.CH.sub.2)-2' and analogs thereof (see, published PCT International Application WO 2008/154401, published on Dec. 8, 2008).
[0309] In certain embodiments, such 4' to 2' bridges independently comprise from 1 to 4 linked groups independently selected from --[C(R.sub.a)(R.sub.b)].sub.n--, --C(R.sub.a).dbd.C(R.sub.b)--, --C(R.sub.a).dbd.N--, --C(.dbd.NR.sub.a)--, --C(.dbd.O)--, --C(.dbd.S)--, --O--, --Si(R.sub.a).sub.2--, --S(.dbd.O).sub.x--, and --N(R.sub.a)--;
[0310] wherein:
[0311] x is 0, 1, or 2;
[0312] n is 1, 2, 3, or 4;
[0313] each R.sub.a and R.sub.b is, independently, H, a protecting group, hydroxyl, C.sub.1-C.sub.12 alkyl, substituted C.sub.1-C.sub.12 alkyl, C.sub.2-C.sub.12 alkenyl, substituted C.sub.2-C.sub.12 alkenyl, C.sub.2-C.sub.12 alkynyl, substituted C.sub.2-C.sub.12 alkynyl, C.sub.5-C.sub.20 aryl, substituted C.sub.5-C.sub.20 aryl, heterocycle radical, substituted heterocycle radical, heteroaryl, substituted heteroaryl, C.sub.5-C.sub.7 alicyclic radical, substituted C.sub.5-C.sub.7 alicyclic radical, halogen, OJ.sub.1, NJ.sub.1J.sub.2, SJ.sub.1, N.sub.3, COOJ.sub.1, acyl (C(.dbd.O)--H), substituted acyl, CN, sulfonyl (S(.dbd.O).sub.2-J.sub.1), or sulfoxyl (S(.dbd.O)-J.sub.1); and each J.sub.1 and J.sub.2 is, independently, H, C.sub.1-C.sub.12 alkyl, substituted C.sub.1-C.sub.12 alkyl, C.sub.2-C.sub.12 alkenyl, substituted C.sub.2-C.sub.12 alkenyl, C.sub.2-C.sub.12 alkynyl, substituted C.sub.2-C.sub.12 alkynyl, C.sub.5-C.sub.20 aryl, substituted C.sub.5-C.sub.20 aryl, acyl (C(.dbd.O)--H), substituted acyl, a heterocycle radical, a substituted heterocycle radical, C.sub.1-C.sub.12 aminoalkyl, substituted C.sub.1-C.sub.12 aminoalkyl, or a protecting group.
[0314] Nucleosides comprising bicyclic sugar moieties are referred to as bicyclic nucleosides or BNAs. Bicyclic nucleosides include, but are not limited to, (A) .alpha.-L-Methyleneoxy (4'-CH.sub.2--O-2') BNA, (B) .beta.-D-Methyleneoxy (4'-CH.sub.2--O-2') BNA (also referred to as locked nucleic acid or LNA), (C) Ethyleneoxy (4'-(CH.sub.2).sub.2--O-2') BNA, (D) Aminooxy (4'-CH.sub.2--O--N(R)-2') BNA, (E) Oxyamino (4'-CH.sub.2--N(R)--O-2') BNA, (F) Methyl(methyleneoxy) (4'-CH(CH.sub.3)--O-2') BNA (also referred to as constrained ethyl or cEt), (G) methylene-thio (4'-CH.sub.2--S-2') BNA, (H) methylene-amino (4'-CH.sub.2--N(R)-2') BNA, (I) methyl carbocyclic (4'-CH.sub.2--CH(CH.sub.3)-2') BNA, and (J) propylene carbocyclic (4'-(CH.sub.2).sub.3-2') BNA as depicted below.
##STR00001## ##STR00002##
wherein Bx is a nucleobase moiety and R is, independently, H, a protecting group, or C.sub.1-C.sub.12 alkyl.
[0315] Additional bicyclic sugar moieties are known in the art, for example: Singh et al., Chem. Commun., 1998, 4, 455-456; Koshkin et al., Tetrahedron, 1998, 54, 3607-3630; Wahlestedt et al., Proc. Natl. Acad. Sci. U.S.A., 2000, 97, 5633-5638; Kumar et al., Bioorg. Med. Chem. Lett., 1998, 8, 2219-2222; Singh et al., J Org. Chem., 1998, 63, 10035-10039; Srivastava et al., J Am. Chem. Soc., 129(26) 8362-8379 (Jul. 4, 2007); Elayadi et al., Curr. Opinion Invens. Drugs, 2001, 2, 558-561; Braasch et al., Chem. Biol., 2001, 8, 1-7; Orum et al., Curr. Opinion Mol. Ther., 2001, 3, 239-243; U.S. Pat. Nos. 7,053,207, 6,268,490, 6,770,748, 6,794,499, 7,034,133, 6,525,191, 6,670,461, and 7,399,845; WO 2004/106356, WO 1994/14226, WO 2005/021570, and WO 2007/134181; U.S. Patent Publication Nos. US2004/0171570, US2007/0287831, and US2008/0039618; U.S. patent Ser. Nos. 12/129,154, 60/989,574, 61/026,995, 61/026,998, 61/056,564, 61/086,231, 61/097,787, and 61/099,844; and PCT International Applications Nos. PCT/US2008/064591, PCT/US2008/066154, and PCT/US2008/068922.
[0316] In certain embodiments, bicyclic sugar moieties and nucleosides incorporating such bicyclic sugar moieties are further defined by isomeric configuration. For example, a nucleoside comprising a 4'-2' methylene-oxy bridge, may be in the .alpha.-L configuration or in the .beta.-D configuration. Previously, .alpha.-L-methyleneoxy (4'-CH.sub.2--O-2') bicyclic nucleosides have been incorporated into antisense oligonucleotides that showed antisense activity (Frieden et al., Nucleic Acids Research, 2003, 21, 6365-6372).
[0317] In certain embodiments, substituted sugar moieties comprise one or more non-bridging sugar substituent and one or more bridging sugar substituent (e.g., 5'-substituted and 4'-2' bridged sugars). (see, PCT International Application WO 2007/134181, published on Nov. 22, 2007, wherein LNA is substituted with, for example, a 5'-methyl or a 5'-vinyl group).
[0318] In certain embodiments, modified sugar moieties are sugar surrogates. In certain such embodiments, the oxygen atom of the naturally occurring sugar is substituted, e.g., with a sulfur, carbon or nitrogen atom. In certain such embodiments, such modified sugar moiety also comprises bridging and/or non-bridging substituents as described above. For example, certain sugar surrogates comprise a 4'-sulfur atom and a substitution at the 2'-position (see, e.g., published U.S. Patent Application US2005/0130923, published on Jun. 16, 2005) and/or the 5' position. By way of additional example, carbocyclic bicyclic nucleosides having a 4'-2' bridge have been described (see, e.g., Freier et al., Nucleic Acids Research, 1997, 25(22), 4429-4443 and Albaek et al., J. Org. Chem., 2006, 71, 7731-7740).
[0319] In certain embodiments, sugar surrogates comprise rings having other than 5-atoms. For example, in certain embodiments, a sugar surrogate comprises a six-membered tetrahydropyran. Such tetrahydropyrans may be further modified or substituted. Nucleosides comprising such modified tetrahydropyrans include, but are not limited to, hexitol nucleic acid (HNA), annitol nucleic acid (ANA), mannitol nucleic acid (MNA) (see Leumann, C J. Bioorg. & Med. Chem. (2002) 10:841-854), fluoro HNA (F-HNA), and those compounds having Formula VII:
##STR00003##
wherein independently for each of said at least one tetrahydropyran nucleoside analog of Formula VII:
[0320] Bx is a nucleobase moiety;
[0321] T.sub.3 and T.sub.4 are each, independently, an internucleoside linking group linking the tetrahydropyran nucleoside analog to the antisense compound or one of T.sub.3 and T.sub.4 is an internucleoside linking group linking the tetrahydropyran nucleoside analog to the antisense compound and the other of T.sub.3 and T.sub.4 is H, a hydroxyl protecting group, a linked conjugate group, or a 5' or 3'-terminal group;
q.sub.1, q.sub.2, q.sub.3, q.sub.4, q.sub.5, q.sub.6 and q.sub.7 are each, independently, H, C.sub.1-C.sub.6 alkyl, substituted C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, substituted C.sub.2-C.sub.6 alkenyl, C.sub.2-C.sub.6 alkynyl, or substituted C.sub.2-C.sub.6 alkynyl; and each of R.sub.1 and R.sub.2 is independently selected from among: hydrogen, halogen, substituted or unsubstituted alkoxy, NJ.sub.1J.sub.2, SJ.sub.1, N.sub.3, OC(.dbd.X)J.sub.1, OC(.dbd.X)NJ.sub.1J.sub.2, NJ.sub.3C(.dbd.X)NJ.sub.1J.sub.2, and CN, wherein X is O, S or NJ.sub.1, and each J.sub.1, J.sub.2, and J.sub.3 is, independently, H or C.sub.1-C.sub.6 alkyl.
[0322] In certain embodiments, the modified THP nucleosides of Formula VII are provided wherein q.sub.1, q.sub.2, q.sub.3, q.sub.4, q.sub.5, q.sub.6 and q.sub.7 are each H. In certain embodiments, at least one of q.sub.1, q.sub.2, q.sub.3, q.sub.4, q.sub.5, q.sub.6 and q.sub.7 is other than H. In certain embodiments, at least one of q.sub.1, q.sub.2, q.sub.3, q.sub.4, q.sub.5, q.sub.6 and q.sub.7 is methyl. In certain embodiments, THP nucleosides of Formula VII are provided wherein one of R.sub.1 and R.sub.2 is F. In certain embodiments, R.sub.1 is fluoro and R.sub.2 is H, R.sub.1 is methoxy and R.sub.2 is H, and R.sub.1 is methoxyethoxy and R.sub.2 is H.
[0323] Many other bicyclic and tricyclic sugar and sugar surrogate ring systems are known in the art that can be used to modify nucleosides (see, e.g., review article: Leumann, J. C, Bioorganic & Medicinal Chemistry, 2002, 10, 841-854).
[0324] In certain embodiments, sugar surrogates comprise rings having more than 5 atoms and more than one heteroatom. For example nucleosides comprising morpholino sugar moieties and their use in oligomeric compounds has been reported (see for example: Braasch et al., Biochemistry, 2002, 41, 4503-4510; and U.S. Pat. Nos. 5,698,685; 5,166,315; 5,185,444; and 5,034,506). As used here, the term "morpholino" means a sugar surrogate having the following structure:
##STR00004##
In certain embodiments, morpholinos may be modified, for example by adding or altering various substituent groups from the above morpholino structure. Such sugar surrogates are referred to herein as "modified morpholinos."
[0325] Combinations of modifications are also provided without limitation, such as 2'-F-5'-methyl substituted nucleosides (see PCT International Application WO 2008/101157 Published on Aug. 21, 2008 for other disclosed 5', 2'-bis substituted nucleosides) and replacement of the ribosyl ring oxygen atom with S and further substitution at the 2'-position (see published U.S. Patent Application US2005-0130923, published on Jun. 16, 2005) or alternatively 5'-substitution of a bicyclic nucleic acid (see PCT International Application WO 2007/134181, published on Nov. 22, 2007 wherein a 4'-CH.sub.2--O-2' bicyclic nucleoside is further substituted at the 5' position with a 5'-methyl or a 5'-vinyl group). The synthesis and preparation of carbocyclic bicyclic nucleosides along with their oligomerization and biochemical studies have also been described (see, e.g., Srivastava et al., J Am. Chem. Soc. 2007, 129(26), 8362-8379).
[0326] Certain Nucleobases
[0327] In certain embodiments, nucleosides of the present invention comprise one or more unmodified nucleobases. In certain embodiments, nucleosides of the present invention comprise one or more modified nucleobases.
[0328] In certain embodiments, modified nucleobases are selected from: universal bases, hydrophobic bases, promiscuous bases, size-expanded bases, and fluorinated bases as defined herein. 5-substituted pyrimidines, 6-azapyrimidines and N-2, N-6 and 0-6 substituted purines, including 2-aminopropyladenine, 5-propynyluracil; 5-propynylcytosine; 5-hydroxymethyl cytosine, xanthine, hypoxanthine, 2-aminoadenine, 6-methyl and other alkyl derivatives of adenine and guanine, 2-propyl and other alkyl derivatives of adenine and guanine, 2-thiouracil, 2-thiothymine and 2-thiocytosine, 5-halouracil and cytosine, 5-propynyl (--C.ident.C.ident.CH.sub.3) uracil and cytosine and other alkynyl derivatives of pyrimidine bases, 6-azo uracil, cytosine and thymine, 5-uracil (pseudouracil), 4-thiouracil, 8-halo, 8-amino, 8-thiol, 8-thioalkyl, 8-hydroxyl and other 8-substituted adenines and guanines, 5-halo particularly 5-bromo, 5-trifluoromethyl and other 5-substituted uracils and cytosines, 7-methylguanine and 7-methyladenine, 2-F-adenine, 2-amino-adenine, 8-azaguanine and 8-azaadenine, 7-deazaguanine and 7-deazaadenine, 3-deazaguanine and 3-deazaadenine, universal bases, hydrophobic bases, promiscuous bases, size-expanded bases, and fluorinated bases as defined herein. Further modified nucleobases include tricyclic pyrimidines such as phenoxazine cytidine([5,4-b][1,4]benzoxazin-2(3H)-one), phenothiazine cytidine (1H-pyrimido[5,4-b][1,4]benzothiazin-2(3H)-one), G-clamps such as a substituted phenoxazine cytidine (e.g. 9-(2-aminoethoxy)-H-pyrimido[5,4-b][1,4]benzoxazin-2(3H)-one), carbazole cytidine (2H-pyrimido[4,5-b]indol-2-one), pyridoindole cytidine (H-pyrido[3',2':4,5]pyrrolo[2,3-d]pyrimidin-2-one). Modified nucleobases may also include those in which the purine or pyrimidine base is replaced with other heterocycles, for example 7-deaza-adenine, 7-deazaguanosine, 2-aminopyridine and 2-pyridone. Further nucleobases include those disclosed in U.S. Pat. No. 3,687,808, those disclosed in The Concise Encyclopedia Of Polymer Science And Engineering, Kroschwitz, J. I., Ed., John Wiley & Sons, 1990, 858-859; those disclosed by Englisch et al., Angewandte Chemie, International Edition, 1991, 30, 613; and those disclosed by Sanghvi, Y. S., Chapter 15, Antisense Research and Applications, Crooke, S. T. and Lebleu, B., Eds., CRC Press, 1993, 273-288.
[0329] Representative United States patents that teach the preparation of certain of the above noted modified nucleobases as well as other modified nucleobases include without limitation, U.S. Pat. Nos. 3,687,808; 4,845,205; 5,130,302; 5,134,066; 5,175,273; 5,367,066; 5,432,272; 5,457,187; 5,459,255; 5,484,908; 5,502,177; 5,525,711; 5,552,540; 5,587,469; 5,594,121; 5,596,091; 5,614,617; 5,645,985; 5,681,941; 5,750,692; 5,763,588; 5,830,653 and 6,005,096, certain of which are commonly owned with the instant application, and each of which is herein incorporated by reference in its entirety.
[0330] Certain Internucleoside Linkages
[0331] In certain embodiments, the present invention provides oligomeric compounds comprising linked nucleosides. In such embodiments, nucleosides may be linked together using any internucleoside linkage. The two main classes of internucleoside linking groups are defined by the presence or absence of a phosphorus atom. Representative phosphorus containing internucleoside linkages include, but are not limited to, phosphodiesters (P.dbd.O), phosphotriesters, methylphosphonates, phosphoramidate, and phosphorothioates (P.dbd.S). Representative non-phosphorus containing internucleoside linking groups include, but are not limited to, methylenemethylimino (--CH.sub.2--N(CH.sub.3)--O--CH.sub.2--), thiodiester (--O--C(O)--S--), thionocarbamate (--O--C(O)(NH)--S--); siloxane (--O--Si(H).sub.2--O--); and N,N'-dimethylhydrazine (--CH.sub.2--N(CH.sub.3)--N(CH.sub.3)--). Modified linkages, compared to natural phosphodiester linkages, can be used to alter, typically increase, nuclease resistance of the oligomeric compound. In certain embodiments, internucleoside linkages having a chiral atom can be prepared as a racemic mixture, or as separate enantiomers. Representative chiral linkages include, but are not limited to, alkylphosphonates and phosphorothioates. Methods of preparation of phosphorous-containing and non-phosphorous-containing internucleoside linkages are well known to those skilled in the art.
[0332] The oligonucleotides described herein contain one or more asymmetric centers and thus give rise to enantiomers, diastereomers, and other stereoisomeric configurations that may be defined, in terms of absolute stereochemistry, as (R) or (S), .alpha. or .beta. such as for sugar anomers, or as (D) or (L) such as for amino acids etc. Included in the antisense compounds provided herein are all such possible isomers, as well as their racemic and optically pure forms.
[0333] Neutral internucleoside linkages include without limitation, phosphotriesters, methylphosphonates, MMI (3'-CH.sub.2--N(CH.sub.3)--O-5'), amide-3 (3'-CH.sub.2--C(.dbd.O)--N(H)-5'), amide-4 (3'-CH.sub.2--N(H)--C(.dbd.O)-5'), formacetal (3'-O--CH.sub.2--O-5'), and thioformacetal (3'-S--CH.sub.2--O-5'). Further neutral internucleoside linkages include nonionic linkages comprising siloxane (dialkylsiloxane), carboxylate ester, carboxamide, sulfide, sulfonate ester and amides (See for example: Carbohydrate Modifications in Antisense Research; Y. S. Sanghvi and P. D. Cook, Eds., ACS Symposium Series 580; Chapters 3 and 4, 40-65). Further neutral internucleoside linkages include nonionic linkages comprising mixed N, O, S and CH.sub.2 component parts.
[0334] Certain Motifs
[0335] In certain embodiments, the present invention provides oligomeric compounds comprising oligonucleotides. In certain embodiments, such oligonucleotides comprise one or more chemical modification. In certain embodiments, chemically modified oligonucleotides comprise one or more modified nucleosides. In certain embodiments, chemically modified oligonucleotides comprise one or more modified nucleosides comprising modified sugars. In certain embodiments, chemically modified oligonucleotides comprise one or more modified nucleosides comprising one or more modified nucleobases. In certain embodiments, chemically modified oligonucleotides comprise one or more modified internucleoside linkages. In certain embodiments, the chemically modifications (sugar modifications, nucleobase modifications, and/or linkage modifications) define a pattern or motif. In certain embodiments, the patterns of chemical modifications of sugar moieties, internucleoside linkages, and nucleobases are each independent of one another. Thus, an oligonucleotide may be described by its sugar modification motif, internucleoside linkage motif and/or nucleobase modification motif (as used herein, nucleobase modification motif describes the chemical modifications to the nucleobases independent of the sequence of nucleobases).
[0336] Certain Sugar Motifs
[0337] In certain embodiments, oligonucleotides comprise one or more type of modified sugar moieties and/or naturally occurring sugar moieties arranged along an oligonucleotide or region thereof in a defined pattern or sugar modification motif. Such motifs may include any of the sugar modifications discussed herein and/or other known sugar modifications.
[0338] In certain embodiments, the oligonucleotides comprise or consist of a region having a gapmer sugar modification motif, which comprises two external regions or "wings" and an internal region or "gap." The three regions of a gapmer motif (the 5'-wing, the gap, and the 3'-wing) form a contiguous sequence of nucleosides wherein at least some of the sugar moieties of the nucleosides of each of the wings differ from at least some of the sugar moieties of the nucleosides of the gap. Specifically, at least the sugar moieties of the nucleosides of each wing that are closest to the gap (the 3'-most nucleoside of the 5'-wing and the 5'-most nucleoside of the 3'-wing) differ from the sugar moiety of the neighboring gap nucleosides, thus defining the boundary between the wings and the gap. In certain embodiments, the sugar moieties within the gap are the same as one another. In certain embodiments, the gap includes one or more nucleoside having a sugar moiety that differs from the sugar moiety of one or more other nucleosides of the gap. In certain embodiments, the sugar modification motifs of the two wings are the same as one another (symmetric gapmer). In certain embodiments, the sugar modification motifs of the 5'-wing differs from the sugar modification motif of the 3'-wing (asymmetric gapmer). In certain embodiments, oligonucleotides comprise 2'-MOE modified nucleosides in the wings and 2'-F modified nucleosides in the gap.
[0339] In certain embodiments, oligonucleotides are fully modified. In certain such embodiments, oligonucleotides are uniformly modified. In certain embodiments, oligonucleotides are uniform 2'-MOE. In certain embodiments, oligonucleotides are uniform 2'-F. In certain embodiments, oligonucleotides are uniform morpholino. In certain embodiments, oligonucleotides are uniform BNA. In certain embodiments, oligonucleotides are uniform LNA. In certain embodiments, oligonucleotides are uniform cEt.
[0340] In certain embodiments, oligonucleotides comprise a uniformly modified region and additional nucleosides that are unmodified or differently modified. In certain embodiments, the uniformly modified region is at least 5, 10, 15, or 20 nucleosides in length. In certain embodiments, the uniform region is a 2'-MOE region. In certain embodiments, the uniform region is a 2'-F region. In certain embodiments, the uniform region is a morpholino region. In certain embodiments, the uniform region is a BNA region. In certain embodiments, the uniform region is a LNA region. In certain embodiments, the uniform region is a cEt region.
[0341] In certain embodiments, the oligonucleotide does not comprise more than 4 contiguous unmodified 2'-deoxynucleosides. In certain circumstances, antisense oligonucleotides comprising more than 4 contiguous 2'-deoxynucleosides activate RNase H, resulting in cleavage of the target RNA. In certain embodiments, such cleavage is avoided by not having more than 4 contiguous 2'-deoxynucleosides, for example, where alteration of splicing and not cleavage of a target RNA is desired.
[0342] Certain Splicing Motifs
[0343] In certain embodiments, oligonucleotides have a certain modification pattern and/or motif designed to alter the splicing of certain nucleic acid transcripts. In certain embodiments, oligonucleotides have a certain modification pattern and/or motif designed to alter the splicing of certain pre-mRNA transcripts. In certain embodiments, oligonucleotides have a certain modification pattern and/or motif designed in such a fashion that the oligonucleotide will not recruit RNase H once bound to a target nucleic acid transcript. For example, in certain such embodiments, an oligonucleotide may have one or more sugar modifications placed throughout the oligonucleotide so as to have no segment comprising more than 4 contiguous 2'-deoxynucleosides. In certain such embodiments, an oligonucleotide may have one or more sugar modifications placed throughout the oligonucleotide so as to have no segment comprising more than 3 contiguous 2'-deoxynucleosides. In certain such embodiments, an oligonucleotide may have one or more sugar modifications placed throughout the oligonucleotide so as to have no segment comprising more than 2 contiguous 2'-deoxynucleosides.
[0344] In certain embodiments, the oligonucleotide compound comprises a modified oligonucleotide consisting of 8 to 30 linked nucleosides and having a nucleobase sequence comprising a complementary region comprising at least 8 contiguous nucleobases complementary to a target region of equal length of a target nucleic acid, wherein the modified oligonucleotide comprises a Ad.sub.2Ad.sub.2Ad.sub.2Ad.sub.2Ad.sub.2A motif, wherein each A independently comprises a bicyclic modification selected from among LNA and cEt and each d comprises a 2'-deoxynucleoside.
[0345] In certain embodiments, the oligonucleotide compound comprises a modified oligonucleotide consisting of 8 to 30 linked nucleosides and having a nucleobase sequence comprising a complementary region comprising at least 8 contiguous nucleobases complementary to a target region of equal length of a target nucleic acid, wherein the modified oligonucleotide comprises a AAddAddAddAddAddAA motif, wherein each A independently comprises a bicyclic modification selected from among LNA and cEt and each d comprises a 2'-deoxynucleoside.
[0346] In certain embodiments, the oligonucleotide compound comprises a modified oligonucleotide consisting of 8 to 30 linked nucleosides and having a nucleobase sequence comprising a complementary region comprising at least 8 contiguous nucleobases complementary to a target region of equal length of a target nucleic acid, wherein the modified oligonucleotide comprises a AABBABBABBABBABBAB motif, wherein each A independently comprises a bicyclic modification selected from among LNA and cEt and each B independently comprises a 2'-modification selected from among a 2'-OMe, 2'-F, or 2'-MOE modification.
[0347] In certain embodiments, the oligonucleotide compound comprises a modified oligonucleotide consisting of 8 to 30 linked nucleosides and having a nucleobase sequence comprising a complementary region comprising at least 8 contiguous nucleobases complementary to a target region of equal length of a target nucleic acid, wherein the modified oligonucleotide comprises a AddAddAddAddAddA motif wherein each A independently comprises a bicyclic modification selected from among LNA and cEt and each d comprises a 2'-deoxynucleoside.
[0348] In certain embodiments, the oligonucleotide compound comprises a modified oligonucleotide consisting of 8 to 30 linked nucleosides and having a nucleobase sequence comprising a complementary region comprising at least 8 contiguous nucleobases complementary to a target region of equal length of a target nucleic acid, wherein the modified oligonucleotide comprises a keekeekeekeekeek motif, wherein each k comprises a cEt modification and each e comprises a 2'-MOE modification.
[0349] In certain embodiments, the oligonucleotide compound comprises a modified oligonucleotide consisting of 8 to 30 linked nucleosides and having a nucleobase sequence comprising a complementary region comprising at least 8 contiguous nucleobases complementary to a target region of equal length of a target nucleic acid, wherein the modified oligonucleotide comprises a kd.sub.2kd.sub.2kd.sub.2kd.sub.2kd.sub.2k motif, wherein each k comprises a cEt modification and each d comprises a 2'-deoxynucleoside.
[0350] In certain embodiments, the oligonucleotide compound comprises a modified oligonucleotide consisting of 8 to 30 linked nucleosides and having a nucleobase sequence comprising a complementary region comprising at least 8 contiguous nucleobases complementary to a target region of equal length of a target nucleic acid, wherein the modified oligonucleotide comprises a kkddkddkddkddkddkk motif, wherein each k comprises a cEt modification and each d comprises a 2'-deoxynucleoside.
[0351] In certain embodiments, the oligonucleotide compound comprises a modified oligonucleotide consisting of 8 to 30 linked nucleosides and having a nucleobase sequence comprising a complementary region comprising at least 8 contiguous nucleobases complementary to a target region of equal length of a target nucleic acid, wherein the modified oligonucleotide comprises a kkeekeekeekeekeeke motif, wherein each k comprises a cEt modification and each e comprises a 2'-MOE modification.
[0352] In certain embodiments, the oligonucleotide compound comprises a modified oligonucleotide consisting of 8 to 30 linked nucleosides and having a nucleobase sequence comprising a complementary region comprising at least 8 contiguous nucleobases complementary to a target region of equal length of a target nucleic acid, wherein the modified oligonucleotide comprises a kddkddkddkddkddk motif wherein each k comprises a cEt modification and each d comprises a 2'-deoxynucleoside.
[0353] In certain embodiments, the oligonucleotide compound comprises a modified oligonucleotide consisting of 8 to 30 linked nucleosides and having a nucleobase sequence comprising a complementary region comprising at least 8 contiguous nucleobases complementary to a target region of equal length of a target nucleic acid, wherein the modified oligonucleotide comprises a keekeekeekeekeek motif, wherein each k comprises a cEt modification and each e comprises a 2'-MOE modification.
[0354] Certain Internucleoside Linkage Motifs
[0355] In certain embodiments, oligonucleotides comprise modified internucleoside linkages arranged along the oligonucleotide or region thereof in a defined pattern or modified internucleoside linkage motif. In certain embodiments, internucleoside linkages are arranged in a gapped motif, as described above for sugar modification motif. In such embodiments, the internucleoside linkages in each of two wing regions are different from the internucleoside linkages in the gap region. In certain embodiments the internucleoside linkages in the wings are phosphodiester and the internucleoside linkages in the gap are phosphorothioate. The sugar modification motif is independently selected, so such oligonucleotides having a gapped internucleoside linkage motif may or may not have a gapped sugar modification motif and if it does have a gapped sugar motif, the wing and gap lengths may or may not be the same.
[0356] In certain embodiments, oligonucleotides comprise a region having an alternating internucleoside linkage motif. In certain embodiments, oligonucleotides of the present invention comprise a region of uniformly modified internucleoside linkages. In certain such embodiments, the oligonucleotide comprises a region that is uniformly linked by phosphorothioate internucleoside linkages. In certain embodiments, the oligonucleotide is uniformly linked by phosphorothioate. In certain embodiments, each internucleoside linkage of the oligonucleotide is selected from phosphodiester and phosphorothioate. In certain embodiments, each internucleoside linkage of the oligonucleotide is selected from phosphodiester and phosphorothioate and at least one internucleoside linkage is phosphorothioate.
[0357] In certain embodiments, the oligonucleotide comprises at least 6 phosphorothioate internucleoside linkages. In certain embodiments, the oligonucleotide comprises at least 8 phosphorothioate internucleoside linkages. In certain embodiments, the oligonucleotide comprises at least 10 phosphorothioate internucleoside linkages. In certain embodiments, the oligonucleotide comprises at least one block of at least 6 consecutive phosphorothioate internucleoside linkages. In certain embodiments, the oligonucleotide comprises at least one block of at least 8 consecutive phosphorothioate internucleoside linkages. In certain embodiments, the oligonucleotide comprises at least one block of at least 10 consecutive phosphorothioate internucleoside linkages. In certain embodiments, the oligonucleotide comprises at least block of at least one 12 consecutive phosphorothioate internucleoside linkages. In certain such embodiments, at least one such block is located at the 3' end of the oligonucleotide. In certain such embodiments, at least one such block is located within 3 nucleosides of the 3' end of the oligonucleotide.
[0358] Certain Nucleobase Modification Motifs
[0359] In certain embodiments, oligonucleotides comprise chemical modifications to nucleobases arranged along the oligonucleotide or region thereof in a defined pattern or nucleobases modification motif. In certain such embodiments, nucleobase modifications are arranged in a gapped motif. In certain embodiments, nucleobase modifications are arranged in an alternating motif. In certain embodiments, each nucleobase is modified. In certain embodiments, none of the nucleobases is chemically modified.
[0360] In certain embodiments, oligonucleotides comprise a block of modified nucleobases. In certain such embodiments, the block is at the 3'-end of the oligonucleotide. In certain embodiments the block is within 3 nucleotides of the 3'-end of the oligonucleotide. In certain such embodiments, the block is at the 5'-end of the oligonucleotide. In certain embodiments the block is within 3 nucleotides of the 5'-end of the oligonucleotide.
[0361] In certain embodiments, nucleobase modifications are a function of the natural base at a particular position of an oligonucleotide. For example, in certain embodiments each purine or each pyrimidine in an oligonucleotide is modified. In certain embodiments, each adenine is modified. In certain embodiments, each guanine is modified. In certain embodiments, each thymine is modified. In certain embodiments, each cytosine is modified. In certain embodiments, each uracil is modified.
[0362] In certain embodiments, some, all, or none of the cytosine moieties in an oligonucleotide are 5-methyl cytosine moieties. Herein, 5-methyl cytosine is not a "modified nucleobase." Accordingly, unless otherwise indicated, unmodified nucleobases include both cytosine residues having a 5-methyl and those lacking a 5 methyl. In certain embodiments, the methylation state of all or some cytosine nucleobases is specified.
[0363] Certain Overall Lengths
[0364] In certain embodiments, the present invention provides oligomeric compounds including oligonucleotides of any of a variety of ranges of lengths. In certain embodiments, the invention provides oligomeric compounds or oligonucleotides consisting of X to Y linked nucleosides, where X represents the fewest number of nucleosides in the range and Y represents the largest number of nucleosides in the range. In certain such embodiments, X and Y are each independently selected from 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, and 50; provided that X.ltoreq.Y. For example, in certain embodiments, the invention provides oligomeric compounds which comprise oligonucleotides consisting of 8 to 9, 8 to 10, 8 to 11, 8 to 12, 8 to 13, 8 to 14, 8 to 15, 8 to 16, 8 to 17, 8 to 18, 8 to 19, 8 to 20, 8 to 21, 8 to 22, 8 to 23, 8 to 24, 8 to 25, 8 to 26, 8 to 27, 8 to 28, 8 to 29, 8 to 30, 9 to 10, 9 to 11, 9 to 12, 9 to 13, 9 to 14, 9 to 15, 9 to 16, 9 to 17, 9 to 18, 9 to 19, 9 to 20, 9 to 21, 9 to 22, 9 to 23, 9 to 24, 9 to 25, 9 to 26, 9 to 27, 9 to 28, 9 to 29, 9 to 30, 10 to 11, 10 to 12, 10 to 13, 10 to 14, 10 to 15, 10 to 16, 10 to 17, 10 to 18, 10 to 19, 10 to 20, 10 to 21, 10 to 22, 10 to 23, 10 to 24, 10 to 25, 10 to 26, 10 to 27, 10 to 28, 10 to 29, 10 to 30, 11 to 12, 11 to 13, 11 to 14, 11 to 15, 11 to 16, 11 to 17, 11 to 18, 11 to 19, 11 to 20, 11 to 21, 11 to 22, 11 to 23, 11 to 24, 11 to 25, 11 to 26, 11 to 27, 11 to 28, 11 to 29, 11 to 30, 12 to 13, 12 to 14, 12 to 15, 12 to 16, 12 to 17, 12 to 18, 12 to 19, 12 to 20, 12 to 21, 12 to 22, 12 to 23, 12 to 24, 12 to 25, 12 to 26, 12 to 27, 12 to 28, 12 to 29, 12 to 30, 13 to 14, 13 to 15, 13 to 16, 13 to 17, 13 to 18, 13 to 19, 13 to 20, 13 to 21, 13 to 22, 13 to 23, 13 to 24, 13 to 25, 13 to 26, 13 to 27, 13 to 28, 13 to 29, 13 to 30, 14 to 15, 14 to 16, 14 to 17, 14 to 18, 14 to 19, 14 to 20, 14 to 21, 14 to 22, 14 to 23, 14 to 24, 14 to 25, 14 to 26, 14 to 27, 14 to 28, 14 to 29, 14 to 30, 15 to 16, 15 to 17, 15 to 18, 15 to 19, 15 to 20, 15 to 21, 15 to 22, 15 to 23, 15 to 24, 15 to 25, 15 to 26, 15 to 27, 15 to 28, 15 to 29, 15 to 30, 16 to 17, 16 to 18, 16 to 19, 16 to 20, 16 to 21, 16 to 22, 16 to 23, 16 to 24, 16 to 25, 16 to 26, 16 to 27, 16 to 28, 16 to 29, 16 to 30, 17 to 18, 17 to 19, 17 to 20, 17 to 21, 17 to 22, 17 to 23, 17 to 24, 17 to 25, 17 to 26, 17 to 27, 17 to 28, 17 to 29, 17 to 30, 18 to 19, 18 to 20, 18 to 21, 18 to 22, 18 to 23, 18 to 24, 18 to 25, 18 to 26, 18 to 27, 18 to 28, 18 to 29, 18 to 30, 19 to 20, 19 to 21, 19 to 22, 19 to 23, 19 to 24, 19 to 25, 19 to 26, 19 to 29, 19 to 28, 19 to 29, 19 to 30, 20 to 21, 20 to 22, 20 to 23, 20 to 24, 20 to 25, 20 to 26, 20 to 27, 20 to 28, 20 to 29, 20 to 30, 21 to 22, 21 to 23, 21 to 24, 21 to 25, 21 to 26, 21 to 27, 21 to 28, 21 to 29, 21 to 30, 22 to 23, 22 to 24, 22 to 25, 22 to 26, 22 to 27, 22 to 28, 22 to 29, 22 to 30, 23 to 24, 23 to 25, 23 to 26, 23 to 27, 23 to 28, 23 to 29, 23 to 30, 24 to 25, 24 to 26, 24 to 27, 24 to 28, 24 to 29, 24 to 30, 25 to 26, 25 to 27, 25 to 28, 25 to 29, 25 to 30, 26 to 27, 26 to 28, 26 to 29, 26 to 30, 27 to 28, 27 to 29, 27 to 30, 28 to 29, 28 to 30, or 29 to 30 linked nucleosides. In embodiments where the number of nucleosides of an oligomeric compound or oligonucleotide is limited, whether to a range or to a specific number, the oligomeric compound or oligonucleotide may, nonetheless further comprise additional other substituents. For example, an oligonucleotide comprising 8-30 nucleosides excludes oligonucleotides having 31 nucleosides, but, unless otherwise indicated, such an oligonucleotide may further comprise, for example one or more conjugates, terminal groups, or other substituents. In certain embodiments, a gapmer oligonucleotide has any of the above lengths. In certain embodiments, an antisense oligonucleotide has any of the above lengths.
[0365] One of skill in the art will appreciate that certain lengths may not be possible for certain motifs. For example: a gapmer having a 5'-wing region consisting of four nucleotides, a gap consisting of at least six nucleotides, and a 3'-wing region consisting of three nucleotides cannot have an overall length less than 13 nucleotides. Thus, one would understand that the lower length limit is 13 and that the limit of 10 in "10-20" has no effect in that embodiment.
[0366] Further, where an oligonucleotide is described by an overall length range and by regions having specified lengths, and where the sum of specified lengths of the regions is less than the upper limit of the overall length range, the oligonucleotide may have additional nucleosides, beyond those of the specified regions, provided that the total number of nucleosides does not exceed the upper limit of the overall length range. For example, an oligonucleotide consisting of 20-25 linked nucleosides comprising a 5'-wing consisting of 5 linked nucleosides; a 3'-wing consisting of 5 linked nucleosides and a central gap consisting of 10 linked nucleosides (5+5+10=20) may have up to 5 nucleosides that are not part of the 5'-wing, the 3'-wing, or the gap (before reaching the overall length limitation of 25). Such additional nucleosides may be 5' of the 5'-wing and/or 3' of the 3' wing.
[0367] Certain Oligonucleotides
[0368] In certain embodiments, oligonucleotides of the present invention are characterized by their sugar motif, internucleoside linkage motif, nucleobase modification motif and overall length. In certain embodiments, such parameters are each independent of one another. Thus, each internucleoside linkage of an oligonucleotide having a gapmer sugar motif may be modified or unmodified and may or may not follow the gapmer modification pattern of the sugar modifications. Thus, the internucleoside linkages within the wing regions of a sugar-gapmer may be the same or different from one another and may be the same or different from the internucleoside linkages of the gap region. Likewise, such sugar-gapmer oligonucleotides may comprise one or more modified nucleobase independent of the gapmer pattern of the sugar modifications. Herein if a description of an oligonucleotide or oligomeric compound is silent with respect to one or more parameter, such parameter is not limited. Thus, an oligomeric compound described only as having a gapmer sugar motif without further description may have any length, internucleoside linkage motif, and nucleobase modification motif. Unless otherwise indicated, all chemical modifications are independent of nucleobase sequence.
[0369] Certain Conjugate Groups
[0370] In certain embodiments, oligomeric compounds are modified by attachment of one or more conjugate groups. In general, conjugate groups modify one or more properties of the attached oligomeric compound including but not limited to pharmacodynamics, pharmacokinetics, stability, binding, absorption, cellular distribution, cellular uptake, charge and clearance. Conjugate groups are routinely used in the chemical arts and are linked directly or via an optional conjugate linking moiety or conjugate linking group to a parent compound such as an oligomeric compound, such as an oligonucleotide. Conjugate groups includes without limitation, intercalators, reporter molecules, polyamines, polyamides, polyethylene glycols, thioethers, polyethers, cholesterols, thiocholesterols, cholic acid moieties, folate, lipids, phospholipids, biotin, phenazine, phenanthridine, anthraquinone, adamantane, acridine, fluoresceins, rhodamines, coumarins and dyes. Certain conjugate groups have been described previously, for example: cholesterol moiety (Letsinger et al., Proc. Natl. Acad. Sci. USA, 1989, 86, 6553-6556), cholic acid (Manoharan et al., Bioorg. Med. Chem. Let., 1994, 4, 1053-1060), a thioether, e.g., hexyl-S-tritylthiol (Manoharan et al., Ann. N.Y. Acad. Sci., 1992, 660, 306-309; Manoharan et al., Bioorg. Med. Chem. Let., 1993, 3, 2765-2770), a thiocholesterol (Oberhauser et al., Nucl. Acids Res., 1992, 20, 533-538), an aliphatic chain, e.g., do-decan-diol or undecyl residues (Saison-Behmoaras et al., EMBO J., 1991, 10, 1111-1118; Kabanov et al., FEBS Lett., 1990, 259, 327-330; Svinarchuk et al., Biochimie, 1993, 75, 49-54), a phospholipid, e.g., di-hexadecyl-rac-glycerol or triethyl-ammonium 1,2-di-O-hexadecyl-rac-glycero-3-H-phosphonate (Manoharan et al., Tetrahedron Lett., 1995, 36, 3651-3654; Shea et al., Nucl. Acids Res., 1990, 18, 3777-3783), a polyamine or a polyethylene glycol chain (Manoharan et al., Nucleosides & Nucleotides, 1995, 14, 969-973), or adamantane acetic acid (Manoharan et al., Tetrahedron Lett., 1995, 36, 3651-3654), a palmityl moiety (Mishra et al., Biochim. Biophys. Acta, 1995, 1264, 229-237), or an octadecylamine or hexylamino-carbonyl-oxycholesterol moiety (Crooke et al., J. Pharmacol. Exp. Ther., 1996, 277, 923-937).
[0371] In certain embodiments, a conjugate group comprises an active drug substance, for example, aspirin, warfarin, phenylbutazone, ibuprofen, suprofen, fen-bufen, ketoprofen, (S)-(+)-pranoprofen, carprofen, dansylsarcosine, 2,3,5-triiodobenzoic acid, flufenamic acid, folinic acid, a benzothiadiazide, chlorothiazide, a diazepine, indo-methicin, a barbiturate, a cephalosporin, a sulfa drug, an antidiabetic, an antibacterial or an antibiotic.
[0372] In certain embodiments, conjugate groups are directly attached to oligonucleotides in oligomeric compounds. In certain embodiments, conjugate groups are attached to oligonucleotides by a conjugate linking group. In certain such embodiments, conjugate linking groups, including, but not limited to, bifunctional linking moieties such as those known in the art are amenable to the compounds provided herein. Conjugate linking groups are useful for attachment of conjugate groups, such as chemical stabilizing groups, functional groups, reporter groups and other groups to selective sites in a parent compound such as for example an oligomeric compound. In general a bifunctional linking moiety comprises a hydrocarbyl moiety having two functional groups. One of the functional groups is selected to bind to a parent molecule or compound of interest and the other is selected to bind essentially any selected group such as chemical functional group or a conjugate group. In some embodiments, the conjugate linker comprises a chain structure or an oligomer of repeating units such as ethylene glycol or amino acid units. Examples of functional groups that are routinely used in a bifunctional linking moiety include, but are not limited to, electrophiles for reacting with nucleophilic groups and nucleophiles for reacting with electrophilic groups. In some embodiments, bifunctional linking moieties include amino, hydroxyl, carboxylic acid, thiol, unsaturations (e.g., double or triple bonds), and the like.
[0373] Some nonlimiting examples of conjugate linking moieties include pyrrolidine, 8-amino-3,6-dioxaoctanoic acid (ADO), succinimidyl 4-(N-maleimidomethyl) cyclohexane-1-carboxylate (SMCC) and 6-aminohexanoic acid (AHEX or AHA). Other linking groups include, but are not limited to, substituted C.sub.1-C.sub.10 alkyl, substituted or unsubstituted C.sub.2-C.sub.10 alkenyl or substituted or unsubstituted C.sub.2-C.sub.10 alkynyl, wherein a nonlimiting list of preferred substituent groups includes hydroxyl, amino, alkoxy, carboxy, benzyl, phenyl, nitro, thiol, thioalkoxy, halogen, alkyl, aryl, alkenyl and alkynyl.
[0374] Conjugate groups may be attached to either or both ends of an oligonucleotide (terminal conjugate groups) and/or at any internal position.
[0375] In certain embodiments, conjugate groups are at the 3'-end of an oligonucleotide of an oligomeric compound. In certain embodiments, conjugate groups are near the 3'-end. In certain embodiments, conjugates are attached at the 3' end of an oligomeric compound, but before one or more terminal group nucleosides. In certain embodiments, conjugate groups are placed within a terminal group.
[0376] In certain embodiments, the present invention provides oligomeric compounds. In certain embodiments, oligomeric compounds comprise an oligonucleotide. In certain embodiments, an oligomeric compound comprises an oligonucleotide and one or more conjugate and/or terminal groups. Such conjugate and/or terminal groups may be added to oligonucleotides having any of the chemical motifs discussed above. Thus, for example, an oligomeric compound comprising an oligonucleotide having region of alternating nucleosides may comprise a terminal group.
[0377] Antisense Compounds
[0378] In certain embodiments, oligomeric compounds of the present invention are antisense compounds. Such antisense compounds are capable of hybridizing to a target nucleic acid, resulting in at least one antisense activity. In certain embodiments, antisense compounds specifically hybridize to one or more target nucleic acid. In certain embodiments, a specifically hybridizing antisense compound has a nucleobase sequence comprising a region having sufficient complementarity to a target nucleic acid to allow hybridization and result in antisense activity and insufficient complementarity to any non-target so as to avoid non-specific hybridization to any non-target nucleic acid sequences under conditions in which specific hybridization is desired (e.g., under physiological conditions for in vivo or therapeutic uses, and under conditions in which assays are performed in the case of in vitro assays).
[0379] In certain embodiments, the present invention provides antisense compounds comprising oligonucleotides that are fully complementary to the target nucleic acid over the entire length of the oligonucleotide. In certain embodiments, oligonucleotides are 99% complementary to the target nucleic acid. In certain embodiments, oligonucleotides are 95% complementary to the target nucleic acid. In certain embodiments, such oligonucleotides are 90% complementary to the target nucleic acid.
[0380] In certain embodiments, such oligonucleotides are 85% complementary to the target nucleic acid. In certain embodiments, such oligonucleotides are 80% complementary to the target nucleic acid. In certain embodiments, an antisense compound comprises a region that is fully complementary to a target nucleic acid and is at least 80% complementary to the target nucleic acid over the entire length of the oligonucleotide. In certain such embodiments, the region of full complementarity is from 6 to 14 nucleobases in length.
[0381] In certain embodiments antisense compounds and antisense oligonucleotides comprise single-strand compounds. In certain embodiments antisense compounds and antisense oligonucleotides comprise double-strand compounds.
[0382] Certain Pathways and Mechanisms Associated With Fibrosis
[0383] TGF.beta.1 and its associated pathways contribute to many processes associated with wound healing and tissue repair. After an injury, TGF.beta.1 contributes to the healing and restoration of normal tissue by, among other things, stimulating the production of certain extracellular matrix proteins and inhibiting the degradation of certain matrix proteins. In certain embodiments, TGF.beta.1 stimulates the production of fibronectin. In certain embodiments, TGF.beta.1 stimulates the production of both the EDA+ and EDA- isoforms of fibronectin. In certain embodiments, excessive amounts of the EDA+ fibronectin isoform causes tissue fibrosis. In certain embodiments, excessive tissue fibrosis induced by TGF.beta.1/EDA+ impairs normal organ function, impairs cellular function, and/or causes cells to change or lose their phenotype. In certain embodiments, the release and/or activation of TGF.beta.1 causes the formation of fibrosis and consequent changes in cell phenotype. In certain embodiments, changes in cell phenotype due to fibrosis include, but are not limited to, modulation of cadherin expression, induction of .alpha. Smooth Muscle Actin (.alpha.SMA), alteration of cortical f-actin localization, induction of connexin 43 (Cx 43) expression, alteration of vimentin, alteration of tight junction protein ZO-1, and/or increased secretion of MMP2 & MMP9. In certain embodiments, the release and/or activation of TGF.beta.1 causes a loss of cell phenotype. In certain embodiments, the loss of cell phenotype due to fibrosis impairs the structure or function of a cell. In certain embodiments, the loss of cell phenotype due to fibrosis destroys the function of a cell.
[0384] In certain embodiments, it is therefore desirable to reduce fibrosis without affecting the healing and/or restoration process. In certain embodiments, it is therefore desirable to reduce the formation of fibrosis in a cell without reducing or altering the amount and/or activity of TGF.beta.1 in the cell. In certain embodiments, it is therefore desirable to reduce the amount of EDA+ fibronectin in a cell without reducing or altering the amount of EDA- fibronectin in the cell. In certain embodiments, the reduction of the amount of EDA+ fibronectin in a cell in response to TGF.beta.1 will result in wound healing and tissue repair without incurring excessive fibrosis. In certain embodiments, the selective reduction of the amount of EDA+ fibronectin in a cell, relative to the amount of EDA- fibronectin in the cell in the response to TGF.beta.1 will stimulate wound healing and tissue repair without incurring changes in cell phenotype associated with fibrosis. In certain embodiments, the reduction of the amount of EDA+ fibronectin in a cell, relative to the amount of EDA- fibronectin in the cell in response to TGF.beta.1 will stimulate wound healing and tissue repair without incurring the loss of cell phenotype due to fibrosis.
[0385] In certain embodiments, it is desirable to reverse the formation of fibrosis in a cell without reducing or altering the wound healing function of TGF.beta.1 in the cell. In certain embodiments, it is therefore desirable to reverse the changes caused by fibrosis in the phenotype of a cell without reducing or altering the wound healing function of TGF.beta.1 in the cell. In certain embodiments, it is therefore desirable to reverse the loss of phenotype in a cell caused by fibrosis without reducing or altering the wound healing function of TGF.beta.1 in the cell.
[0386] Certain Target Nucleic Acids and Mechanisms
[0387] In certain embodiments, antisense compounds comprise or consist of an oligonucleotide comprising a region that is complementary to a target nucleic acid. In certain embodiments, the target nucleic acid is an endogenous RNA molecule. In certain embodiments, the target nucleic acid is a pre-mRNA. In certain embodiments, the target nucleic acid is a fibronectin transcript. In certain embodiments, the target RNA is a fibronectin pre-mRNA.
[0388] In certain embodiments, an antisense compound is complementary to a region of fibronectin pre-mRNA. In certain embodiments, an antisense compound is complementary within a region of fibronectin pre-mRNA comprising an exon encoding EDA. In certain embodiments, an antisense compound is complementary to a region of fibronectin pre-mRNA comprising an intron-exon splice junction. In certain embodiments, an antisense compound is complementary to a region of fibronectin pre-mRNA comprising the intron-exon splice junction adjacent to the EDA exon. In certain embodiments, an antisense compound is complementary within a region of fibronectin pre-mRNA consisting of an exon encoding EDA. In certain embodiments, an antisense compound is complementary within a region of fibronectin pre-mRNA comprising an exonic splicing silencer within an exon encoding EDA. In certain embodiments, an antisense compound is complementary within a region of fibronectin pre-mRNA comprising an exonic splicing enhancer within an exon encoding EDA.
[0389] In certain embodiments, an antisense compound comprises a modified oligonucleotide consisting of 8 to 30 linked nucleosides and having a nucleobase sequence comprising a complementary region comprising at least 8 contiguous nucleobases complementary to a target region of equal length of a fibronectin transcript. In certain embodiments, the target region is within nucleobase 55469 and nucleobase 55790 of SEQ ID NO.: 1. In certain embodiments, the target region is within nucleobase 55469 and nucleobase 55511 of SEQ ID NO.: 1. In certain embodiments, the target region is within nucleobase 55511 and nucleobase 55732 of SEQ ID NO.: 1. In certain embodiments, the target region is within nucleobase 55732 and nucleobase 55790 of SEQ ID NO.: 1.
[0390] In certain embodiments, an antisense oligonucleotide modulates splicing of a pre-mRNA. In certain embodiments, an antisense oligonucleotide modulates splicing a fibronectin pre-mRNA. In certain embodiments, an antisense oligonucleotide increases the amount of fibronectin mRNA. In certain embodiments, an antisense oligonucleotide increases the amount of EDA- fibronectin mRNA. In certain embodiments, an antisense oligonucleotide decreases the amount of EDA+ fibronectin mRNA. In certain embodiments, an antisense oligonucleotide decreases the amount of EDA+ fibronectin mRNA in the presence of TGF.beta.1. In certain embodiments, an antisense oligonucleotide decreases the amount of EDA+ fibronectin mRNA in a cell without substantially affecting the healing and/or restoration functions of the cell.
[0391] In certain embodiments, an antisense oligonucleotide alters the ratio of EDA+/EDA- fibronectin. In certain embodiments, an antisense oligonucleotide increases the ratio of EDA+/EDA- fibronectin. In certain embodiments, it is desirable to increase the ratio of EDA+/EDA- fibronectin to create a fibrosis model. In certain embodiments, it is desirable to increase the ratio of EDA+/EDA- fibronectin to create a fibrosis phenotype. In certain embodiments, it is desirable to increase the ratio of EDA+/EDA- fibronectin in the presence of TGF.beta.1 to create a fibrosis model. In certain embodiments, it is desirable to increase the ratio of EDA+/EDA- fibronectin in the presence of TGF.beta.1 to create a fibrosis phenotype. In certain embodiments, it is desirable to increase the ratio of EDA+/EDA- fibronectin to create a fibrosis mouse model. In certain embodiments, it is desirable to increase the ratio of EDA+/EDA- fibronectin to create a fibrosis mouse phenotype. In certain embodiments, it is desirable to increase the ratio of EDA+/EDA- fibronectin in the presence of TGF.beta.1 to create a fibrosis mouse model. In certain embodiments, it is desirable to increase the ratio of EDA+/EDA- fibronectin in the presence of TGF.beta.1 to create a fibrosis mouse phenotype.
[0392] In certain embodiments, an antisense oligonucleotide alters the ratio of EDA+/EDA- fibronectin. In certain embodiments, an antisense oligonucleotide decreases the ratio of EDA+/EDA- fibronectin. In certain embodiments, it is desirable to decrease the ratio of EDA+/EDA- fibronectin to create a fibrosis model. In certain embodiments, it is desirable to decrease the ratio of EDA+/EDA- fibronectin to create a fibrosis phenotype. In certain embodiments, it is desirable to decrease the ratio of EDA+/EDA- fibronectin in the presence of TGF.beta.1 to create a fibrosis model. In certain embodiments, it is desirable to decrease the ratio of EDA+/EDA- fibronectin in the presence of TGF.beta.1 to create a fibrosis phenotype. In certain embodiments, it is desirable to decrease the ratio of EDA+/EDA- fibronectin to create a fibrosis mouse model. In certain embodiments, it is desirable to decrease the ratio of EDA+/EDA- fibronectin to create a fibrosis mouse phenotype. In certain embodiments, it is desirable to decrease the ratio of EDA+/EDA- fibronectin in the presence of TGF.beta.1 to create a fibrosis mouse model. In certain embodiments, it is desirable to decrease the ratio of EDA+/EDA- fibronectin in the presence of TGF.beta.1 to create a fibrosis mouse phenotype.
[0393] In certain embodiments, an antisense oligonucleotide alters the ratio of EDA-/EDA+ fibronectin. In certain embodiments, an antisense oligonucleotide increases the ratio of EDA-/EDA+ fibronectin. In certain embodiments, it is desirable to increase the ratio of EDA-/EDA+ fibronectin to create a fibrosis model. In certain embodiments, it is desirable to increase the ratio of EDA-/EDA+ fibronectin to create a fibrosis phenotype. In certain embodiments, it is desirable to increase the ratio of EDA-/EDA+ fibronectin in the presence of TGF.beta.1 to create a fibrosis model. In certain embodiments, it is desirable to increase the ratio of EDA-/EDA+ fibronectin in the presence of TGF.beta.1 to create a fibrosis phenotype. In certain embodiments, it is desirable to increase the ratio of EDA-/EDA+ fibronectin to create a fibrosis mouse model. In certain embodiments, it is desirable to increase the ratio of EDA-/EDA+ fibronectin to create a fibrosis mouse phenotype. In certain embodiments, it is desirable to increase the ratio of EDA-/EDA+ fibronectin in the presence of TGF.beta.1 to create a fibrosis mouse model. In certain embodiments, it is desirable to increase the ratio of EDA-/EDA+ fibronectin in the presence of TGF.beta.1 to create a fibrosis mouse phenotype.
[0394] In certain embodiments, an antisense oligonucleotide alters the ratio of EDA-/EDA+ fibronectin. In certain embodiments, an antisense oligonucleotide decreases the ratio of EDA-/EDA+ fibronectin. In certain embodiments, it is desirable to decrease the ratio of EDA-/EDA+ fibronectin to create a fibrosis model. In certain embodiments, it is desirable to decrease the ratio of EDA-/EDA+ fibronectin to create a fibrosis phenotype. In certain embodiments, it is desirable to decrease the ratio of EDA-/EDA+ fibronectin in the presence of TGF.beta.1 to create a fibrosis model. In certain embodiments, it is desirable to decrease the ratio of EDA-/EDA+ fibronectin in the presence of TGF.beta.1 to create a fibrosis phenotype. In certain embodiments, it is desirable to decrease the ratio of EDA-/EDA+ fibronectin to create a fibrosis mouse model. In certain embodiments, it is desirable to decrease the ratio of EDA-/EDA+ fibronectin to create a fibrosis mouse phenotype. In certain embodiments, it is desirable to decrease the ratio of EDA-/EDA+ fibronectin in the presence of TGF.beta.1 to create a fibrosis mouse model. In certain embodiments, it is desirable to decrease the ratio of EDA-/EDA+ fibronectin in the presence of TGF.beta.1 to create a fibrosis mouse phenotype.
[0395] Certain Pharmaceutical Compositions
[0396] In certain embodiments, the present invention provides pharmaceutical compositions comprising one or more antisense compound. In certain embodiments, such pharmaceutical composition comprises a suitable pharmaceutically acceptable diluent or carrier. In certain embodiments, a pharmaceutical composition comprises a sterile saline solution and one or more antisense compound. In certain embodiments, such pharmaceutical composition consists of a sterile saline solution and one or more antisense compound. In certain embodiments, the sterile saline is pharmaceutical grade saline. In certain embodiments, a pharmaceutical composition comprises one or more antisense compound and sterile water. In certain embodiments, a pharmaceutical composition consists of one or more antisense compound and sterile water. In certain embodiments, the sterile saline is pharmaceutical grade water. In certain embodiments, a pharmaceutical composition comprises one or more antisense compound and phosphate-buffered saline (PBS). In certain embodiments, a pharmaceutical composition consists of one or more antisense compound and sterile phosphate-buffered saline (PBS). In certain embodiments, the sterile saline is pharmaceutical grade PBS.
[0397] In certain embodiments, antisense compounds may be admixed with pharmaceutically acceptable active and/or inert substances for the preparation of pharmaceutical compositions or formulations. Compositions and methods for the formulation of pharmaceutical compositions depend on a number of criteria, including, but not limited to, route of administration, extent of disease, or dose to be administered.
[0398] Pharmaceutical compositions comprising antisense compounds encompass any pharmaceutically acceptable salts, esters, or salts of such esters. In certain embodiments, pharmaceutical compositions comprising antisense compounds comprise one or more oligonucleotide which, upon administration to an animal, including a human, is capable of providing (directly or indirectly) the biologically active metabolite or residue thereof. Accordingly, for example, the disclosure is also drawn to pharmaceutically acceptable salts of antisense compounds, prodrugs, pharmaceutically acceptable salts of such prodrugs, and other bioequivalents. Suitable pharmaceutically acceptable salts include, but are not limited to, sodium and potassium salts.
[0399] A prodrug can include the incorporation of additional nucleosides at one or both ends of an oligomeric compound which are cleaved by endogenous nucleases within the body, to form the active antisense oligomeric compound.
[0400] Lipid moieties have been used in nucleic acid therapies in a variety of methods. In certain such methods, the nucleic acid is introduced into preformed liposomes or lipoplexes made of mixtures of cationic lipids and neutral lipids. In certain methods, DNA complexes with mono- or poly-cationic lipids are formed without the presence of a neutral lipid. In certain embodiments, a lipid moiety is selected to increase distribution of a pharmaceutical agent to a particular cell or tissue. In certain embodiments, a lipid moiety is selected to increase distribution of a pharmaceutical agent to fat tissue. In certain embodiments, a lipid moiety is selected to increase distribution of a pharmaceutical agent to muscle tissue.
[0401] In certain embodiments, pharmaceutical compositions provided herein comprise one or more modified oligonucleotides and one or more excipients. In certain such embodiments, excipients are selected from water, salt solutions, alcohol, polyethylene glycols, gelatin, lactose, amylase, magnesium stearate, talc, silicic acid, viscous paraffin, hydroxymethylcellulose and polyvinylpyrrolidone.
[0402] In certain embodiments, a pharmaceutical composition provided herein comprises a delivery system. Examples of delivery systems include, but are not limited to, liposomes and emulsions. Certain delivery systems are useful for preparing certain pharmaceutical compositions including those comprising hydrophobic compounds. In certain embodiments, certain organic solvents such as dimethylsulfoxide are used.
[0403] In certain embodiments, a pharmaceutical composition provided herein comprises one or more tissue-specific delivery molecules designed to deliver the one or more pharmaceutical agents of the present invention to specific tissues or cell types. For example, in certain embodiments, pharmaceutical compositions include liposomes coated with a tissue-specific antibody.
[0404] In certain embodiments, a pharmaceutical composition provided herein comprises a co-solvent system. Certain of such co-solvent systems comprise, for example, benzyl alcohol, a nonpolar surfactant, a water-miscible organic polymer, and an aqueous phase. In certain embodiments, such co-solvent systems are used for hydrophobic compounds. A non-limiting example of such a co-solvent system is the VPD co-solvent system, which is a solution of absolute ethanol comprising 3% w/v benzyl alcohol, 8% w/v of the nonpolar surfactant Polysorbate 80.TM. and 65% w/v polyethylene glycol 300. The proportions of such co-solvent systems may be varied considerably without significantly altering their solubility and toxicity characteristics. Furthermore, the identity of co-solvent components may be varied: for example, other surfactants may be used instead of Polysorbate 80.TM.; the fraction size of polyethylene glycol may be varied; other biocompatible polymers may replace polyethylene glycol, e.g., polyvinyl pyrrolidone; and other sugars or polysaccharides may substitute for dextrose.
[0405] In certain embodiments, a pharmaceutical composition provided herein is prepared for oral administration. In certain embodiments, pharmaceutical compositions are prepared for buccal administration.
[0406] In certain embodiments, a pharmaceutical composition is prepared for administration by injection (e.g., intravenous, subcutaneous, intramuscular, etc.). In certain of such embodiments, a pharmaceutical composition comprises a carrier and is formulated in aqueous solution, such as water or physiologically compatible buffers such as Hanks's solution, Ringer's solution, or physiological saline buffer. In certain embodiments, other ingredients are included (e.g., ingredients that aid in solubility or serve as preservatives). In certain embodiments, injectable suspensions are prepared using appropriate liquid carriers, suspending agents and the like. Certain pharmaceutical compositions for injection are presented in unit dosage form, e.g., in ampoules or in multi-dose containers. Certain pharmaceutical compositions for injection are suspensions, solutions or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending, stabilizing and/or dispersing agents. Certain solvents suitable for use in pharmaceutical compositions for injection include, but are not limited to, lipophilic solvents and fatty oils, such as sesame oil, synthetic fatty acid esters, such as ethyl oleate or triglycerides, and liposomes. Aqueous injection suspensions may contain substances that increase the viscosity of the suspension, such as sodium carboxymethyl cellulose, sorbitol, or dextran. Optionally, such suspensions may also contain suitable stabilizers or agents that increase the solubility of the pharmaceutical agents to allow for the preparation of highly concentrated solutions.
[0407] In certain embodiments, a pharmaceutical composition is prepared for transmucosal administration. In certain of such embodiments penetrants appropriate to the barrier to be permeated are used in the formulation. Such penetrants are generally known in the art.
[0408] In certain embodiments, a pharmaceutical composition provided herein comprises an oligonucleotide in a therapeutically effective amount. In certain embodiments, the therapeutically effective amount is sufficient to prevent, alleviate or ameliorate symptoms of a disease or to prolong the survival of the subject being treated. Determination of a therapeutically effective amount is well within the capability of those skilled in the art.
[0409] In certain embodiments, one or more modified oligonucleotide provided herein is formulated as a prodrug. In certain embodiments, upon in vivo administration, a prodrug is chemically converted to the biologically, pharmaceutically or therapeutically more active form of an oligonucleotide. In certain embodiments, prodrugs are useful because they are easier to administer than the corresponding active form. For example, in certain instances, a prodrug may be more bioavailable (e.g., through oral administration) than is the corresponding active form. In certain instances, a prodrug may have improved solubility compared to the corresponding active form. In certain embodiments, prodrugs are less water soluble than the corresponding active form. In certain instances, such prodrugs possess superior transmittal across cell membranes, where water solubility is detrimental to mobility. In certain embodiments, a prodrug is an ester. In certain such embodiments, the ester is metabolically hydrolyzed to carboxylic acid upon administration. In certain instances the carboxylic acid containing compound is the corresponding active form. In certain embodiments, a prodrug comprises a short peptide (polyaminoacid) bound to an acid group. In certain of such embodiments, the peptide is cleaved upon administration to form the corresponding active form.
[0410] In certain embodiments, the present invention provides compositions and methods for reducing the amount or activity of a target nucleic acid in a cell. In certain embodiments, the cell is in an animal. In certain embodiments, the animal is a mammal. In certain embodiments, the animal is a rodent. In certain embodiments, the animal is a primate. In certain embodiments, the animal is a non-human primate. In certain embodiments, the animal is a human.
[0411] In certain embodiments, the present invention provides methods of administering a pharmaceutical composition comprising an oligomeric compound of the present invention to an animal. Suitable administration routes include, but are not limited to, oral, rectal, transmucosal, intestinal, enteral, topical, suppository, through inhalation, intrathecal, intracerebroventricular, intraperitoneal, intranasal, intraocular, intratumoral, and parenteral (e.g., intravenous, intramuscular, intramedullary, and subcutaneous). In certain embodiments, pharmaceutical intrathecals are administered to achieve local rather than systemic exposures. For example, pharmaceutical compositions may be injected directly in the area of desired effect (e.g., into the eyes, ears).
[0412] In certain embodiments, a pharmaceutical composition is administered to an animal having at least one symptom associated with fibrosis. In certain embodiments, such administration results in amelioration of at least one symptom. In certain embodiments, administration of a pharmaceutical composition to an animal results in a decrease of EDA+ fibronectin mRNA in a cell of the animal. In certain embodiments, such administration results in an increase in EDA- fibronectin mRNA. In certain embodiments, such administration results in a decrease in EDA+ fibronectin protein and an increase EDA- fibronectin protein. In certain embodiments, a fibronectin protein lacking EDA amino acids is preferred over a fibronectin protein having EDA amino acids. In certain embodiments, the administration of certain antisense oligonucleotides delays the onset of fibrosis. In certain embodiments, the administration of certain antisense oligonucleotides slows the progression of fibrosis. In certain embodiments, the administration of certain antisense oligonucleotides prevents the formation of fibrosis. In certain embodiments, the administration of certain antisense oligonucleotides reverses fibrosis. In certain embodiments, the administration of certain antisense oligonucleotides rescues cellular phenotype. In certain embodiments, the administration of certain antisense oligonucleotides rescues cellular morphology.
[0413] Nonlimiting Disclosure and Incorporation by Reference
[0414] While certain compounds, compositions and methods described herein have been described with specificity in accordance with certain embodiments, the following examples serve only to illustrate the compounds described herein and are not intended to limit the same. Each of the references, GenBank accession numbers, and the like recited in the present application is incorporated herein by reference in its entirety.
[0415] Although the sequence listing accompanying this filing identifies each sequence as either "RNA" or "DNA" as required, in reality, those sequences may be modified with any combination of chemical modifications. One of skill in the art will readily appreciate that such designation as "RNA" or "DNA" to describe modified oligonucleotides is, in certain instances, arbitrary. For example, an oligonucleotide comprising a nucleoside comprising a 2'-OH sugar moiety and a thymine base could be described as a DNA having a modified sugar (2'-OH for the natural 2'-H of DNA) or as an RNA having a modified base (thymine (methylated uracil) for natural uracil of RNA).
[0416] Accordingly, nucleic acid sequences provided herein, including, but not limited to those in the sequence listing, are intended to encompass nucleic acids containing any combination of natural or modified RNA and/or DNA, including, but not limited to such nucleic acids having modified nucleobases. By way of further example and without limitation, an oligomeric compound having the nucleobase sequence "ATCGATCG" encompasses any oligomeric compounds having such nucleobase sequence, whether modified or unmodified, including, but not limited to, such compounds comprising RNA bases, such as those having sequence "AUCGAUCG" and those having some DNA bases and some RNA bases such as "AUCGATCG" and oligomeric compounds having other modified or naturally occurring bases, such as "AT.sup.meCGAUCG," wherein .sup.meC indicates a cytosine base comprising a methyl group at the 5-position.
EXAMPLES
[0417] The following examples illustrate certain embodiments of the present invention and are not limiting. Moreover, where specific embodiments are provided, the inventors have contemplated generic application of those specific embodiments. For example, disclosure of an oligonucleotide having a particular motif provides reasonable support for additional oligonucleotides having the same or similar motif. And, for example, where a particular high-affinity modification appears at a particular position, other high-affinity modifications at the same position are considered suitable, unless otherwise indicated.
Example 1: In Vitro Screening of Human Fibronectin Splicing with Antisense Oligonucleotides in HKC-8 Cells
[0418] Antisense oligonucleotides were designed targeting a fibronectin nucleic acid and were tested for their effects on the alternative splicing of the fibronectin gene sequence in vitro. The newly designed antisense oligonucleotides in Table 1 were designed as uniform MOE oligonucleotides. Each nucleoside in the oligonucleotide has a 2'-MOE modification. The internucleoside linkages throughout each oligonucleotide are phosphorothioate (P.dbd.S) linkages. All cytosine residues throughout each oligonucleotide are 5-methylcytosines. "Start site" indicates the 5'-most nucleoside to which the oligonucleotide is targeted in the human gene sequence. "Stop site" indicates the 3'-most nucleoside to which the oligonucleotide is targeted human gene sequence. Each oligonucleotide listed in Table 1 is targeted to SEQ ID NO: 1 (the complement of GENBANK Accession No. NT_005403.14 truncated from nucleotides 66434501 to 66510708). ISIS 141923 (CCTTCCCTGAAGGTTCCTCC (SEQ ID NO: 25), no known human target) was used as a negative control.
[0419] Cultured HKC-8 cells, which are SV40-transformed human proximal tubular cells, were transfected using 3 .mu.L LipofectAMINE2000.RTM./mL OptiMEM with 200 nM antisense oligonucleotide. After a treatment period of approximately 4 hours, the medium was removed and new medium was added, left in culture overnight. RNA was isolated from the cells and the ratio of Extra Domain A positive fibronectin (EDA.sup.+FN) to EDA negative fibronectin (EDA.sup.-FN) was measured by conventional PCR. Human primers with forward sequence GGAGAGAGTCAGCCTCTGGTTCAG, designated herein as SEQ ID NO: 2; reverse sequence TGTCAACTGGGCGCTCAGGCTTGTG, designated herein as SEQ ID NO: 3) was used to measure mRNA levels. To compare the efficacy of antisense treatments performed in different experiments and allow for inter-assay variability, ratios were indexed on the corresponding negative control. Results are presented in Table 1 and demonstrate that treatment with antisense oligonucleotides targeted to the EDA region of fibronectin resulted in decreased expression of the EDA.sup.+FN isoform compared to the negative control. `null` indicates that the EDA.sup.+ band was undetectable for that sample.
TABLE-US-00001 TABLE 1 Ratio of EDA.sup.+FN to EDA.sup.-FN in HKC-8 cells after treatment with antisense oligonucleotides targeted to SEQ ID NO: 1 ISIS SEQ ID NO: 1 SEQ ID NO: 1 EDA.sup.+FN/ SEQ NO Start Site Stop Site Sequence EDA.sup.-FN ID NO 511399 55469 55483 GCAAATTAATGGTAA 0.07 5 511400 55473 55487 TTAGGCAAATTAATG 0.07 6 511401 55477 55491 TCTGTTAGGCAAATT 0.05 7 511402 55480 55494 ATGTCTGTTAGGCAA 0.09 8 511403 55483 55497 TCAATGTCTGTTAGG 0.04 9 511404 55486 55500 CGATCAATGTCTGTT 0.04 10 511405 55489 55503 GGGCGATCAATGTCT 0.03 11 511406 55493 55507 TTTAGGGCGATCAAT 0.03 12 511407 55497 55511 GTCCTTTAGGGCGAT 0.4 13 511408 55732 55746 CCAATCAGGGGCTGG 0.02 14 511409 55736 55750 GGTTCCAATCAGGGG null 15 511410 55740 55754 ACTGGGTTCCAATCA 0.01 16 511411 55743 55757 TGGACTGGGTTCCAA 0.02 17 511412 55746 55760 CTGTGGACTGGGTTC null 18 511413 55749 55763 TACCTGTGGACTGGG 0.06 19 511414 55752 55766 ATATACCTGTGGACT 0.04 20 511415 55756 55770 AACCATATACCTGTG 0.05 21 511416 55760 55774 AATTAACCATATACC 0.15 22 511417 55482 55499 GATCAATGTCTGTTAGGC 0.12 23 511418 55744 55761 CCTGTGGACTGGGTTCCA null 24 141923 n/a n/a CCTTCCCTGAAGGTTCCTCC 1.00 25
Example 2: In Vitro Screening of Human Fibronectin Splicing with Antisense Oligonucleotides in Primary Human Proximal Tubular Cells
[0420] The antisense oligonucleotides described in Example 1 were also tested for their effects on the alternative splicing of the fibronectin gene sequence in primary human proximal tubular cells (PTEC). Cultured PTEC cells were transfected using 2 .mu.L LipofectAMINE2000.RTM./mL OptiMEM with 100 nM antisense oligonucleotide for 4 hours, the medium was removed and new medium added, left in culture overnight, and then treated with 0.1% BSA (vehicle) or 2.5 ng/mL TGF.beta.1 in 0.1% BSA for 24 hrs. RNA was isolated from the cells and levels were measured by conventional PCR. The ratio of EDA.sup.+FN to EDA.sup.-FN for the given oligonucleotide-treated cells to the ratio for the negative control-treated cells was calculated. Results are presented in Table 2 and indicate that treatment with antisense oligonucleotides targeted to the EDA region of fibronectin resulted in decreased expression of the EDA.sup.+FN isoform compared to the negative control, even after induction with TGF.beta.1. `null` indicates that the EDA.sup.+ band was undetectable for that sample.
TABLE-US-00002 TABLE 2 Ratio of EDA.sup.+FN to EDA.sup.-FN in PTEC cells after treatment with antisense oligonucleotides EDA.sup.+FN/ EDA.sup.+FN/ EDA.sup.-FN EDA.sup.-FN (without (with SEQ ID ISIS NO TGF.beta.1) TGF.beta.1) NO 511399 0.13 0.17 5 511400 0.23 0.26 6 511401 0.14 0.26 7 511402 0.20 0.27 8 511403 0.13 0.23 9 511404 0.09 0.11 10 511405 0.06 0.08 11 511406 0.03 0.04 12 511407 0.41 0.66 13 511408 null null 14 511409 null null 15 511410 null null 16 511411 0.10 0.09 17 511412 null null 18 511413 0.08 0.09 19 511414 0.15 0.13 20 511415 0.34 0.42 21 511416 0.62 0.97 22 511417 0.17 0.20 23 511418 null null 24 141923 1.00 1.61 25
Example 3: Effect of Antisense Oligonucleotides Targeting the EDA Region of Fibronectin on TGF.beta.1 Induction of EDA.sup.+FN mRNA Expression in Primary Human Proximal Tubular Cells
[0421] Antisense oligonucleotides selected from the studies described above were tested for their effects on the alternative splicing of the fibronectin gene sequence in primary human proximal tubular cells (PTEC) treated with TGF.beta.1. One set of cultured PTEC cells were transfected using 2 .mu.L LipofectAMINE2000.RTM./mL OptiMEM with 100 nM antisense oligonucleotide. These cells were treated for 4 hours with antisense oligonucleotide; the medium was removed and new medium added; left in culture overnight; and then treated with 0.1% BSA (vehicle) or 2.5 ng/mL TGF.beta.1 in 0.1% BSA for 24 hrs. These cells were designated as pre-TGF.beta.1. Another set of cells were first treated with 0.1% BSA (vehicle) or 2.5 ng/mL TGF.beta.1 in 01% BSA for 24 hrs; then transfected using 2 .mu.L LipofectAMINE2000.RTM./mL OptiMEM with 100 nM antisense oligonucleotide for 4 h; the medium was removed and new medium added; and then left in culture overnight. These cells were designated as post-TGF.beta.1. RNA was isolated from the cells and levels were measured by conventional PCR. The ratio of EDA.sup.+FN to EDA.sup.-FN for the given oligonucleotide-treated cells to the ratio for the negative control-treated cells was calculated. Results are presented in Tables 3 and 4, and indicate that treatment with antisense oligonucleotides targeted to the EDA region of fibronectin resulted in decreased expression of the EDA.sup.+FN isoform compared to the negative control, irrespective of whether the treatment with antisense oligonucleotides took place before or after induction with TGF.beta.1 `null` indicates that the EDA.sup.+ band was undetectable for that sample.
TABLE-US-00003 TABLE 3 Ratio of EDA.sup.+FN to EDA.sup.-FN in pre- TGF.beta.1 PTEC cells after treatment with antisense oligonucleotides EDA.sup.+FN/ EDA.sup.+FN/ EDA.sup.-FN EDA.sup.-FN (without (with SEQ ID ISIS NO TGF.beta.1) TGF.beta.1) NO 511399 0.13 0.17 5 511403 0.13 0.23 9 511407 0.41 0.66 13 511408 null null 14 511412 null null 18 511416 0.62 0.97 22 141923 1.00 1.61 25
TABLE-US-00004 TABLE 4 Ratio of EDA.sup.+FN to EDA.sup.-FN in post-TGF.beta.1 PTEC cells after treatment with antisense oligonucleotides EDA.sup.+FN/ EDA.sup.+FN/ EDA.sup.-FN EDA.sup.-FN (without (with SEQ ID ISIS NO TGF.beta.1) TGF.beta.1) NO 511399 0.68 0.75 5 511403 0.48 0.30 9 511407 0.68 0.68 13 511408 0.22 0.16 14 511412 null null 18 511416 0.79 0.69 22 141923 1.00 1.57 25
Example 4: Effect of Antisense Oligonucleotides Targeting the EDA Region of Fibronectin on TGF.beta.1 Induction of EDA.sup.+FN Protein Expression in Primary Human Proximal Tubular Cells
[0422] The antisense oligonucleotides described above were tested for their effects on the alternative splicing of the fibronectin gene sequence in primary human proximal tubular cells (PTEC) treated with TGF.beta.1. Cultured PTEC cells were transfected using 2 .mu.L LipofectAMINE2000/mL OptiMEM with 100 nM antisense oligonucleotide. The cells were treated for 4 hours with antisense oligonucleotide; the medium was removed and new medium added; left in culture overnight; and then treated with 0.1% BSA (vehicle) or 2.5 ng/mL TGF.beta.1 in 01% BSA for 48 hrs. The cells were lysed in lysis buffer (20 mM Tris-HCl, 150 mM NaCl, 1 mM EDTA, 1% Triton X, 0.5% sodium deoxycholate, 0.1% SDS; pH 7.2) and protein was extracted as described in Phanish M K et al., Biochem J. 2006 Jan. 15; 393(Pt 2):601-7. The protein samples were run on an SDS-PAGE and analyzed via western analysis using the anti-Fibronectin antibody [IST-9] (Abcam, ab6328) that reacts with an epitope located in the ED-A sequence of cellular fibronectin. Results are presented in Table 5, and indicate that treatment with antisense oligonucleotides targeted to the EDA region of fibronectin resulted in decreased protein expression of the EDA.sup.+FN isoform compared to the negative control.
TABLE-US-00005 TABLE 5 EDA.sup.+FN expression in PTEC cells after treatment with antisense oligonucleotides (densitometric analysis on one Western blot) EDA.sup.+FN EDA.sup.+FN (without (with SEQ ID ISIS NO TGF.beta.1) TGF.beta.1) NO 511399 0.07 0.03 5 511403 0.02 0.04 9 511407 0.13 0.75 13 511408 0.08 0.77 14 511412 0.25 0.30 18 511416 0.61 0.58 22 141923 0.31 0.74 25
Example 5: Effect of ISIS 511403 on TGF.beta.1 Induction of Fibrosis in Primary Human Proximal Tubular Cells
[0423] ISIS 511403 was tested for its effect on the alternative splicing of the fibronectin gene sequence in primary human proximal tubular cells (PTEC) treated with TGF.beta.1. Cultured PTEC cells were treated with 0.1% BSA (vehicle) or with 2.5 ng/mL TGF.beta.1 in 01% BSA for 24 hrs and then transfected using 2 .mu.L LipofectAMINE2000.RTM./mL OptiMEM with 100 nM ISIS 511403 or 100 nM ISIS 141923 for 24 h. After a recovery period of 24 h in normal growth medium, RNA was isolated and the ratio of EDA.sup.+FN to EDA.sub..quadrature.FN was measured by conventional PCR. In addition, the individual expressions of EDA.sup.+FN and EDA.sup.-.quadrature.FN normalized to 18s RNA were also measured (human primer probe set for 18S: forward sequence: GTAACCCGTTGAACCCCATT (SEQ ID NO: 26), reverse sequence: CCATCCAATCGGTAGTAGCG (SEQ ID NO: 27)). In addition, the expression of total fibronectin was also measured by quantitative real-time PCR (probe set Hs01549940_m1, Applied Biosystems). The results are presented in Table 6 and indicate that treatment with ISIS 511403 decreased the ratio of EDA.sup.+FN to EDA.sup.-FN, decreased expression of EDA.sup.+FN, increased expression of EDA.sup.-FN, and had no effect on total fibronectin expression compared to that of the negative control cells.
TABLE-US-00006 TABLE 6 Effect of ISIS 511403 in PTEC cells treated with TGF.beta.1 without with TGF.beta.1 TGF.beta.1 EDA.sup.+FN/ ISIS 141923 0.90 1.54 EDA.sup.-.quadrature.FN ISIS 511403 0.21 0.12 EDA.sup.+FN/18S ISIS 141923 0.21 0.21 ISIS 511403 0.07 0.68 EDA.sup.-.quadrature.FN/18S ISIS 141923 0.23 0.11 ISIS 511403 0.32 0.86 Total ISIS 141923 1.00 (0.82-1.23) 3.98 (3.60-4.40) Fibronectin (range) ISIS 511403 1.37 (1.17-1.60) 4.14 (4.05-4.23)
[0424] The effect of treatment with ISIS 511403 on lactate dehydrogenase (LDH) release by the cells was also measured using the CytoTox 96.RTM. Non-Radioactive Cytotoxicity Assay (Promega, G1780). The results are presented in Table 7 and indicate the decrease in LDH release in cells treated with ISIS 511403 compared to the cells treated with the negative control. This demonstrates that ISIS 511403 can rescue certain pronounced changes in cell phenotype caused by TGF.beta.1 induction, e.g. the release of LDH.
TABLE-US-00007 TABLE 7 Effect of ISIS 511403 on LDH release in PTEC cells treated with TGF.beta.1 Absorbance at 490 nm ISIS 141923 without TGF.beta.1 0.14 with TGF.beta.1 0.12 ISIS 511403 without TGF.beta.1 0.33 with TGF.beta.1 0.16
[0425] The effect of treatment with ISIS 511403 on .alpha.SMA mRNA expression by the cells was also measured by quantitative real-time PCR, using primer probe set Hs00909449_m1 (Applied Biosystems). The results are presented in Table 8 and indicate the decrease in .alpha.SMA in cells treated with ISIS 511403 compared to the cells treated with the negative control. The numbers in parentheses indicate the range. This demonstrates that ISIS 511403 can rescue certain pronounced changes in cell phenotype caused by TGF.beta.1 induction, e.g. the induction of .alpha.SMA.
TABLE-US-00008 TABLE 8 Effect of ISIS 511403 on .alpha.SMA expression in PTEC cells treated with TGF.beta.1 Fold increase over basal levels ISIS 141923 without TGF.beta.1 1.00 (0.79-1.26) with TGF.beta.1 1.96 (1.70-2.25) ISIS 511403 without TGF.beta.1 0.70 (0.59-0.83) with TGF.beta.1 0.79 (0.68-0.91)
[0426] The data presented in Tables 7 and 8 indicate that treatment with antisense oligonucleotides inhibiting the splicing and inclusion of the EDA region of fibronectin resulted in decreased fibrosis in primary human PTEC and therefore have therapeutic benefit in the prevention, treatment, or amelioration of fibrosis.
[0427] Additionally, by staining it was observed that prevention of EDA inclusion by treatment with ISIS 511403 resulted in a significant reduction in .alpha.SMA compared to treatment with a control (ISIS 141923). By western blot analysis, it was also observed that prevention of EDA inclusion by treatment with ISIS 511403 resulted in reduction in secretion of MMP2 & MMP9. The fold-change in the cell motility marker, S 100A4 was measured and is presented in Table 9. Treatment with ISIS 511403 resulted in significant reduction in S100A4 in TGF-.beta.-treated cells.
TABLE-US-00009 TABLE 9 Effect of ISIS 511403 on S100A4 expression in PTEC cells treated with TGF.beta.1 Fold increase over basal levels ISIS 141923 without TGF.beta.1 1.00 with TGF.beta.1 1.45 ISIS 511403 without TGF.beta.1 0.62 with TGF.beta.1 0.74
[0428] By staining and by western blot analysis, it was also observed that prevention of EDA inclusion by treatment with ISIS 511403 resulted in near complete inhibition of Connexin 43. By staining, it was also observed that prevention of EDA inclusion by treatment with ISIS 511403 resulted in a moderate increase in f-actin localization.
Example 6: Design of Antisense Oligonucleotides Targeting Human and Murine Fibronectin
[0429] Antisense oligonucleotides were designed targeting a fibronectin nucleic acid. The newly designed chimeric antisense oligonucleotides in Table 10 were designed as uniform MOE oligonucleotides. Each nucleoside in the oligonucleotide has a 2'-MOE modification. The internucleoside linkages throughout each oligonucleotide are phosphorothioate (P.dbd.S) linkages. All cytosine residues throughout each oligonucleotide are 5-methylcytosines. "Human Start site" indicates the 5'-most nucleoside to which the oligonucleotide is targeted in the human gene sequence. "Murine Start Site" indicates the 5'-most nucleoside to which the oligonucleotide is targeted murine gene sequence. Each oligonucleotide listed in Table 10 is targeted to the human fibronectin genomic sequence, SEQ ID NO: 1 (the complement of GENBANK Accession No. NT_005403.14 truncated from nucleotides 66434501 to 66510708) or to murine fibronectin genomic sequence, SEQ ID NO: 29 (the complement of Accession No. NT_039170.2 truncated from nucleotides 20696091 to 20764741), or both. Several of the oligonucleotides are cross-reactive with human and mouse gene sequences. The greater the complementarity between the oligonucleotide and the gene sequence, the more likely the oligonucleotide can target the gene sequence. `Mismatches` indicates the number of nucleotides in the oligonucleotide that are mismatched with the gene sequence. `n/a` indicates that the oligonucleotide contains more than 2 mismatches with the particular gene sequence.
TABLE-US-00010 TABLE 10 Antisense oligonucleotides targeted to SEQ ID NO: 1 and SEQ ID NO: 29 Human target Mismatches Mouse Target Mismatches SEQ ID Start Site with SEQ Start Site with SEQ NO of (SEQ ID NO: 1) ID NO: 1 Sequence ISIS No (SEQ ID NO: 29) ID NO: 29) oligo 55458 0 GTAAGAGGTTATGTG 594692 49712 0 30 55464 0 TTAATGGTAAGAGGT 594693 49718 0 31 55478 0 AATGTCTGTTAGGCAAAT 594685 49732 0 32 55479 0 CAATGTCTGTTAGGCAAA 594686 49733 0 33 55480 0 TCAATGTCTGTTAGGCAA 594687 49734 0 34 55481 0 AATGTCTGTTAGGCA 594681 49735 0 35 55481 0 ATCAATGTCTGTTAGGCA 594688 49735 0 36 55482 0 CAATGTCTGTTAGGC 594682 49736 0 37 55483 0 CGATCAATGTCTGTTAGG 594689 49737 0 38 55484 0 ATCAATGTCTGTTAG 594683 49738 0 39 55484 0 GCGATCAATGTCTGTTAG 594690 49738 0 40 55485 0 GATCAATGTCTGTTA 594684 49739 0 41 55485 0 GGCGATCAATGTCTGTTA 594691 49739 0 42 55501 0 GCCAGTCCTTTAGGG 594694 49755 0 43 55507 0 GTGAATGCCAGTCCT 594695 49761 0 44 55513 0 ACATCAGTGAATGCC 594696 49767 0 45 55519 0 ACATCCACATCAGTG 594697 49773 0 46 55525 0 GAATCGACATCCACA 594698 49779 0 47 55531 0 TTGATGGAATCGACA 594699 49785 0 48 55537 0 GCAATTTTGATGGAA 594700 49791 0 49 55543 0 TCCCAAGCAATTTTG 594701 49797 0 50 55549 0 GGGCTTTCCCAAGCA 594702 49803 0 51 55555 0 CCCTGTGGGCTTTCC 594703 49809 0 52 55561 0 ACTTGCCCCTGTGGG 594704 49815 0 53 55567 0 CTGGAAACTTGCCCC 594705 49821 0 54 55573 0 CTGTACCTGGAAACT 594706 49827 0 55 55579 0 GTCACCCTGTACCTG 594707 49833 0 56 55585 0 GAGTAGGTCACCCTG 594708 49839 0 57 55591 0 GGGCTCGAGTAGGTC 594709 49845 0 58 55597 0 TCCTCAGGGCTCGAG 594710 49851 0 59 55603 0 ATTCCATCCTCAGGG 594711 49857 0 60 55609 0 TCATGGATTCCATCC 594712 49863 2 61 55615 0 AATAGCTCATGGATT 594713 n/a n/a 62 55621 0 GCAGGGAATAGCTCA 594714 49875 2 63 55627 0 TCAGGTGCAGGGAAT 594715 49881 1 64 55633 0 TCACCATCAGGTGCA 594716 49887 0 65 55639 0 TCTTCTTCACCATCA 594717 49893 1 66 55645 0 GCAGTGTCTTCTTCA 594718 49899 1 67 55651 0 AGCTCTGCAGTGTCT 594719 49905 1 68 55657 0 CCTTGCAGCTCTGCA 594720 49911 1 69 55663 0 CTGAGGCCTTGCAGC 594721 49917 1 70 55669 0 CCCGGTCTGAGGCCT 594722 49923 2 71 55675 0 TCAGAACCCGGTCTG 594723 49929 2 72 55681 0 GTGTACTCAGAACCC 594724 49935 1 73 55687 0 CTGACTGTGTACTCA 594725 49941 0 74 55693 0 ACCACACTGACTGTG 594726 49947 0 75 55699 0 AAGGCAACCACACTG 594727 49953 0 76 55705 0 TCGTGCAAGGCAACC 594728 49959 0 77 55711 0 ATATCATCGTGCAAG 594729 49965 0 78 55717 0 CTCTCCATATCATCG 594730 49971 0 79 55723 0 GGCTGGCTCTCCATA 594731 49977 0 80 55736 1 GATTCCAATCAGGGG 594670 49990 0 81 55740 1 ACTGGATTCCAATCA 594671 49994 0 82 55743 1 TGGACTGGATTCCAA 594672 49997 0 83 55744 1 CCTGTGGACTGGATTCCA 594677 49998 0 84 55746 1 CTGTGGACTGGATTC 594673 50000 0 85 55749 1 TACCTGTGGACTGGA 594674 50003 0 86 55756 1 AACGATATACCTGTG 594675 50010 0 87 55760 2 AATTAATCATAAACC 594676 39337 0 88 55765 0 GGTGCAATTAACCAT 594732 n/a n/a 89 55771 0 CCTGGTGGTGCAATT 594733 n/a n/a 90
Example 7: In Vitro Screening of Uniform MOE Antisense Oligonucleotides Targeting Human and/or Mouse Fibronectin in MHT Cells
[0430] Some of the antisense oligonucleotides presented in Example 6 were tested for potency in cultured primary PTEC cells. ISIS 511403 was also included in the study.
[0431] Cultured PTEC cells were transfected using 2 .mu.L LipofectAMINE2000/mL OptiMEM with 100 nM antisense oligonucleotide for 4 hours, the medium was removed and new medium added, left in culture overnight, and then treated with 0.1% BSA (vehicle) or 2.5 ng/mL TGF.beta.1 in 0.1% BSA for 24 hrs. RNA was isolated from the cells and levels of EDA.sup.+FN mRNA were measured by RT-PCR using primer probe sets RTS3963_MGB (forward sequence GCCTTGCACGATGATATGGA, designated herein as SEQ ID NO: 91; reverse sequence TGTGGGTGTGACCTGAGTGAA, designated herein as SEQ ID NO: 92; probe sequence ATTGGAACCCAGTCCAC, designated herein as SEQ ID NO: 93), as well as with primer probe set RTS3964 (forward sequence GAATCCAAGCGGAGAGAGTCA, designated herein as SEQ ID NO: 94; reverse sequence ACATCAGTGAATGCCAGTCCTTT, designated herein as SEQ ID NO: 95; probe sequence TTCAGACTGCAGTAACCAACATTGATCGCC, designated herein as SEQ ID NO: 96), both of which are designed to the EDA+ variant of the FN mRNA transcript (NM_212478.1, designated herein as SEQ ID NO: 97) and which target different regions of the transcript. For data analysis, the levels of EDA.sup.+FN mRNA were normalized to the levels of the house-keeping gene, the large ribosomal protein transcript (Human RPLPO, Applied Biosystems, cat#4333761F). For each antisense oligonucleotide, the ratio of EDA.sup.+FN to RPLPO in antisense oligonucleotide-treated cells was then normalized to the ratio of EDA.sup.+FN mRNA to RPLPO in untreated cells. The results are presented in Table 11. The results indicate that treatment with antisense oligonucleotides reduced expression of the EDA+ transcript compared to untreated cells, both in the presence or absence of TGF.beta.1.
TABLE-US-00011 TABLE 11 EDA.sup.+FN mRNA levels compared to untreated cells (designated 1.00) in primary PTEC cells without with ISIS No PPset Used TGF.beta.1 TGF.beta.1 511403 RTS3963_MGB 0.21 0.21 594692 RTS3963_MGB 0.17 0.29 594693 RTS3963_MGB 0.21 0.32 594694 RTS3963_MGB 0.02 0.03 594695 RTS3963_MGB 0.15 0.24 594696 RTS3963_MGB 0.23 0.41 594697 RTS3963_MGB 0.40 0.70 594698 RTS3963_MGB 0.50 0.81 594699 RTS3963_MGB 0.51 0.76 594700 RTS3963_MGB 0.13 0.18 594701 RTS3963_MGB 0.33 0.47 594702 RTS3963_MGB 0.30 0.49 594703 RTS3963_MGB 0.16 0.32 594704 RTS3963_MGB 0.56 0.73 594705 RTS3963_MGB 0.40 0.68 594706 RTS3963_MGB 0.40 0.81 594707 RTS3963_MGB 0.29 0.40 594708 RTS3963_MGB 0.06 0.05 594709 RTS3963_MGB 0.03 0.02 594710 RTS3963_MGB 0.18 0.16 594711 RTS3963_MGB 0.43 0.27 594712 RTS3963_MGB 0.36 0.31 594713 RTS3963_MGB 0.14 0.15 594714 RTS3963_MGB 0.06 0.08 594715 RTS3963_MGB 0.05 0.07 594716 RTS3963_MGB 0.18 0.16 594717 RTS3963_MGB 0.71 0.68 594718 RTS3963_MGB 0.22 0.33 594719 RTS3963_MGB 0.46 0.44 594720 RTS3963_MGB 0.13 0.14 594721 RTS3963_MGB 0.14 0.13 594722 RTS3963_MGB 0.07 0.15 594723 RTS3963_MGB 0.05 0.05 594724 RTS3963_MGB 0.11 0.17 594725 RTS3963_MGB 0.06 0.07 594726 RTS3963_MGB 0.12 0.17 594727 RTS3964 0.06 0.10 594728 RTS3964 0.03 0.02 594729 RTS3964 0.08 0.06 594730 RTS3964 0.39 0.38 594731 RTS3964 0.10 0.07 594732 RTS3963_MGB 0.92 0.79 594733 RTS3963_MGB 0.37 0.38
Example 8: In Vitro Screening of Uniform MOE Antisense Oligonucleotides Targeting Human and/or Mouse Fibronectin in MHT Cells
[0432] Antisense oligonucleotides were designed targeting a fibronectin nucleic acid and were tested for their effects on blocking of splicing in vitro. The newly designed chimeric antisense oligonucleotides in Table 12 were designed as uniform MOE oligonucleotides. Each oligonucleotide is 15 nucleosides long and each nucleoside in the oligonucleotide has a 2'-MOE modification. The internucleoside linkages throughout each oligonucleotide are phosphorothioate (P.dbd.S) linkages. All cytosine residues throughout each oligonucleotide are 5-methylcytosines. "Human Start site" indicates the 5'-most nucleoside to which the oligonucleotide is targeted in the human gene sequence. "Murine Start Site" indicates the 5'-most nucleoside to which the oligonucleotide is targeted murine gene sequence. Each oligonucleotide listed in Table 12 is targeted to the human fibronectin genomic sequence, SEQ ID NO: 1 or to murine fibronectin genomic sequence, SEQ ID NO: 22, or both. Several of the oligonucleotides are cross-reactive with human and mouse gene sequences. The greater the complementarity between the oligonucleotide and the gene sequence, the more likely the oligonucleotide can target the gene sequence. `Mismatches` indicates the least number of nucleotides in the oligonucleotide that are mismatched with the gene sequence; the antisense oligonucleotide may target the gene sequence with more mismatches. `n/a` indicates that the antisense oligonucleotide has more than 3 mismatches with the particular gene sequence.
[0433] Cultured MHT cells, a mouse hepatocellular carcinoma cell line (Koller, E. et al., Nucleic Acids Research, 2011, 1-13), were transfected using 5 .mu.l LipofectAMINE2000.RTM./mL OptiMEM with 50 nM antisense oligonucleotide. After a treatment period of approximately 4 hours, the medium was removed and new medium was added, and the cells were left in culture overnight. RNA was isolated from the cells and measured by RT-PCR. EDA.sup.+FN mRNA expression was measured with mouse primer probe set LTS01050 (forward sequence AAACTGCAGTGACCAACATTGATC, designated herein as SEQ ID NO: 98; reverse sequence CTTGCCCCTGTGGGCTTT, designated herein as SEQ ID NO: 99; probe sequence CTGATGTGGATGTCGATT, designated herein as SEQ ID NO: 100), as well as with LTS01052 (forward sequence GCCAGCCCCTGATTGGA, designated herein as SEQ ID NO: 101; reverse sequence CCGGTAGCCAGTGAGCTGAA, designated herein as SEQ ID NO: 102; probe sequence CACCAATCTGAAGTTC, designated herein as SEQ ID NO: 103). The primer probe sets target different regions of the mouse sequence.
[0434] Results are presented in Table 12 and are the average of the values measured in three separate experiments. The results demonstrate blocking of splicing, as represented by EDA.sup.+FN expression. The expression value of untreated cells was taken as 1.00. `n.d.` indicates that the mRNA expression level values were not considered because the oligonucleotide targeted an amplicon region of the specific primer probe set.
TABLE-US-00012 TABLE 12 EDA .sup.+FN mRNA levels compared to untreated cells (designated 1.00) in MHT cells Mis- % % Human matches Mouse inhibition inhibition SEQ Start with Start ISIS with with ID Site human Sequence Site No LTS01050 LTS01052 NO 55469 0 GCAAATTAATGGTAA 49723 511399 0.43 0.44 104 55486 0 CGATCAATGTCTGTT 49740 511404 n.d. 0.27 105 55746 1 CTGTGGACTGGATTC 50000 594673 0.61 n.d. 85 55756 1 AACGATATACCTGTG 50010 594675 0.28 n.d. 87 55481 0 AATGTCTGTTAGGCA 49735 594681 n.d. 0.37 35 55501 0 GCCAGTCCTTTAGGG 49755 594694 n.d. 0.46 43 55531 0 TTGATGGAATCGACA 49785 594699 n.d. 0.93 48 55561 0 ACTTGCCCCTGTGGG 49815 594704 n.d. 0.94 53 55591 0 GGGCTCGAGTAGGTC 49845 594709 0.18 0.37 58 55711 0 ATATCATCGTGCAAG 49965 594729 0.50 0.33 78 55418 3 TCCATACCATGCAAA 49670 598110 1.11 1.04 106 20288 3 ATATTTCCATACCAT 49675 598111 1.11 1.02 107 51489 3 17531 3 CAAGCATATTTCCAT 49680 598112 0.93 1.03 108 19804 3 23642 3 42202 3 43710 2 TGAAACAAGCATATT 49685 598113 1.04 1.15 109 55431 2 55436 1 AGTTGTGAAACAAGC 49690 598114 0.42 0.58 110 55441 0 AAGCAAGTTGTGAAA 49695 598115 0.08 0.35 111 55446 0 GTGAAAAGCAAGTTG 49700 598116 0.85 0.94 112 55451 0 GTTATGTGAAAAGCA 49705 598117 0.63 0.68 113 55456 0 AAGAGGTTATGTGAA 49710 598118 0.58 0.54 114 55461 0 ATGGTAAGAGGTTAT 49715 598119 0.47 0.43 115 55466 0 AATTAATGGTAAGAG 49720 598120 0.49 0.53 116 55471 0 AGGCAAATTAATGGT 49725 598121 0.27 0.29 117 55476 0 CTGTTAGGCAAATTA 49730 598122 0.23 0.34 118 55491 0 TAGGGCGATCAATGT 49745 598123 n.d. 0.29 119 55496 0 TCCTTTAGGGCGATC 49750 598124 n.d. 0.39 120 55506 0 TGAATGCCAGTCCTT 49760 598125 n.d. 0.70 121 55511 0 ATCAGTGAATGCCAG 49765 598126 n.d. 0.54 122 55516 0 TCCACATCAGTGAAT 49770 598127 n.d. 0.53 123 55521 0 CGACATCCACATCAG 49775 598128 n.d. 0.47 124 55526 0 GGAATCGACATCCAC 49780 598129 n.d. 0.32 125 55536 0 CAATTTTGATGGAAT 49790 598130 n.d. 0.26 126 55541 0 CCAAGCAATTTTGAT 49795 598131 n.d. 0.45 127 55546 0 CTTTCCCAAGCAATT 49800 598132 n.d. 0.51 128 55551 0 GTGGGCTTTCCCAAG 49805 598133 n.d. 0.92 129 55556 0 CCCCTGTGGGCTTTC 49810 598134 n.d. 0.59 130 55566 0 TGGAAACTTGCCCCT 49820 598135 n.d. 0.70 131 55571 0 GTACCTGGAAACTTG 49825 598136 n.d. 0.50 132 55576 0 ACCCTGTACCTGGAA 49830 598137 78 0.27 133 55581 0 AGGTCACCCTGTACC 49835 598138 78 0.27 134 55586 0 CGAGTAGGTCACCCT 49840 598139 71 0.41 135 55596 0 CCTCAGGGCTCGAGT 49850 598140 73 0.42 136 55601 0 TCCATCCTCAGGGCT 49855 598141 63 0.42 137 55606 1 CGGATTCCATCCTCA 49860 598142 52 0.35 138 55611 2 GCTCCCGGATTCCAT 49865 598143 78 0.31 139 48384 3 GAAAAGCTCCCGGAT 49870 598144 0.20 0.28 140 55616 3 55621 2 GCAGGGAAAAGCTCC 49875 598145 0.19 0.21 141 55626 1 CAGGTGCAGGGAAAA 49880 598146 0.32 0.33 142 55631 0 ACCATCAGGTGCAGG 49885 598147 0.31 0.30 143 55636 0 TCTTCACCATCAGGT 49890 598148 0.47 0.38 144 55641 1 TGTCGTCTTCACCAT 49895 598149 0.39 0.37 145 55646 1 TGCAGTGTCGTCTTC 49900 598150 0.66 0.41 146 55651 1 AGCTCTGCAGTGTCG 49905 598151 0.29 0.24 147 55656 1 CCTGCAGCTCTGCAG 49910 598152 0.40 0.42 148 55661 1 GAGGCCCTGCAGCTC 49915 598153 0.25 0.21 149 55666 2 GGCCTGAGGCCCTGC 49920 598154 0.79 0.80 150 55671 2 ACCCCGGCCTGAGGC 49925 598155 0.48 0.54 151 55676 2 CTCAGACCCCGGCCT 49930 598156 0.68 0.76 152 55681 1 GTGTACTCAGACCCC 49935 598157 0.57 0.41 153 55686 0 TGACTGTGTACTCAG 49940 598158 0.56 0.54 154 55691 0 CACACTGACTGTGTA 49945 598159 0.59 0.51 155 55696 0 GCAACCACACTGACT 49950 598160 0.54 0.49 156 55701 0 GCAAGGCAACCACAC 49955 598161 0.27 0.27 157 55706 0 ATCGTGCAAGGCAAC 49960 598162 0.56 0.49 158 55716 0 TCTCCATATCATCGT 49970 598163 0.31 0.22 159 55721 0 CTGGCTCTCCATATC 49975 598164 0.66 n.d. 160 55741 1 GACTGGATTCCAATC 49995 598165 0.56 n.d. 161 55751 0 TATACCTGTGGACTG 50005 598166 0.39 n.d. 162 55761 3 CGGTTAACGATATAC 50015 598167 0.30 0.25 163 n/a n/a GGGTGCGGTTAACGA 50020 598168 0.91 0.95 164 n/a n/a GTGGTGGGTGCGGTT 50025 598169 0.95 0.51 165 7620 3 CCCGGGTGGTGGGTG 50030 598170 0.81 0.79 166 n/a n/a AAGCACCCGGGTGGT 50035 598171 0.92 1.00 167 n/a n/a CCCAGAAGCACCCGG 50040 598172 1.36 1.32 168 50882 3 CTGTTCCCAGAAGCA 50045 598173 1.44 1.41 169 23948 1 AGCCACTGTTCCCAG 50050 598174 1.11 1.14 170 47171 1 55796 2 CATAAAGCCACTGTT 50055 598175 0.94 0.91 171 64745 2 55801 3 CAAGGCATAAAGCCA 50060 598176 1.13 0.97 172 n/a n/a GCCAGCAAGGCATAA 50065 598177 0.78 0.95 173 61226 3 ATAACGCCAGCAAGG 50070 598178 1.08 1.10 174 n/a n/a AAAGTATAACGCCAG 50075 598179 1.13 1.08 175 3323 3 CCAGTAAAGTATAAC 50080 598180 1.09 1.20 176 55824 3 60705 3
Example 9: Antisense Inhibition of Fibronectin mRNA in MHT Cells by Uniform MOE Oligonucleotides Designed by Microwalk
[0435] Additional antisense oligonucleotides were designed based on the ISIS oligonucleotides that demonstrated significant effect on fibronectin splicing in the studies described above. These oligonucleotides were designed by creating oligonucleotides shifted slightly upstream and downstream (i.e. "microwalk") of ISIS 511417, ISIS 594685, ISIS 594686, ISIS 594686, ISIS 594687, ISIS 594688, ISIS 594689, ISIS 594690, ISIS 594691, and ISIS 598145. The newly designed antisense oligonucleotides in Tables 13 and 14 were designed as uniform MOE oligonucleotides. Each oligonucleotide is 18 nucleosides long and each nucleoside in the oligonucleotide has a 2'-MOE modification. The internucleoside linkages throughout each oligonucleotide are phosphorothioate (P.dbd.S) linkages. All cytosine residues throughout each oligonucleotide are 5-methylcytosines. The oligonucleotides are presented in the tables below. "Human Start site" indicates the 5'-most nucleoside to which the oligonucleotide is targeted in the human gene sequence. "Murine Start Site" indicates the 5'-most nucleoside to which the oligonucleotide is targeted murine gene sequence. Each oligonucleotide listed in the tables is targeted to the human fibronectin genomic sequence, SEQ ID NO: 1 or to murine fibronectin genomic sequence, SEQ ID NO: 29, or both. Several of the oligonucleotides are cross-reactive with human and mouse gene sequences. The greater the complementarity between the oligonucleotide and the gene sequence, the more likely the oligonucleotide can target the gene sequence. `Mismatches` indicates the least number of nucleotides in the oligonucleotide that are mismatched with the gene sequence; the antisense oligonucleotide may target the gene sequence with more mismatches. `n/a` indicates that the antisense oligonucleotide has more than 3 mismatches with the particular gene sequence. Cultured MHT cells were transfected using 5 .mu.l LipofectAMINE2000.RTM./mL OptiMEM with 10 nM antisense oligonucleotide. After a treatment period of approximately 4 hours, the medium was removed and new medium was added, left in culture overnight. RNA was isolated from the cells and measured by RT-PCR. EDA.sup.+FN mRNA expression was measured with mouse primer probe set LTS01050, as well as with LTS01052.
[0436] Results are presented in Tables 13 and 14, and are the average of the values measured in three separate experiments. The results demonstrate blocking of splicing, as represented by EDA.sup.+FN expression. The expression value of untreated cells was taken as 1.00. `n.d.` indicates that the mRNA expression level values were not considered because the oligonucleotide targeted an amplicon region of the specific primer probe set.
TABLE-US-00013 TABLE 13 EDA .sup.+FN mRNA levels compared to untreated cells (designated 1.00) in MHT cells Human Mismatches Murine SEQ Start with human ISIS Start ID Site sequence Sequence No Site LTS01050 LTS01052 NO 55471 0 GTTAGGCAAATTAATGGT 606663 49725 n.d. 0.77 177 55472 0 TGTTAGGCAAATTAATGG 606664 49726 n.d. 0.80 178 55473 0 CTGTTAGGCAAATTAATG 606665 49727 n.d. 0.78 179 55474 0 TCTGTTAGGCAAATTAAT 606666 49728 n.d. 0.73 180 55475 0 GTCTGTTAGGCAAATTAA 606667 49729 n.d. 0.70 181 55476 0 TGTCTGTTAGGCAAATTA 606668 49730 n.d. 0.62 182 55477 0 ATGTCTGTTAGGCAAATT 606669 49731 n.d. 0.66 183 55478 0 AATGTCTGTTAGGCAAAT 594685 49732 n.d. 0.79 32 55479 0 CAATGTCTGTTAGGCAAA 594686 49733 0.57 0.50 33 55480 0 TCAATGTCTGTTAGGCAA 594687 49734 1.21 0.99 34 55481 0 ATCAATGTCTGTTAGGCA 594688 49735 1.04 0.83 36 55482 0 GATCAATGTCTGTTAGGC 511417 49736 0.70 0.63 184 55483 0 CGATCAATGTCTGTTAGG 594689 49737 n.d. 0.66 38 55484 0 GCGATCAATGTCTGTTAG 594690 49738 n.d. 0.64 40 55485 0 GGCGATCAATGTCTGTTA 594691 49739 n.d. 0.85 42 55486 0 GGGCGATCAATGTCTGTT 606670 49740 n.d. 0.83 185 55487 0 AGGGCGATCAATGTCTGT 606671 49741 n.d. 0.82 186 55488 0 TAGGGCGATCAATGTCTG 606672 49742 n.d. 0.80 187 55489 0 TTAGGGCGATCAATGTCT 606673 49743 n.d. 0.56 188 55490 0 TTTAGGGCGATCAATGTC 606674 49744 n.d. 0.56 189 55491 0 CTTTAGGGCGATCAATGT 606675 49745 n.d. 0.55 190 55492 0 CCTTTAGGGCGATCAATG 606676 49746 n.d. 0.47 191 55493 0 TCCTTTAGGGCGATCAAT 606677 49747 n.d. 0.57 192 55494 0 GTCCTTTAGGGCGATCAA 606678 49748 n.d. 0.62 193 55495 0 AGTCCTTTAGGGCGATCA 606679 49749 n.d. 0.94 194 55496 0 CAGTCCTTTAGGGCGATC 606680 49750 n.d. 0.92 195 55523 0 GGAATCGACATCCACATC 606681 49777 n.d. 0.68 196 55524 0 TGGAATCGACATCCACAT 606682 49778 n.d. 0.70 197 55525 0 ATGGAATCGACATCCACA 606683 49779 n.d. 0.66 198 55526 0 GATGGAATCGACATCCAC 606684 49780 n.d. 0.63 199 55527 0 TGATGGAATCGACATCCA 606685 49781 n.d. 0.63 200 55528 0 TTGATGGAATCGACATCC 606686 49782 n.d. 0.88 201 55529 0 TTTGATGGAATCGACATC 606687 49783 n.d. 0.93 202 55533 0 CAATTTTGATGGAATCGA 606688 49787 n.d. 1.05 203 55534 0 GCAATTTTGATGGAATCG 606689 49788 n.d. 0.81 204 55535 0 AGCAATTTTGATGGAATC 606690 49789 n.d. 0.60 205 55536 0 AAGCAATTTTGATGGAAT 606691 49790 n.d. 0.66 206 55537 0 CAAGCAATTTTGATGGAA 606692 49791 n.d. 0.56 207 55538 0 CCAAGCAATTTTGATGGA 606693 49792 n.d. 0.61 208 55539 0 CCCAAGCAATTTTGATGG 606694 49793 n.d. 0.84 209 55576 0 GTCACCCTGTACCTGGAA 606695 49830 n.d. 0.88 210 55577 0 GGTCACCCTGTACCTGGA 606696 49831 1.32 1.07 211 55578 0 AGGTCACCCTGTACCTGG 606697 49832 0.74 0.81 212 55579 0 TAGGTCACCCTGTACCTG 606698 49833 0.61 0.69 213 55580 0 GTAGGTCACCCTGTACCT 606699 49834 0.52 0.49 214 55581 0 AGTAGGTCACCCTGTACC 606700 49835 0.48 0.57 215 55582 0 GAGTAGGTCACCCTGTAC 606701 49836 0.45 0.59 216 55583 0 CGAGTAGGTCACCCTGTA 606702 49837 0.60 0.80 217 55584 0 TCGAGTAGGTCACCCTGT 606703 49838 0.60 0.91 218 55585 0 CTCGAGTAGGTCACCCTG 606704 49839 0.60 0.78 219 55586 0 GCTCGAGTAGGTCACCCT 606705 49840 0.59 0.69 220 55587 0 GGCTCGAGTAGGTCACCC 606706 49841 0.57 0.57 221 55588 0 GGGCTCGAGTAGGTCACC 606707 49842 0.53 0.58 222 55589 0 AGGGCTCGAGTAGGTCAC 606708 49843 0.62 0.63 223 55590 0 CAGGGCTCGAGTAGGTCA 606709 49844 0.45 0.50 224 55591 0 TCAGGGCTCGAGTAGGTC 606710 49845 0.60 0.60 225 55592 0 CTCAGGGCTCGAGTAGGT 606711 49846 0.83 0.86 226 55593 0 CCTCAGGGCTCGAGTAGG 606712 49847 0.95 0.99 227 55594 0 TCCTCAGGGCTCGAGTAG 606713 49848 0.95 0.83 228 55595 0 ATCCTCAGGGCTCGAGTA 606714 49849 0.67 0.61 229 55596 0 CATCCTCAGGGCTCGAGT 606715 49850 0.58 0.59 230 55597 0 CCATCCTCAGGGCTCGAG 606716 49851 0.65 0.58 231 55598 0 TCCATCCTCAGGGCTCGA 606717 49852 0.64 0.54 232 55599 0 TTCCATCCTCAGGGCTCG 606718 49853 0.65 0.62 233 55600 0 ATTCCATCCTCAGGGCTC 606719 49854 0.87 0.88 234 55601 0 GATTCCATCCTCAGGGCT 606720 49855 0.87 0.82 235 55602 0 GGATTCCATCCTCAGGGC 606721 49856 0.53 0.66 236 55603 1 CGGATTCCATCCTCAGGG 606722 49857 0.48 0.51 237 55604 2 CCGGATTCCATCCTCAGG 606723 49858 0.58 0.50 238 55605 2 CCCGGATTCCATCCTCAG 606724 49859 0.53 0.49 239 55606 2 TCCCGGATTCCATCCTCA 606725 49860 0.51 0.53 240 55607 2 CTCCCGGATTCCATCCTC 606726 49861 0.61 0.62 241 55608 2 GCTCCCGGATTCCATCCT 606727 49862 0.68 0.75 242 55609 2 AGCTCCCGGATTCCATCC 606728 49863 0.83 0.90 243 55610 3 AAGCTCCCGGATTCCATC 606729 49864 0.48 0.68 244 55611 3 AAAGCTCCCGGATTCCAT 606730 49865 0.26 0.53 245 55612 3 AAAAGCTCCCGGATTCCA 606731 49866 0.32 0.52 246 55613 3 GAAAAGCTCCCGGATTCC 606732 49867 0.37 0.52 247 55614 3 GGAAAAGCTCCCGGATTC 606733 49868 0.49 0.59 248 55615 3 GGGAAAAGCTCCCGGATT 606734 49869 0.61 0.57 249 55621 2 GCAGGGAAAAGCTCC 598145 49875 0.78 0.92 141
TABLE-US-00014 TABLE 14 EDA .sup.+FN mRNA levels compared to untreated cells (designated 1.00) in MHT cells Human Mismatches Murine SEQ Start with human ISIS Start ID Site sequence Sequence No Site LTS01050 LTS01052 NO 48384 3 AGGGAAAAGCTCCCGGAT 606735 49870 0.95 0.77 250 55617 3 CAGGGAAAAGCTCCCGGA 606736 49871 1.04 0.83 251 55618 3 GCAGGGAAAAGCTCCCGG 606737 49872 0.85 0.82 252 55619 3 TGCAGGGAAAAGCTCCCG 606738 49873 0.71 0.76 253 55620 3 GTGCAGGGAAAAGCTCCC 606739 49874 0.65 0.68 254 55621 2 GCAGGGAAAAGCTCC 598145 49875 0.79 0.55 141 55621 2 GGTGCAGGGAAAAGCTCC 606740 49875 0.79 0.76 255 55622 1 AGGTGCAGGGAAAAGCTC 606741 49876 0.88 0.83 256 55623 1 CAGGTGCAGGGAAAAGCT 606742 49877 0.77 0.88 257 55624 1 TCAGGTGCAGGGAAAAGC 606743 49878 1.11 0.98 258 55625 1 ATCAGGTGCAGGGAAAAG 606744 49879 1.05 0.97 259 55626 1 CATCAGGTGCAGGGAAAA 606745 49880 0.76 0.79 260 55627 1 CCATCAGGTGCAGGGAAA 606746 49881 0.50 0.63 261 55628 0 ACCATCAGGTGCAGGGAA 606747 49882 0.53 0.73 262 55629 0 CACCATCAGGTGCAGGGA 606748 49883 0.70 0.77 263 55630 0 TCACCATCAGGTGCAGGG 606749 49884 0.83 0.85 264 55631 0 TTCACCATCAGGTGCAGG 606750 49885 1.11 0.94 265 55632 0 CTTCACCATCAGGTGCAG 606751 49886 0.88 0.82 266 55633 0 TCTTCACCATCAGGTGCA 606752 49887 0.68 0.71 267 55634 1 GTCTTCACCATCAGGTGC 606753 49888 0.49 0.55 268 55635 1 CGTCTTCACCATCAGGTG 606754 49889 0.90 0.53 269 55636 1 TCGTCTTCACCATCAGGT 606755 49890 1.17 0.49 270 55637 1 GTCGTCTTCACCATCAGG 606756 49891 1.58 0.57 271 55638 1 TGTCGTCTTCACCATCAG 606757 49892 1.48 0.64 272 55639 1 GTGTCGTCTTCACCATCA 606758 49893 1.27 0.96 273 55640 1 AGTGTCGTCTTCACCATC 606759 49894 0.78 0.75 274 55641 1 CAGTGTCGTCTTCACCAT 606760 49895 0.52 0.54 275 55642 1 GCAGTGTCGTCTTCACCA 606761 49896 0.47 0.53 276 55643 1 TGCAGTGTCGTCTTCACC 606762 49897 0.49 0.55 277 55644 1 CTGCAGTGTCGTCTTCAC 606763 49898 0.61 0.54 278 55645 1 TCTGCAGTGTCGTCTTCA 606764 49899 0.93 0.57 279 55646 1 CTCTGCAGTGTCGTCTTC 606765 49900 0.98 0.67 280 55647 1 GCTCTGCAGTGTCGTCTT 606766 49901 0.72 0.83 281 55648 1 AGCTCTGCAGTGTCGTCT 606767 49902 0.71 0.65 282 55649 1 CAGCTCTGCAGTGTCGTC 606768 49903 0.71 0.62 283 55650 1 GCAGCTCTGCAGTGTCGT 606769 49904 0.64 0.60 284 55651 1 TGCAGCTCTGCAGTGTCG 606770 49905 0.40 0.47 285 55652 1 CTGCAGCTCTGCAGTGTC 606771 49906 0.35 0.53 286 55653 1 CCTGCAGCTCTGCAGTGT 606772 49907 0.47 0.56 287 55654 1 CCCTGCAGCTCTGCAGTG 606773 49908 0.71 0.97 288 55655 1 GCCCTGCAGCTCTGCAGT 606774 49909 0.83 0.97 289 55656 1 GGCCCTGCAGCTCTGCAG 606775 49910 0.91 0.73 290 55657 1 AGGCCCTGCAGCTCTGCA 606776 49911 0.74 0.64 291 55658 1 GAGGCCCTGCAGCTCTGC 606777 49912 0.60 0.66 292 55659 1 TGAGGCCCTGCAGCTCTG 606778 49913 0.49 0.50 293 55660 1 CTGAGGCCCTGCAGCTCT 606779 49914 0.47 0.57 294 55661 2 CCTGAGGCCCTGCAGCTC 606780 49915 0.54 0.65 295 55698 0 GCAAGGCAACCACACTGA 606781 49952 0.60 0.71 296 55699 0 TGCAAGGCAACCACACTG 606782 49953 0.75 0.79 297 55700 0 GTGCAAGGCAACCACACT 606783 49954 0.75 0.63 298 55701 0 CGTGCAAGGCAACCACAC 606784 49955 0.53 0.59 299 55702 0 TCGTGCAAGGCAACCACA 606785 49956 0.46 0.46 300 55703 0 ATCGTGCAAGGCAACCAC 606786 49957 0.48 0.55 301 55704 0 CATCGTGCAAGGCAACCA 606787 49958 0.46 0.45 302 55708 0 ATATCATCGTGCAAGGCA 606788 49962 0.36 0.45 303 55709 0 CATATCATCGTGCAAGGC 606789 49963 0.59 0.49 304 55710 0 CCATATCATCGTGCAAGG 606790 49964 1.00 0.72 305 55711 0 TCCATATCATCGTGCAAG 606791 49965 1.00 0.58 306 55712 0 CTCCATATCATCGTGCAA 606792 49966 0.78 0.54 307 55713 0 TCTCCATATCATCGTGCA 606793 49967 0.61 0.46 308 55714 0 CTCTCCATATCATCGTGC 606794 49968 0.52 n.d. 309 55715 0 GCTCTCCATATCATCGTG 606795 49969 0.69 n.d. 310 55716 0 GGCTCTCCATATCATCGT 606796 49970 0.70 n.d. 311 55717 0 TGGCTCTCCATATCATCG 606797 49971 0.71 n.d. 312 55718 0 CTGGCTCTCCATATCATC 606798 49972 1.37 n.d. 313 55719 0 GCTGGCTCTCCATATCAT 606799 49973 1.82 n.d. 314 55749 1 ATATACCTGTGGACTGGA 606800 50003 0.77 n.d. 315 55750 1 GATATACCTGTGGACTGG 606801 50004 0.56 n.d. 316 55751 1 CGATATACCTGTGGACTG 606802 50005 0.40 n.d. 317 55752 1 ACGATATACCTGTGGACT 606803 50006 0.34 n.d. 318 55753 1 AACGATATACCTGTGGAC 606804 50007 0.33 n.d. 319 55754 1 TAACGATATACCTGTGGA 606805 50008 0.47 n.d. 320 55755 1 TTAACGATATACCTGTGG 606806 50009 0.57 n.d. 321 55756 2 GTTAACGATATACCTGTG 606807 50010 0.73 n.d. 322 55757 3 GGTTAACGATATACCTGT 606808 50011 0.59 n.d. 323 55758 3 CGGTTAACGATATACCTG 606809 50012 0.40 n.d. 324 55759 3 GCGGTTAACGATATACCT 606810 50013 0.40 n.d. 325 55760 3 TGCGGTTAACGATATACC 606811 50014 0.40 n.d. 326 55761 3 GTGCGGTTAACGATATAC 606812 50015 0.43 0.46 327 55762 3 GGTGCGGTTAACGATATA 606813 50016 0.48 0.59 328 n/a n/a GGGTGCGGTTAACGATAT 606814 50017 0.77 0.83 329
Example 10: In Vitro Screening of Antisense Oligonucleotides with (S)-cEt Modifications Targeting Human and/or Mouse Fibronectin in b.END Cells
[0437] Antisense oligonucleotides were designed targeting a fibronectin nucleic acid and were tested for their effects on blocking of fibronectin splicing in vitro. ISIS 606793 was also included in the study. The newly designed antisense oligonucleotides in Tables 15-22 were designed as deoxy and (S)-cEt oligonucleotides. Each nucleoside in the oligonucleotide has a 2'-MOE, deoxy, or (S)-cEt modification, as presented in the Chemistry column of the tables. `e` indicates MOE; `k` indicates (S)-cEt; `d` indicates deoxy modifications. The internucleoside linkages throughout each oligonucleotide are phosphorothioate (P.dbd.S) linkages. All cytosine residues throughout each oligonucleotide are 5-methylcytosines. "Human Start site" indicates the 5'-most nucleoside to which the oligonucleotide is targeted in the human gene sequence. "Murine Start Site" indicates the 5'-most nucleoside to which the oligonucleotide is targeted murine gene sequence. Each oligonucleotide listed in Tables 15-22 is targeted to the human fibronectin genomic sequence, SEQ ID NO: 1 or to murine fibronectin genomic sequence, SEQ ID NO: 29, or both. Several of the oligonucleotides are cross-reactive with human and mouse gene sequences. The greater the complementarity between the oligonucleotide and the gene sequence, the more likely the oligonucleotide can target the gene sequence. `Mismatches` indicates the least number of nucleotides in the oligonucleotide that are mismatched with the gene sequence; the antisense oligonucleotide may target the gene sequence with more mismatches. `n/a` indicates that the antisense oligonucleotide has more than 3 mismatches with the particular gene sequence.
[0438] Cultured b.END cells were transfected using 2 .mu.l Cytofectin/mL with 3 nM antisense oligonucleotide. After a treatment period of approximately 4 hours, the medium was removed and new medium was added, left in culture overnight. RNA was isolated from the cells and measured by RT-PCR. EDA.sup.+FN mRNA expression was measured with mouse primer probe set LTS01050, as well as with LTS01052.
[0439] Results are presented in Tables 15-22, and are the average of the values measured in three separate experiments. The results demonstrate blocking of splicing, as represented by EDA.sup.+FN expression. The expression value of untreated cells was taken as 1.00. `n.d.` indicates that the mRNA expression level values were not considered because the oligonucleotide targeted an amplicon region of the specific primer probe set.
TABLE-US-00015 TABLE 15 EDA .sup.+FN mRNA levels compared to untreated cells (designated 1.00) in b.END cells measured with LTS01050 Mismatches Human to the Murine SEQ Start human Start ISIS ID Site sequence Site Sequence No Chemistry EDA + FN NO 48386 3 49872 AGGGAAAAGCTCCCGG 607180 kddkddkddkddkddk 0.80 330 55578 0 49832 GTCACCCTGTACCTGG 607170 kddkddkddkddkddk 0.86 331 55582 0 49836 GTAGGTCACCCTGTAC 607171 kddkddkddkddkddk 0.71 332 55586 0 49840 TCGAGTAGGTCACCCT 607172 kddkddkddkddkddk 0.56 333 55590 0 49844 GGGCTCGAGTAGGTCA 607173 kddkddkddkddkddk 0.41 334 55594 0 49848 CTCAGGGCTCGAGTAG 607174 kddkddkddkddkddk 0.50 335 55598 0 49852 CATCCTCAGGGCTCGA 607175 kddkddkddkddkddk 0.44 336 55602 0 49856 ATTCCATCCTCAGGGC 607176 kddkddkddkddkddk 0.42 337 55606 2 49860 CCGGATTCCATCCTCA 607177 kddkddkddkddkddk 0.47 338 55610 2 49864 GCTCCCGGATTCCATC 607178 kddkddkddkddkddk 0.18 339 55614 3 49868 AAAAGCTCCCGGATTC 607179 kddkddkddkddkddk 0.31 340 55622 1 49876 GTGCAGGGAAAAGCTC 607181 kddkddkddkddkddk 0.73 341 55626 1 49880 TCAGGTGCAGGGAAAA 607182 kddkddkddkddkddk 0.72 342 55630 0 49884 ACCATCAGGTGCAGGG 607183 kddkddkddkddkddk 0.36 343 55634 0 49888 CTTCACCATCAGGTGC 607184 kddkddkddkddkddk 0.49 344 55638 1 49892 TCGTCTTCACCATCAG 607185 kddkddkddkddkddk 0.34 345 55642 1 49896 AGTGTCGTCTTCACCA 607186 kddkddkddkddkddk 0.22 346 55646 1 49900 CTGCAGTGTCGTCTTC 607187 kddkddkddkddkddk 0.36 347 55650 1 49904 AGCTCTGCAGTGTCGT 607188 kddkddkddkddkddk 0.19 348 55654 1 49908 CTGCAGCTCTGCAGTG 607189 kddkddkddkddkddk 0.71 349 55658 1 49912 GGCCCTGCAGCTCTGC 607190 kddkddkddkddkddk 0.29 350 55662 1 49916 CTGAGGCCCTGCAGCT 607191 kddkddkddkddkddk 0.32 351 55666 2 49920 CGGCCTGAGGCCCTGC 607192 kddkddkddkddkddk 0.48 352 55670 2 49924 ACCCCGGCCTGAGGCC 607193 kddkddkddkddkddk 0.33 353 55674 2 49928 TCAGACCCCGGCCTGA 607194 kddkddkddkddkddk 0.34 354 55678 2 49932 GTACTCAGACCCCGGC 607195 kddkddkddkddkddk 0.27 355 55682 1 49936 CTGTGTACTCAGACCC 607196 kddkddkddkddkddk 0.63 356 55686 0 49940 CTGACTGTGTACTCAG 607197 kddkddkddkddkddk 0.61 357 55690 0 49944 CACACTGACTGTGTAC 607198 kddkddkddkddkddk 0.57 358 55694 0 49948 CAACCACACTGACTGT 607199 kddkddkddkddkddk 0.51 359 55698 0 49952 AAGGCAACCACACTGA 607200 kddkddkddkddkddk 0.47 360 55702 0 49956 GTGCAAGGCAACCACA 607201 kddkddkddkddkddk 0.28 361 55706 0 49960 CATCGTGCAAGGCAAC 607202 kddkddkddkddkddk 0.27 362 55710 0 49964 ATATCATCGTGCAAGG 607203 kddkddkddkddkddk 0.44 363 55713 0 49967 TCTCCATATCATCGTGCA 606793 eeeeeeeeeeeeeeeeee 0.13 308 55714 0 49968 CTCCATATCATCGTGC 607204 kddkddkddkddkddk 0.18 364 55718 0 49972 GGCTCTCCATATCATC 607205 kddkddkddkddkddk 0.22 365 55722 0 49976 GGCTGGCTCTCCATAT 607206 kddkddkddkddkddk 0.53 366 55738 1 49992 CTGGATTCCAATCAGG 607207 kddkddkddkddkddk 0.17 367 55742 1 49996 TGGACTGGATTCCAAT 607208 kddkddkddkddkddk 0.17 368 55746 1 50000 CCTGTGGACTGGATTC 607209 kddkddkddkddkddk 0.23 369 55750 0 50004 TATACCTGTGGACTGG 607210 kddkddkddkddkddk 0.24 370 55754 1 50008 ACGATATACCTGTGGA 607211 kddkddkddkddkddk 0.51 371 55758 2 50012 GTTAACGATATACCTG 607212 kddkddkddkddkddk 0.40 372 55762 3 50016 TGCGGTTAACGATATA 607213 kddkddkddkddkddk 0.18 373 n/a n/a 50020 TGGGTGCGGTTAACGA 607214 kddkddkddkddkddk 1.39 374
TABLE-US-00016 TABLE 16 EDA .sup.+FN mRNA levels compared to untreated cells (designated 1.00) in b.END cells measured with LTS01052 Mismatches Human to the Murine SEQ Start human Start ISIS ID Site sequence Site Sequence No Chemistry EDA + FN NO 55466 0 49720 AAATTAATGGTAAGAG 607142 kddkddkddkddkddk 0.19 375 55470 0 49724 AGGCAAATTAATGGTA 607143 kddkddkddkddkddk 0.20 376 55474 0 49728 TGTTAGGCAAATTAAT 607144 kddkddkddkddkddk 0.53 377 55478 0 49732 TGTCTGTTAGGCAAAT 607145 kddkddkddkddkddk 0.59 378 55482 0 49736 TCAATGTCTGTTAGGC 607146 kddkddkddkddkddk 0.59 379 55486 0 49740 GCGATCAATGTCTGTT 607147 kddkddkddkddkddk 0.65 380 55490 0 49744 TAGGGCGATCAATGTC 607148 kddkddkddkddkddk 0.67 381 55494 0 49748 CCTTTAGGGCGATCAA 607149 kddkddkddkddkddk 0.68 382 55498 0 49752 CAGTCCTTTAGGGCGA 607150 kddkddkddkddkddk 0.68 383 55502 0 49756 ATGCCAGTCCTTTAGG 607151 kddkddkddkddkddk 0.71 384 55506 0 49760 GTGAATGCCAGTCCTT 607152 kddkddkddkddkddk 0.75 385 55510 0 49764 ATCAGTGAATGCCAGT 607153 kddkddkddkddkddk 0.75 386 55514 0 49768 CCACATCAGTGAATGC 607154 kddkddkddkddkddk 0.83 387 55518 0 49772 ACATCCACATCAGTGA 607155 kddkddkddkddkddk 0.84 388 55522 0 49776 ATCGACATCCACATCA 607156 kddkddkddkddkddk 0.88 389 55526 0 49780 TGGAATCGACATCCAC 607157 kddkddkddkddkddk 0.90 390 55530 0 49784 TTGATGGAATCGACAT 607158 kddkddkddkddkddk 0.91 391 55534 0 49788 AATTTTGATGGAATCG 607159 kddkddkddkddkddk 0.91 392 55538 0 49792 AAGCAATTTTGATGGA 607160 kddkddkddkddkddk 0.91 393 55542 0 49796 TCCCAAGCAATTTTGA 607161 kddkddkddkddkddk 0.95 394 55546 0 49800 GCTTTCCCAAGCAATT 607162 kddkddkddkddkddk 0.96 395 55550 0 49804 GTGGGCTTTCCCAAGC 607163 kddkddkddkddkddk 0.97 396 55554 0 49808 CCCTGTGGGCTTTCCC 607164 kddkddkddkddkddk 0.97 397 55558 0 49812 TTGCCCCTGTGGGCTT 607165 kddkddkddkddkddk 1.00 398 55562 0 49816 AAACTTGCCCCTGTGG 607166 kddkddkddkddkddk 1.06 399 55566 0 49820 CTGGAAACTTGCCCCT 607167 kddkddkddkddkddk 1.09 400 55570 0 49824 GTACCTGGAAACTTGC 607168 kddkddkddkddkddk 1.16 401 55574 0 49828 CCCTGTACCTGGAAAC 607169 kddkddkddkddkddk 1.17 402 55713 0 49967 TCTCCATATCATCGTGCA 606793 eeeeeeeeeeeeeeeeee 0.16 308
TABLE-US-00017 TABLE 17 EDA .sup.+FN mRNA levels compared to untreated cells (designated 1.00) in b.END cells measured with LTS01050 Mismatches Human to the Murine SEQ Start human Start ISIS ID Site sequence Site Sequence No Chemistry EDA + FN NO 55713 0 49967 TCTCCATATCATCGTGCA 606793 eeeeeeeeeeeeeeeeee 0.16 308 55578 0 49832 GTCACCCTGTACCTGG 607243 keekeekeekeekeek 0.83 331 55582 0 49836 GTAGGTCACCCTGTAC 607244 keekeekeekeekeek 0.97 332 55586 0 49840 TCGAGTAGGTCACCCT 607245 keekeekeekeekeek 0.27 333 55590 0 49844 GGGCTCGAGTAGGTCA 607246 keekeekeekeekeek 0.65 334 55594 0 49848 CTCAGGGCTCGAGTAG 607247 keekeekeekeekeek 0.71 335 55598 0 49852 CATCCTCAGGGCTCGA 607248 keekeekeekeekeek 0.85 336 55602 0 49856 ATTCCATCCTCAGGGC 607249 keekeekeekeekeek 0.59 337 55606 2 49860 CCGGATTCCATCCTCA 607250 keekeekeekeekeek 0.72 338 55610 2 49864 GCTCCCGGATTCCATC 607251 keekeekeekeekeek 0.52 339 55614 3 49868 AAAAGCTCCCGGATTC 607252 keekeekeekeekeek 0.38 340 48386 3 49872 AGGGAAAAGCTCCCGG 607253 keekeekeekeekeek 0.64 330 55622 1 49876 GTGCAGGGAAAAGCTC 607254 keekeekeekeekeek 0.61 341 55626 1 49880 TCAGGTGCAGGGAAAA 607255 keekeekeekeekeek 0.80 342 55630 0 49884 ACCATCAGGTGCAGGG 607256 keekeekeekeekeek 0.47 343 55634 0 49888 CTTCACCATCAGGTGC 607257 keekeekeekeekeek 0.83 344 55638 1 49892 TCGTCTTCACCATCAG 607258 keekeekeekeekeek 0.53 345 55642 1 49896 AGTGTCGTCTTCACCA 607259 keekeekeekeekeek 0.40 346 55646 1 49900 CTGCAGTGTCGTCTTC 607260 keekeekeekeekeek 0.84 347 55650 1 49904 AGCTCTGCAGTGTCGT 607261 keekeekeekeekeek 0.55 348 55654 1 49908 CTGCAGCTCTGCAGTG 607262 keekeekeekeekeek 0.93 349 55658 1 49912 GGCCCTGCAGCTCTGC 607263 keekeekeekeekeek 0.88 350 55662 1 49916 CTGAGGCCCTGCAGCT 607264 keekeekeekeekeek 0.87 351 55666 2 49920 CGGCCTGAGGCCCTGC 607265 keekeekeekeekeek 0.82 352 55670 2 49924 ACCCCGGCCTGAGGCC 607266 keekeekeekeekeek 0.46 353 55674 2 49928 TCAGACCCCGGCCTGA 607267 keekeekeekeekeek 0.84 354 55678 2 49932 GTACTCAGACCCCGGC 607268 keekeekeekeekeek 0.67 355 55682 1 49936 CTGTGTACTCAGACCC 607269 keekeekeekeekeek 0.78 356 55686 0 49940 CTGACTGTGTACTCAG 607270 keekeekeekeekeek 0.75 357 55690 0 49944 CACACTGACTGTGTAC 607271 keekeekeekeekeek 0.90 358 55694 0 49948 CAACCACACTGACTGT 607272 keekeekeekeekeek 0.41 359 55698 0 49952 AAGGCAACCACACTGA 607273 keekeekeekeekeek 0.30 360 55702 0 49956 GTGCAAGGCAACCACA 607274 keekeekeekeekeek 0.35 361 55706 0 49960 CATCGTGCAAGGCAAC 607275 keekeekeekeekeek 0.24 362 55710 0 49964 ATATCATCGTGCAAGG 607276 keekeekeekeekeek 0.24 363 55714 0 49968 CTCCATATCATCGTGC 607277 keekeekeekeekeek 0.20 364 55718 0 49972 GGCTCTCCATATCATC 607278 keekeekeekeekeek 0.35 365 55722 0 49976 GGCTGGCTCTCCATAT 607279 keekeekeekeekeek 0.84 366 55738 1 49992 CTGGATTCCAATCAGG 607280 keekeekeekeekeek 0.28 367 55742 1 49996 TGGACTGGATTCCAAT 607281 keekeekeekeekeek 0.54 368 55746 1 50000 CCTGTGGACTGGATTC 607282 keekeekeekeekeek 0.42 369 55750 0 50004 TATACCTGTGGACTGG 607283 keekeekeekeekeek 0.50 370 55754 1 50008 ACGATATACCTGTGGA 607284 keekeekeekeekeek 0.16 371 55758 2 50012 GTTAACGATATACCTG 607285 keekeekeekeekeek 0.18 372 55762 3 50016 TGCGGTTAACGATATA 607286 keekeekeekeekeek 0.20 373 n/a n/a 50020 TGGGTGCGGTTAACGA 607287 keekeekeekeekeek 1.28 374
TABLE-US-00018 TABLE 18 EDA .sup.+FN mRNA levels compared to untreated cells (designated 1.00) in b.END cells measured with LTS01052 Mismatches Human to the Murine SEQ Start human Start ISIS ID Site sequence Site Sequence No Chemistry EDA + FN NO 55713 0 49967 TCTCCATATCATCGTGCA 606793 eeeeeeeeeeeeeeeeee 0.19 308 55466 0 49720 AAATTAATGGTAAGAG 607215 keekeekeekeekeek 0.55 375 55470 0 49724 AGGCAAATTAATGGTA 607216 keekeekeekeekeek 0.39 376 55474 0 49728 TGTTAGGCAAATTAAT 607217 keekeekeekeekeek 0.67 377 55478 0 49732 TGTCTGTTAGGCAAAT 607218 keekeekeekeekeek 0.87 378 55482 0 49736 TCAATGTCTGTTAGGC 607219 keekeekeekeekeek 0.74 379 55486 0 49740 GCGATCAATGTCTGTT 607220 keekeekeekeekeek 0.60 380 55490 0 49744 TAGGGCGATCAATGTC 607221 keekeekeekeekeek 0.59 381 55494 0 49748 CCTTTAGGGCGATCAA 607222 keekeekeekeekeek 0.71 382 55498 0 49752 CAGTCCTTTAGGGCGA 607223 keekeekeekeekeek 0.97 383 55502 0 49756 ATGCCAGTCCTTTAGG 607224 keekeekeekeekeek 0.83 384 55506 0 49760 GTGAATGCCAGTCCTT 607225 keekeekeekeekeek 1.00 385 55510 0 49764 ATCAGTGAATGCCAGT 607226 keekeekeekeekeek 1.09 386 55514 0 49768 CCACATCAGTGAATGC 607227 keekeekeekeekeek 0.84 387 55518 0 49772 ACATCCACATCAGTGA 607228 keekeekeekeekeek 0.96 388 55522 0 49776 ATCGACATCCACATCA 607229 keekeekeekeekeek 0.84 389 55526 0 49780 TGGAATCGACATCCAC 607230 keekeekeekeekeek 0.95 390 55530 0 49784 TTGATGGAATCGACAT 607231 keekeekeekeekeek 0.96 391 55534 0 49788 AATTTTGATGGAATCG 607232 keekeekeekeekeek 0.83 392 55538 0 49792 AAGCAATTTTGATGGA 607233 keekeekeekeekeek 0.65 393 55542 0 49796 TCCCAAGCAATTTTGA 607234 keekeekeekeekeek 0.73 394 55546 0 49800 GCTTTCCCAAGCAATT 607235 keekeekeekeekeek 0.96 395 55550 0 49804 GTGGGCTTTCCCAAGC 607236 keekeekeekeekeek 0.93 396 55554 0 49808 CCCTGTGGGCTTTCCC 607237 keekeekeekeekeek 0.99 397 55558 0 49812 TTGCCCCTGTGGGCTT 607238 keekeekeekeekeek 0.92 398 55562 0 49816 AAACTTGCCCCTGTGG 607239 keekeekeekeekeek 0.95 399 55566 0 49820 CTGGAAACTTGCCCCT 607240 keekeekeekeekeek 0.79 400 55570 0 49824 GTACCTGGAAACTTGC 607241 keekeekeekeekeek 0.68 401 55574 0 49828 CCCTGTACCTGGAAAC 607242 keekeekeekeekeek 0.84 402
TABLE-US-00019 TABLE 19 EDA .sup.+FN mRNA levels compared to untreated cells (designated 1.00) in b.END cells measured with LTS01050 Mismatches Human to the Murine SEQ Start human Start ISIS ID Site sequence Site Sequence No Chemistry EDA + FN NO 55713 0 49967 TCTCCATATCATCGTGCA 606793 eeeeeeeeeeeeeeeeee 0.20 308 55578 0 49832 AGGTCACCCTGTACCTGG 607388 kkeekeekeekeekeeke 0.76 212 55582 0 49836 GAGTAGGTCACCCTGTAC 607389 kkeekeekeekeekeeke 0.76 216 55586 0 49840 GCTCGAGTAGGTCACCCT 607390 kkeekeekeekeekeeke 0.83 220 55590 0 49844 CAGGGCTCGAGTAGGTCA 607391 kkeekeekeekeekeeke 1.03 224 55594 0 49848 TCCTCAGGGCTCGAGTAG 607392 kkeekeekeekeekeeke 0.88 228 55598 0 49852 TCCATCCTCAGGGCTCGA 607393 kkeekeekeekeekeeke 0.74 232 55602 0 49856 GGATTCCATCCTCAGGGC 607394 kkeekeekeekeekeeke 1.16 236 55606 2 49860 TCCCGGATTCCATCCTCA 607395 kkeekeekeekeekeeke 0.81 240 55610 3 49864 AAGCTCCCGGATTCCATC 607396 kkeekeekeekeekeeke 0.71 244 55614 3 49868 GGAAAAGCTCCCGGATTC 607397 kkeekeekeekeekeeke 0.74 248 55618 3 49872 GCAGGGAAAAGCTCCCGG 607398 kkeekeekeekeekeeke 0.69 252 55622 1 49876 AGGTGCAGGGAAAAGCTC 607399 kkeekeekeekeekeeke 0.57 256 55626 1 49880 CATCAGGTGCAGGGAAAA 607400 kkeekeekeekeekeeke 0.80 260 55630 0 49884 TCACCATCAGGTGCAGGG 607401 kkeekeekeekeekeeke 0.64 264 55634 1 49888 GTCTTCACCATCAGGTGC 607402 kkeekeekeekeekeeke 0.65 268 55638 1 49892 TGTCGTCTTCACCATCAG 607403 kkeekeekeekeekeeke 0.46 272 55642 1 49896 GCAGTGTCGTCTTCACCA 607404 kkeekeekeekeekeeke 0.51 276 55646 1 49900 CTCTGCAGTGTCGTCTTC 607405 kkeekeekeekeekeeke 0.39 280 55650 1 49904 GCAGCTCTGCAGTGTCGT 607406 kkeekeekeekeekeeke 0.75 284 55654 1 49908 CCCTGCAGCTCTGCAGTG 607407 kkeekeekeekeekeeke 0.40 288 55658 1 49912 GAGGCCCTGCAGCTCTGC 607408 kkeekeekeekeekeeke 1.00 292 55662 2 49916 GCCTGAGGCCCTGCAGCT 607409 kkeekeekeekeekeeke 0.64 403 55666 2 49920 CCCGGCCTGAGGCCCTGC 607410 kkeekeekeekeekeeke 0.24 404 55670 2 49924 AGACCCCGGCCTGAGGCC 607411 kkeekeekeekeekeeke 0.47 405 55674 2 49928 ACTCAGACCCCGGCCTGA 607412 kkeekeekeekeekeeke 0.62 406 55678 2 49932 GTGTACTCAGACCCCGGC 607413 kkeekeekeekeekeeke 0.74 407 55682 1 49936 GACTGTGTACTCAGACCC 607414 kkeekeekeekeekeeke 0.53 408 55686 0 49940 CACTGACTGTGTACTCAG 607415 kkeekeekeekeekeeke 1.03 409 55690 0 49944 ACCACACTGACTGTGTAC 607416 kkeekeekeekeekeeke 0.95 410 55694 0 49948 GGCAACCACACTGACTGT 607417 kkeekeekeekeekeeke 0.83 411 55698 0 49952 GCAAGGCAACCACACTGA 607418 kkeekeekeekeekeeke 0.80 296 55702 0 49956 TCGTGCAAGGCAACCACA 607419 kkeekeekeekeekeeke 0.78 300 55706 0 49960 ATCATCGTGCAAGGCAAC 607420 kkeekeekeekeekeeke 0.88 412 55710 0 49964 CCATATCATCGTGCAAGG 607421 kkeekeekeekeekeeke 0.71 305 55714 0 49968 CTCTCCATATCATCGTGC 607422 kkeekeekeekeekeeke 0.84 309 55718 0 49972 CTGGCTCTCCATATCATC 607423 kkeekeekeekeekeeke 0.42 313 55738 1 49992 GACTGGATTCCAATCAGG 607424 kkeekeekeekeekeeke 0.47 413 55742 1 49996 TGTGGACTGGATTCCAAT 607425 kkeekeekeekeekeeke 0.49 414 55746 1 50000 TACCTGTGGACTGGATTC 607426 kkeekeekeekeekeeke 0.48 415 55750 1 50004 GATATACCTGTGGACTGG 607427 kkeekeekeekeekeeke 0.30 316 55754 1 50008 TAACGATATACCTGTGGA 607428 kkeekeekeekeekeeke 0.19 320 55758 3 50012 CGGTTAACGATATACCTG 607429 kkeekeekeekeekeeke 0.19 324 55762 3 50016 GGTGCGGTTAACGATATA 607430 kkeekeekeekeekeeke 0.41 328 n/a n/a 50020 GGTGGGTGCGGTTAACGA 607431 kkeekeekeekeekeeke 0.44 416
TABLE-US-00020 TABLE 20 EDA .sup.+FN mRNA levels compared to untreated cells (designated 1.00) in b.END cells measured with LTS01052 Mismatches Human to the Murine SEQ Start human Start ISIS ID Site sequence Site Sequence No Chemistry EDA + FN NO 55713 0 49967 TCTCCATATCATCGTGCA 606793 eeeeeeeeeeeeeeeeee 0.19 308 55466 0 49720 GCAAATTAATGGTAAGAG 607360 kkeekeekeekeekeeke 0.51 417 55470 0 49724 TTAGGCAAATTAATGGTA 607361 kkeekeekeekeekeeke 0.53 418 55474 0 49728 TCTGTTAGGCAAATTAAT 607362 kkeekeekeekeekeeke 0.64 180 55478 0 49732 AATGTCTGTTAGGCAAAT 607363 kkeekeekeekeekeeke 1.06 32 55482 0 49736 GATCAATGTCTGTTAGGC 607364 kkeekeekeekeekeeke 0.85 184 55486 0 49740 GGGCGATCAATGTCTGTT 607365 kkeekeekeekeekeeke 1.12 185 55490 0 49744 TTTAGGGCGATCAATGTC 607366 kkeekeekeekeekeeke 0.44 189 55494 0 49748 GTCCTTTAGGGCGATCAA 607367 kkeekeekeekeekeeke 0.88 193 55498 0 49752 GCCAGTCCTTTAGGGCGA 607368 kkeekeekeekeekeeke 1.09 419 55502 0 49756 GAATGCCAGTCCTTTAGG 607369 kkeekeekeekeekeeke 1.04 420 55506 0 49760 CAGTGAATGCCAGTCCTT 607370 kkeekeekeekeekeeke 0.97 421 55510 0 49764 ACATCAGTGAATGCCAGT 607371 kkeekeekeekeekeeke 0.95 422 55514 0 49768 ATCCACATCAGTGAATGC 607372 kkeekeekeekeekeeke 1.05 423 55518 0 49772 CGACATCCACATCAGTGA 607373 kkeekeekeekeekeeke 1.04 424 55522 0 49776 GAATCGACATCCACATCA 607374 kkeekeekeekeekeeke 0.94 425 55526 0 49780 GATGGAATCGACATCCAC 607375 kkeekeekeekeekeeke 1.07 199 55530 0 49784 TTTTGATGGAATCGACAT 607376 kkeekeekeekeekeeke 1.05 426 55534 0 49788 GCAATTTTGATGGAATCG 607377 kkeekeekeekeekeeke 0.89 204 55538 0 49792 CCAAGCAATTTTGATGGA 607378 kkeekeekeekeekeeke 0.88 208 55542 0 49796 TTTCCCAAGCAATTTTGA 607379 kkeekeekeekeekeeke 0.97 427 55546 0 49800 GGGCTTTCCCAAGCAATT 607380 kkeekeekeekeekeeke 1.09 428 55550 0 49804 CTGTGGGCTTTCCCAAGC 607381 kkeekeekeekeekeeke 1.05 429 55554 0 49808 GCCCCTGTGGGCTTTCCC 607382 kkeekeekeekeekeeke 1.26 430 55558 0 49812 ACTTGCCCCTGTGGGCTT 607383 kkeekeekeekeekeeke 1.26 431 55562 0 49816 GGAAACTTGCCCCTGTGG 607384 kkeekeekeekeekeeke 1.07 432 55566 0 49820 ACCTGGAAACTTGCCCCT 607385 kkeekeekeekeekeeke 0.91 433 55570 0 49824 CTGTACCTGGAAACTTGC 607386 kkeekeekeekeekeeke 0.85 434 55574 0 49828 CACCCTGTACCTGGAAAC 607387 kkeekeekeekeekeeke 1.03 435
TABLE-US-00021 TABLE 21 EDA .sup.+FN mRNA levels compared to untreated cells (designated 1.00) in b.END cells measured with LTS01050 Mismatches Human to the Murine SEQ Start human Start ISIS ID Site sequence Site Sequence No Chemistry EDA + FN NO 55713 0 49967 TCTCCATATCATCGTGCA 606793 eeeeeeeeeeeeeeeeee 0.15 308 55578 0 49832 AGGTCACCCTGTACCTGG 607316 kkddkddkddkddkddkk 0.47 212 55582 0 49836 GAGTAGGTCACCCTGTAC 607317 kkddkddkddkddkddkk 0.66 216 55586 0 49840 GCTCGAGTAGGTCACCCT 607318 kkddkddkddkddkddkk 0.78 220 55590 0 49844 CAGGGCTCGAGTAGGTCA 607319 kkddkddkddkddkddkk 0.78 224 55594 0 49848 TCCTCAGGGCTCGAGTAG 607320 kkddkddkddkddkddkk 0.60 228 55598 0 49852 TCCATCCTCAGGGCTCGA 607321 kkddkddkddkddkddkk 0.72 232 55602 0 49856 GGATTCCATCCTCAGGGC 607322 kkddkddkddkddkddkk 0.68 236 55606 2 49860 TCCCGGATTCCATCCTCA 607323 kkddkddkddkddkddkk 0.69 240 55610 3 49864 AAGCTCCCGGATTCCATC 607324 kkddkddkddkddkddkk 0.31 244 55614 3 49868 GGAAAAGCTCCCGGATTC 607325 kkddkddkddkddkddkk 0.58 248 55618 3 49872 GCAGGGAAAAGCTCCCGG 607326 kkddkddkddkddkddkk 0.52 252 55622 1 49876 AGGTGCAGGGAAAAGCTC 607327 kkddkddkddkddkddkk 0.28 256 55626 1 49880 CATCAGGTGCAGGGAAAA 607328 kkddkddkddkddkddkk 0.45 260 55630 0 49884 TCACCATCAGGTGCAGGG 607329 kkddkddkddkddkddkk 0.34 264 55634 1 49888 GTCTTCACCATCAGGTGC 607330 kkddkddkddkddkddkk 0.16 268 55638 1 49892 TGTCGTCTTCACCATCAG 607331 kkddkddkddkddkddkk 0.23 272 55642 1 49896 GCAGTGTCGTCTTCACCA 607332 kkddkddkddkddkddkk 0.18 276 55646 1 49900 CTCTGCAGTGTCGTCTTC 607333 kkddkddkddkddkddkk 0.17 280 55650 1 49904 GCAGCTCTGCAGTGTCGT 607334 kkddkddkddkddkddkk 0.41 284 55654 1 49908 CCCTGCAGCTCTGCAGTG 607335 kkddkddkddkddkddkk 0.44 288 55658 1 49912 GAGGCCCTGCAGCTCTGC 607336 kkddkddkddkddkddkk 0.42 292 55662 2 49916 GCCTGAGGCCCTGCAGCT 607337 kkddkddkddkddkddkk 0.23 403 55666 2 49920 CCCGGCCTGAGGCCCTGC 607338 kkddkddkddkddkddkk 0.14 404 55670 2 49924 AGACCCCGGCCTGAGGCC 607339 kkddkddkddkddkddkk 0.15 405 55674 2 49928 ACTCAGACCCCGGCCTGA 607340 kkddkddkddkddkddkk 0.15 406 55678 2 49932 GTGTACTCAGACCCCGGC 607341 kkddkddkddkddkddkk 0.22 407 55682 1 49936 GACTGTGTACTCAGACCC 607342 kkddkddkddkddkddkk 0.17 408 55686 0 49940 CACTGACTGTGTACTCAG 607343 kkddkddkddkddkddkk 0.39 409 55690 0 49944 ACCACACTGACTGTGTAC 607344 kkddkddkddkddkddkk 0.58 410 55694 0 49948 GGCAACCACACTGACTGT 607345 kkddkddkddkddkddkk 0.38 411 55698 0 49952 GCAAGGCAACCACACTGA 607346 kkddkddkddkddkddkk 0.43 296 55702 0 49956 TCGTGCAAGGCAACCACA 607347 kkddkddkddkddkddkk 0.56 300 55706 0 49960 ATCATCGTGCAAGGCAAC 607348 kkddkddkddkddkddkk 0.20 412 55710 0 49964 CCATATCATCGTGCAAGG 607349 kkddkddkddkddkddkk 0.22 305 55714 0 49968 CTCTCCATATCATCGTGC 607350 kkddkddkddkddkddkk 0.44 309 55718 0 49972 CTGGCTCTCCATATCATC 607351 kkddkddkddkddkddkk 0.29 313 55738 1 49992 GACTGGATTCCAATCAGG 607352 kkddkddkddkddkddkk 0.15 413 55742 1 49996 TGTGGACTGGATTCCAAT 607353 kkddkddkddkddkddkk 0.51 414 55746 1 50000 TACCTGTGGACTGGATTC 607354 kkddkddkddkddkddkk 0.23 415 55750 1 50004 GATATACCTGTGGACTGG 607355 kkddkddkddkddkddkk 0.24 316 55754 1 50008 TAACGATATACCTGTGGA 607356 kkddkddkddkddkddkk 0.21 320 55758 3 50012 CGGTTAACGATATACCTG 607357 kkddkddkddkddkddkk 0.14 324 55762 3 50016 GGTGCGGTTAACGATATA 607358 kkddkddkddkddkddkk 0.23 328 n/a n/a 50020 GGTGGGTGCGGTTAACGA 607359 kkddkddkddkddkddkk 0.25 416
TABLE-US-00022 TABLE 22 EDA .sup.+FN mRNA levels compared to untreated cells (designated 1.00) in b.END cells measured with LTS01052 Mismatches Human to the Murine SEQ Start human Start ISIS ID Site sequence Site Sequence No Chemistry EDA + FN NO 55713 0 49967 TCTCCATATCATCGTGCA 606793 eeeeeeeeeeeeeeeeee 0.14 308 55466 0 49720 GCAAATTAATGGTAAGAG 607288 kkddkddkddkddkddkk 0.75 417 55470 0 49724 TTAGGCAAATTAATGGTA 607289 kkddkddkddkddkddkk 0.62 418 55474 0 49728 TCTGTTAGGCAAATTAAT 607290 kkddkddkddkddkddkk 0.47 180 55478 0 49732 AATGTCTGTTAGGCAAAT 607291 kkddkddkddkddkddkk 0.88 32 55482 0 49736 GATCAATGTCTGTTAGGC 607292 kkddkddkddkddkddkk 0.4 184 55486 0 49740 GGGCGATCAATGTCTGTT 607293 kkddkddkddkddkddkk 0.49 185 55490 0 49744 TTTAGGGCGATCAATGTC 607294 kkddkddkddkddkddkk 0.35 189 55494 0 49748 GTCCTTTAGGGCGATCAA 607295 kkddkddkddkddkddkk 0.53 193 55498 0 49752 GCCAGTCCTTTAGGGCGA 607296 kkddkddkddkddkddkk 0.66 419 55502 0 49756 GAATGCCAGTCCTTTAGG 607297 kkddkddkddkddkddkk 0.58 420 55506 0 49760 CAGTGAATGCCAGTCCTT 607298 kkddkddkddkddkddkk 0.67 421 55510 0 49764 ACATCAGTGAATGCCAGT 607299 kkddkddkddkddkddkk 0.67 422 55514 0 49768 ATCCACATCAGTGAATGC 607300 kkddkddkddkddkddkk 0.78 423 55518 0 49772 CGACATCCACATCAGTGA 607301 kkddkddkddkddkddkk 0.72 424 55522 0 49776 GAATCGACATCCACATCA 607302 kkddkddkddkddkddkk 0.65 425 55526 0 49780 GATGGAATCGACATCCAC 607303 kkddkddkddkddkddkk 0.84 199 55530 0 49784 TTTTGATGGAATCGACAT 607304 kkddkddkddkddkddkk 0.88 426 55534 0 49788 GCAATTTTGATGGAATCG 607305 kkddkddkddkddkddkk 0.62 204 55538 0 49792 CCAAGCAATTTTGATGGA 607306 kkddkddkddkddkddkk 0.78 208 55542 0 49796 TTTCCCAAGCAATTTTGA 607307 kkddkddkddkddkddkk 0.59 427 55546 0 49800 GGGCTTTCCCAAGCAATT 607308 kkddkddkddkddkddkk 0.61 428 55550 0 49804 CTGTGGGCTTTCCCAAGC 607309 kkddkddkddkddkddkk 1.08 428 55554 0 49808 GCCCCTGTGGGCTTTCCC 607310 kkddkddkddkddkddkk 1.13 430 55558 0 49812 ACTTGCCCCTGTGGGCTT 607311 kkddkddkddkddkddkk 1.14 431 55562 0 49816 GGAAACTTGCCCCTGTGG 607312 kkddkddkddkddkddkk 0.94 432 55566 0 49820 ACCTGGAAACTTGCCCCT 607313 kkddkddkddkddkddkk 0.65 433 55570 0 49824 CTGTACCTGGAAACTTGC 607314 kkddkddkddkddkddkk 0.68 434 55574 0 49828 CACCCTGTACCTGGAAAC 607315 kkddkddkddkddkddkk 0.77 435
Example 11: Dose-Dependent Antisense Inhibition of Fibronectin with Deoxy, MOE and (S)-cEt Antisense Oligonucleotides in b.END Cells
[0440] Antisense oligonucleotides from the studies described above exhibiting significant in vitro inhibition of EDA.sup.+FN mRNA were selected and tested at various doses in b.END cells. Cells were transfected using Cytofectin reagent with 0.19 nM, 0.39 nM, 0.78 nM, 1.56 nM, 3.125 nM, or 6.25 nM concentrations of antisense oligonucleotide, as specified in Tables 23-27. After a treatment period of approximately 16 hours, RNA was isolated from the cells and EDA.sup.+FN mRNA levels were measured by quantitative real-time PCR. Primer probe sets LTS01050 and LTS01052 were used to measure mRNA levels. EDA.sup.+FN mRNA levels were adjusted according to total RNA content, as measured by RIBOGREEN.RTM.. The results demonstrate blocking of splicing, as represented by EDA.sup.+FN expression. The expression value of untreated cells was taken as 1.00. Different primer probe sets were used for different antisense oligonucleotide-treated cells to avoid the amplicon effect. Each table represents a separate experiment.
[0441] The half maximal inhibitory concentration (IC.sub.50) of each oligonucleotide is also presented in Tables 23-27. As illustrated in the tables, EDA.sup.+FN mRNA levels were significantly reduced in a dose-dependent manner in antisense oligonucleotide treated cells.
TABLE-US-00023 TABLE 23 EDA.sup.+FN mRNA levels compared to untreated cells (designated 1.00) by 16-mer MOE, deoxy and (S)-cEt antisense oligonucleotides in b.END cells measured with LTS01050 0.19 0.39 0.78 ISIS No nM nM nM 1.56 nM 3.125 nM 6.25 nM IC.sub.50 607178 0.7 0.6 0.5 0.3 0.2 0.1 0.59 607186 0.6 0.5 0.4 0.2 0.2 0.1 0.39 607188 0.8 0.6 0.4 0.3 0.2 0.1 0.67 607204 0.6 0.4 0.3 0.2 0.1 0.1 0.27 607205 0.6 0.5 0.4 0.3 0.2 0.1 0.34 607207 0.5 0.4 0.3 0.2 0.1 0.1 0.21 607208 0.9 0.5 0.4 0.3 0.2 0.2 0.62 607209 0.7 0.6 0.5 0.3 0.3 0.2 0.68 607210 0.8 0.6 0.5 0.3 0.3 0.2 0.77
TABLE-US-00024 TABLE 24 EDA.sup.+FN mRNA levels compared to untreated cells (designated 1.00) by 16-mer MOE, deoxy and (S)-cEt antisense oligonucleotides in b.END cells measured with LTS01052 0.19 0.39 0.78 ISIS No nM nM nM 1.56 nM 3.125 nM 6.25 nM IC.sub.50 607148 0.6 0.5 0.6 0.4 0.2 0.1 0.60 607149 0.7 0.5 0.3 0.3 0.1 0.1 0.44
TABLE-US-00025 TABLE 25 EDA.sup.+FN mRNA levels compared to untreated cells (designated 1.00) by 18-mer MOE, deoxy and (S)-cEt antisense oligonucleotides in b.END cells measured with LTS01050 0.19 0.39 0.78 ISIS No nM nM nM 1.56 nM 3.125 nM 6.25 nM IC.sub.50 607330 0.6 0.4 0.3 0.2 0.2 0.1 0.28 607332 0.6 0.5 0.3 0.2 0.1 0.1 0.35 607333 0.6 0.6 0.5 0.3 0.2 0.2 0.59 607338 0.8 0.9 0.8 0.7 0.5 0.4 3.64 607339 0.8 0.8 0.7 0.6 0.6 0.5 5.89 607340 0.7 0.6 0.5 0.3 0.3 0.2 0.63 607341 0.6 0.5 0.4 0.3 0.2 0.1 0.44 607342 0.9 0.7 0.5 0.5 0.4 0.4 1.54 607348 0.9 0.7 0.5 0.3 0.2 0.2 0.96 607352 0.4 0.4 0.2 0.1 0.1 0.1 0.16 607357 0.7 0.5 0.4 0.2 0.2 0.1 0.48
TABLE-US-00026 TABLE 26 EDA.sup.+FN mRNA levels compared to untreated cells (designated 1.00) by 16-mer MOE, deoxy and (S)-cEt antisense oligonucleotides in b.END cells measured with LTS01050 0.19 0.39 0.78 ISIS No nM nM nM 1.56 nM 3.125 nM 6.25 nM IC.sub.50 607245 0.9 0.9 0.5 0.5 0.4 0.4 2.04 607275 0.8 0.8 0.5 0.5 0.2 0.2 1.09 607276 0.8 0.6 0.4 0.3 0.2 0.2 0.57 607277 0.7 0.6 0.4 0.2 0.2 0.1 0.48 607284 0.6 0.6 0.3 0.1 0.1 0.1 0.37 607285 0.4 0.4 0.2 0.1 0.1 0.1 0.12 607286 0.7 0.4 0.3 0.2 0.1 0.1 0.36
TABLE-US-00027 TABLE 27 EDA.sup.+FN mRNA levels compared to untreated cells (designated 1.00) by MOE, deoxy and (S)-cEt antisense oligonucleotides in b.END cells measured with LTS01050 Length 0.19 0.39 0.78 1.56 3.125 ISIS No (nt) nM nM nM nM nM 6.25 nM IC.sub.50 607428 18 0.5 0.3 0.1 0.1 0.1 0.1 0.16 607429 18 0.6 0.7 0.5 0.3 0.2 0.1 0.58 607213 16 0.9 0.8 0.5 0.3 0.2 0.2 0.95
Example 12: Dose-Dependent Antisense Inhibition of Fibronectin with Uniform MOE Antisense Oligonucleotides in b.END Cells
[0442] Antisense oligonucleotides from the studies described above exhibiting significant in vitro inhibition of EDA.sup.+FN mRNA were selected and tested at various doses in b.END cells. Cells were transfected using Cytofectin reagent with 0.39 nM, 0.78 nM, 1.56 nM, 3.125 nM, 6.25 nM or 12.5 nM concentrations of antisense oligonucleotide, as specified in Tables 28-31. After a treatment period of approximately 16 hours, RNA was isolated from the cells and EDA.sup.+FN mRNA levels were measured by quantitative real-time PCR. Primer probe sets LTS01050 and LTS01052 were used to measure mRNA levels. EDA.sup.+FN mRNA levels were adjusted according to total RNA content, as measured by RIBOGREEN.RTM.. The results demonstrate blocking of splicing, as represented by EDA.sup.+FN expression. The expression value of untreated cells was taken as 1.00. Different primer probe sets were used for different antisense oligonucleotide-treated cells to avoid the amplicon effect. Each table represents a separate experiment.
[0443] The half maximal inhibitory concentration (IC.sub.50) of each oligonucleotide is also presented in Tables 28-31. As illustrated in the tables, EDA.sup.+FN mRNA levels were significantly reduced in a dose-dependent manner in antisense oligonucleotide treated cells.
TABLE-US-00028 TABLE 28 EDA.sup.+FN mRNA levels compared to untreated cells (designated 1.00) by 18-mer uniform MOE oligonucleotides in b.END cells measured with LTS01050 0.39 0.78 1.56 ISIS No nM nM nM 3.125 nM 6.25 nM 12.5 nM IC.sub.50 606708 1.1 0.8 0.6 0.4 0.3 0.2 2.79 606723 0.8 0.8 0.6 0.4 0.2 0.1 2.39 606729 0.8 0.6 0.3 0.2 0.1 0.1 1.10 606753 0.8 0.5 0.4 0.3 0.2 0.1 1.09 606770 0.7 0.5 0.4 0.2 0.1 0.1 0.87 606785 0.5 0.3 0.2 0.1 0.1 0.1 0.37 606787 0.5 0.3 0.3 0.1 0.1 0.1 0.30 606788 0.4 0.2 0.2 0.1 0.1 0.1 0.21 606793 0.3 0.3 0.2 0.1 0.1 0.1 0.09 606804 0.5 0.3 0.3 0.1 0.1 0.1 0.40 606812 0.4 0.3 0.2 0.1 0.1 0.1 0.23
TABLE-US-00029 TABLE 29 EDA.sup.+FN mRNA levels compared to untreated cells (designated 1.00) by ISIS 606675 in b.END cells measured with LTS01052 0.39 nM 0.8 0.78 nM 0.6 1.56 nM 0.5 3.125 nM 0.3 6.25 nM 0.1 12.5 nM 0.1 IC.sub.50 1.38
TABLE-US-00030 TABLE 30 EDA.sup.+FN mRNA levels compared to untreated cells (designated 1.00) by 15-mer uniform MOE oligonucleotides in b.END cells measured with LTS01050 0.39 0.78 1.56 ISIS No nM nM nM 3.125 nM 6.25 nM 12.5 nM IC.sub.50 598137 1.0 0.8 0.7 0.5 0.4 0.2 4.08 598138 0.8 0.9 0.6 0.6 0.4 0.2 4.11 598144 0.9 0.7 0.4 0.4 0.2 0.1 1.75 598151 0.7 0.5 0.3 0.2 0.1 0.1 0.79 598153 0.9 0.6 0.5 0.3 0.2 0.1 1.54 598161 0.9 0.5 0.5 0.3 0.2 0.2 1.50 598163 0.6 0.5 0.4 0.3 0.1 0.1 0.60 594675 0.8 0.6 0.4 0.3 0.1 0.1 1.18 598145 0.9 0.7 0.5 0.3 0.2 0.1 1.58
TABLE-US-00031 TABLE 31 EDA.sup.+FN mRNA levels compared to untreated cells (designated 1.00) by 15-mer uniform MOE oligonucleotides in b.END cells measured with LTS01052 0.39 0.78 1.56 ISIS No nM nM nM 3.125 nM 6.25 nM 12.5 nM IC.sub.50 511404 0.9 0.8 0.7 0.4 0.3 0.2 2.81 598130 0.9 1.0 0.9 0.9 0.7 0.5 13.18
Example 13: Efficacy and Tolerability of Antisense Oligonucleotides Targeting Fibronectin in C57BL/6 Mice
[0444] C57BL/6 mice are a multipurpose mice model, frequently utilized for safety and efficacy testing. The mice were treated with ISIS antisense oligonucleotides selected from studies described above and evaluated for efficacy, as well as changes in the levels of various plasma chemistry markers.
Study with Uniform MOE Oligonucleotides
Treatment
[0445] Groups of eight-week old C57BL/6 mice were injected subcutaneously twice a week for 3 weeks with 100 mg/kg of ISIS 594675, ISIS 598145, ISIS 598151, ISIS 598153, ISIS 598163, ISIS 606770, ISIS 606785, ISIS 606787, ISIS 606788, ISIS 606793, ISIS 606804, or ISIS 606812. One group of eight-week old C57BL/6 mice was injected subcutaneously twice a week for 3 weeks with PBS. Mice were euthanized 48 hours after the last dose, and organs and plasma were harvested for further analysis.
RNA Analysis
[0446] To evaluate the effect of ISIS oligonucleotides on blocking fibronectin splicing, mRNA levels of EDA.sup.+FN were measured by RT-PCR using mouse primer probe set LTS01050 and LTS01052. The results are presented in Table 32, normalized to total fibronectin. The results demonstrate blocking of splicing, as represented by EDA.sup.+FN expression. The expression value in untreated mice was taken as 1.00. `n.d.` indicates that the mRNA expression level values were not considered because the oligonucleotide targeted an amplicon region of the specific primer probe set.
TABLE-US-00032 TABLE 32 EDA.sup.+FN expression after antisense oligonucleotide treatment in C57BL/6 mice Lungs Kidneys EDA.sup.+FN/ EDA.sup.+FN/ EDA.sup.+FN/ EDA.sup.+FN/ total FN total FN total FN total FN ISIS No (LTS01050) (LTS01052) (LTS01050) (LTS01052) 594675 0.43 0.43 0.52 0.57 598145 0.65 0.61 0.61 0.64 598151 0.40 0.33 0.43 0.36 598153 0.75 0.57 1.07 0.69 598163 0.24 0.23 0.15 0.17 606770 0.50 0.38 0.54 0.52 606785 0.31 0.33 0.22 0.29 606787 0.36 0.32 0.26 0.32 606788 0.40 0.36 0.19 0.22 606793 0.28 0.23 0.12 0.14 606804 0.32 n.d. 0.27 n.d. 606812 0.39 n.d. 0.42 n.d.
Plasma Chemistry Markers
[0447] To evaluate the effect of ISIS oligonucleotides on liver and kidney function, plasma levels of transaminases, bilirubin, albumin, and BUN were measured using an automated clinical chemistry analyzer (Hitachi Olympus AU400e, Melville, N.Y.). The results are presented in Table 33. ISIS oligonucleotides did not cause any changes in the levels of any of the liver or kidney function markers outside the expected range for antisense oligonucleotides.
TABLE-US-00033 TABLE 33 Plasma chemistry markers in C57BL/6 mice plasma ALT AST Bilirubin BUN (IU/L) (IU/L) (mg/dL) (mg/dL) PBS 26 46 0.19 35 ISIS 594675 19 42 0.20 31 ISIS 598145 25 49 0.20 29 ISIS 598151 30 67 0.18 35 ISIS 598153 26 71 0.17 34 ISIS 598163 64 102 0.19 38 ISIS 606770 22 54 0.18 29 ISIS 606785 48 94 0.17 32 ISIS 606787 30 71 0.15 30 ISIS 606788 82 116 0.15 33 ISIS 606793 50 83 0.15 32 ISIS 606804 31 56 0.16 28 ISIS 606812 29 49 0.15 27
Organ Weights
[0448] Liver, spleen and kidney weights were measured at the end of the study, and are presented in Table 34. ISIS oligonucleotides did not cause any changes in organ weights outside the expected range for antisense oligonucleotides.
TABLE-US-00034 TABLE 34 Organ weights (% of the PBS control) of C57BL/6 mice ISIS No Liver Kidneys Spleen 594675 102 102 99 598145 98 105 117 598151 108 103 90 598153 106 100 88 598163 102 102 94 606770 106 104 93 606785 101 102 98 606787 108 99 93 606788 98 97 99 606793 103 94 99 606804 95 98 89 606812 105 101 86
Study with Deoxy, (S)-cEt and MOE Oligonucleotides
Treatment
[0449] Groups of eight-week old C57BL/6 mice were injected subcutaneously twice a week for 3 weeks with 100 mg/kg of ISIS 607149, ISIS 607186, ISIS 607204, ISIS 607205, ISIS 607207, ISIS 607277, ISIS 607285, ISIS 607286, ISIS 607330, ISIS 607332, ISIS 607341, ISIS 607352, ISIS 607428, or ISIS 607429. One group of eight-week old C57BL/6 mice was injected subcutaneously twice a week for 3 weeks with PBS. Mice were euthanized 48 hours after the last dose, and organs and plasma were harvested for further analysis.
RNA Analysis
[0450] To evaluate the effect of ISIS oligonucleotides on blocking fibronectin splicing, mRNA levels of EDA.sup.+FN were measured by RT-PCR using mouse primer probe set LTS01050 and LTS01052. The results are presented in Table 35, normalized to total fibronectin. The results demonstrate blocking of splicing, as represented by EDA.sup.+FN expression. The expression value in untreated mice was taken as 1.00. `n.d.` indicates that the mRNA expression level values were not considered because the oligonucleotide targeted an amplicon region of the specific primer probe set.
TABLE-US-00035 TABLE 35 EDA.sup.+FN expression after antisense oligonucleotide treatment in C57BL/6 mice Lungs Kidneys EDA.sup.+FN/ EDA.sup.+FN/ EDA.sup.+FN/ EDA.sup.+FN/ total FN total FN total FN total FN ISIS No (LTS01050) (LTS01052) (LTS01050) (LTS01052) 607149 n.d. 0.32 n.d. 0.07 607186 0.26 0.14 0.02 0.02 607204 0.15 0.13 0.02 0.03 607205 0.30 n.d. 0.03 n.d. 607207 0.42 n.d. 0.04 n.d. 607277 0.33 0.27 0.05 0.08 607285 0.21 n.d. 0.29 n.d. 607286 0.13 n.d. 0.02 n.d. 607330 0.29 0.27 0.02 0.06 607332 0.08 0.13 0.01 0.05 607341 0.15 0.24 0.10 0.16 607352 0.11 n.d. 0.01 n.d. 607357 0.12 n.d. 0.09 n.d. 607428 0.12 n.d. 0.07 n.d. 607429 0.33 n.d. 0.20 n.d.
Plasma Chemistry Markers
[0451] To evaluate the effect of ISIS oligonucleotides on liver and kidney function, plasma levels of transaminases, bilirubin, albumin, and BUN were measured using an automated clinical chemistry analyzer (Hitachi Olympus AU400e, Melville, N.Y.). The results are presented in Table 36. ISIS oligonucleotides that caused any changes in organ weights outside the expected range for antisense oligonucleotides were excluded from further studies.
TABLE-US-00036 TABLE 36 Plasma chemistry markers in C57BL/6 mice plasma ALT AST Bilirubin BUN (IU/L) (IU/L) (mg/dL) (mg/dL) PBS 38 96 0.18 36 ISIS 607149 35 170 0.29 31 ISIS 607186 22 73 0.21 26 ISIS 607204 41 75 0.15 29 ISIS 607205 38 83 0.15 32 ISIS 607207 70 92 0.19 32 ISIS 607277 54 108 0.16 30 ISIS 607285 78 139 0.32 28 ISIS 607286 40 94 0.38 27 ISIS 607330 23 40 0.16 30 ISIS 607332 41 66 0.20 28 ISIS 607341 70 102 0.24 28 ISIS 607352 20 75 0.13 27 ISIS 607357 85 100 0.15 26 ISIS 607428 21 82 0.24 25 ISIS 607429 21 50 0.17 26
Organ Weights
[0452] Liver, spleen and kidney weights were measured at the end of the study, and are presented in Table 37. ISIS oligonucleotides that caused any changes in organ weights outside the expected range for antisense oligonucleotides were excluded from further studies.
TABLE-US-00037 TABLE 37 Organ weights (% of the PBS control) of C57BL/6 mice ISIS No. Liver Kidneys Spleen 607149 103 103 99 607186 91 106 101 607204 93 97 116 607205 112 114 276 607207 98 99 96 607277 98 100 108 607285 99 97 105 607286 96 103 98 607330 97 101 85 607332 102 98 97 607341 93 98 92 607352 98 101 84 607357 88 101 113 607428 96 101 90 607429 91 101 99
Sequence CWU
1
SEQUENCE LISTING
<160> NUMBER OF SEQ ID NOS: 435
<210> SEQ ID NO 1
<211> LENGTH: 76208
<212> TYPE: DNA
<213> ORGANISM: Homo sapiens
<400> SEQUENCE: 1
tattttatgg gttttcttcc tcacaaaata cactcctata agcagagatt ccccccctcc 60
accccgaaga gaggtgacgc aatgtcctca aacactacca ccacccccaa taaaaaagaa 120
aagggaaggg ggagcgtctt gcaacccctt cgcttcacac aagtccagcc actccctttc 180
ctcccagccg cttcccatcc cttcccccat cccctaaaaa gtttgatgac cgcaaaggaa 240
accgaaaaaa agttgtcttg ccccagtcct ggcgggccat cagcatctct tttgttcgct 300
gcgaacccac agtcccccgt gacgtcaccc ggagcccggg ccaatcggcg cgcggtcggc 360
tgcggcggcc ggcgggcggg cgggcgggtg gggtggggcg gggcggggac agcccggcgg 420
gtctctcctc ccccgcgccc cgggcctcca gaggggcggg aggggaccgt cccatataag 480
ccccggctcc cggcgctcgg acgcccgcgc cggctgtgct gcacaggggg aggagaggga 540
accccaggcg cgagcgggaa gaggggacct gcagccacaa cttctctggt cctctgcatc 600
ccttctgtcc ctccacccgt ccccttcccc accctctggc ccccaccttc ttggaggcga 660
caacccccgg gaggcattag aagggatttt tcccgcaggt tgcgaaggga agcaaacttg 720
gtggcaactt gcctcccggt gcgggcgtct ctcccccacc gtctcaacat gcttaggggt 780
ccggggcccg ggctgctgct gctggccgtc cagtgcctgg ggacagcggt gccctccacg 840
ggagcctcga agagcaagag gcaggctcag caaatggttc agccccagtc cccggtggct 900
gtcagtcaaa gcaagcgtga gtactgaccg cgggctgaaa caggctgcct cagggatggg 960
accctaaagc cgaccaaagt tggggctgaa gttttgtgcg cgcgcgtgtg tgcgagtgtg 1020
tgcgcgcttt actgagagaa accagctgtg cacacaaaag gaccgagttt tgagcacgct 1080
ggttctgagg gcctgggatg ataagaccgt gcattggagg acgaggactc tgcgactttc 1140
ccgtgttcta ataaattctg cacgttcaga ttgtccttct aggaattaac caaaacttgc 1200
ctttaaagag aaaaatgatg catgtctata aattttccgt ctgggattag tgtggtcctt 1260
actgctactt atttccttct gttaaataat tggtcaaata ttttcaacat gggggtggaa 1320
agggggtatt gaaatagctg tcttgtttct aactaacttg gaagagatgt aattggttca 1380
gacctcttta gggccgctca ggatacttca ccaagaacag aggttggaat tctttccgtt 1440
tttcaaagac acaccctcct tttgctttga gaaagctgct taaagttgtc ctttttgact 1500
attactccaa aagaatattt aagttccttg catgttttaa aaatgtgact tcaattgtct 1560
gccttccaaa atgtttccaa cttttttatg tagacccctg gccagatgga aatgacatca 1620
ttgtatataa cttttagcaa agttaaaagg aaaaaaatat gtacgtcaat attcacatga 1680
agaaaattcc ataattttgg gaaaaggaga aatgcaaatg taacgttttc cttcaattat 1740
ttgcagccgg ttgttatgac aatggaaaac actatcagat aaatcaacag tgggagcgga 1800
cctacctagg caatgcgttg gtttgtactt gttatggagg aagccgaggt tttaactgcg 1860
agagtaaacc tgaaggtaag tgacaacaag ccccatagtt agtatctttt aatacatgaa 1920
gtggtaattg ttaaactttg cattagtaag taaaaataca tacaccattt ttctaataga 1980
attacctgtc atttcctctt aagtttaaaa actgcttata tttgcttttc acatgctttt 2040
acctttaaaa caaagaaacg aatctttccc aaattagttc ctagagtctt ctttttgctt 2100
tactctccca aagtttttga tgagaaaaat gaaagatttt gtgtgtcctc cgacaaaaaa 2160
aattgcttat aaaattttaa tttattagaa agcagtctca aatcttaaac tgttagttta 2220
tgagccagaa aacactttgg ggacttacat cgtaaaatga tttgtcagcg gcagttaaca 2280
caaaaccatt agccacttca aagttctcat tcctttagga ccaatgatat ttttctcata 2340
aattatagca actctgtcag agaagcactg atcaggggaa aatggaaatc ataggattaa 2400
caactgtcaa ggccttgtgg gaggtgggga tcttcgaatt gtttgtttgt ttttgttttg 2460
ttttgttttt gagacagagt cttgctctgt caccaggctg gagtgcagta gcactatctc 2520
agctcactgc aacctctgcc tccagggttc aagcaattct cctgcctcag cctcctgagt 2580
agctgggact acaggcacat gccaccacac ccagctaatt ttcatatttt tagtagagac 2640
ggggtttcac cgtattggtc agggtggtct cgaattcctg acctcaggtg atccacccgc 2700
ctcagcctcc caaagtgctg ggattacagg cgtgagccac tgtgcccggc caatcgtttg 2760
ctttttatgt gaaccttgct ttgactttct gagtcagaga ttggaatgtg aaacccttca 2820
caaatctagc tctgtcataa gttagtactt tatatggcct tttcctaaga gcctgagatt 2880
tttctacaat atgaataatt tacagaaaat ttgacaatat gtcaaggtca aaaaccatgg 2940
ccttattaga gcttaggata aaaatctgta tctctcactt cattttattc tttgaggtgt 3000
accatgttac ttgtggaata gagaagtggg ttttccttta gaggggatta gtgaactaga 3060
aaagcttgta cctaagtgag gctcacatgg actttccttt tcccctcagc tgaagagact 3120
tgctttgaca agtacactgg gaacacttac cgagtgggtg acacttatga gcgtcctaaa 3180
gactccatga tctgggactg tacctgcatc ggggctgggc gagggagaat aagctgtacc 3240
atcgcaagta aggaagagat tgtgtaaaat gatgccaaaa tatcaaatat gaatttctct 3300
gttaccatca ctgtcatttt ctgttatcca tgactggata ttccgaactt tgaggtttgc 3360
ccctggtgac caggtactct taagtggtca cccaactggt tcctgtgttt cttaaagacg 3420
ggtatgagca cagatggaat cagtgtttga tgtgtgtgcg tttatgagtg tgtgtgcatt 3480
tatgagtgtg tgtgtttctg tacatagtag aaccaagaga cctcttgggt tccatttcag 3540
taagacatgc ttaggggagt tgcccatttt aaatcacctg gatatcttca agctagacaa 3600
atcatgagac ttttctgcag tgactgggaa ggtgttcatg aagagtgaac cagccatgtg 3660
ttgtctggtc ttcatgtttg caatgcagag acctcttgca cctcacagaa acagtctggt 3720
ttcttggtga ccagtaggtt atacccagga agcagatgtc actattccta gggataatac 3780
aaaattatta acccaataga gtttgctaag gaactttggg aaccgggctg attctcaact 3840
ctagtttagc taaggcactc tttccagtat gattcactgg gttaccaata gattctatta 3900
agatagtatt taagtttttt aatccattct ttaaatataa gtcgtcttaa agacttctat 3960
tcaaaagaac aagtcccgtg tgaataggcc caatcaactt tccccatatt tcatgttagg 4020
gtttatccaa gttcacaggc aaatcgcaag aggcaagggt ccatagtgtt tacaatctag 4080
ttcagcattt gaatgtgcca ttgggcttaa caacttagaa aactaccagg atttccacac 4140
tttatatgca tatgtctgtt tgctttccac caaaatgaca tttctatcct agggtaaaat 4200
acaggctctc catgctccca aaagctggag tgctgtgcct gatgtggcct tttcactgaa 4260
ttagtctcag tcttagcctg ctgtgtatga gtgaagacca agcctcccag cctttctttt 4320
ctgcttagga cccaatttcc tgtgatctct ctgggaaagc aggattcatg acctcttcct 4380
tgccatccag atttctctgt ggttttccat tgtgttctaa gcaagacact taactgaatt 4440
gactccaagt gaccagacct gttaacgttt cccctgtctc tgatgggaaa gctgttgtct 4500
gtgtctctac tttagccaac ctaagtacct accatgggtg gaatatgaga ccaaaaaaaa 4560
aaatctgttc tgccctctcc taacattttc gttgtatctt caacagaccg ctgccatgaa 4620
gggggtcagt cctacaagat tggtgacacc tggaggagac cacatgagac tggtggttac 4680
atgttagagt gtgtgtgtct tggtaatgga aaaggagaat ggacctgcaa gcccataggt 4740
gtgtgagtct tagggctgag caagagctgg gatgcttagt tctaatgtgg ggttggacca 4800
gaatcacatc tacataggtc atagacctga attccagtga aaaccaataa agaaatggga 4860
attttgtttg aaataatgaa ttattatata atccatagtc ttcttacagg agttagatca 4920
aaaagtactg actacacata gaagtcttaa ctttgcttca aaagcataag gtagaattga 4980
aagatttaga atggagtcat ttcttttacc taatagctga tctcagattc ctccttcgtc 5040
aagatataat ttatttaaaa gaaaaaaaaa tgacactttg gacacatttc tatatggaat 5100
gtcctggacc gaaacatgaa atagtgtgtg cttgtcacac tctgctcatt tcttttcaaa 5160
ttaaaagttg ttgagcttct ttggatctca atcctcagtt gaattttgta agtacaagcc 5220
tgaaagtttc tggctataaa ttttactctg tttacttgtc ttctaattta gaggtttttg 5280
tcttgttttg tattgttttg ctttccaata tttaaaaata gctttctttg tcattgtatt 5340
taggccactc aaaattcata attggtcatt tataattaag attggaattt tgcatatgta 5400
gtctcccaca gactagatac atacatagat ccttgctact ggaaatgctg ctgggaagtt 5460
tggggctcgc tgaaaatatg tagtccatgt acttattagg agaatggaat ttctgcctgc 5520
caactcagct tgagctttct tttgccttgg ctacttactg tgtgcttaga tgctgggtgt 5580
gtcattcttt ctgaacagag tgccacttaa aaaaaatgtg gctgaatttt tgcttacaca 5640
ctacacttta aattacaggg agcttgcaca attcaaaata accttttttt cctgtttttc 5700
ttccaaattt ccctacagct gagaagtgtt ttgatcatgc tgctgggact tcctatgtgg 5760
tcggagaaac gtgggagaag ccctaccaag gctggatgat ggtagattgt acttgcctgg 5820
gagaaggcag cggacgcatc acttgcactt ctagaagtat gttttacatc tttatgttaa 5880
agattaagcc aggtattgtt ttctggattc ctagagagaa gggtaatact atgttactca 5940
gaacacatcc agtatatcag catgctttgg taacttctgg aagtcaagaa aactttcata 6000
accaacttat tccgcatctt cagagaagac tacataaata gaaaaacata tcactttgat 6060
aaggttcaat ctcagctcac tgccactgac atagagttga acaaaaggtt taggtttcct 6120
tctatgtttg aaatttaaat agggcacatt cacaggctaa attgataaaa ttaaaaagaa 6180
tttatcccat aaattaaaat gatttatcta ctctggagtt agggatagtg tctctgacct 6240
aacgcatttg attagtgctg taaagaagct ggcctctggt gtctttactg ctccttctaa 6300
gattgtcttg gggtcttaat tgttgccttt gggtttgaag gctccttttt tgatattgta 6360
aactaataac agctagagag tttgttgaag taaaacagcc attaactact ggtgttgtaa 6420
ataagtttaa aatcaaatcc aaataatttg aacctgtttt atttatctag ctgaacccat 6480
ttaactacct ttaacatagc catcatccaa attcaaattc tttgctaaca aaaataggtc 6540
tctcatgaaa agtggtaacc attttgacca aagctttccc agaaacttgc tggtttatta 6600
gatattttgc atttaaaatg ttactgtgat catcagactt ccaagatctt tgtggcaata 6660
ttttagctta agacaaatta gatgtctgat tcaaacctta tctgttattt agaactcttt 6720
aaatagcaag ttgggaaaag tttctcaaag agaagtcatt tattccagaa aattttataa 6780
ggacttactt tgttcaaggt attatagggg tgcagatatg aaatgaacat tagcccagcc 6840
ttcaaagagt acttaggggg tcagggagat gagaaagtct tatacatatt tatcatctgc 6900
aaaacacagt attaaagatt tcaacagaaa tactgaaagt agtgctatgg aggttcaggg 6960
gatgataata cttttcgctg gggatttggg aaaaagctct aatcagtaat tataccttca 7020
tgcaaacttc tattcttgtg gtagatggat gtgggtgtgt atttgtttga acctacatca 7080
actattaatt ttttttctct aacccaggag ttgcaacaat atccaattca caaagacatc 7140
agatcctcta tactcacatc gtggcacaga gcaaatttgg attataattt aaataatcta 7200
tttaccagat aaatgcacgc atagactaat ggtcatttag ttacaaatta tcattttatg 7260
ttgatcccac tcttccagtg gagggctaac actgaataat ttggggctat tttgctagtg 7320
atttttaaat actgtagatg tttgggtata ggggaaggga aaataatatt ttagtcaaag 7380
aaattgtgca tcctctacat tttttacata acaaatgaag aaagagatac taccaccttc 7440
ttatagcttc tttgtagcca ttggtgaaga ccctttgata cctgcttgcc tccccattgt 7500
tataagcttt tttttgtttg cttgtttttt ttgttttgtt ttgttttgtt ttgtttttga 7560
gacagtctca ccctgtcgcc caggctggag tgcaatggtg tgatctcagc tcattgcaac 7620
ctccacctcc cgggttcaag cgattctctt gcctcagctt cccgagtagc ttggattaca 7680
ggcgcccgcc accacagccg gctaattttt tttggtattt ttagtagaga cgggggtttc 7740
accatgttgc ccaggctggt cttgaactcc tgactgcagg tgatccaccc tcctaaagta 7800
ctaggattac aggcgtgagc caccgcgctt agcctgtttt tagttttcta aagcaaggtc 7860
cctattgaaa ggcaggccat aaacagtgat gactaagaaa aatcctggaa gagcctgaga 7920
aggaaaaaga tgaaatataa tgccagagaa tgaagttagt caaaggaaca gtgtgaaaac 7980
aataaataaa tagataaatg aaaatgttat ttgacagaga gatgaaacta gactaaacca 8040
ttcagctgcc tttccactgt aacaaatgta atttcatctt tcagaagtgt aataccttgc 8100
agcaccagag ctgaatatga acatattacc aaaaatagat taccaggcat agatagcatt 8160
ccttttttaa gtttgaattg accacttgcg actctcgacc tgatgtatgt atgtgcttcc 8220
tttgtgacac agatagatgc aacgatcagg acacaaggac atcctataga attggagaca 8280
cctggagcaa gaaggataat cgaggaaacc tgctccagtg catctgcaca ggcaacggcc 8340
gaggagagtg gaagtgtgag aggcacacct ctgtgcagac cacatcgagc ggtgaggcac 8400
aggacgagca ggggcgggaa atggggaagc aggtcaagaa atatttccgc aaatccatct 8460
ttcctttgac atgccatttg aggataattt gcagtgtttc agctaataac ctaagataat 8520
ttacacatta ttggttgtta aaactttttt taatgtcaag ttttaaattt ttcagaaaaa 8580
aagaaaaatg acatacaaat aaaccttagg gggaaaaaag ccagatttat ctccaaaaga 8640
taaaactgag ttttaaagaa tgctagcatc ataaaactta ccatggatag atcacgcaca 8700
cacgcacaca cacacgtatt ttgaatatcc aaagttcatt tgaaaggaaa tgagagttat 8760
aattaattat atgactacct ggttcttctg ctaggaaagg acaaaaaaag tgcatttgga 8820
ttttttgttt gtttgttttt gaatgaaata tacttccctg tcccgacatt gaactctttt 8880
tgtagtggaa accatccttt atatgtggtt tctatgctct ggcaaacttt gttacattct 8940
ataaagtaac acacaattat ttccttcatg tattggcatt cgaaatttta gaaattcaga 9000
gaggacttag agatggccat gaaagacatg atatctaagc attcttttta aaaaacaagt 9060
tttaatcatt tttggcatga gaaaaagatt tttacgtcat aaatgtttca taaaaatctg 9120
aagagagaaa tatggccaac aaggacgtgc actcctctca ttatttttaa tatgttttga 9180
ttaacttttt actatatgat gtgccaacat cattacgtag tgtctcagcc atccttcaat 9240
taaaaatatt aattgttcta atttttcttc ttttgatgag tttttgtctt gctttgagca 9300
cttatgaagg tgaacaagat tagatttgat aatatctttg agttatttta ttatcattaa 9360
taaaattgct actggccaaa aaaaattata aacatcggcc acgcgcggtg gctcacgcct 9420
gtaatcccag cactttggga ggccgaggca ggcggatcac gaggtcagga gatcaagacc 9480
atcctggcta acacggtgaa accccatctc tactaaaaat acaaaaaatt aaccaggcgt 9540
tgtggcgggc gcctgtagtc ccagctactc gggaggctga ggcaggagaa tggcatgaac 9600
ccgggaggtg gagtttgcag tgacccgaga tcgcaccact gcactccagc ctgggtgata 9660
cagcgagacc ccatctcaaa aaaataaaat aaaataaaaa ataaaaaaaa ttataaatgt 9720
cagtctacca aaatagatta aaagtgtagg tgggaattaa atggggataa acactcaata 9780
aatgttagct atatatgaat attgccaata ctgaaaagat tccattgttc aaaaaagttt 9840
gagaagcaat gggttaaaca aaatggaacc tgctctgcag aatctgtgtg ttcctttaca 9900
tcatactctc catggtagag tgtaggggat gggcgccatg tctccctagt acgtttgacc 9960
ttgggattct ttgtctgtga acatctttgg gttctagtgt tcagcagcac ttagggaggc 10020
actgaattca gtgtaccttt ggtctagcct cagccctgat tctgttctgc ggtgggccct 10080
ggccttcaag agaacagata tctaaaagtt gaaagaaaag atcggccggg cgcggtggct 10140
cacgcctgta atcccagcac tttgggaggc caaggcgggt ggatcacaag gtcaggagat 10200
cgagaccatc ctggctaaca cggtgaaacc ccgtctctac taaaaataca aaaaattagc 10260
cgggcgtggt ggcgggtgcc tgtagtccca gctactcggg aggctgaggc aggagaatgg 10320
cgtgaacccg ggaggcagag cttgcagtga gccgagattg cgccactgca ctccagcctg 10380
ggtgacagag tgagactccg tctcaaaaaa aaaaaaaaaa aaaaaaagaa aaaagaaaag 10440
atcaacacat cctgttgtgt tattctgaaa ggaaagctgt cttaagagga tcaattggtt 10500
ttagaaaaaa cacaatagaa tcacaaataa tccagaggag aaataaaatg tggaaggtgg 10560
aggtgacctc cagaaaatcc aggacagctg ctgaaggcac cctctgatga gctcggttac 10620
tcagaagagt gaggatgtgt tgaaggtatc tgctgtatgg agtggcagga tgatgtctgt 10680
gattgagaaa tataatcccg gccaggcgag gtggctcatg cctgtaatcc cagcactttg 10740
ggaggccgaa gcgggtggat cccctgaggt caggagtttg agacaggagt ttgaggtcag 10800
gagtttgcca acatggcaaa accccgtctc tactaaaaaa tacaaaaaaa atcagctggg 10860
catggtggtg cgtgcctgta attgcagcta cttgggaggt tgaggcagga gaatagcttg 10920
aacccaggag gcagaggttg cagtgagccg agaccgcgcc actgcactcc agcctgggca 10980
acagagtgag accccatctc aaaaacaacc caaaaaacca aaaaacaaac aaacaaaaag 11040
aaatataatc ccagtagccc cagctgagct ggaggatgga gaccacttgg tagacacttg 11100
tggattattt cctaggctaa atgcaaaagc tactgctgaa taagggacat ttttttccag 11160
tcccaggcca gtagcgacat agatttcaga gtgatctctg tgagatcctg aagatcctga 11220
ctgcagaaag tagtgaattg tcttctctca cccagttttg tgacattccc ttttcatgcc 11280
attaggatct ggccccttca ccgatgttcg tgcagctgtt taccaaccgc agcctcaccc 11340
ccagcctcct ccctatggcc actgtgtcac agacagtggt gtggtctact ctgtggggat 11400
gcagtggctg aagacacaag gaaataagca aatgctttgc acgtgcctgg gcaacggagt 11460
cagctgccaa gagacaggta tgcattatct ttttgaagaa taggactgat gactttatta 11520
tttagttttt gaaggacaat acattttcaa tgtgaaacaa taaaacaaac aagaagcctg 11580
taatcttacc accctgtgat aacaattagg gttggcattt gaaatagttt cttccaatct 11640
ttttaattta tgtattttct ttctggtcat ggatatcatg ggtaaaaatt ttattgtatt 11700
tatctgtcta aagtgttgtt acaagagagc tactttctga ataatcatca atgttttata 11760
ttctaaatct caaatttcag cagctttgtg atgtaaacat cttccaataa cctaatatat 11820
gtattctgca ctacaaacat ggtagtcact atggcaataa caattgctac acaattctcc 11880
cccagaatag tctcatatat taattttatg gcatagatat agtcataaat attatcccaa 11940
catccttaag cagcatcctt aattgacctg tataaatata gctttacaaa tagagaaact 12000
gaggcatggc agcagaagtg gtcatgaagg acatcagcag aagaactcag gtgtcgttct 12060
atccacagta gacatggatt cctgagtaat gcattttgac tgaaattaac gagatgatca 12120
tctatactca tagcttcttc ctttgagggc acaagctcag tatctcattg aagccataaa 12180
taagcagctg ctggtgggag ataaagcatc tctgtttact gacactcttt tgattatgat 12240
tgtagctgta acccagactt acggtggcaa ctcaaatgga gagccatgtg tcttaccatt 12300
cacctacaat ggcaggacgt tctactcctg caccacagaa gggcgacagg acggacatct 12360
ttggtgcagc acaacttcga attatgagca ggaccagaaa tactctttct gcacagacca 12420
cactggtgag tgtcccaagg gggagccaca gaagtgagaa aaactcactt tcatgcccta 12480
gttttatttg ccagcattct agccatttat tttgaacccg cccaagaagc atcgcttttg 12540
ttcagtttgg actcaagaga tcgcagcgct cacgtaacag ctgaggattc ttccatcttc 12600
cccagtactg ttgggaaatg acaccaaggg agtagccttc cagttcattt gatttaacac 12660
attgggatta tgatgtgatt aaagatactt gtattttgga atcagtagat gatcccacag 12720
ggctgaggaa tacaaaggat gaatgtttta gtgccttagc ttattttcca gttaaaacaa 12780
tgttttattc aaagctatca tttaatcttt tgtggggggg gtgctgggga aatgacagtg 12840
aaagtgggat ttaaacctgt tttgaaggtg tgaaggtaaa tatgctaaga agcttagaac 12900
tatattatca gacatttttt attctgagat agactgtctg tgaatgagct gcagaaacct 12960
ggctctctca gaccagtaat tctgtgtaca ttggaaagct cagcggtaat cttttccttc 13020
tttgttgtgt attgttcctg gcagttttgg ttcagactcg aggaggaaat tccaatggtg 13080
ccttgtgcca cttccccttc ctatacaaca accacaatta cactgattgc acttctgagg 13140
gcagaagaga caacatgaag tggtgtggga ccacacagaa ctatgatgcc gaccagaagt 13200
ttgggttctg ccccatggct ggtaagatga agcccttgtg ggttgtcttg tttgacaaca 13260
atttagggag tagagactaa agactagtgt ccagtttact cccatttcat tcattaacac 13320
aattttgaga caacagaaaa cttcatgtga agtgtgtttg tgtgtgtgtg tgtgtgtgtg 13380
tgtgtgtgtg atgttacatc atatacataa ggattgggaa gaataattag ataattattt 13440
atataatttt taaacctcat tgacatgatt taatgtcaaa aatataatta cttatttgta 13500
agtctggaaa tatgaatttg cacaggtttg tctttgtaaa gagcacacaa ctgagtagct 13560
tacaacattt aatatatgta tgacggcttt agtcacagag ctacaatatt gacacatggt 13620
tgtggtttga tgggcataag ctctatcact tattaataag tgccaaagtg actaaaactc 13680
aatgttttct aacaggtagg gaatctcact ctttttttaa aggtccccag tttgtataga 13740
tggcgaacaa atggaaacga atacctttta cttgttttca gatttcaaga accccataga 13800
ttccctttaa ttttccagtt gtagaaacaa gagcctgggc ggtaggcact gtcaagtgtg 13860
actatgagac aaagaaattg cttatacttt tatttctttc aacaaaagaa gatgctgagt 13920
ttagaagaaa aaacccactt ttgcttgtaa ttctatatcc aaacccatag tttttatttg 13980
atccagaata aactggaact gggaaaagtt atgaagctgt agttaaatcc aggcttctag 14040
aacagcaaga accctttgtg tggatgtgta gatattatct tagtttaaca tcccctaacc 14100
cttcctgtaa ctattttcta tgacacgttt ggactacgtt ttctgcctcc agggctcaaa 14160
aattctaccc cttcacctga cagcacttag atgtctttga tgcacacaaa gcttcttccc 14220
aagtgagaat tcttaggatg accaaactga actgatcctt ttgcacacat acatgtttag 14280
acctggtgat catttatcaa gtgcatttct tatccatttc caaacagccc acgaggaaat 14340
ctgcacaacc aatgaagggg tcatgtaccg cattggagat cagtgggata agcagcatga 14400
catgggtcac atgatgaggt gcacgtgtgt tgggaatggt cgtggggaat ggacatgcat 14460
tgcctactcg cagcttcgag gtatgctggc tgattaacaa aaatatttga gatggcaaaa 14520
ggtacagaaa gggacacttt tttttatgaa aacttgcact atgccaaaag caggggaaga 14580
aatatggaat gccacgtcat tcattagtct actgtgcatg gtaagataag cctgaaaggc 14640
ttagcaggca gcctgctaag acaagcggca tagcaatgct aatgttctga aacactccta 14700
gcatgtaagt acttaggctg agccaaaaag atggcttcaa aagtaagaat gaaacatttg 14760
atccattcag ctttaggcta tgccactgga ttcatgtcta gaaaagatag gataatttct 14820
gtaaagaaat gaagaccttg ctattctaaa atcagatcct tacagatcca gatttcagga 14880
aacaaataca taggggacta actttccttg ttcagattag tttttctcct ttgcacccag 14940
ctatataata tgaggaagta ttgacttttt aaaagtgttt tagttttcca tttctttgat 15000
atgaaaagta atatttcggg agaaccctga gctattaata atctatgtgg ctagtgcgta 15060
gatattggtc tgaatttgtt ctccttttgt ggtgtccagt gggtaacacc atccgggagt 15120
aataattaca tgtggtgttg cagaactgaa agagacctta ataacacata gagacctcac 15180
tctatataga tcaaggagct gagacccaaa aaggaaaaag taattttctc aggatctctc 15240
aaagagtgag caacagagtt ggcctaattt attttagcgt tgtgaatact gttgacattt 15300
tatttcccaa atctaagtat ctcctcccct tccccctatt ccagagacca gaccaccaca 15360
tcatgctggg tgttagataa atatgtttaa tcttcttctt atttatccta acaagcagat 15420
atttaaagga aattatcaac taagcaagaa attttcagaa agtaagacat gtatttgttc 15480
aaatactggc ttctcacagg aaagtgtatt ttaccacatt ctttacttga gcatactgta 15540
acctctgcaa aagttacaca ttttgggaag aaaaaaattt ttttggcaaa aattgtatta 15600
ctgaccaaac tttgaaaaaa atgttattct atgcttgtag aaaagttatt ttagtggaag 15660
gtgttgataa ttaagtggaa gtagttgtat gctttgagaa gcataccttt tttctttcat 15720
caatggaact ttaaaaagtt tctcactcac ccacctgttt cctaaacaga tcagtgcatt 15780
gttgatgaca tcacttacaa tgtgaacgac acattccaca agcgtcatga agaggggcac 15840
atgctgaact gtacatgctt cggtcagggt cggggcaggt ggaagtgtga tcccgtcggt 15900
gagtagccct atttccctag atgagtttgc acagggggaa tggttagcaa gtttcagata 15960
agaaaagcta tgtgaaatca catgactgaa gttggctcca gactttgatc agttgcttgc 16020
aaagaacttt gcaaagtctt ctctctaata ctggaccaaa atatctcgat attggtagtc 16080
gtctggtttt tgctgaattt ggtgacaaat ttaggcttat tttaattgaa tggaatttat 16140
tcttgggttt agaatcataa agataatcca tgctattaaa agtattcttt cctttttttt 16200
ttgtttgttt ttgtttttgt ttttgttttt ttgagagaga gtttcgctct tgttgcccag 16260
gctggagtgt atggcacaat ctcggctcac tgcaacctct gcttcctggg ttcaagcaat 16320
tctgctgcct cagcctcctg agtagctggg attacaggca tgcgccacca ggcccagcta 16380
attttgtatc tttagtagag atggggtttc tccatgtggg tcaggctggt ctcaaactca 16440
cttccttacc agctgtgtaa cagcatgagc aaagggtgta aatatcaccc accaaaacac 16500
tctaggtttt tttttggccg cccttcaaaa tagaactaag caaatagtga aggctgagcc 16560
ttaaaagagc tgtgttacca gcactacaaa gtttaaggtg atccattact atttctttac 16620
caaaagagac aggttgctca ctgagaaaac aaactgataa catccgtttg tttgacgtga 16680
gattaccaga actgagagag aagcctgaga ggttttctta gaagctgctc agcaggtata 16740
ctcgtaaagt ctagttcatt catttaaatg tcaaacagtt tctttaaatt ttgaagaagt 16800
aaggaaaatg aaattattgc agattttttt cttgctattt aaatgttaag ccagttatat 16860
taatatgggt aaaaataata actaatattt aaaattaatg tgtagattat caatatacac 16920
tgaaatctaa atctttacat ttttatttag aaatattacc ttttagaaaa ctaaatattc 16980
ctcctaatag gtactttggt ttttttttta ctacaaactg tcctgtaagg taaagaatgt 17040
gaacaaaata tttttttaac tgcatatatt tgtaagaaca attgcaaatt tctatttaag 17100
ctaaatgtat gctctagcac cctgaaatta aattcgtagt tataagtctt caaggctgtt 17160
tatcttttcc ttccatgtat tttagaccaa tgccaggatt cagagactgg gacgttttat 17220
caaattggag attcatggga gaagtatgtg catggtgtca gataccagtg ctactgctat 17280
ggccgtggca ttggggagtg gcattgccaa cctttacaga cctatccaag taagtagctc 17340
tattactgca agttgagaac tgccaattgg gttataacaa cagggcagtg attattaatg 17400
ctctcatgcc taagttgggg gtctcccctc tttcccaccc ttttctcttg ttattatcta 17460
ataatcaatt gaatttttga ttaaaataat ttttctctct tcctctatca agtaaaaggt 17520
agagaaggct atgaaaatgt gcctgtttat aattttactt cttaactctg taaaatattc 17580
tgttaggtta agacactctg gctaatttca tcttatatcc atacatggaa ataaaaacca 17640
ccaagtgagt tatgctggga gtaaaggttt ggggctttat attatgattc ttaacagaga 17700
agctgcatag agagatggca tgaaatgcag cataaggtac gtgttcattc aacatgtcat 17760
ctaagctccc tttgcatcaa acttttcatt tgtttgatca gttgccacca ggaacacagt 17820
atgttgggcc aagggttgag taacttggtc aactctctgc ccacacagtt caaacactct 17880
caaatgttta ttgctgggtt tttccaggtc acaaagacat catgcctagc tgtaggtgta 17940
attagttcat ttggggggaa aattgcattt aaatattcac tgagtgatta taataaaaca 18000
tgttaataaa acatgaaagg ctaattaaaa ggcatcagtt atttgagcaa ctgctgaggt 18060
gcaaagtctc caaagtcttc actaacgttt gactgaaaat atggcctaca ttcagaaaca 18120
aaagagtttc agggtgtcag aatctgcatg cgacagaaat taagattaac tctgtgataa 18180
aagattcact gtgacagaga acaagctatg ggaacaactt ggccaaaggt agtgttagcc 18240
aagcctcatt cctccatttc ctcatctgta atatgggaag attgtagctg attaccttta 18300
atgttccatc ctaaatacta aacacccaga tgcacctttt ctaggaactt ggaagattct 18360
gcttttccca accctcagac actgtcagtg ctggggaagg tgacttcact tttgaaggct 18420
tatagcacag attgaccaac ctcctaaatt gtatttcttg gaggatttag gtgtaggaat 18480
cacttaattt tttgtaactt aatatatatt taaatctgat tgtggaagta ctataagtat 18540
atgaatggtt tgtttgttta tatgatgcaa atgatactta aatggtagaa acttctaaaa 18600
aaatgctctg tggtttctat atttatgatt gttattggtg ttgcaatttg ctgaaaatga 18660
tttccttctg aatgattgag agagatcttc gtctctctca acataaggct gtccacatag 18720
ctgcttgctg gaagcattta ggtggacatg ttggagataa aatctggaaa ggaaggaatc 18780
cttgagtatt ggagtattac atgttgacct tactcctact ctttaaaaag gagaacagca 18840
agatcccact gagcatagag gtgatttcgg agggaagaga ttggaatttg acctcagata 18900
tgctctttgg tgcttatctg tatgtctggt ttgctccgtg gcctagcacg tagggcttta 18960
agagtgtggt gagaataagg gaacagcaga ttaccaacag attgtctctg agtcctgcct 19020
tgtttgttcc tcctacagag aacttggtag agttgttcaa actagcaaaa gataagaggc 19080
atttggtttg tcaataagca actagaaaag cacagatctc agcaaaataa atagagaaaa 19140
aaaggactga gtcaaaaaat cataaatgtt taacttctcc aaggacacta ctattggaaa 19200
ttattcattt agactttatt tgaaactaat tttaaaagtg tagacattgt actatctcct 19260
ttttttggta tcatctcaac tattttattg ttagtttatt catattgaat aagagaggga 19320
gtaaagattt cacaatggcg atagctagta tatgccaatt aagttaattt aaaaagttat 19380
accaactacc agtagcgaaa aaggactgtc aaaagtttaa atctaaataa tgtaaaagat 19440
gtcataattt ttaacttttc tgtctttaaa ggatacatag tataagctag agtaattata 19500
cgtagtataa gctagaatat aggaatttaa ttgatctaag aaataactga cacaaagtct 19560
ctttacttcc tgaacaaaaa catgctaaat tccatgctgt tcagtccatt tcctttaaag 19620
gtgggctatg ccacagggct agattttaaa acgtggaatt tcacaccagt gctcgaaatc 19680
ttatgaaagc aaaagggacc tctgtagttg tactccactt tggcttgagt aaaaaccact 19740
gctgtaccct ttttctttcc tttccctgcc catttttatc ctcctccttg tgtccttgtg 19800
gacatagaaa tatgattagg cttagaggtg aacagtaaag gtcatttatg ttatcttttc 19860
aaaacttaat agacatttat ccatcataag cttgtccccc ctcaaaatca tgattgacaa 19920
gactaaataa agtgtatatc aggtgtctct ttatggagga aattgtagta ggatttattt 19980
aaaggatcaa tatttaaata gccctatgcc aattatcata aataattaag gacatgatat 20040
tcctagcttt cctgatttac atggaagtac gttaaatagt cacatctcca aaatttttct 20100
tgaatagttg tctttaaaaa tgtgtttaca tttgtaagga tcttcataaa cagaaggggt 20160
aattcaaaga taggcatgga attgacttat gccaattgat taaaacaaac atcctgtgtg 20220
ttctgtgaaa tacatacaac tttaaaatga aaaactcata attttatgca tgaattttgg 20280
tgttcatgtg gcttggaaat atgtgcatta aatggaatta agattcaaag tatttgctaa 20340
tcttcaacca actttgaatt gttactggtg tggaagtgag catattgttt tagaatttct 20400
gaatctacat ggatatccaa gttatatatt ttttctgcta cagaaagctt tgttttccaa 20460
gagaatttaa tggcttagat aataaagttt gaaaatcaat gtattttttt tcctagaagc 20520
tttcagaaaa cttaaatctg ttaataatct ggtgaagtgc tttattacac atacaaaatt 20580
ttgctctgtt tgacagagtg tcagttagaa attcttgaaa aggttactat aagacacaat 20640
ttttatttct agtaatttaa acattgactg acatcataaa gatagtgttt taagaaaaga 20700
tagttttctg ttctgcaagc ataaattttc tagctatttc attattatct taaatggagt 20760
taacactact tagaaattga tgctacttcc cttattttcc ttttatttta aacaaaagaa 20820
ccaaaaccat actttaaatt ttgttgataa cagtgatata catcaaggtg tagaaatact 20880
gaatttagta tacacttcat aaagtcattt ctgttgacaa ctgattttgg aaaaaaaata 20940
aatttaatca cttaataatt tgatggatca atggtgtgat ttgggagtaa acttcttgaa 21000
taaaaataaa acttgatgtt ttttccaaac tgatagactg cttagactga tgagaaataa 21060
aactaggtct ttaattatta cctttgctat ttgtctaaga ttctaccccc atttagaaat 21120
gtgtttgttt tacatcatct catatggcct ttggaatgtt gtttccttct taggtagtag 21180
attcattctt gatgaaaacc ttccaaaatt agaatttgct ttaaaagagg ctcaatacaa 21240
taagtaaatg aagtctgtgt tctgtattac attatttttg taggatcgtt tcacaatttt 21300
ctcacaattc ttactttgat agtagagaaa ataaaagcaa gccaagagac ttttttttaa 21360
aaatatattt tatttgctat aaacaactat gatttgcatt tctcatgtga agaataataa 21420
ttatcggcta aaaatggatt tgctgcattg attttcaacg taaatattta aaagattaat 21480
gccagataat tttattatac tcacatttaa cgacaagcaa agctgtttat aatgatgact 21540
gtccatgtac acagttttaa gttgaagtga gtgaatattc aagataatta aatgctacat 21600
tttcattttc aggctcaagt ggtcctgtcg aagtatttat cactgagact ccgagtcagc 21660
ccaactccca ccccatccag tggaatgcac cacagccatc tcacatttcc aagtacattc 21720
tcaggtggag acctgtgagt atcccaccca gaaaccttgg atactgagtc tcctaatctt 21780
atcaattctg atggtttctt tttttcccag cttttgagcc aacaactctg attaactatt 21840
cctatagcat ttactatatt tgtttagtga acaaacaata tgtggtcaat taaattgact 21900
tgtagactga ggggattttg gttttggttt tgggttttgt ttttttgcgg tgggggggct 21960
ggtatttgga agaatttagc tctttatgtt acagaaatct tttttgcaag gacttagaaa 22020
tgataatgct taagattgtt cttgcccaat gtgggaagag aatctaaggt ttttatatgt 22080
cttgcaacct catcaaagga aaattactgg catcattttc ataatttgaa aaaaaaagcc 22140
aaattaatat atttcttttt tgattcactt tttaagtgat catttttaaa actttacttt 22200
tgacccactg aatttattta gatagaagga aaagagatga tgggagggaa gtttagataa 22260
aggatggaag ttggttttat ttaaacaata gccctgtgat ttcctaatga gaagtgacta 22320
gaaattgaag aaaccaaata aggaggatat tggtcaattt agctttagtt tctcttactc 22380
tctcaagcct gccctgttta actccaaagt tcatggctca taatttgaga aacactgttt 22440
taaacacagg agaaaaaaat gtccatttta aatcatagct attgaattct acaattacaa 22500
agaaacaaac aaacaaaatt tgaccaaccc aggcggttaa atttaaactc ttcaggaaaa 22560
atttaagctg ttaaaattat tctttttcta aatttctaaa gtggagggac agaatttttc 22620
agatttaaaa gggcctccta ggtgcccaga aaattagtgg aaagaaccac gtctagacgc 22680
atctttgatg tgtcagagtt ccaaggataa aaagaaactt ttaaagtctt ctatactcag 22740
ccaggttatc aatcaaatat gagggcaaaa taatattttc agacagattt taggcagttt 22800
atcttccata tatccttttc tttaagggta tttgtagata cactccagaa aaacaagagt 22860
gaaatatgaa ggaagttgtg gggtccagca aacagtgctt ccaaatcaga cccctgatag 22920
aggtggaaaa ctttgcaatg caacaactgc gtagctggct tagaggacag ccaatacaga 22980
tggaacagaa agatgaggat gggattgagg gatcagggat tgaggtctcc aagaataaaa 23040
agggacttca tggaaaaagt aggcttgtgg ataattaatc acaggggcaa ataatgcagt 23100
taaaataaca acatgacaat caggtggagg aatgtataat aaacccaaat gtggctgggt 23160
agagtggctc acacctgtaa tcccagcact ttgggaggcc aagccgggca gattacctga 23220
ggtcaggagt tcgagaccag cttggccaac atggcgaaac cccgtctcta ctaaaaatac 23280
aaaaattagc caggcttggg ggcgcacgcc tgtagtccca gctcctcagg agctgaggta 23340
ggagaatcac ttgaacccag gaggcaaagg ttgcagggag ttgagccaag atcgcgccat 23400
tgcaccctag cctgggcaac agagcgagat tctgtttcaa aaaaccccca agtgtattat 23460
aaggcaataa ttcctatacg aagcaaacta aaatgcagca atattaaggt ataaaaacaa 23520
agaggaataa ttccattgaa ccttgattct ggaaactttg atccacccag cagtcatgat 23580
gttagactca ttgaaaagaa tgtatttcta atgcatgatg cgatcggtct atagatgtgt 23640
catggaaact tggttgcaac ttcaagacaa aataaaaagt aaacatttac atgaaaaatg 23700
gtggatatgg aaggtggaga agagaggaga taacagcttt atctttcaaa atagagaatt 23760
gagagatggt accaaaagct gatgaagtaa aaaaaaaaaa aaaaaaaaaa gatacttaat 23820
ataatacttt aaattacaaa tataaacaca agaagaacaa atataatgat acaaatgtca 23880
gacactggga atgtccaaga ttctggaagg aaagggtggt attattgagc taaatcctca 23940
actttgtctg ggcacagtgg ctaaaaatta gccgggcatg gtagcatgca cctgtagtcc 24000
cagctacttg ggaggctgag gcggaaggat cgcttgagct tgagaggcgg aagttgcagt 24060
gagccaagat ggcactactg cactccagcc tgggagacag agaaagaccc tgtgtcaaca 24120
taaataaata tataaataaa tcatcaagtc tcatattaaa gactctgtaa atatgactta 24180
ttgttgacaa atgaaacaaa tagaggtgta agcatgttgt ctacatggag gcaagaccag 24240
aataatagaa aatggaaaca gattccctta aagaggggaa tcgtgtcttt ctcattggct 24300
caatgtagtc tccgtagagt ctagaatgct tcagcacctg gcacactgct taacaaatgg 24360
tgaatgaaaa aaaaaaaaag aaaagtcatt ctttttcttc tttcacccta tgtccataat 24420
ctggccattt gcagaacttg atgtccagtg atcgaaatca acagcatcag tgcatccaat 24480
atcttctagt ctctcatctt cttattacat cattaatttt atttacttta aaattaagga 24540
tatccaaagt attatgtgag accattgcaa tgggagactt aaaagtggta taaaatgtac 24600
tttgggccag gcgcagtggc tcacgcctgt aatcccagca ctttgggagg ccaaggtggg 24660
cggatcacga ggtcaagaga tcgagagcat cctggccaac atggtgaaac cccgtctcta 24720
ttaaaaatac aaaaaaatta gctgggcatg gtggcgcata cctgtaatcc cagctactcg 24780
ggaagctgag gcaggagaat cgcttgaaac cagaaggcgg aggttgcagt gagccaggat 24840
cacgccactg cactccagcc tgggcaacaa gagcgaaact ccatctcaaa aaaaaaaaaa 24900
aaaaagtaca ttgaattgga aagtcttcaa aaagcagcag tgatgaattt tttgagattt 24960
ttaacaatta caaaaattca gggttttttc taatggatgc cacctgagac tttattttct 25020
gttattttct tgtaataact aaccaaacaa gctcatgttg aaaaatgatt actaaatttg 25080
agctaattgc aatgactggt ttcaaaattt tccacagtgt atttgagtta aaatttcact 25140
gtgaagagta ctacgatcac tctcgcttat tccaaaaata taaatggaca cttgagtatt 25200
tgaattattg aggaaatggt tgactgggta atttttaaaa atcactgggc acaaaaaata 25260
tattttgact tatattagtt tagagtattt acacttgaaa gagtctcatc ttttctgaag 25320
ggtgtttctt tcatacacat tttattgcac tgagttttgt gacccatggc atattaatga 25380
agctgaacag gatgtgaaat ataaactgga agcaaaagat taaataaacc aaaattgcat 25440
tttttctgta gtcttgtcca aaattgggta accacttctg atggggtagc tcatatccaa 25500
gaatgagtca caaaaccaga ctcgttgaac ctggtatatg atgagtcaca aagcaacatt 25560
ctgcctttgt tttttcagga caagaaactt gaattgtatc ccactgagtt aaaagataaa 25620
atatatggca ttggcatttc tgtacttcag agaggaatat atctgtttgt ggtaggaata 25680
aaaaataagt gagagaggca aagcttaggt tcatcatatt atgttactga tataacacaa 25740
ttaacttggt aaaagtgaag gtgtgggtgg gcgtggtggc tcacgcttgt aatcccagca 25800
ctttgggagt ccgaggcggg tggatcacct gaggtcggga gttcgagacc agcctgacca 25860
acatggagaa accccatctc tactaaaaat ataaaattag ccaggcatgg tggcacacgc 25920
ctctaatccc agctactcgg gaggctgagg caggagaagc gcttaaacct gggaggtgga 25980
gtttgcagtg agctgagatt gagccactgc actctagcct gggcaacaag agcaaaactc 26040
tgtctcaaaa aaaaaaaaaa aaagtgaagg tgcccagtgt ctgcaactat gtcaccccgg 26100
gcatatcaca tatcactctg tttttccgtc tgtaaaacgg gagcaacaat gccattgcct 26160
tatcatcaga aggatatgga gactaaatgg gagaatgtag gtaaacagca cagagtatgg 26220
gtatcagtaa gtaaactgca gcagtttgtt gatgttaaca atagttagca ttatatctaa 26280
ctatatctaa cgatataacc attgggaatc cagttttcca tgattttcct ctagaatgga 26340
gctgcctaag tcctgcttaa gtcatttttc tttgaagatt actgaacatc atcttcaaat 26400
gttcatcctt gtaaacacgt gtgtgtgtgt gtgtgtgtgt taatttaaat tttcagaaaa 26460
attctgtagg ccgttggaag gaagctacca taccaggcca cttaaactcc tacaccatca 26520
aaggcctgaa gcctggtgtg gtatacgagg gccagctcat cagcatccag cagtacggcc 26580
accaagaagt gactcgcttt gacttcacca ccaccagcac cagcacacct gtgaccagta 26640
tgtacacaac caccctcatg cctcctaccc ccgaggttcc tagagctagg ctctcctgag 26700
gcaatgcttt ccttctcaat tcatattctt ccaggagggg caccaacgtt ttttaaaatg 26760
atgttggcga cgaggacggt aaattttcta gatgactgaa ggctgacttt cccctttctg 26820
tgactctcta ggcaacaccg tgacaggaga gacgactccc ttttctcctc ttgtggccac 26880
ttctgaatct gtgaccgaaa tcacagccag tagctttgtg gtctcctggg tctcagcttc 26940
cgacaccgtg tcgggattcc gggtggaata tgagctgagt gaggagggag atgagccaca 27000
gtacctgggt aagctcaata tgtcgctcaa gacaggttca gggcagctgc tggaaaactc 27060
tccttgtggg ggtgggtggc ctctaggcag gtggtatctg tggtttggaa ctggttgaca 27120
gctcagactg aacaaaccac cctctggcat gaggaaggga aggactgact ctttctaaga 27180
agtggccggg tttttcccaa gccactgtca catgttcctg gtccctgatg ccagctgcat 27240
catgcgccta cctgtgcaca agttcctaca gcaaaagctg tgttcttggt ggaagtaatt 27300
accaggactg cagctgacaa tgtgagcaca gtacggtcac tcatactttt caaattgtta 27360
tggtgagggg cctttaaaaa acttcattgg cgcactgaag tgtgtgccat cgtaagcact 27420
gagttcagtg aatttgaatt cttataaagt gaacacacca caagaccagc acccagatca 27480
aggaaaagaa tatctctcta ccctcacccc atcatcttcc gccaataatc actaccctga 27540
ctcttactgc agagagctat ttttaaaaat ttggcattcg attacaaaaa ttatacgtct 27600
ttagaaaaaa agttggaaaa atgaaaggaa gaaggaggag gaggagaaag gagaaagaca 27660
agaagtggtg ttttcccata gtacattaat aatcacagat taggtgggtg cggtggctaa 27720
ctcctataat ctcagcactt cgggaagctg aggctggtgg atcacttgag gccaggagtt 27780
cgagatcagc ctggccaaca tggtgaacct ccatctctaa taaaaatgca aaaaaaatag 27840
ccgggtgtgg tggtgtgcac ctgtaatccc agctactcgg gaggccgagg cagaagaatt 27900
gcttgaaccg gaaaggtaga ggatgcagtg agctgaaatt gtgccactgc actccagcct 27960
gggcaacaca gcaagactct gtgtaaaaat aataataata atcactgatt agctattagc 28020
acattacctt ctagtcgctt ttccctatga atatataatt cttaaaatat ccttcttata 28080
agctgtagag tcatttgagg gactagtttg ctctgattag ttaccttttc ttttcatttc 28140
aaagatcttc caagcacagc cacttctgtg aacatccctg acctgcttcc tggccgaaaa 28200
tacattgtaa atgtctatca gatatctgag gatggggagc agagtttgat cctgtctact 28260
tcacaaacaa caggtacatg tgtgctacat agtgttaaaa gaatcttttt ctgtaaaaca 28320
caggcctgta gtagcacttc ctgactgttt gccccacttt ctttctttct tagcgcctga 28380
tgcccctcct gacacgactg tggaccaagt tgatgacacc tcaattgttg ttcgctggag 28440
cagaccccag gctcccatca caggtcagct aagcgtcccc ctctttggct gctatgttaa 28500
tcttaatgac atcagcaggg agggcgcaga ttctgactgc ggacctgcat atcactttaa 28560
atctccaata taatttatgg gagaggggtt tgtgtgtgtg tgtgtgtgtg tgtgtggcgg 28620
gggtggggga gttattttct atggcacatt tccccttgaa accatttcac caactccctt 28680
atacacacac accacaacat acacacaacc tgtaaagcca gctcattggc ttattaaagc 28740
aagtgttccc agggttgaag aggtgtaatt tcctgaaaac gttgctctaa gatttatcct 28800
taaggagaaa gctgagctgt cgtcttagct cattaggtga ttcaactgcc tcatcactga 28860
agttccaaaa agacacacac agtgctagac aactctgctt aggctggttc attaattgct 28920
tccctcgtct ggagctcaaa gaggaaaaat cagcttaaca tgaatatttt cacctaatgg 28980
catctctaat tgacatttat taaggatgtc aggtcttcaa ggatgacatt tattattaaa 29040
aaggttcgca tgactgttct tattttatct tcgtgctgaa tagtcattat tagaagaagt 29100
ggcaatattc aaagagtcaa aaagtatcac tggctcttca ctaatcaagc aagatgctaa 29160
gggatattag aaaagggagg atttatggtg tttctaagcc tctgtctcaa agaaaacagt 29220
gcatcttact tttgctcatg aatctgcagg gtacagaata gtctattcgc catcagtaga 29280
aggtagcagc acagaactca accttcctga aactgcaaac tccgtcaccc tcagtgactt 29340
gcaacctggt gttcagtata acatcactat ctatgctgtg gaagaaaatc aagaaagtac 29400
acctgttgtc attcaacaag aaaccactgg caccccacgc tcaggtaact tttttaagaa 29460
gacacttcct atgttatctt atcaggattg ttcctgaagg agggttgttt tgtctctgtc 29520
aacagtcctc tcattcaaga aatcttatat attagttttt ccctaaactt ctgatattta 29580
gctgaaatgt cataagtaac ttatcaaagc tggctactgg cctttctgat taaaaactga 29640
caccataacg tccatctaca aattttcccc tagaagctta agggtcattt catttttgat 29700
tcttaagtat tataaaatga ttcagtaaaa caaaaactgt tacattattt tctgcagtta 29760
tttcaaaggc tttttctaaa aaatttttta gtatcttttc ttataaccct ctccccccac 29820
caccatatga cacttcatat gctggtaact cacttattac ctattttaga taaaaggttc 29880
aaatgtcata atttaagcac tatgactgga ccatgaaaat gtgatctgat taagagacaa 29940
aacttagcaa aactctcgaa tgagaggctc aatgaactgc ctaacatatc caagaaactg 30000
gcttcttaaa agtaatcttc agcagagaat gtgaatgacc agttgactct tgtctgtcag 30060
atacagtgcc ctctcccagg gacctgcagt ttgtggaagt gacagacgtg aaggtcacca 30120
tcatgtggac accgcctgag agtgcagtga ccggctaccg tgtggatgtg atccccgtca 30180
acctgcctgg cgagcacggg cagaggctgc ccatcagcag gaacaccttt gcagaagtca 30240
ccgggctgtc ccctggggtc acctattact tcaaagtctt tgcagtgagc catgggaggg 30300
agagcaagcc tctgactgct caacagacaa ccagtatgtc ttctcctatc tctatctccc 30360
ctccaaattc tccaccctca cttgcagcct gtgagaaagt gcagtaaacc attcactcag 30420
aggtgtatgg cttagagaga gggaaatacc cagccggcaa gggaatgcat agtgaacaca 30480
aagcacatta aacttgaaaa caaaactcag acaagctcca tggatgctaa gtggtaaccc 30540
atttctaaaa tacatgtacc agctgaaggg tactaagagg ggagaactga agagaatcta 30600
atttgagtgc atttttcgtg taactaaata tatctagatc aaagttaaaa tgcaggatca 30660
taacacttag agtagaattc atttaacaat agcaattgtc aagtgtctag tattactagc 30720
caccagctta tctgctcagt ttttacaagc attattctca tatttactct ttgttttgac 30780
cttaggaagg aaggtcttat tattattatt ttatttattt atttttttga gatggagtct 30840
cgctctgtcg ccagggctgg agtacagtgg caccatctca gctcactgga acctctacca 30900
cctgggttca agcaattctc ctgcctcagc ctcccgagta gctgggacta caggcgtgtg 30960
ccaccatgcc ctgctaattt ttgtgttttt agtagaaatg ggtttcgctg tgttggccaa 31020
gctggtctga aactcctgac ctcaagtgat ccacccactt tggcctccca aagtgctggg 31080
attacaggcg tgagccatcg tgcccagccg gaaggtctta ctagtatccg tattgaatac 31140
ttaaagaaac tgaggcttta aaaaagttct gcaacttgta gggtcacaga gataggaagg 31200
gatagagctg gctctataac ctatgtccga agcccatgct ctcaattatt atactcgact 31260
gcctcttaaa gatttcctct atttgaaagg taatttaaat ttcggtggga aaactgctgg 31320
ttattattct caagaataaa ctccacaact tatgtgattc tgatagtgca aactcaccag 31380
tatcctacca tgaatctgag gatacgttat cattactgta attactgtct aatctgaacc 31440
atgtgaaaat aacttttatt tctctagcaa agggctattc acagaatatt gcttttgacc 31500
catagagagc ttcttcttgc tgtcatttta ggaggcatat ccctttttcc ttaatctgtt 31560
tggctcagag ctaactgtga acttcagaag tgtttgtttt gcctttttaa aaataccatt 31620
gctttaatgt aactataatt tctgagactg atgcgaaagt cttgctggaa aattagactt 31680
cccaaaggat cacagtcaag caaaatggtt ccacaatttc tcatgactgg cagagttttg 31740
gcaaagtttt gtgtagcact caatctctta ctggctcagt ttttccaggg ttttgacttt 31800
cacatagtta caaccttgag gagagaaaac ttagacattc aatcaagttt caggacttga 31860
gttatgatca ttactgatct aaatatttct tggcatgttt catctttttt cctagaactg 31920
gatgctccca ctaacctcca gtttgtcaat gaaactgatt ctactgtcct ggtgagatgg 31980
actccacctc gggcccagat aacaggatac cgactgaccg tgggccttac ccgaagagga 32040
cagcccaggc agtacaatgt gggtccctct gtctccaagt acccactgag gaatctgcag 32100
cctgcatctg agtacaccgt atccctcgtg gccataaagg gcaaccaaga gagccccaaa 32160
gccactggag tctttaccac acgtaagctg aaaattaagt gccttttctt aactatattt 32220
acattctcta ttcttcatgc tttaaaacaa aacaaaacaa aacaaaaaaa acattaaaaa 32280
attagtacat aatttaaatc agtgatacta aaaatgtgct ccatagactg gctgctggcc 32340
cgttaattgt ttgctgctag tctgcaacaa gaaaaacggt tgtgccagaa cgtaaatcac 32400
aaagcacact gcttagtaca gctgagaatt tttctgaagc cagattttct tgatgaagga 32460
agcagtgtgt taatttgcac acattgccaa gctcgctctt tcctctaggg ccagcacttt 32520
gagtaacatg ggtttaaagc agtctgttat tagaaaaatt aaattcgatt acattaaatg 32580
aatttaccaa acactagtta acgcaagaaa aaattagcac ctatgtctac attctattac 32640
tttgggcatt gaatagtaac tataaatgca gaataaaaat atctatggat tgaatgggaa 32700
ccaactaatt gaacatgaag ccaaggaaat gatttcttta tgagtgttgg ctgcagaaga 32760
ttaaagtact tttgcagacg gaatcgctct tttcttaaat tactcttgaa attcctcaga 32820
ggagaaaaat actaacaata atttttggtc atgtctatcc ttttgctcaa cattttaaag 32880
gaagtggtct taaatctccc acatatctac atcacaataa caacctctat tcacaaaccg 32940
attcctatta aatacatttc catttacatt acagagaatt atgagactcc ttatttctag 33000
ctgaacatca tttgttattt tcaactcgac attttgaatt atagaagcac ctaacataag 33060
tactttttca gcatatattc taaccatgga ctagtttgca attttctaag agctttcaac 33120
aaatgttact cttcgactaa tttaaaagta tggatgttaa aaagcattca aaaagtccat 33180
acaagcctag tttgtaaata actatggaat tgatttccca aagaaaatac aaacttttcc 33240
ccataagaat tcatacttta agaaaaactt acttccattt aaatttactg tatgaagttt 33300
ggctcatgaa ggctttttcc taaataatag ttaatcgtaa gcaagtaaaa ttcactttta 33360
atttgcaaat aagcttactt gaaaatttgg ctaaaatttt acacggttct aagatagtct 33420
aagatctact ctcatgaaat taatgtcttt atatttcttg taaatattca tttcttataa 33480
atgtccttca gtgaattaga atggagattt cagtgaatgc gccctttcag tagatgtcgt 33540
cttttactaa aatgtagaat tctatagttg tcttgttcat tccttaacat gagacatatt 33600
ttatgtagtt tcttttgttg aacacagtgc ttataaaaga aaaagcattt ttaatgatgc 33660
taacaataat taagggaagg tggtgggcca agatatttca agtacttctg aagactgata 33720
tattggatat attattttat gctttgcata atacattcat ataaaatata atgattttaa 33780
ctgaagtact gatagccaaa actaatttta ttagataaag gttaacatag tgtctggaac 33840
attgtatgct ttcaaaaact atttggtgaa tagataattg agaaaggaat aataataaaa 33900
acagctaaat gaagcttata tttaaataaa ctaatgtaag cagggtattc tacaactcca 33960
tttgaacttt aagcactccc taaggctgta aacatccaca aggcttgcat gtttttgaaa 34020
ttactaaatt tctgtagttt tttactatct tactaagctg aattctggga gtaacttttc 34080
tgagttttat aacttgtgct aaattcttaa gagcaaatgt gagaaaagtt aggggaaaaa 34140
gctgtttctg gggaaaattc agcttagtct tatattgata gggcaaattt tatttcttta 34200
acagctgggc tgttcttccc taacaagacc tgccagaacc catagctcac acttagaatc 34260
acatcctttg tttgacatcg tttgtgggtt tgtggtttgg tgattttccc ataatggcct 34320
tcccaggcag agagcatcat cttaaacttg ggaagactct aggtggctgg ctcaagcaat 34380
agaaaatacc tagtcttaaa gcccaggaca gttgaggcga atataatttg taaaaaaagt 34440
tgtggttttc acagatgttc agtgaaagaa actgactgtt ctctgaattg ttttttgtgg 34500
gccattaaaa atggtcacac agggctggcc atggcatttt ggcacagtca ccagcagtca 34560
agtggtgtat aatttcagag gtactaaaag gcatcgggtc acccatccca gtcatgtccc 34620
cccacccccc accaaacacc atcaaaataa taacatacat agatgaaaca gcccactaaa 34680
ccagtagtac ctcaattcag ccattagagc tatcattatg aagtggccca cacatatatt 34740
tggctttttc tcacacaata tttttaaaat aaaaataaaa aatggctcct tagaatccag 34800
actgaaaaaa aaatgcgaga attgcgatgt tgattctaaa ttcccacatg gcaaagaaaa 34860
aaaaattgac tggagttgag ttgagactgg agtctgaaca ctttttaatc cctgtttgta 34920
taactctgga gactaattct ttgtcttgcc agccattcat aatttagtat aaatgcattc 34980
agaggttttt tcccaatggg aacaaaattt gattgagatg taaagagagg aagaattgtg 35040
gagatgtcaa acatgtgacc agagctatga acacacttga tacccttgaa cttaaactta 35100
cccaactcaa aatatctggc cttctgcgat cttacctttc tacatttata ataagatttg 35160
caaggttgtt ggaaatctct atcttaactt tatatataca tgcctctttc tttctttttc 35220
tttcctttcc tttccctttc tttctttctc tttccttcct tccttccttt ctctctctct 35280
cttttcttcc tttcctttcc tttccttcct ttctttcttc ctttctttct ttctttcttt 35340
ctttctttct ttctttcttt ctttctttct tttctttctt tctctctcac tctctctctc 35400
tttctttctt tcttattttt ggtgctaaaa cccaaaacaa atcttttatt taaaaataag 35460
attttttttt tttttggcca ggtgtgatgg ctcatgcctg taattccagc actttgggag 35520
gccgaggtgg gtagatcacc taaggtcagg agttcgagac tggcctggcc aacatagtga 35580
aaccccatct ttactaaaaa tacaaaaatt agctggatgt ggtggtgggc aactgtagtc 35640
ccagctactt gggagtctga ggcaggagaa tcacttgaac ccaggaggct gaggttacag 35700
tgagatgaga ttgcgccact gcactccagc ctgggtgaca gagcaagagt ccatctcaaa 35760
aaaaaaattg tttaagtaaa attttatttt ctttcttttt tttttttttt tttttttttg 35820
agatggagcc ttgctctctc accctggctg gagtgcagtg gtgtgatctt ggctcactga 35880
aacctccatc tcccaggttc aggtgattct cctgcctcag cttcccaagc agctaggatt 35940
acaggcatcc accatcacac ctggctaatt tttatatttt tagcagagac aaggtttcac 36000
catgttggcc aggttggtct tgaactcctg gcctcaagtg attcacctac atcagcctcc 36060
caaagtgctg ggattacagg catgagccac tgcgcctggc caaagtaata ttttcaataa 36120
gaaaaataac agtgatgtca ggatgctaga aaatgcaaaa taaatttgtt ataattcctg 36180
attctggtga taaaatacta aatttttgca gtattattct gaaagaataa tcacgtattt 36240
aaagtacaaa tctttagact tcaaagtgca tccatggtgg cagattttgt ttaactttta 36300
tatagcatct tttattgcaa ccaaaaatag ctgaccatta ttgtggaata attcagcgta 36360
aagctttttt tttttctttt tttgagacgg agtctcattc tgtcacccag gctggagtgc 36420
aatggcatga tctcggctca ctgcaacttc tatctccagg gttcaagcga ttcttgtgtc 36480
tcagcctccc aagaagctgg gactacaggc atgagccacc atgacagtta atttttcata 36540
tttttaatag agacagggtt tcaccatgtt tgccagcctg gtctcgaact cctgacctca 36600
agtgatccac ccacctcggc ttcccaaagt gctgggatta cagtcatgag ccaccgatcc 36660
ccgcccagca taaagctgtt tttagatcac cttctataat ttaccattgt tcttaaatta 36720
atggttaaga aacaatatga taatcagttt gtggtggcca gttttacatt ttataaggga 36780
ttttacactg acgatatagg gaaatttatt gtcatcaaag tcaaatccca acaatcataa 36840
aaagacatga attagattat ataatttcaa tgaaaggacc accttagcaa acatctaacc 36900
ccttgttact caggtatcat tcacgggcca gcagaattgg tattatctgt gtttgtcaga 36960
aatgcaaact ccctagtttt ttgttggacc tccagaaaca gaatctgcat tttagccaga 37020
ccccagatga tgtgtgtggc acattaaaga ttgagaagcc tgatcctctc ccaattctca 37080
cccaatgaaa aaatatgtta catcctctat ccactgcttg gttaaactga ggttctccat 37140
aaaaatactt gttatctata tgctatgcaa tcatctgtga gtttgagttt tgaatatgtg 37200
cattgattct ctctcacagt gcagcctggg agctctattc caccttacaa caccgaggtg 37260
actgagacca ccattgtgat cacatggacg cctgctccaa gaattggttt taaggtaaac 37320
tgcagatgtt cctaatctct gtgatacagc cctgagctgt ccttgtggtt cccatgtagt 37380
ggaaacaggg tgctcaggag tcaggagacc tgggttttgt cacctgcttc tgtccataca 37440
tctttgacta cattgtcagg gcctaacagt ccttccctgc ctacctcact gaattgttgg 37500
aagggtagat ggaggctgcg aaagtgtttt gcaaaggata aaacattagc acgaagctgc 37560
tgcttattgt tatcttattt tctctatcct ttcctgcagg gaattacatt tcaaaaaaac 37620
atgggaaaac tttatttgat gtgttgttct aaatgagtgt gaacaagttc acaaaagcca 37680
gtttagggag accagttaaa ctcagagtca cttaaaaatc gcattttcat ccaatcagtt 37740
tcatctccaa ctgttcaaag cactgagggt gaatctctta atagaagtta agattaaggt 37800
ttccctgtgg atatctggat tcatcttctt taaagtaatg atattaggga agcggtgaat 37860
acaaatgaat atgtttaaaa gaattccatt ctttggcatt tagtgtgaag agagaaatat 37920
ttgttatcgc tggaaatcat gactcaatcc ccttgatcgt ttaaaaaaat acaccaaaga 37980
taaagtttgt aaatggccat atttatgatt atgctactca aatatagaag aactttctga 38040
agagtgccag tatacctttt aattccctta ataatgtcat gctgactttc agaagcctta 38100
tgatgtgtga aggatctctc tagagttgaa cactattgga taacagtgtt acctaagttt 38160
ttgaaataga atcttaaaag gattttaaat tatgggcata gttattctaa ttcttctctt 38220
gtaatgtatc atcctgcagt tgaagctatg tacatatctc ttcaaaaggt gtgtttttgc 38280
aatacagttg ctacaggggc tggtgccttt aaatggcaac taaaaggtta attgaatgtg 38340
aataactcgt taaagggaga gctcagacat tccttctagc acacacacag aaaaatagaa 38400
atgaactacc atgtgaccca cagtccctgt atacgtctgg tttgtaacaa gagattcttt 38460
atcaagcaaa acagtatgta atgacatttc tctggaacct tccattacaa gccaccttaa 38520
tgcagtttgg aagatacctc ccccacctgg gggaatttcc agctaaagta tataaaagag 38580
tccccaaatc atttcccaat aaaagtacac tgtgcagttt ctgaagagtt tacactattt 38640
aaagcataat catagcctca cagcagtaac agtcctctgg aaatatttgt ccttggtgtt 38700
tactttgcat tccttcctct agctgggtgt acgaccaagc cagggaggag aggcaccacg 38760
agaagtgact tcagactcag gaagcatcgt tgtgtccggc ttgactccag gagtagaata 38820
cgtctacacc atccaagtcc tgagagatgg acaggaaaga gatgcgccaa ttgtaaacaa 38880
agtggtgaca cgtaagaaga attttttccc ttttctatta gtttttaaaa ctgttctact 38940
tttcgaaaaa agctagtgtc aatatcactt tttacttatg agaatggcac aggggagata 39000
tcttatcctt acttatatta ttaatgctat tcctgaattt ggagtagcag gttcaattca 39060
tgctttatat tttatggcat cagaaatgtt ctttccatgt caagaatatt tatgaactgg 39120
caagatgaaa ataatttcaa tagtattgca aaatcattaa tcataaagaa gtctttgtca 39180
gagaattact gctgtccatc atattttcat aatgtaacct atatttttat gggagggagg 39240
gagggaggga agaagcatgg aagagaggga ggtagggaag gaggaaagat tacacaggtc 39300
aagagctttg tgtcagcttt gacttttaaa atgttctttc tgcatagcat tgtctccacc 39360
aacaaacttg catctggagg caaaccctga cactggagtg ctcacagtct cctgggagag 39420
gagcaccacc ccaggtaagt ttgggatgga tcagagggca agtatacacc ataccttccc 39480
aagacaaaga ttttagaaac tgtgtttctt tcagagaaag aagggattca aattacaaat 39540
gcttagctct ccataaaaac tatagcagta catgatgtac atcatggagc agcctgcagg 39600
atgctttaat gcacgttgac ttcaatcaca ggaagcagaa caaccttaca ctagtctagg 39660
gggacaagac agatcctcac acagctgtag ggctgaagaa aagcactgtg gaaggtggct 39720
tttgctgagt gcattaaaaa ttgccaaaca aatggttgaa gtcatattac gtaatttccc 39780
ttttgtgagt tgttacagag cctaagttta ttattccctg aagttttatg aatgttttgt 39840
catgggttgc accacaaata tttaagggtg atgaaaggca gaaatacctt cattttacag 39900
aataagaaaa ctgagactta gaaaaaattg gcctactcat agtcacacat tttaaatgtt 39960
acaaaactgg gattgtaact taagtttgta gactccttct cacacccaat gtcacatatt 40020
tggaatgtaa ttttttttta attatattct atgcaaactg aaaattctga ttaaggggtt 40080
tcctgaccat ttttagagct ttaaatgaag catttgtcta aattccttgt tcacatatat 40140
ttgaaaatta tttataaaat gctaaaatgt ataaagatag ttgttaacaa tattcaaaca 40200
gcatgacgta ctatagcaat aacaggaaat tttagatacc cattactttt gccaaaacca 40260
catggaagtc tcaacaaacc tatggagaaa aatcttaaac aaaaataaaa gttccaatta 40320
atgttgattg cattcttacc tcatatactt gttaatttaa gggatatgtt taggttatta 40380
tttagctatt tctaatttta ctgtaaaatt cttgtgaaat ttttgtttaa aaaaaagtat 40440
tatatagttc ttatctttgc cggggcacag agctaaggct atcatctcta aatctgatta 40500
atgtatgcaa acacacagaa tgaaactagc tcagaatatc tcttttaatc tccctctgaa 40560
gtagagtgat tttggtaaag ttttcattat ctgcggaaac attgtttaag ccaaagctat 40620
acaatttcca gctgagttgc tctgaatttg aaactttaag ttgacaatct tcgtgcttgt 40680
tagcagcagg atcattaata tctcgtctca atggcccagc ccacacatat ggatgaccac 40740
tagcaagtgt aatgatctca atatttattt ctcattcagt tgggtttcct tgtatttgcc 40800
acattagtgt ttaccctgtt cctaatggca aaatattctg tcatctcctt gccttttata 40860
aagtttaata tactttctca ttttaatctg tccccacaga tctctagtca tcactgtttt 40920
tatttgaatg tctctcatcc ctctcaactc ttttactgcc caatttctgt gattcctgaa 40980
gacttcaaca atcaatactc tctttttttg tttgttttgt tttttttttt tgagacagag 41040
tctcactctg tcacccaggc ttggagtgca gtggcgccat ctcaactcac tgcaacctcc 41100
gtctcctggg ctcaagcgat tctcgtgcct cagcctcccc aagtagctgg gactacagac 41160
atgcgccacc aagcccagct attttttaga tttttagtag agacagggtt ttaccgtgtt 41220
ggccaggctg gtctcgaact cccaacctca ggtgatctgc ctgcctcaac ctcccaatca 41280
atactctttc tagaataagt atcagcactt ttgtttctca ccttttctcc tttcttggtt 41340
ctcttcctat aaatcccata gtttcagacc ttttaaatta ggagagctct ctggggaatg 41400
tgcttaaggt ggagagcgat tctatactag gcaggtagaa aggaatattc ctcagctgtc 41460
ttcaaatgat tcattaagga aaagcagggt acagtgatag gaccatgaga tttggaaaca 41520
aagaaagctt tggggaatca ctcccctggt tcaagatttc ctttaaagtg aggatcttgg 41580
cggaggttga agtgagccaa gatcacaccg ctgcactcca gcctgggtga tagagggaga 41640
ctgtctcaaa aaataaaaat aaaaaaataa agtgaggatc ttagtactgc ctgaaaggat 41700
tgttgcaagc attgaataac agtgacagtg gagtcctcag taaatgccaa gtcctgcatt 41760
ccgccctgtg aatccatcat tggagtctag ttaaatatgc tctggctcac agatcctctg 41820
tgcaataact tcccttttct tttttctcca gacattactg gttatagaat taccacaacc 41880
cctacaaacg gccagcaggg aaattctttg gaagaagtgg tccatgctga tcagagctcc 41940
tgcacttttg ataacctgag tcccggcctg gagtacaatg tcagtgttta cactgtcaag 42000
gatgacaagg aaagtgtccc tatctctgat accatcatcc caggtaatag aaaaataagc 42060
tgctatcctg agagtgacac ttccaataag agtggggatt agcatcttaa tccccagatg 42120
cttaagggtg tcaactatat ttgggattta attccgatct cccagctgca ctttccaaaa 42180
ccaagaagtc aaagcagcga tttggacaaa tgcttgctgt taacactgct ttactgtctg 42240
tgcttcactg ggatgctgtg tgttgcagcg agtatgtaat ggagtggcag ccatggcttt 42300
aactctgtat tgtctgctca catggaagta tgactaaaac actgtcacgt gtctgtactc 42360
agtactgata ggctcaaagt aatatggtaa atgcatccca tcagtacatt tctgcccgat 42420
tttacaatcc atatcaattt ccaacagctg cctataaaat agttttgtcc ctgtatgtga 42480
gcactgaaac agcatttggt tgacacatct agtttttcat cttgcagttt caaatccttc 42540
tttttgaaaa ttggatttta aaaaaaagaa gtaaaagtca caccttcagg gtgttctttc 42600
ttgtggcttg aaagacaaca ttgcaaaggc ctgtctaagg ataggcttgt ttgtccattg 42660
ggttataaca taatgaaagc attggacaga tcgtgtcccc ctttggactc ttcagtagaa 42720
tgcttttact aacgctaatt acatgttttg attatgaatg aactaaaata gtggcaatgg 42780
ccttaacctt aggcctgtct ttcctcagcc tgaatgtgct tttgaatggc acatttcaca 42840
ccatacattc ataatgcatt agcgttatgg ccatgatgtt gtcatgagtt ttgtatggga 42900
gaaaaaaaat caatttatca cccatttatt attttttaac cttcttcatg caagcttatt 42960
ttctactaaa acagttttgg aattattaaa agcattgctg atacttactt cagatattat 43020
gtctaggctc taagaatggt tttgacatcc taaacagcca tatgattttt aggaatctga 43080
acagttcaaa ttgtaccctt taaggatgtt ttcaaaatgt aaaaaatata tatatatata 43140
tattccctaa aagaatattc ctgtttattc ttctagggaa gcaaactgtt catgatgctt 43200
aggaagtctt ttcagagaat ttaaaacaga ttgcatatta ccatcattgc tttaacattc 43260
caccaatttt actactagta acctgatata cactgcttta ttttttcctc tttttttccc 43320
tctattttcc ttttgcctcc ccctcccttt gctttgtaac tcaatagagg tgccccaact 43380
cactgaccta agctttgttg atataaccga ttcaagcatc ggcctgaggt ggaccccgct 43440
aaactcttcc accattattg ggtaccgcat cacagtagtt gcggcaggag aaggtatccc 43500
tatttttgaa gattttgtgg actcctcagt aggatactac acagtcacag ggctggagcc 43560
gggcattgac tatgatatca gcgttatcac tctcattaat ggcggcgaga gtgcccctac 43620
tacactgaca caacaaacgg gtgaattttg aaaacttctg cgtttgagac atagatggtg 43680
ttgcatgctg ccaccagtta ctccggttaa atatggatgt ttcatggggg aagtcagcaa 43740
ttggccaaag attcagatag ggtggattgg ggggataagg aatcaaatgc atctgctaaa 43800
ctgattggag aaaaacacat gcaagtattc ttcagtacac tctcatttaa accacaagta 43860
gatataaagc tagagaaata cagatgtctg ctctgttaaa tataaaatag caaatgttca 43920
ttcaatttga agacctagaa tttttcgtct taaataccaa acacgaatac caaattgcgt 43980
aagtaccaat taattataag aaatatatca ccaaaatgta ccatcatgat cttccttcta 44040
ccctttgata aactctacca tgctccttct ttgtagctaa aaacccatca aaatttaggg 44100
tagagtggat gggcattgtt ttgaggtagg agaaaagtaa acttgggagc attctaggtt 44160
ttgttgctgt cactaggtaa agaaacacct ctttaaccac agtctgggga caagcatgca 44220
acattttaaa ggttctctgc tgtgcatggg aaaagaaaca tgctgagaac caatttgcat 44280
gaacatgttc acttgtaagt agaattcact gaatggaact gtagctctag atatctcaca 44340
tggggggaag tttaggaccc tcttgtcttt ttgtctgtgt gcatgtattt ctttgtaaag 44400
tactgctatg tttctctttg ctgtgtggca acttaagcct cttcggcctg ggataaaata 44460
atctgcagtg gtattaataa tgtacataaa gtcaacatat ttgaaagtag attaaaattt 44520
tttttaaata tatcaatgat ggcaaaaagg ttaaaggggg cctaacagta ctgtgtgtag 44580
tgttttattt ttaacagtag tacactataa cttaaaatag acttagatta gactgtttgc 44640
atgattatga ttctgtttcc tttatgcatg aaatattgat tttacctttc cagctacttc 44700
gttagcttta attttaaaat tacattaact gagtcttcct tcttgttcga aaccagctgt 44760
tcctcctccc actgacctgc gattcaccaa cattggtcca gacaccatgc gtgtcacctg 44820
ggctccaccc ccatccattg atttaaccaa cttcctggtg cgttactcac ctgtgaaaaa 44880
tgaggaagat gttgcagagt tgtcaatttc tccttcagac aatgcagtgg tcttaacaag 44940
taagcagttg aatgtatctg ttccataaat attaacctag agcatagcaa atgaattcta 45000
aattctcaag taggaggagc taagagcaag agagctgcaa ccaagctaca aactaaactc 45060
tgaattcaat gcacagctcc attaattttg aaagatgtaa tgtttgttgc tatcttaata 45120
tacttttgat atctacagct ttaaaaaaat catagtggaa aaacacctgc aggaaagttc 45180
catgacttca aacaaattct gcttctaaat aagcacgtaa aaataagtga atatcaagag 45240
aaattatatg actaaatcta aatctttaga gaaaaaaatg agaactgaaa atagtgtcac 45300
catatgtgct ttattctcat ttttataaaa aaagtgtcag cagttgattg atttaggatt 45360
tgaatactta gaaaagtgac tgattgtttg gtctagatta gaatgttgtt gtgaagagag 45420
tcagaagttt aatttgtact tcaaaaagaa tctgttagaa ggatttctca gaagactgag 45480
agcttagaaa aaaaactgac attaaataaa taacaacaat ttatggaaat tgtctctttc 45540
tagtcccaac cattatagaa tagacatctt ttgttaaaga ataaaacagt aggctgcaag 45600
atggtgctgt gtttcacata aacagtgctt tttattattt tcactgtaat agtcaaatat 45660
ataacaacag caaaagattc tacataaggg aaaaatagct tacatttagg tacattacca 45720
agtattagtc tgaaaacatc tacctttcaa acataattta gataatgaaa cacaaagaag 45780
agcagctcag cgtgaccata atcttggttt cttactttgt ggctgagggc aagaatatct 45840
ttatattggc atatccacca ccccagggct gttgcttctg ttctagagca ccctggaatc 45900
actaattaca gcatcaccca gtatacaagc ccctgcatca caatgtctgt cccttagccg 45960
tagacctgtc acatgctaat catgtgttct aagaccttat tataatccta atgctacaga 46020
tgacctcagg gtagcccctc tccctcctag caaagtcatt attatcctct tttaaagatg 46080
aagcaaacca gtgcagtggc tctcgcctgt ataatcccag cactttggga ggctgaggtg 46140
ggccaattgc ttgagcccag gagttcgaga ccagcctggg caacacagtg agaccaagtc 46200
tctacaaaaa atacaaaaat tagccgggca tggtggtgca cacctgtggt ctcagctatg 46260
taggaagttg aggtaggagg atcacctgag cctggggagg ttgaggctgc agcaagccat 46320
gatcgtgcca ctgcactcca gcctgggtga cagagtgaga ccctgtctca aaaaaataaa 46380
caaacaaata aacatgaagc cgtcgaggtc cccagcagtt aagtaaattg ccactggcca 46440
gctagtatgg tggaaatgga atccaggcat ctggtcctcc attctggcac ttttccaaac 46500
ttttgtaggg ggctttatag aaacgctgaa gggcaaatgg tgtgcagggg aatgagggtt 46560
tagtgagtag gagttccaaa tttagaaacc tcactctctg tatcttttag atatacaaat 46620
atttaccata tattacagtt gcctctagtg ttcagtacag taacatgctg cacaggctca 46680
tagcctagga gcaataggct agaccacata gcttatagct taggtgtgtc aaaggctcta 46740
ccatctaggt tttttgtttt gttttgtttt gttttgtttt tgagacggag tctccctctg 46800
ttgcccagga tggagtgcag tggcacgatc tgggctcact gcaacctcca ccaccaaggc 46860
tcaagtgatt ctcctgcctc agcctcccga gtagctggga ttacaggcgt gagccaccac 46920
gcccagctaa tttttttgta tttttagtag acgaggggtt tcaccatgtt ggccaggctg 46980
gtttcaaact cctgacctca agtgatccac cctcctcggc ctcccaaagt gctgggatta 47040
caagcccatc taggtttgtg taggtacact ctatgatgct tacacaataa aatcaccaaa 47100
tcacacactt atcaaaatgt atctccacca ttaagctatg cctgactgtg tatcaaaatg 47160
gaagaagaag ctgggcacag tggctcacgc ctgtaatccc agcactttga gaggccaagg 47220
cgggtggatc acaaggtcag gatttccagt ccaagcctgg ttaacacggt gaagccccgt 47280
ctctattaaa aatacaaaaa ttagccaggc atggtggcag gcacctgtaa tcccagctac 47340
tcaggagtct gaggcaggag aatcacttga acccaggagg cagaggtttc agtgagccaa 47400
gatcacacca ctgcactccg gcctgggcaa cagagtaaaa cctcgtcaaa aagaaaaaat 47460
aataaaaata aaaaaaaatg gaacaagata ctcagggatg tatatttaat tttttaaaaa 47520
atattctgct ctcattttaa tatggcagaa ccgattgctt tctaagtgtg gcttttttcc 47580
agtaaaggtt aattattaag accactagtc ctggcctggg tcaatcccag tatgatcctg 47640
ggcaagtaaa ttaaagaaga taacttctct gtgcctcagt ttttttttgt tttgtttttt 47700
gttttttcat ttacaaaatg gagataattg tagtaaatca aatttttaga ggtgataggt 47760
ttgttcattt cttgaatgcg gtgatggtct cccaagtcac acatatgtaa aaacccatca 47820
ctttaaagat atgcagtacg ttgtatgaca agaaattgct tttaaaagga gcaaactacc 47880
ttccagggtt gttgtgaggc ataaatggca atccacagca ccacagcaag gattatcatg 47940
tgccctccag agacatactc tcaggtggat gcgagaaata tccagctgtt gcagcaactt 48000
catcccactc gaaatccagc tgagtcacac tcacaggtgg aatggagggc ttcgagaggc 48060
catggggcaa ggtgaccctt ccttatcatc taattacaga ccttctcaag gtctgttcac 48120
tgaacacttc gctgtagtgt tcacttaggt gtaagtaggc tataggactg gacatttgga 48180
tatttcatca gttcaaatag tcctgggcgt gctttagttt ctcatgcttt tgagcagagt 48240
tttaaaataa gccccatttg cccctacaga tctcctgcct ggtacagaat atgtagtgag 48300
tgtctccagt gtctacgaac aacatgagag cacacctctt agaggaagac agaaaacagg 48360
tgagtggtgt tggcagtatg actatccagt agcttttgcc tatcaattct gtataacaaa 48420
tgaaatgcta cttctaaaaa tacatctcca ttttttgttg tcatggtgtg tgtacctttg 48480
tcatcacagt atgattttat cgctggtctc aaaaactaaa agatacctta ctcaacaatc 48540
acctagactt tcagtcacta acaaattaag aaatttgttg tctgtccttt taaaaaacat 48600
tttctaagaa gatctttgtt atttagattt agcagacatt ccttttcatt aggcagctct 48660
gtctaatggc tgacccaaca ctcattgtca tctatttgtc ttcctttact aagccagcaa 48720
gtttacattt tctttttact taataaaata tgcatttact agaaggaagt tgaattgaat 48780
ctcataaata ttacatactt aaatatgaat gcttttaatt ttttctttca aaaggtacac 48840
tttagtgtat tcattaattt atttatagtc cacttgcttc caaaaaggac ttatgatatc 48900
ttagtttggt ttcttattga aaagaactag taaatgctgt aactgaaaca gaaatttgct 48960
ggaagtccca gagactaagt gatttgaatt tgcaacaaac tctgaatttt tgtgcatttt 49020
tgaaaaatgc atttttcaaa actgtcaatt cacgaggaat tatcagcatt gtaatttgtc 49080
tgggataatg tctttagttt cagaaagttt tgtgtttggc atcattacca ctctgttgac 49140
atataaattt cctcttgagc ttaggaggct tctctgagag tcaaacattt actttgagag 49200
tgggcagatc ttgctttact tggaaggata cacttacagg atagaaacac agaatacttg 49260
aacactgaag aatttgaaaa tgtcaattct cagaagatct tgaacactta tctccaaatg 49320
tgacacagaa acttactgta ataaccccta aaatctgctt gaattactta gcacaagaaa 49380
aaaatgaatg cttgagctgg ctattttgaa ttgagtcaat ttaagatttt aaaattcata 49440
tgtagcttag aatcagtaca tcttactctt tggtttatgg caaatcatgg tattgatgag 49500
acaggaacga aatgttggat gtacgttaat ttcccctaca ccttcctcac ttcctaaact 49560
ggtggtgtct tttctttttt ttttctcttc ctcccccggg tgggaaaaac aggtcttgat 49620
tccccaactg gcattgactt ttctgatatt actgccaact cttttactgt gcactggatt 49680
gctcctcgag ccaccatcac tggctacagg atccgccatc atcccgagca cttcagtggg 49740
agacctcgag aagatcgggt gccccactct cggaattcca tcaccctcac caacctcact 49800
ccaggcacag agtatgtggt cagcatcgtt gctcttaatg gcagagagga aagtccctta 49860
ttgattggcc aacaatcaac aggtaacttt tcttgtctgc aaagaaactc agaagacttt 49920
cctacccagt tggtagattc tgtaaagtag cttgctgttg tctgtcatca gctctcaaaa 49980
aaaaaaaaaa aaaaaaaaaa aatagatcat tgtcatggta catggagagg gaagtgagaa 50040
aatgtggaga aacatcttcc ttagaatatg gtaaagaagc ccgggcgtgg tggcagtaaa 50100
gaagataatt tttttcctct caagaaattt ctcacctgat ttgggtattt atgcatttct 50160
aataacacaa gttttgttga aaatgtagaa aattggccgg acggggtggc tcacgtcagt 50220
aatctcagca ctttgggagg ccgaaatggg cagatcactt gaggtcagaa gttcaagacc 50280
agcctggcca acatagtgaa accccatctc tactaaatat acaaaaatta gcaaggtgtg 50340
gtggcatgca cctgtaatcc cagctactgg ggaggctgag gcaggagaat ctttgaacct 50400
gggaggcgaa ggttgcagtg agctgagatc aggccattgc actccaacct gggtgacaga 50460
gcaagaccct gtctcaaaaa aaaaaaaaaa aaaagggcca ggcgcaatgg ctcacgcttg 50520
taatcccagc actttgggag gccaaggcgg gtggatcacg aggtcaagag atcgagacca 50580
tcctggccaa catgatgaaa cctcgtctct actaaaaata caaaaattag ctgggcgtgg 50640
tggcatgcac ctgtagtccc agctactcag gaggctgagg caggagaatt gcttgaaccc 50700
aggaggcgga ggttgcagta agccaagatt gtgtcactgc actccagcct ggtgacagag 50760
ggagactctg tctcaaaaaa aaaaaaaaaa aaggtggaaa actgaacact gtttcaaagt 50820
acctttaaaa atataatttt agggtaatag tgtcattgtt cttagcagat agaggctgaa 50880
gtacttacgg gaacagtagc atcatgttat ctgtatttta gtctcaagtc gtcaagccag 50940
agacaaatac ctaagggaag ggtatatagg tgttcattgt attacttttt tttttttttt 51000
tttcttcctg aaatggagtc ttgctctgtc gcccaggctg gagtgcaatg gtgggatctt 51060
ggctcactgc aacctctgcc tcccaggctc gagcaattct cttgcctcag cctcccaagt 51120
agctgggact acaggtgccc gccaccacgc ccggctaatt tttgtatttt tagtagagat 51180
gggattttac catgttggcc aggctggttt tgaactcctg acctcaaatg atccacccgc 51240
ctcggcctcc caaagtgctg ggattacagg cgtgagccac cacgcccggc cttgtatcac 51300
tttttttttt tttttttttt ttaacttttc tgtagttttg aaatttttcc aaataaaatg 51360
ttgagggaaa aaaactcttc cccaaatttg aaataatcat tttatcacaa tttgaatggg 51420
ctctgtaacc ccttatcttg aattcgtcat aatataaaat tctgctaatt acacgtagta 51480
tttacatgat tgtatggaag aatcattaag acaattatct ggaaaatgaa caaacagtaa 51540
atctgaatat tgtttgaaaa ttacggatgt gaaaagtttc cctttttttt ctagtttctg 51600
atgttccgag ggacctggaa gttgttgctg cgacccccac cagcctactg atcagctggg 51660
atgctcctgc tgtcacagtg agatattaca ggatcactta cggagagaca ggtacagcag 51720
taaaatgcta ttttacactc tgattaaatc agattctgtt gtggataacc tgaaagccca 51780
acagtgaaca aagaattaaa gaaactttgg caagtccatt caacggagcc cttgtttttt 51840
ccaagaaaat acgtaagata tagatgatat aatttgttct aaaacccaaa taaaaagttg 51900
tttatatact acaactagag ggggaacggc agagctgagg aaataaaagg attgtaaatt 51960
cacaaacata ttatcagtgg tggaaataag tgatttttat tttttcttct ctttactttt 52020
ctgtattttc caaattttat ttaaaaggaa tgtattctgt taaaagtttt aaaaaggaca 52080
caatgcatgc aatcctgggt tgagggctta ccttctccca cttctaatgc tactctacta 52140
ctcagtgaca ttttaaagct gaaatgttaa aacagcgcta actgtaattt tctctcaatg 52200
tttatacact taccaaggtt tgctacatgc ataaataccc ctttctgttc aagatagcgc 52260
tctttaaaag ggaataagca agaagatgtg atttacatgc tgctataaat gtggtaattc 52320
aattaatcag taatacccaa gtagctctaa acccctcaca ctctgaacta accctttttc 52380
atacaggagg aaatagccct gtccaggagt tcactgtgcc tgggagcaag tctacagcta 52440
ccatcagcgg ccttaaacct ggagttgatt ataccatcac tgtgtatgct gtcactggcc 52500
gtggagacag ccccgcaagc agcaagccaa tttccattaa ttaccgaaca ggtacaaact 52560
tctactctgg ggtgacacca gcttttactt attcagatac tgttttgcaa tgttctccca 52620
aggtattttt ctaattgtag aatagatttt cctttttaat gagcaacaac ctgcagctag 52680
cacctgcagc gaacagagtt ttgagccaga taaagaagga agcaccccaa gggcaggaag 52740
ttcagtcagt tttgtcgata tattccgcat gtctgcaata cgacaggcat agagagtgtt 52800
cagtaagtat ttgtgggaaa agaatggatg agttgataaa gtaggaagag acacctgctt 52860
gtggaatgta gcttctttgt gaatgaagca accatctcaa aaataggaaa tggtattgag 52920
atgcctgccc catccctcta aaagctctct ctgtattctt tcgagaagaa atacctttct 52980
catgtaagcg atcattcgaa tatgtaccag acctagagag gaggacttgt ccaatcttgt 53040
ctccaaggac tggggcttca ctggtttctc cctgctttta tttgtagaaa ttgacaaacc 53100
atcccagatg caagtgaccg atgttcagga caacagcatt agtgtcaagt ggctgccttc 53160
aagttcccct gttactggtt acagagtaac caccactccc aaaaatggac caggaccaac 53220
aaaaactaaa actgcaggtc caggtaagaa tcatctgcat ctcggccagg tgcggtggct 53280
cactcctata atcccagaac tttgggaggc tgatgcgggc agatcacttg aggttaggag 53340
ttcgagacca gcctggccaa tatggcgaaa ccccgtctgt actaaaaaat acaaaaaaat 53400
tagctgggca tggtggcttg tgcctgtaat cccagctact caggaggctg aggcaggaga 53460
atggcttgaa gtctggaggc agaggttgca gtgagccaag atagccccac tgcactccag 53520
cctgggtgac agagtgagag actccatctc agggaaaaaa aaaaaaaaag agtaatctgc 53580
atctcatata caacaggata gatggggtag gaccacctaa tattcttttt tatataaatg 53640
gctaccttgt tgtgagtact atgtattttt ttgtcctatg tcatcattgt ccccattcat 53700
gagttcaggg ctcaagatca ttatcaaccc ttttcacagt agaagtctta agtgcatttc 53760
tgtttttaca tggatagttc tatttagtga tatggacatc ttaaattact agattcaccc 53820
ttctggtttt gtttatcatt cacactaaga agagataaat ggcctaactg actttttcag 53880
ctctttttag ctatgttgtc tttgttttta aatagaatac ttgtgaaatt aggatcttaa 53940
ggcaatttat tagagtcaag ttaattttca ttttttctga gagcagtatc actaattgtt 54000
gggggcatca tattaagttt tagatcttat ccttgagtgt gacttcactc ccatatggta 54060
atttgtatta gcaatgaaca ggtttgtcca agaggaaatc aaagtctgac tctccatatt 54120
tttgttacaa ttctgcaaat aaaaattcta ggccaccata tgtttactac caaactctag 54180
acgccacttg aggactttat agtggatgac gtggatgttg catttgcttt tcactccctt 54240
tgcagatcaa acagaaatga ctattgaagg cttgcagccc acagtggagt atgtggttag 54300
tgtctatgct cagaatccaa gcggagagag tcagcctctg gttcagactg cagtaaccag 54360
tacgtaacca ctgcttggtt tccattttca aagtcaaatt ttgttcttgg gtgtctgaat 54420
gcccacgaca tgtcttttgc aattacacat agggaaagtg aacttgttgg ttagtttatg 54480
tcttgagctg agccctttac gaacatcttt tttccttctc agtgccaagc gaggaattta 54540
cagagaaaga agttgtgaaa ccaccatagt tagttgctgt gctttgaatt tcttttgctc 54600
aaatggcctc agcgaaatct tatttgccta tagcaaatct acaaaaaatt ttcctagacc 54660
gtcttttcta caactggatg gtaaagttga ttgaagtgtg cctcatgtag ctttatgttt 54720
ggggcatttg aagggctatg gctggaccag agtgtaatat aaatgcttaa tagagagggg 54780
aaaagaagag tgtaagaacc attatagggc tgggctcacg cctgtaatcc cagcattttg 54840
ggaggctgag gcaggcggat cacgaggtca ggagttcgag accagcctga ccaacatggt 54900
gaaaccccat ctctactaaa aatacaaaaa ttagccagtc gcggtggcac gtgcctgtaa 54960
tcccagctac tcaggaggct gaggcagaag aatcacttgg acccaggagg cagaagttgc 55020
agtgagccaa gatcatgcct ctgcacccca gcctaggtga tagagtgaga ctccatctca 55080
aaaaaaaaca aaacaaaaca attataacaa tttgaatctg acattgcaaa tcagctttac 55140
cacttccaag gtatagaaaa tccaggtcta tgagactaac atcacattgt aaaaatcaaa 55200
tcgtggtaga atatctttaa attaatataa atacatcccc attgtgggga cattttgcag 55260
ggtatctgct tatctcacat acacctatgt tttaataagt gatgcaacat tgcatatttt 55320
ctaaaccaag aaaaattaag caagtgttta agtgattttt ccttttgata gtgggttaat 55380
tggacttcat caaagaaaat ggtatctgca aaactgcttt gcatgttata aaaatgctta 55440
tttcacaact tgcttttcac ataacctctt accattaatt tgcctaacag acattgatcg 55500
ccctaaagga ctggcattca ctgatgtgga tgtcgattcc atcaaaattg cttgggaaag 55560
cccacagggg caagtttcca ggtacagggt gacctactcg agccctgagg atggaatcca 55620
tgagctattc cctgcacctg atggtgaaga agacactgca gagctgcaag gcctcagacc 55680
gggttctgag tacacagtca gtgtggttgc cttgcacgat gatatggaga gccagcccct 55740
gattggaacc cagtccacag gtatatggtt aattgcacca ccaggtgccc atgggagcag 55800
cggctttatg ccctactgaa tgaattatgc ttcactgggc tattgattcc cgtgtaaggg 55860
tgaaaaagaa ttattaggaa agatcctctt taaagaggaa tggtaagaaa caataaaact 55920
taggtgatat ttaaggaaac aagtctgatt aaaagaaatt ttggagtatc ctggcttata 55980
cacaagacca taaagcaaga catttgaaga ggatactaaa gttgtggatt atttcctaag 56040
ctctgactcc ctgtgattac cctcactatg tataaagaaa agaagtttgg cattacagag 56100
cttacttata aaaaggaacc caaactcggg catttcatag cagcatgatt ctgagcacac 56160
gtgggtaaga cctttcttct ctggttagat atcatatgct ggtgtataat tagcttaaat 56220
gattgtgatt tagacaccta ggaaataatc aatagggcaa ttgctttcca taatacttta 56280
tcttcttgtg ctttatttct gaagcagagt agaatgctaa agatgtatcc tagtgacagc 56340
ataaacccta gaggtgacag tctgtattat tgcttttcgc ttctcttttc tgcttctgtt 56400
gggagccagt tttcttctta cgccgcatta cagagagaac gtcaaattta gcagccatat 56460
ctgccatagg gtccaaataa agagacaata aaaacattat tctctctttt ttggatggaa 56520
tactgcgtga aatggttatc catacaaaga tactttatgt agaatagaaa aaggaggccg 56580
ggtgcagtgg ctcacacatg taatcctagt gctttgggag gctaagccgg gagcactgat 56640
tgaggccagg agttcatgat cagcctgggc aatgaagtga gaccccgtct ctacaaaaaa 56700
atatgaaaaa attagcgagg tgtggtgaca catgcctgta gtcccagcta ctcaagaggc 56760
tgaggtagag gatcacttga gcctacgagt tcaaggctgc agtgagctat gataactcca 56820
ctgcactgcc gcctggatga cacagagaga ccgtttctaa attaattaat taacaatttt 56880
aagaaagaaa aagggccatt gcttattttt ccatacaaaa gtaaaataaa tcataatggc 56940
caataagcca atgtaacttt tttttttaag ggaaagcaaa acttgtaaaa cctaaaatct 57000
cttagagttt tggcatttac ccaaatgttt tcagtgattc tgagaattgg tggatataaa 57060
acacatttct cagcaaacac tttcttcatt ttgcatccct tactgtacgt actttcttgt 57120
actgaatctt tgcttgacca gggaacccac ctagcccaac aagaacaatc cattctactt 57180
cttggaactc actttatttt ccttttcccc catttcctat aagataacct ctaaccaatg 57240
acaatctcga cagctattcc tgcaccaact gacctgaagt tcactcaggt cacacccaca 57300
agcctgagcg cccagtggac accacccaat gttcagctca ctggatatcg agtgcgggtg 57360
acccccaagg agaagaccgg accaatgaaa gaaatcaacc ttgctcctga cagctcatcc 57420
gtggttgtat caggacttat ggtaagacat gaccgttgtt cattggaata aagatggaga 57480
tcatctctaa cacagtttct aaggtggtga aaatataata tcataataaa tctaactgtt 57540
cttttcctct gcatcaaata atcttattgt aattttatat caacggaatt cctttatgtt 57600
gacctaagtt ttccagatga ctattgggac agaattttat aaatagcttt ggattttgtg 57660
cagctctttt agatgtattg tgcttatttt aaaaggttgt ggggggcaat ttacatatcc 57720
attggttgaa tgcataaatc gacttagtta tgcattttct gagctctgtt accttggtaa 57780
agaatatttt acagtttgta ccagtctacc ttgagcctac cctcattaaa acattttaaa 57840
atccttccag acatacatgc agaaaactgc taggaaccta ggggactgat gtacctctta 57900
acataaggcc aatttcaggg gaaactacag aaagagggtt cagagacaaa atggaacatt 57960
ctctttgcct ctctatgata aggaaaaaat tatgatttac acctgtcaga tcataaaaaa 58020
gaaaaatacg ctaataccca cttttctcat tttttttacc agcttagttt aagtatataa 58080
tctatggctt acttaagctt aaccgctaag agcattttaa aattgataaa tacatttatc 58140
acctgcactg taggaatgaa attaatctag gaattttcaa ggttgtgggt tttgctggtt 58200
tgtttatttt ttattttcta accattgcat ttacctaatg ctgtagtgaa actccttggg 58260
tttcagttga ggacgttgct aaagctcacc atgcccttat ttctctaggt ggccaccaaa 58320
tatgaagtga gtgtctatgc tcttaaggac actttgacaa gcagaccagc tcagggagtt 58380
gtcaccactc tggagagtaa gtaacaaaat gtcttcatat ggacaaacct tctgtataga 58440
caaaaattaa agaatggtaa atcagtgggg ttcagtggct catgtctaaa atccaagcac 58500
tttgggaagc tgaggcggga gcgtcacttg aggccaggag tttgagacct acccgggcaa 58560
atagcaaggc cctgtctctt aaaaaaaata aaataaataa aataaataat tttttagatt 58620
tatatgttaa cagtggaatg agtcctaatt tgaaaatcaa tttgattgcc tttttgacgc 58680
atgactgtca tcttttatac tccttcagaa aggggtctac tgacccataa aatggaatca 58740
cttcataagc ttataatgtt gatattatgg actatgactg acatctagtt tatgctctac 58800
ttgttagaat ttgttttcat agagctaagc ttggggagac cccactggct tctgctatat 58860
cttaacaatg catattaggc cattcttgca ttactataaa gaaataccgg agactgggta 58920
atttctaaag aaaagaggct taattggccc acaggccagc aggctttaca ggaagcatgg 58980
tgctggtatc ttcttggctt ctagggaggc cttgggaagc ttactcatgg tggaaggcca 59040
agggggagca ggcacatcac atggctgtgg caaaagcaag accgagagag agagagagtt 59100
ggggggggag gaccttatac atttaaatga cccagtctct tgagaactca ctgtcataaa 59160
gagggcacca agccacaagg gatctgcccc catgatccaa acacctctca ccaggcccca 59220
cctccagcat tggagattac aactcaacag agatttggac agggacaaat atccaaatta 59280
tatcacagca cagtaaccat tggaccaaat caggcttaga ttctagtctt ctgttatatc 59340
aataccttga tgtatgcctt ttcaaaagtc aggtaaagtg tcaaagtttt atcatttata 59400
aaagagggat ggcattgtac ctgttgagag aaaatacaaa atacttgccg taatattaga 59460
cacacacaca cacacacaca cacacacact ctctctctct ctcacacaca catacacaca 59520
cacacacaca aaattgttag ctggccatgt tattgtaact cctaccacac atatttttac 59580
attataatac attaataatt ttaatattta ttgaagtatt tgtagatact ataaagccag 59640
ccctgggaac cactggtagt atctataaag cttttcagct cttcaaaata aaatgtctga 59700
gaggtagata ttttcctatt ttctaattac agttgacctt tctctctgaa tgccaaagga 59760
gataatctac acattactag ttatatattt cttgaaatgg atgaatttga tatataccaa 59820
ggaaacgttt taaaatacca aaactttaca tggatgagcc aagcaggcac taatctctag 59880
ctatgctcct gtgcagatgt cagcccacca agaagggctc gtgtgacaga tgctactgag 59940
accaccatca ccattagctg gagaaccaag actgagacga tcactggctt ccaagttgat 60000
gccgttccag ccaatggcca gactccaatc cagagaacca tcaagccaga tgtcagaagc 60060
tacaccatca caggtcaggg aactcattgc actaaccaca tttgttaaca aatacccaca 60120
atgtaaacgg gcttattaac tgttctacga ctgacactga taaaatttat tttcagtgtt 60180
atcatcataa cccagtttta gaacgttatt ttcatgctat gatcagaaat agttttgtcc 60240
tttgaatgcc tgattttgtg taatatttgt catggaaatt gcgtaagtgt caatcaacaa 60300
gtttgatctt ccatcattgt gccctttctt atttaaaaaa ttgtaacata aggtttaaaa 60360
ctaaaagaaa taaaaaacag tgatgtatag atcttagcat taaaaagcat agttaatata 60420
aaagtaaaca ataccactta ataaaggcca aaattgtaac cgaagaatat tcaatatctg 60480
aggtcttttt tagcttttta aaattgtgat tccaaggctc aactattgac catctgatta 60540
cggtaaagag aaaacctcaa taagtggctg acccccattc tgcaagaggg cctcttccaa 60600
catagcattt ttgcattcca gaatttactt taccagtgtc cttgtctgta tcagtgattc 60660
actttcgaga tatgtttctt gttaacagtt aacatccata gcatgctcta ctttactgtt 60720
caaatgtgga ccactttggt agtctatata aatatgggat gatagaagaa cccagaaaaa 60780
ttgcaggcta gcttgagaat tctcctagta aaaagcaaga actgttaaaa atcatctctt 60840
ctcaaatccc aggtttacaa ccaggcactg actacaagat ctacctgtac accttgaatg 60900
acaatgctcg gagctcccct gtggtcatcg acgcctccac tggtaactat accttctact 60960
gaggaaatgc cattgacttg tatgcaatca gtttcatgaa ctcaaaaaac aaatgtgagg 61020
cgtatatttt tgtattatag attccagaga atcttgtttc cggtttacag tattctcaga 61080
ttcttttaag tgtgtttaga acggctcggg agaaaagtgt gggagtaatt ttcttggtta 61140
tttgccttct tagagactta attttgtttt ctttcagcca ttgatgcacc atccaacctg 61200
cgtttcctgg ccaccacacc caattccttg ctggtatcat ggcagccgcc acgtgccagg 61260
attaccggct acatcatcaa gtatgagaag cctgggtctc ctcccagaga agtggtccct 61320
cggccccgcc ctggtgtcac agaggctact attactggta ttgctgcttc catgctgtca 61380
ttttccttct tactacctag gacacatgaa gtccttagca aactcccaca gcgtctttga 61440
tactgtgtca tgagaatgcg aaactctgtt cctgataacc tcaaaaagca ttctctgtgt 61500
aggagtggta gagcctaata catcccaaaa ggcatgagtg aaggaaaatg caatttcaag 61560
actgtactaa tggcatgact agactcatgt tttcctttcg ctgcaagttt gccagatacc 61620
tgtcaattca gtcctggaga aagatatttt tcaaagcata ctagctgatt gtgattctgt 61680
cattacactc agctctctat agatatggca atcttgcagg acttgccagt gcaccacctg 61740
ccattgacct tgttgaccac tatcacagga taggtcttga ggcagagcag tcccaaccac 61800
ccacattgga agaatgcctg gaatggggaa taagagttgt ctaccttggt gggaaagact 61860
ataagcctct agtattattt ttgcccaaga gatgaaatat ttaaactatc tgtattagtc 61920
tgttttcata ctgctataaa gaggtttaat tgactcacag ttccgcatgg ctggggaggc 61980
ctcagaaaat gtacaatcat ggtggaagga aaagcaggca tgtcttacat ggcagcagga 62040
gagagaagca cacaggagga acttccagat acttacaaaa ctatcagatc ttgtgagaac 62100
tcactatcat gagaacagcc tgggggaacc accccatgat ccaatcacct cctctcctca 62160
atacatgggg attacaattc cagatgagat ttggatgcag acacagagcc aaaccatatc 62220
agtctgtata gagtatcacc tggactttaa aattcccaca gaacatacag acattagaag 62280
gagacactgg ctttttagaa ttggggggaa caggaaaata gaagcagaca tgagaggaat 62340
tgaactagac acttcccaca gaggctgcac aaacactggc caatctctcc tacccttcac 62400
ttgcctttag tttcactttt cattgatctg ccactgagga ctgcttggtt attaggccta 62460
agtagattca tgtatataat ctgcaggact ctctttcaaa tttatattcc agtggtggta 62520
tatgatgctg atagattttc ttaaattcaa aaaggcaaat aagaccacgt taaaagaata 62580
ccctggaaag gccaggcgcg gtggctcacg cctgtaatcc cagcactttg ggaggccgag 62640
gcaggcagat cacaaggtca ggagatcgag accatcctgg ctaacacggt gaaaccccat 62700
ctctactaaa aatacaaaaa caaaattagc caggcgtggt gatgggtgcc tgtagtccca 62760
gctactcggg tggctgaggc aggagaatgg ctgaacctgg gaagcggagc ttgcagtgag 62820
ccgagatagc accactgcac tccagcctgg gtgacagagc cagactccat ctcaaaaaaa 62880
aaaaaaaaaa aaaaaaaaag aataccctgg aaaagttagc caaaaaatgt ctattcaggc 62940
gtcagatatg atagtaagat aattagtttg cgatgcggac tttatatgca ggatatttgg 63000
gtgtttatgg aggaaaagtg aagtcgattt taccttcaag aggccaacag ccagctggag 63060
aggaagtgcc tgctcccagt agcgtctgct ggtgagaccg acttccactt gactagctga 63120
gcccattgac ataatgtgat ggttctattc tcccttcagg cctggaaccg ggaaccgaat 63180
atacaattta tgtcattgcc ctgaagaata atcagaagag cgagcccctg attggaagga 63240
aaaagacagg taagagtatc ttgcaggtaa caaggagaaa gataggacaa aactaataac 63300
aaatgagcaa tcttgcaata tgaaaaggtt ctccatgttt tgatgcattt cttgtgattt 63360
tttttatcta acagcatagt gtatatattg tattctttaa taggagaaat aatttaacat 63420
gcactgcaga gtttggtttt attttttttc tttactacag ccactcaata taaagccttg 63480
ttattcacct tttaaaaatt caaacaagat gttaaaatgt aaaagaagag ctatcattgc 63540
tcttctttta taccttctgt tgaattttaa aatgtttcct tttttaaagg agggagagaa 63600
acctctcaca tttatcttta tttggtttct acaacttaga gctaaataat gtcttacttt 63660
tgcatccagt ttcagttaat ttcaagaaaa tgtgtattcc tgatatagga aaatttcaaa 63720
aatgaacatg tgtgttttat ctatttttac catttcaaac catgaaaaac tgttgagcca 63780
aacctctgta attctcatac ttatgacact gatatgatta gtctggattc tacttcctac 63840
aacttgcttc tcaaatttaa aaaagaaaga gagaaagaga aagactgcac atttcagttc 63900
cattaggtct aatttgagca gaggcagctt ctacggggct cagcggttta aagctgtgtg 63960
tatgataaat tcatactaac acttttttct ttctaaacta taaagaaacc tttgagaaaa 64020
atcctaaaga tttctttctg gaaaaagtgt tttgtgatct cagaactgct cattttctgg 64080
tggcttttat caaattgatg aacagtcatt gttgcctgaa tcgattatta tcattgctgc 64140
tacttcctgg agcttaatgc gctttgcttt tttggctcta acctctctcg gctagacgag 64200
cttccccaac tggtaaccct tccacacccc aatcttcatg gaccagagat cttggatgtt 64260
ccttccacag ttcaaaagac ccctttcgtc acccaccctg ggtatgacac tggaaatggt 64320
attcagcttc ctggcacttc tggtcagcaa cccagtgttg ggcaacaaat gatctttgag 64380
gaacatggtt ttaggcggac cacaccgccc acaacggcca cccccataag gcataggcca 64440
agaccatacc cgccgaatgt aggtgaggaa atccaaattg gtcacatccc cagggaagat 64500
gtagactatc acctgtaccc acacggtccg ggactcaatc caaatgcctc tacaggacaa 64560
gaagctctct ctcagacaac catctcatgg gccccattcc aggacacttc tgagtacatc 64620
atttcatgtc atcctgttgg cactgatgaa gaacccttac aggtaattaa ttgttctctt 64680
cacttctcat ggggcagcac agaaaggaat aagttaggta actgaagtga ccagccctcg 64740
aataaaaagt ggcttcatgg ccgggtgtga tggctcacgc ctgtaatccc agcactttgg 64800
gaggccgagg caggtggatc atttgaggtt aggagttcaa gaccagcctg gccaacatgg 64860
tgaaacctcg tctcttgaaa aaaaaaaaaa aaaaaaagtg gctccacttt tagaacctct 64920
tagaagatgg cacatttaag ccctgctttt tttttttttt aaatcccaat atggctctac 64980
tttggaggac ataccagaga gtcactagct tttatttcat agagaaaatg aaactatttc 65040
tcttattctc acacatttga ggttcctttt tgagtaagat agatgattct agaaaagaaa 65100
gatattctac ctgaatttcc atttgtgtgc agaagtctaa aacactacct ttacgatttg 65160
tccttgaaga accccactat ctacaacata tctaaagaaa aaaaaaaaca ggcgaagctg 65220
tgcatagcag ctgataagtg attgattctc taaaacgtat attatttaat ttgtgttgac 65280
agtatccatt tttttttttc cccgagatgg agtcttgctc tatggccctg gctggagtgc 65340
agtggcgtga tctcggctca ctgcaacctc tgcctcccag gttcaagcaa ttctcctgcc 65400
tcagcctccc aaatagctgg gattacaggc atgtgccacc gcacccagct aatttttgta 65460
tttttagtag agacggggtt tcacgatgtt ggccaggatg gtctcgatct cctgacctcg 65520
tgatccgccc gccttggcct cccaaagtgc tgggactaca agcatgagcc acccactaca 65580
cccggcccac tgacagtatc aatttttatt gtgttgttac ttttagaaag tggcagaatt 65640
taaaaactga caacactgta ggaaatttat gagcttagaa acatgagttt gaggatttgc 65700
ccaactgttt taaggactcc acactggggt cagatgtcac ctggaggagc atgaccgtgt 65760
ctcccatata gcgcagtgtc caggttttat gtgaagcaaa catggccagg gcttccagag 65820
ggcttatgca gacctgcgac tgaagcaaga tcaatggcag gccgtctcta gtattgtcga 65880
gggctcctgt taactacgga gcacgtaggt agattgttgg caggaaaatc tggcaggaac 65940
gatggcccct atccttgttc catttctctc ctcagctggt taggaccact ataccctccc 66000
tctttttttt ttttttgttt tttgtttttt gtcttccttt gctttgttta aacagtgagg 66060
gttattggta agaggagagc ccgtgtcatt cctcactata atgctttctc tctgctttgg 66120
atgtaccgat aattgcagtt cagggttcct ggaacttcta ccagtgccac tctgacaggc 66180
ctcaccagag gtgccaccta caacgtcata gtggaggcac tgaaagacca gcagaggcat 66240
aaggttcggg aagaggttgt taccgtgggc aactctggta tgtaaacacg tactatttag 66300
acacaggctc ccctctgctg tacaccagag atgggctttt ctgttgactg tacctttgtt 66360
gccattgtct ttttatcttt gggatttaat gcaacacatc aacatgaaat aaatgagcaa 66420
ctttatatta aattaatctc tcccccacct cctgccatat cctgttgtct tcacaaaatg 66480
catacgtaat tgacagactc tcaaatggtg atatgattat agatctggaa gggatttcaa 66540
atattattta gtacaacact ctgagtcctt acttctgagt atctgagttg atatagggca 66600
caggtttcct gatgtctttt cccagaccct ctccatctca ccatgctgct gtcctcttga 66660
gtgattaaat actgaaacga ttacctataa agaaaatacc ccttctgcag acatggggac 66720
agttggcttt tgctcctgat ataaaatgct accaacattg tgcatttctg tctgcagaga 66780
atgttattcc aatgttattt ccattttttt ccaatgttat ttccattttt ttttctgact 66840
atacaggtta aaagcttcta tagaggttaa aagatcatta actcttcttt gtagcacctg 66900
ggaaatcctt ttaaatcaat agcgtgccac ctggctgctc aatttgcagc agctgaaaat 66960
tcaccaaggc acatgagata ggggataatc aaaaccgtga atccccaatc ttccaacagg 67020
agagttctct actccacacc aacagagagt gctaagtcct gtctatgcca agtgacagat 67080
tttattccta aggccagttg tttaatttta gccccttccc tcatctgata gaagactgtg 67140
ctactttaca tgtataaatt cctgtgaatt aagcagttga gcatttggct ggagagaggt 67200
tgggaggaga ttattttgtg tttgttgtat tacatatcca cagtaatgct tatctttgcc 67260
ttttgtggtt ttactagtag aatgccacgt gaacagaatt ttcaagagca aaaaggtctt 67320
tgtgcttttc taagtcattt tttttttttt tttttaaaga ttccatctct ttaactttag 67380
ttaggatgga atttgaactc ctggctcttt tgagtataga aacccctagt aacaatttaa 67440
gttccttcca tttttctttt aaactcctta ttcccagcag cagtattcta cattctaacc 67500
aggttctccc agctttgaga cgtctcagac ttaccagttc tccaaaacgc tattttcttt 67560
aagggtgaca ccttttaaaa attaggcacc tcaaatatct actgcttttg agcttttgag 67620
ttttgcactg taaaaagaaa aatacacagt gggattttaa gtcaaattag tttatctaat 67680
ttttagggaa taatttgaag catgctttgt ttgcatagat ttttttaaaa taagcttttc 67740
caaatcataa agagataaga tcttaggtaa catgaagaga ctcccttact tattcctaaa 67800
tcatctatat tccaagggca ttttcttatt tggaacagtt gacctcactg ataaagctgt 67860
ctcaccacta taataacaat gtccaaaatc taggctttct gcactattat gcaaaaatta 67920
caataataaa agtgaaaatt acattataat ggtatattaa aatgctaaga cttttgcatt 67980
ataagcaaaa gacagccttt aataattatt ctttatttag tgaacatttt ctaagtcttg 68040
gaaaagggtc aatgttttga attcatggcc ttatataatc ttcacaagat tccccaggag 68100
gtatagatat ttttattatt acgctagtat tgcagatgag ggaagcaagg cagagtggta 68160
ttaaatagct ggcccaaggt cactcaggta ccaatggaga ggcatcatta gtctttgcat 68220
cccactaaag ttctccacta gcttcaattg cctcaagatc tgttccatgt tctatgaagt 68280
agtttcaaca gaaatggcaa ttatcttaga agcaagggaa aaataaaaga tgggcttcct 68340
gtcgggtgcc tgtgacaggt gtcacatcta accatggttt tttagagcag ttaatgcctt 68400
gatagaacag atgaatgcct cttaatcctc ctggaattct tgttttagat taagtcattg 68460
tatacagtca ttcgattttc ttcttatggt ccaaatcgat taataagatg tctctttttg 68520
ctttttcttc cttttcttca tagtcaacga aggcttgaac caacctacgg atgactcgtg 68580
ctttgacccc tacacagttt cccattatgc cgttggagat gagtgggaac gaatgtctga 68640
atcaggcttt aaactgttgt gccagtgctt aggctttgga agtggtcatt tcagatgtga 68700
ttcatctagt gagtagttgc tttgtccatc cacttccgtg tttgtctcct caagttccat 68760
gcatgcactc atgtgccaag gaagcatgtt tggaagacac aggttcttcc aaacatgaag 68820
caaacaagag aatactgttt gactcgaagt aatattttgc atcatagaaa aatgatggga 68880
aattttactt gttggacatt gcttcatttc aagggttgta tgccaataca actattaatt 68940
acacataaga ttatggtgct aatttgattt ttgaaatttt ctgtgaaaac aaatggataa 69000
agacttttgg aaccaggtct atttaagagt attagagaca cagaaaaacc tcaaatctct 69060
tttaatcttc agtgttgaat gagatcagag gtgaacattt agactcaaaa acagcctcct 69120
tcaacataaa ccaaacatgc acatatcata gtacccatgc acacactttt gcgtcacaca 69180
catagcccag gtagcttgaa cgttgctaga aatatgaaag aaaaaacaga taatctgctt 69240
ttagatcatt aaaaatcaac ttgaattgat aaatgtttga ttttcaaatt ctaatacgtt 69300
ttaattttca aattttttaa gttaaaatgt gcctaggaaa tatctattat gctttgagat 69360
taggattaga atttataaac ctttcattta ttctttgtgt ttaggagatg tgatgattat 69420
tgacaattgg ttcattttta taggtgttga ccgttatgcc tataaataag cctcctatag 69480
acatacagaa atcatatcct gtggaattag aatataagac ttggtaaaag agattttcaa 69540
agtattttac ttaacttgta tacttgaaat catttaatcc agactgaagt tgtaaaagcc 69600
agccagtgtt ttcaatatag acttccatgt ttgaccatct gaaaatgaaa aacactaaaa 69660
acatcacatg ctgtttagga gctggaaatt ttaatatttg acttcaagta gatggttttt 69720
aactcctgaa atcgaactac gtttaagttt gtatgtttat tacctgtttg agcacttagg 69780
tgcaattgtg ggagcgggga tgtcaagttc atttatgtga ctctttggct caacttacat 69840
aatctttgtt ttgatatcac agttgtctaa ttattttact ttgtagctta aggcaggctg 69900
aattgttgat aaaatggaaa aagtagtata ttgttatata agcttctgag gtgtgttttg 69960
ttgtataagc cctggaggtt aaaaagtcat cccttatgta tagtagttaa aggcataaaa 70020
ctgtgacttt tagatattcc acagaaccag acttatttga tgtggataat aaccaatgat 70080
ttagcatttt gtttgctttt gttttatttt atccgggttc attttttact cttcccatgt 70140
acatgaaaca ggtggtggcg tgtagagatc agctgatcct tgttttatgg ttaattgaac 70200
tactttgtat ccagggtttc tgcaaatcca aaagtgattt ttcatctagg atctattcct 70260
aacagtctac tccaatccca ctttagtttt ccacaatttt aaatcttaat agtgagaatt 70320
caaatgaaag tcatttcatt tgactattct gatgacatga ttgtggcaga ataaattggg 70380
tcttaaaatg ccctagaaaa tggtaaatga taaaaaataa tattttaaaa ttcaaccaaa 70440
gaaatggccc attggccagg tgtggtggct cacacctgta atcccagcac ttttggaggc 70500
tgaggcgggt ggatcacctg agctcacgag tttgagacca gcctacccaa catggtaaaa 70560
ccccatctct acaaaaaata caaaaaaaaa aaaaaaaaaa aaaatagcac tgtggggagt 70620
gcctgtaatc ccagctactc aggaggctga ggcaggataa ctgcatgaac ccaggagatg 70680
gaggttacag tgagccgaga ttgcaccact tcactccagt ctgggcgaca gagaaagact 70740
ttgtctcaaa aaaaaaaaaa aaaataaaaa gtaaataaat aaataaaata aatggcccat 70800
tataggggtt tttatcttta acttgctatt tttccagatc atggttctga agaccctgtg 70860
acacgtccca gttcacctac tgtcttgtga gtcagaatat acaaataact ttttggtcct 70920
gactttcccc acccctacag gatggtgcca tgacaatggt gtgaactaca agattggaga 70980
gaagtgggac cgtcagggag aaaatggcca gatgatgagc tgcacatgtc ttgggaacgg 71040
aaaaggagaa ttcaagtgtg accctcgtat gtcatcacag atcattttta gtgccttatt 71100
aagcattctc actttcatta tcaggctgta actctcattc acagaaatga ttggagactt 71160
taggtctcct tgaggagtga acagtgggtt tcttaatctt ttgatttggg aaagtggaga 71220
caagcttcaa aaatgagtca tgatttaatg ttattacagg acactttagc acttgtccaa 71280
cctgagtatt ttgaccatta tctgcagtaa aatgctacaa agaagcttta ttggtctgta 71340
gattcaactt ttaaaatatg atttccatct tcccgttgga ccctttccag tgtattaggt 71400
ctaatttttg gaagtgccac cctaagatct gtatagcagt actgctctta gggatgattc 71460
acataaatat gtggtgtttg cgctgtgatg atacaaattt aggacagaaa tagaacccac 71520
ccctagatca agtctgcagt attgttctca gcttatgcgt gcatctgtct tgtgtctata 71580
tgcagatgag gcaacgtgtt atgatgatgg gaagacatac cacgtaggag aacagtggca 71640
gaaggaatat ctcggtgcca tttgctcctg cacatgcttt ggaggccagc gggtaagact 71700
ggatgtgcca ggctccctac aagttagata agataaaggg tgggctcctg caaggatgtg 71760
tcgtacacac aggaggggca gagacccttc ggaagtatta aaataccaca tttcctgttg 71820
gcatacaact gctgacatag agctctagag cagctctatg tctaccttac atgccattca 71880
ttctttctat tactcttagt agaaagaatg aatgaatggc atgtagagta ccaaaaacac 71940
aagtcttgag tcattcttaa tagcaacacc tgtcatttat atgatgttag aatcattttc 72000
ctaagctccc tagcatgtca gagatactat ttacactgaa aaatagtgaa gcagagatac 72060
tattcaaatt aattagtggt aaatagaatg tgtttcattt cagccggttc tccccatcct 72120
gggcagcctg agaccctccc ctcccctact attctcaggc tgcttctatt tttcagcaaa 72180
gtgttaagtg cagtgtagct ctaggcctcc aactccattc tgatggacag gtgtcccatg 72240
gcaacgttgt taaatatttt gaataatatc tcagatgtaa gaaaatgcca cttcttttaa 72300
cctctctctt gattcagaac agatgcttgt tataggtcta gcactgtgct aagtagtata 72360
ggaaaaacag aggaaatgag aaatggcttg gctcttaatg atatagttga agatgttaaa 72420
ttagcataca tttcaaagtc aagctaatta agttctaagt gggtctgaca aatacagttc 72480
tgggtaggct ggaattagca agaaagagaa gcatgaactg gctgaggttt acgatgacta 72540
aggtttagtt gggaggggag aaagcagaga gacacacccc ctgggataga aaggagctgg 72600
cccaggtggg ctttggtgag ccaaccctct gcctgctgtc ttctggtaag aaaatagatg 72660
ggaagaagtg gcttatggag ggccttggca acccattatt taagccagta cttctcaacc 72720
atttctaaaa tatgcccagt ataacaaaaa ataataagcc tttctctaat atgatttcaa 72780
atttcaaaat gaaattatgt gtaactcaaa agcaatggaa tgtgacagcc ctttgttttc 72840
aacgaagaca tgccctccca gcaactcccc aaatcctggt gggtgagggg catgcttcac 72900
actcaagggt gagactcatt ggttaatgcc aaatgcatta accaattaca ggtatccaag 72960
atgcaaagaa acatgatgga aaatagtctt tgggaaaatt aatctggcag caggggtgtt 73020
caggggcctg tcttggctcc accaggggca gcccatggaa actactatga tcttgtttca 73080
cccccagtga ttacatgggg agggaggtgc tcccaattct gatggaggag aattggagat 73140
tggaatttag attgaattca gtatctctct ctgtctctct ctctctctct ctcccattaa 73200
cacttacaac gactgtgatt gtatgacctt agaactcagt cattctggta tgaaattgtg 73260
tgatggagaa tgaatttgct gggaagttga ttttggtctc acttcagcat cttctcatta 73320
tttatgcaca tgaaaccttt catgtgcgac acttattcta ttctcaagtg ctaaatgaaa 73380
catttaagac aggagtggaa actgttcact ttctcatatg aaagcaagat tcagtgattc 73440
tgtaaggagg tagtcactgg tattgtgtta ggtattaagg ggcatatgtg cttaaacaga 73500
gaaatatgtc taaaatattt aaattctaat ataaaaaaga aagtgactgt attatttagg 73560
gctgcatttt agttgtaaga aaaaagtcca actcaagcaa aaatggccca cacaatggaa 73620
cagtcccagg acccaccggc ttcaggggct gctccagcaa tggcgcccgg actccctctt 73680
gctccgcgtg ccttcccatg cactggcttc gtgcttcagc ggggtctctg ctgatggtgc 73740
cattgatgac tgacctccat gagcttgctt taccccctgc cagcttaaga acagtagtga 73800
aagagaacat gtgtgtcctc ccatttccag taaaaacttc aggcaggagc ctcactggct 73860
cagcttggtc ccgtttccat ctcccatgcc atctccggcc aggtgacagg ctaccatgtc 73920
actgcctagg gaagtttagg aagagagtgg caaagtggtg cattagaaag aacatggcca 73980
ggtcacccca cctcctgggc ggcaggccca actccaccag tggtccactg tgtgacttcc 74040
ctgctccctc taagcaagtc actcctctcc tctgggtctc tgtttcctta cctataaaat 74100
gagaacgttt cttcatgtga tctcaagtcc cttttaaaat cgctaggatt ctttgaaaac 74160
cttttctatc atctagtgca gagaacttgt tgaggaagtt gggattggaa tgagcctcag 74220
cagatgggca aggtttgaat aggaagagaa gagacatttc aggagaaaga aacaacatag 74280
agagacagat gtaggtataa gatatggtaa taagccaaaa tgtattaaga gttataaatg 74340
catgaaatca tcatcaaagc ttgcttagtg attaactgct tatattttgc cagtgcatat 74400
gatgtgacat ttttctttaa ctcaaacact aaattacgat gtcctcaggt tatcataaac 74460
cccatttgac ttcatgcctc tactctctca gggctggcgc tgtgacaact gccgcagacc 74520
tgggggtgaa cccagtcccg aaggcactac tggccagtcc tacaaccagt attctcagag 74580
ataccatcag agaacaaaca ctgtaagtgc attagcagca caagtgtgtt ccctcatact 74640
agacagtctc tttctacagg tatctttctt cagaatgaac caagtgtttt aattaattaa 74700
aaaaaaaaac aactcataaa tgacttaagt gaaacactgt attccataat atagtttaag 74760
ttataattta tgtaactctt gaacatctcc tattgcccag tatgctgcta ggttcttgaa 74820
actaggaaga aatattatcc tatctataag cagctgtcat gagtccccac ctccccgcat 74880
ttttttttct gtacacttta cagtatttgc cactaatttt tttttccttc ttccttttta 74940
acagaatgtt aattgcccaa ttgagtgctt catgccttta gatgtacagg ctgacagaga 75000
agattcccga gagtaaatca tctttccaat ccagaggaac aagcatgtct ctctgccaag 75060
atccatctaa actggagtga tgttagcaga cccagcttag agttcttctt tctttcttaa 75120
gccctttgct ctggaggaag ttctccagct tcagctcaac tcacagcttc tccaagcatc 75180
accctgggag tttcctgagg gttttctcat aaatgagggc tgcacattgc ctgttctgct 75240
tcgaagtatt caataccgct cagtatttta aatgaagtga ttctaagatt tggtttggga 75300
tcaataggaa agcatatgca gccaaccaag atgcaaatgt tttgaaatga tatgaccaaa 75360
attttaagta ggaaagtcac ccaaacactt ctgctttcac ttaagtgtct ggcccgcaat 75420
actgtaggaa caagcatgat cttgttactg tgatatttta aatatccaca gtactcactt 75480
tttccaaatg atcctagtaa ttgcctagaa atatctttct cttacctgtt atttatcaat 75540
ttttcccagt atttttatac ggaaaaaatt gtattgaaaa cacttagtat gcagttgata 75600
agaggaattt ggtataatta tggtgggtga ttatttttta tactgtatgt gccaaagctt 75660
tactactgtg gaaagacaac tgttttaata aaagatttac attccacaac ttgaagttca 75720
tctatttgat ataagacacc ttcgggggaa ataattcctg tgaatattct ttttcaattc 75780
agcaaacatt tgaaaatcta tgatgtgcaa gtctaattgt tgatttcagt acaagatttt 75840
ctaaatcagt tgctacaaaa actgattggt ttttgtcact tcatctcttc actaatggag 75900
atagctttac actttctgct ttaatagatt taagtggacc ccaatattta ttaaaattgc 75960
tagtttaccg ttcagaagta taatagaaat aatctttagt tgctcttttc taaccattgt 76020
aattcttccc ttcttccctc cacctttcct tcattgaata aacctctgtt caaagagatt 76080
gcctgcaagg gaaataaaaa tgactaagat attaaaagta tttgaatagt ataatatgga 76140
ggagttttat cttagggaaa ccccatggta tgataacccc catctaacat gtcttacttt 76200
gggtcagc 76208
<210> SEQ ID NO 2
<211> LENGTH: 24
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Primer
<400> SEQUENCE: 2
ggagagagtc agcctctggt tcag 24
<210> SEQ ID NO 3
<211> LENGTH: 25
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Primer
<400> SEQUENCE: 3
tgtcaactgg gcgctcaggc ttgtg 25
<210> SEQ ID NO 4
<400> SEQUENCE: 4
000
<210> SEQ ID NO 5
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 5
gcaaattaat ggtaa 15
<210> SEQ ID NO 6
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 6
ttaggcaaat taatg 15
<210> SEQ ID NO 7
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 7
tctgttaggc aaatt 15
<210> SEQ ID NO 8
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 8
atgtctgtta ggcaa 15
<210> SEQ ID NO 9
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 9
tcaatgtctg ttagg 15
<210> SEQ ID NO 10
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 10
cgatcaatgt ctgtt 15
<210> SEQ ID NO 11
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 11
gggcgatcaa tgtct 15
<210> SEQ ID NO 12
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 12
tttagggcga tcaat 15
<210> SEQ ID NO 13
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 13
gtcctttagg gcgat 15
<210> SEQ ID NO 14
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 14
ccaatcaggg gctgg 15
<210> SEQ ID NO 15
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 15
ggttccaatc agggg 15
<210> SEQ ID NO 16
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 16
actgggttcc aatca 15
<210> SEQ ID NO 17
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 17
tggactgggt tccaa 15
<210> SEQ ID NO 18
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 18
ctgtggactg ggttc 15
<210> SEQ ID NO 19
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 19
tacctgtgga ctggg 15
<210> SEQ ID NO 20
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 20
atatacctgt ggact 15
<210> SEQ ID NO 21
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 21
aaccatatac ctgtg 15
<210> SEQ ID NO 22
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 22
aattaaccat atacc 15
<210> SEQ ID NO 23
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 23
gatcaatgtc tgttaggc 18
<210> SEQ ID NO 24
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 24
cctgtggact gggttcca 18
<210> SEQ ID NO 25
<211> LENGTH: 20
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 25
ccttccctga aggttcctcc 20
<210> SEQ ID NO 26
<211> LENGTH: 20
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Primer
<400> SEQUENCE: 26
gtaacccgtt gaaccccatt 20
<210> SEQ ID NO 27
<211> LENGTH: 20
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Primer
<400> SEQUENCE: 27
ccatccaatc ggtagtagcg 20
<210> SEQ ID NO 28
<400> SEQUENCE: 28
000
<210> SEQ ID NO 29
<211> LENGTH: 68651
<212> TYPE: DNA
<213> ORGANISM: Mus musculus
<220> FEATURE:
<221> NAME/KEY: misc_feature
<222> LOCATION: (45900)..(45900)
<223> OTHER INFORMATION: n is a, c, g, or t
<220> FEATURE:
<221> NAME/KEY: misc_feature
<222> LOCATION: (45905)..(45905)
<223> OTHER INFORMATION: n is a, c, g, or t
<400> SEQUENCE: 29
tttcccttcc cacaaaatac actctggtgt gcacagactt ttctcagagg tgacgcaatg 60
ttctcaaaca ccaccacagc caccaattta aaaaaaaaaa agttaagaga tgaggggggt 120
aagccttacc accccaggct tccttaggct ccagcccctc cctccctttc cttcgagtct 180
acatcacttt acagccgttt cccatcccta cccccaatcc tcctcccaaa agtttgacga 240
ccgcaaagga aaccagaaag gggaaaaaag ttctctagtc ccagacctgg cgggagatca 300
gcatctcttt tgttcggggc gaacccaccg taccccgtga cgtcacccgg actctgggcc 360
aataggcgcg cggtcggcgg cggctgcggc ggcaggaggg gcgggaggag tcggaccgga 420
ccctcctccc cggcgcgcag ggcctcgtgg ggggcgggaa ggtactgtcc catataagcc 480
tctgctcttg gggctcaacc gctcgcaccc gctgcgctgc acagggggag aaaaggagcc 540
cagggtgtga gccggacaac ttctggtcct ctccttccat ctccttaccg gcgtccccac 600
ctcaggactt ttcccgcagg ctgcgagggg acccacagtt cgtggccact tgcctcctgg 660
ggagggcgac tctcctccca tccactcaag atgctcaggg gtccgggacc cgggcggctg 720
ctgctgctgg cagtcctgtg cctggggacc tcggtgcgct gcaccgaagc cgggaagagc 780
aagaggcagg ctcagcaaat cgtgcagcct caatccccgg tggctgtcag tcagagcaag 840
cgtgagtacc gacagtctgg ttcaaaccgg ccggcggcag ggatgggttg gtcctcaagc 900
gcccgctcaa gttgtggcta aagtttttgc gcgcgtgcgt ggctgtgcga acgtgtgtga 960
gtgcgcgctt tatcgaggga aaccagctgt ggacacaaaa ggcttaggtc tgaacaggct 1020
ggttgctggt gaagtggagg tagggaccgt ctgttcttcc cctcaagtgc gctaacaaat 1080
tctacacctt cagttcgccc ttccaggaac caaaacgtgt gaaagagaaa agagacacga 1140
acttacaaat tttacatcag agattattgt ggttcccctg atccttattt tctttatcag 1200
caaatagctg gttaaatatt taacacgggg aggaggtgag actatctaaa taggtagttt 1260
cttaccaact tgaaagagat gttagttggc tcagtgcttt gggggggggg gggtagccta 1320
ggattctttc cccaagagca aggatagcca tttctcttcc agtttttcag agacacactc 1380
ttcctttatc ttgggctaga ggaaaattta aaagttctcc ctcctttttt tctttttctt 1440
ttcttttctt ttcttttctt ttttttttct tttttttttt tttttttttt ttttgccatg 1500
atctcacact gtagcctaag ctagcctggc attctcctgt gttgtccagg cttgtgtgtt 1560
caacttggga gcaattcttc tgcctcagtt tctacagagc tggggttatt ggcatagtca 1620
tcaagacacc caacttaagt tttctttctt gtctttttgt tgttgttgtt aagagtattg 1680
aagccctcag gatttaaaag taatttctat ttctggcctc tcagagtgtt tcaagtctgc 1740
tgaggtagtt cccctgccca taaggacatg acgtcattgt ataactttta cccaagttaa 1800
aagataagaa ggaaaaaacc cctaaacatc catctacata aacaatgctt aaatctttga 1860
ttagctagtt tccacatctg aactttagtg gaatattgct tttaagagtt tttttgtttg 1920
tgcaggctca ccaagtcagt tggcaaaatt cagtagtttt gtaggggaaa aaagagaggg 1980
agggatggaa ctgttaataa ctttccccat caattcttcg cagctggctg ttttgacaat 2040
gggaagcact atcagataaa tcagcagtgg gaacggacct acctaggcaa cgccctggtt 2100
tgtacctgct atggaggaag ccggggtttt aactgcgaga gcaagcctga gcgtaagtgg 2160
aaggcagtct gggccctggc agagatgatg ctctaagtaa aaccacattt gccttctcct 2220
cctccctgct ccagtcgctt gtaattccct cttattagac ttcttgcact ggcttttcac 2280
atgctcttac ctctaaaaca aatgtaatcc acacgagtct ccaaagccgc ctttttattc 2340
tcttggagct tttgattaga aaatgagagg ttttgcgtgt ctcccttcaa aaagaaaact 2400
tataaaagtt tgcttataaa agtttaattt attagaaagt gatctcggat cttttggctc 2460
ccaattatgg gccagaagtt gctttgaggc actgggttgt aaagtgattt gttagctgca 2520
gttccgtgaa aaaaacaaaa acaacaaccc actaccactt cggagactcc tgaagcccct 2580
tgatacgctt ccggtgagct acagcagtcc cttcagagag gctgctgagg gagggtacag 2640
gacaaatgtt tcagtggggc tgacaaaggc cagccactgc tgggaggccg gcaaccttca 2700
aactgtttgt gtcccttgtg acccttgaat tgatttccct ggtttgagac tggaatttgg 2760
aatctttcct ctgcaactca gctggtcaca gggtgtggct ttttcctggg aactctttac 2820
attataaata agggaaccgc tgagagctgg ccaaaggtca agagctctgg ttttattaaa 2880
gcctaactta aaaacttgtc tctcttaagt ttcagagtcg ccatgtatgt gtgtgagact 2940
cacatggact tttttttttt cccctttcca cagctgaaga gacttgcttt gacaaataca 3000
ctgggaacac ttacaaagtg ggtgacactt atgagcgccc taaagattcc atgatctggg 3060
actgtacctg catcggggct gggagaggca ggatcagctg taccattgca agtaagagag 3120
gccttctgtg gagttattga ggtcacatat acacacttcc ctctggcctg tccttgcctt 3180
ttcctgttat ccctgactga atagtgaata ctttttactt caatgaccaa accccatgtc 3240
gtcacccacc tagctcctct acatctggaa gatggatcta agcagagatg gaatctctct 3300
gtctctctct ctgtatgtgt gtgtgtgtgt gtgtgtgtgt gtggacagtg gaagatctct 3360
tggttctttt caataagata tgcccaaggg acctacctat tttaaattat ctgggcctct 3420
ttaagccaga ttgatcattt tatcctctgc agctatgagc cagaagggtt tttgctcttt 3480
gtcatggagt ctggttcttt gtgatgagta gattagattt ggggagaaaa ccttgcggtt 3540
ctcaaattca acacaggctg atgagcacag tgcatctcca aggaacttta ggtcctgggc 3600
tttctctcag gaagtctaca gctgcggcag tctttctcgt gtgactcatt gggttgccag 3660
tacgttctat taataagact ttctctctaa aaaccaactt ttaaatataa gtcctctgtc 3720
caaaagaacc aattagtccc ttctgaatag accaaatcaa tatttccaac atttaacatg 3780
agggtttttt ccaagtttcc tggcaaagcc caagagtcga tggtacactt gtgaccctgc 3840
gtacaattca gccattggat ttcacagcct aagaaagtat cagggtttcc aaccctcatg 3900
agtgtgtctg cttgctttct gccagagtgc tatttccacc ctggagtaga atgcaggctc 3960
tccgtcctcc aggagatcgg aatgctatgc ccaagtagct caccttgctg tctaggagga 4020
cagttccccc agctcttctc tgtctaggga acagattgcc tgtgatgtct ccggggaacc 4080
acaatttatg acttcttgcc attcagagtt ctccatggct ttcctttttg tgctttaacg 4140
attgacccaa agtgggctga tatggtgtta gccttctttc tgcttttttt tttttttttg 4200
gcaggagagc tgcctgccaa aaaaatccct caggattagg gattgcattt tggccaacat 4260
acatacttat ttatctcagg cagaacatga gatgagcacc ccctgaattc tctcaatccc 4320
ctaacgtttg cctttgatct gtaacagatc gctgccatga agggggtcag tcctacaaga 4380
ttggcgacaa gtggaggagg ccacatgaga ctggtggcta catgttagag tgtctgtgtc 4440
tgggaaatgg aaaaggggaa tggacctgca aacctatagg taagtggctc gtgtgtgtga 4500
tcgaggggaa cggagccaca agcagatagc ctaagcaaac cagtggccgg gatagctgaa 4560
tcacagcata aaaaccagtg aaatgtgctg cgagtcacca gccttaagga aatcagatcc 4620
tgaactatgg aacataaagg aatcttaatt ttgtttgaaa agcacaaggt ggagttaaaa 4680
tctttaggaa gaagtgattt cttttgttta tatactatgc tgtccccttg gtgaagaaga 4740
catgttattt aaaggaggaa aaattacact attgacacat ttcttgttgg aacacagttt 4800
gttaaagcac aaaatgccac gtggctccgg tcacaccttg gcaatttcct taaaaacaaa 4860
cattaaaggt tgtgggggat ttttgttggt ttgttttatt tattttttct gtttttttgt 4920
cttagccttg gttgtactct gaagcccaaa gttttgggtt ctctttctta gatctccaag 4980
tcagacgtgt gttttttcaa atttgttttg tttttgtttt ttacattagt ctaaaattta 5040
aagagcgctc ctctcattct ttgtaagtcg ttcatatttt atagtggttt agtttaggga 5100
cacacagatc agtggtagag agcacttgct gaggctaaca taaggttctg ggttcaattc 5160
ccaggactga attaatgagt taaaagagaa aggttgggat tttgcatagg gtcgtctccc 5220
acagggtaaa gacttgcatt tctttccact tgaaatgtta gtgggaagct tgggacaggc 5280
agaaaaatcc ggtctgtgta ctcattagga caacagaatt tacttgcagc aaggctgggg 5340
cttcctcttg ctccggcttc ttgctccgtg cttagctgca gggcgtgcct gctcatctga 5400
acagagtgcc actttaagaa atgtggctgg ggttttgatt ccatgctaca ctgtaaatta 5460
tagggagacg ctatcatttt aaatcgctct tcctcctttc tttttgcttt cccatttctt 5520
ctccagctga gaagtgtttt gatcatgctg ctgggacgtc ctacgtcgtg ggggagacct 5580
gggaaaagcc ctaccaaggc tggatgatgg tggactgtac ttgtctaggc gaaggcaatg 5640
gacgcatcac ctgtacctcc agaagtaggt ttagctcttt tctgttgaca atgcagccca 5700
ctgttgcttc tggatcccta gagagagttg tgatgccttg gtgactctgt ggtatcataa 5760
gatgtccaga aaaactgtat aaccatcacc ttctgcttct tcagaggaca ctcaataact 5820
aggaaaggca gttctcagtt caaccctgcc ttaggcagtc agctagtaaa aatgaaaaga 5880
gccttagtgg tattcgcttg ctggatgggt cttccttgat ctgggaatta tctcagagat 5940
acctttctgg taccgaggac aattaaatcc ctaaagtagc atgtaaatga atcctttgac 6000
ctgggggagc gattggaaat aaaaggctct accccatgtt cggatttcct tctatgtttg 6060
aagtttaaat aaggtttact gactctaaac aagaacctag tggaaatgag tccgtgccca 6120
gtattatcct tcaaatagga aagtggaatg aatttctgtg tgttgtttgt tcatcgattg 6180
ggcagagaga ctgttaaatt ataacccatc cttgctctta cgctacaatg tgggcagtaa 6240
gggtctaact ttgtgactta aatattgctg catttgcagt gtcaggaaaa aaaaatcaac 6300
cattgattca ggcaaatgca tagacacaca agaacagagg tccaagaccc cagctaacag 6360
tgttgtcaaa cctgaacctg ttttcagtat ctttgaatca gtatctcttg aaactcctaa 6420
tgctgagctt tgtaagtgat taatacatga gccttcctca tctttgacct actaagtgtt 6480
ctctgaaggc tgatgcccag ttcgtatttc cctccccata ttgccacata caaagtaagt 6540
acttataaaa ttttgttgat cacatgctat ttgtttgaga aactttgcat gctgtcagaa 6600
gggttttaaa tgataggtaa gagtctgaat tagatttctt tctacatgtg tttattttgt 6660
gtgtggaggt gggaggcaca cacgccacag tgtgcatgtg gagggcaaag gacagtttgg 6720
accgcgcagg gtgcagtgac ctcaggttgt caggtttggt ggcaaggttc tttactcact 6780
aagccagctc agtggctcag aattagatgt ctaatttgtc ttcaatgaaa atactgccac 6840
aaacgacttg gaagactgaa gctcatcaca gttttaaatc aaaagatcta aggatcctat 6900
aagtttgggg gaaacatttg atctttttcc atgacttatt tttgtgtggc aaagaatttg 6960
aacttgggtg gtatttttaa ttactagttt aagctggata aacaaaacac attcaagata 7020
tctagatttg actttttttt tttttgcatg cgttttaaaa ttcatgcttc agcaaattcc 7080
aaggctgttg ttagtttgaa attctaaatg gaactttgaa ggcagaagca gcaattaaga 7140
cttcaagaca atcttagaag cgggagggaa gaaggatgcc tggggccagc tttttacaag 7200
gataataaga gacagcatcc ttaactccag aagagacctt ttaaccgtgg gataagccat 7260
tttgtcgttg ctattggtta ttgtcactgt tattattaca attactatta tacagggagg 7320
attctcataa gcccaggctg gcctagaact tactgtgttg ctgagagaga ccttgggctc 7380
ttaacactcc tgctcctacc tcccagacgc tggggttaac cacgtgggtg actttgtaat 7440
tgtaaaacag gtggttttgg gtggggcaag aaaagagaac cttctagcca gagaagttgt 7500
ttttccacag gaatactttt acataacaag tggagagatt ggtgtggtta actttttagc 7560
ttccctgggg cagtcggaag agacctgcct ccttattgtt tattgaaagg agggccatgg 7620
gctgtaatta cagaaaaagg tctggaagac actgaggagt aaagagtaga ttgccagata 7680
attaattgag tcaaagaacc aatgtagaaa atcttaattt tttttaatca ataaaagaca 7740
ctgaatagta ttttttcttt ttttcctttg gcaaatggag aggtagggct gtactgtaac 7800
gaaccgggta tctgaatttt aatatatgca tcaccagcac tgggtaggat gtactaacac 7860
caacaacagc cactcagaag cattcaactg cagcattccc atcttagtgt ggatggctgc 7920
gtgtcggtta ctagataact tctatattca atgcttctct cctgaaacag acagatgcaa 7980
cgatcaggac acccggacat cctataggat tggagacacg tggagcaaga aggacaaccg 8040
aggaaacctg cttcagtgtg tctgcacagg caatggcaga ggggagtgga agtgtgagcg 8100
acatgctcta caaagtgctt cagccggtga ggcgctggga ccggggacag ctccacgcca 8160
gggtgattta tagcgtttca gctaagaagc tggaatcgtt cacataactg tttaaaaata 8220
ttcattctat attgtgaaca aagttgagtg gaatgaagtt gagacgtgcc tttagcacag 8280
agggctgggt tggaaagcat agtgtactct ggtcatggct ctattagtat aggctttggc 8340
ttatgagcat gagactcaga gttcagtcta gaaccaaagt aaatatccaa gtgtgatggt 8400
gttatcccag caccaagaag gtggaggcag gaggatacct ggggattaca gaccagccag 8460
cttacactac tttggaagtg tgggggtggt tccaggttag tgagatggtg tggctggcca 8520
gcccactttt cttgggggag ttgggggaag ttgtgttcta ggtttgtgaa agatggtgtc 8580
atagaaaaca agatggctct gggcataatc cctgccttct acatgcacaa gctctccaca 8640
cgcatgcgca catagataat gtgcatgcac cctccctcac atggacaagc aatagtgagt 8700
gaatgtgtgg tatgtacttg gaatcctcaa gccctgggtt cagttcccag caccctccca 8760
aaacacccca ataattatta tataaattta aaagaataac taaaacaaag aaaggtattt 8820
gtatgtatct tggatgcttg gtcagagtct gaggaagggg tcggagcact tgccaaccat 8880
gcgcaaagcc ctggttctgg ttccccatca ctaaataaaa ggagggtgtg ttgtgcctgc 8940
gattccaggg atcaggaagt agagggacgg aggatcagaa gtccagagtc agccttggct 9000
acgtagtgag ttctagtcaa acctgctcaa tgtggctcag tgggtaagag cacccaactg 9060
ctcttccgaa ggtccagagt tcaaatccca gcaaccacat ggtggctcac aaccacccgt 9120
aacgagatct gacgccctct tctggtgtgt ctgaagacag ctatggtgta cttacatgta 9180
ataaataaat aaatctttaa aaaaaaataa aaaaaaaaaa agatgctgtc tctcatgcac 9240
acacacatcg gaagaaggaa gtgcagctct tgtgggtggt accttcccgc tattgcgctc 9300
tgggtttcca tctagctttt actgtgtgat agtccagcct tgttacttag cctcttagca 9360
gtcagtcatt caggcaatag taattagatt tttttcccct tttgacgagt ttatctggac 9420
ctaattaatc cttgtgaaag caaacaaggt tacatttgat gatctctaca ttatccaatt 9480
atcatcgata aaaacagcta ttggccataa ggcagaggaa gaacagttac gaatgtcagt 9540
cgactgaact acatgaagga ttaactgagc taactgggat taaacaatac gtgttaacta 9600
tttttatggc atcactaata taccgaggtg tttcactatt aaagggtttg agaaacactg 9660
ttaaacgaaa caacctcttc taggagggcc ttgccgtcct tctgtatggt gggccttgac 9720
accattggcg tcctctgtct gagttctctt tgggtatttg tgctcgtcag cgctggggga 9780
agaggctaga ttcattctag aagctcttcc gctgccatac ggactctgac cttcaaaagc 9840
cagatttcta aaagagaagc tagcacaatc tgttgtgtta actatccgag gaaacttgtg 9900
aggattggtt gcttctagga aaacaaacag acatcctaag gaattctgct gagcaccgac 9960
acccaggaag agggataact taggaaatcc gtagctctcc agggtgtcct cctgagagcc 10020
aagttttaga gaaggcagga tatcccctgt gggtcttcag gggtctctca ggaagaggaa 10080
aggccacaca cagagcatat gagagctatg agggaagaca ggcaaggcag accatttcag 10140
atgagtgggg agccataggg agaaggcagg agcatggtac ccaggaatga tgagcagctc 10200
agtgggttga agcttagaac agggcaggga aggctagcag ccaggcggga ggggagagtg 10260
gtagaggggt gtggagctca cagatggatc gcttcctagc gtgactgaag gtttgtgaaa 10320
gataacctgt tgtgttgtgc ggcaggataa tgttgtcgct tagatgtgct gttcaggtgt 10380
ggctccgatg aggattatat gaggagtctt gtgaaccact tcttgggctg agtgcggaag 10440
ttccgggtca agccaagaag actctggact cattgacttc tcccttccag ttttataact 10500
ttttcattct cctgccctta ggatctggct ccttcactga tgtccgaaca gctatttacc 10560
aaccgcagac tcacccccag cccgctccct acggccactg tgtcaccgac agtggtgtgg 10620
tctactctgt gggaatgcag tggctgaagt cgcaaggaaa caagcaaatg ctgtgcacgt 10680
gcctgggcaa tggcgtcagc tgccaggaga caggtaggca ccatctgccc acggatgcca 10740
gaggacctac attcagtgtc tgcagtatct tagctgttcg taaaaaaaaa tgtaaaacca 10800
taaatccaga aaagtttata atcctgtgat aaaaatcata gtagctgaca ttttcttctc 10860
tggtcttttt tttttttttt ggttttttga gacagggttt ctctgtgtat ccctggctgt 10920
ggccttgaac tcagaaatcc ccctgcctct gcttcctgaa tgctgggatt aaaggcgtgt 10980
gccaccacgc ccggctcttc tctagtatta taacttgtat attttcttcc tatcatgagg 11040
atcaaactgc tttgtagtat ctgtatttgc cgaaagggat gctgcaagaa caccattttt 11100
ttcctgtttg tttttgtttt ttctcaacta gccaataatc tgtactctga gttcaatttg 11160
gaattataga tgtcttttag cagcacatgg cctcttctgg gtcaaacatg ctctctttta 11220
taattgtttt tctagagcag ccatatatac tgtttcttct gagaatgtaa gcaagcatgt 11280
atcgctctgt gccgtcttca aatcataata atttgtatta ataaagcttt acaagtgggg 11340
aaactgagtc acggtagcag aagtgtctcc caaagacatt aaaaggagaa ctctggctca 11400
cccttaacca gctgactaga cttttcatct tggcccttta gtagcacagt ttccatttaa 11460
attagaaatt tgtcaccact ggggtcagag gtgagggtgg gaaacaactg tactgactga 11520
gactcttggt tatgcttgta gccgtgaccc agacttatgg tggcaattca aacggggagc 11580
cctgtgtcct cccgttcacc tacaacggta ggaccttcta ttcctgcacc accgaagggc 11640
ggcaagacgg acatctgtgg tgtagcacaa cttccaatta cgaacaagac cagaagtatt 11700
ccttctgcac agaccatgcg ggtgagtgtc ctgggaggaa ccagagaggg cggtcgtctg 11760
tctgtccttg ccgtgcacac ccttctgtgt gccagcagtc agtcagtcat tccgaggctg 11820
cacgggaact atagctttga tctatttgaa cccacagcta atcccttagc agaggcaggc 11880
agtttccatg tcccttagcg ccactgggga aatgtcactg agggaaaagc cctatggttt 11940
gattatttcg acacatgggg attatgatgt gattaaagac actcaagtat tgaaatcagt 12000
ggatgatccc acagagccga tgaacacaca ggataaatgt caagggtgcc ggtacttatc 12060
ttctgtgtag agtcgaattt tacacaaagc tatcatttaa tctttttttt ccccccttgg 12120
ctgggaaaat gagaaaacat gagatttaaa tctattttga aagtgaagat gaaaatccac 12180
taagaagctt agggctgtat tatcagatat ctttttattt gtggataggc cctctgggac 12240
ttaacagccg gaacctggct ctgtctaagc ctgcggtagt ctctccttgt cgtacacaac 12300
acagctcagc tgtaatcttc gggtttgtgt gttgtcttgg gcagttttgg ttcagactcg 12360
aggcggaaat tccaatggtg ctctgtgcca cttccccttc ctgtacaaca accggaatta 12420
caccgactgt acttctgagg gtcgcaggga caacatgaaa tggtgcggca ccacccagaa 12480
ctacgatgcc gatcagaagt ttggattctg cccaatggct ggtaagagga agccctgtga 12540
gttatgggtg tggacccgct agcagcctgt tgatggtctg ggagagtacg atgtgcatct 12600
atgtattata tcttacattt gcaaattgag aaaactgtca atggcaatgt attctggcaa 12660
atacagagct gtcctcattt tacctggata cagaaagagg aatcagggat tgcttattgt 12720
ttttaagttt cgagagtccg gtagaagaca tcttttccag ttgtagaacc aatagcctga 12780
gggtcatgga gagtcatgtg ctcagacgca aggaaactac actttttgtt tttctcattt 12840
caacagaaga tgacattggg tttaagaggg acagtcactt ttacctggga ttttatgctc 12900
acagtttccc tttgaacttg agtgaaccag gtgaagtcac aaggctatag ttaaatccag 12960
tcctctagac aacgagaatc aatgagtata tgagattttc ctagtctaat cttcttcagc 13020
ccttttggta tttctctcca atctcctctg gaccggttct ttcctggaga gttcaaaact 13080
ccaccttcat ccagctacat gcatgcaagt cttcttccca aaggagagag aattgtcagg 13140
attatcaaac aagactgcta tcttcacata actatccatt tgtattccat ggctgtttac 13200
caagtgtttc tcctccattt ccaaccagcc cacgaggaga tctgcacaac caatgaaggg 13260
gtcatgtatc gcattgggga tcagtgggat aagcagcatg acctgggcca catgatgagg 13320
tgcacgtgtg tggggaacgg tcgtggagaa tgggcctgca tcccctactc ccagctccga 13380
ggtatgctgg tgtgttgacc agagagtttg tgtgaaagcc tgtagttgca aaagcagaga 13440
gggaagcatg cagtgtgtag ctatccactc acccgctgtg ctgaagaggt ctcttgattc 13500
caggagcccg ctgagaaaag ctggcgagtg agttgaatag ttctagggct ctggaaatat 13560
tctcaggatg taagcattta ggttgagcca aaaggatggc tttcccaaag agagatcaat 13620
atttgaaatc cttttagctc aaggttctgc ccgtgtttat gtctagagaa gatggtatca 13680
tttctccaag ccgggggtgg ggggggtggg gggggtggga ggggcgggaa tggatggata 13740
ttttctattt gtcaaattta aggtgatgaa tacatcacat cctcagacta atttcttttt 13800
ttcaaatcag ctttttttcc cctttggact cagatgtgtg ataggaggag ctgttaatgt 13860
attaaagcaa tttcagcttc tttgattgga aaagtaacat ttaggtggaa ctcagtgggt 13920
aaacagttcc catagccagt ccataaacag tgcgccctac attgattcct ttaatggtgt 13980
ccaatggcta gagatatctg ggagtcctct ttgttactta gaacattcca gagcaggagg 14040
aaaactaata agacatgcaa aacagccctt agtttgacag atgagaaaat ggggtcccaa 14100
agatagaatg taacttattc gggatttctc attgagtgag gaacagcatt gatttacatt 14160
ctaaaacttt ctgaacatca cagatgtcat tgtatttccc agatccaatt accttctgtc 14220
ttaggcttct attgctgtgg aacaccatga gcaaaaccaa accaaaccca accaaaccaa 14280
accatcttgg ggaggaaaag gttaatttta gcttacacct ttcaggccac agtccatcac 14340
tggggagagt cagggcagga agtcaaggca ggcatctgga ggtaggaact gaagcagcag 14400
aggccccaca gaccgaggag cccagcttac aggcttgctc tcccctgact tgttcaacct 14460
cctttgttat atagctcagg actacctgcc caggggtaac actacctgcc tgccatggac 14520
tgggtcctcc tccagttaac cactcatcaa atcagttcct cccagactgg cctgcaggcc 14580
agtgttgtgc agacagtttt ctcaatcgag attctctcat ctcagatctg tgtagattat 14640
gtcaagttgg taaaacccaa ccagcgcaca ctgctctcca tcccagaaag gagactacca 14700
catggtggtg tatgctatgt aaatttctct cttcgtctta gggtaacaac caaaaattta 14760
actaaaatca tcaactaaat gaggatgtta gaggaactaa ggcatgcctt tgttgagaaa 14820
ttagtttctc cacaggaaac tatattttac catggctttt agtttaatgg actgtaatcc 14880
ctgacaatta caagtctatt agtcagaata agaggggagt aaaaattaat attattaagc 14940
tttgaaaaaa agattattct gtgccagtag aaaatgtatt ttagcaggtg ttaaatccag 15000
cagtagaact gactgccttg aaaaaatgca gtttcttttg atttcattag tcaaagctta 15060
tcactcaccc aactgttccc tggacagacc agtgcatcgt tgatgacatt acttacaatg 15120
tgaacgacac gttccacaag cgtcacgagg agggacatat gctgaactgt acctgctttg 15180
gtcagggccg gggcagatgg aagtgtgacc ccattggtaa gtggccgcct ctgcttggtt 15240
ggttttcacc gaggacgttg gctggttggt tggttggttg gttggccact tgcagataag 15300
gaaagctatt tggtatcgcc agacttcctt ctctccaaac ctgcctcatc catcagtctg 15360
cagagagcct tgcaaatgtg ttggtaacaa gggtggcttt actgcagtga gtgagtgggg 15420
ttagctttgt tggttctgag tcatgacaaa ggaagtttcg ttactgactg cagaaaagaa 15480
acatgggtat aggactcagc cagtagatgc ctgcctccgg ccaaaacact tcagcttttg 15540
cctctctgta caataagtag ataaatagat agggctgggc catcactgag cgatcaacat 15600
taaaaggagc ctattcccca aatccaaagt ttaagataat cagttcttac tcctttactg 15660
aaggaggcag actgcttact gagacagcaa attgatccca gcagtttgtt cggcctgcga 15720
ttgtaaagcc gagaggtccc gggaggcttg cttagaaagc tgttcatgct ttaaatttag 15780
ctcattaatg taaagctacc tactgaattc cgaagaagta cacaaaatga aatcattgca 15840
aagttctttt cttattttac agatggcaag ttttaaaact tttaattggt atctagtttc 15900
ctaaaattaa ttttcagatt ttggctatat gctgaaattt taatctttac atttttttta 15960
aatttagcaa tgtttcccct gtaggacacc aaatatcctt cccaaaaggt acattttaat 16020
tttaacgact aattttccca taaggtaaat gacttgaata aaatattact ttaggactgg 16080
ggaaatggtt tcacacaaca tatgcacgta tctcacacac aagcacatat cacacacaca 16140
aacacataca cttataactt actttaacta tatttgtaag aactggaatt tttatattca 16200
tactttaaga atacacttca tcacactaca gtgatgtgtt tgaggctgtt ttaatctttt 16260
ctttgtgttt gttttagacc agtgccaaga ttcagagacc cggacatttt accagattgg 16320
tgactcctgg gagaagtttg tgcatggtgt ccgataccag tgttactgct acggccgtgg 16380
catcggggag tggcactgtc aacctctgca gacctaccca ggtaagtagc tctgagacag 16440
aagcagaccc atggatgcca gtctatgcta ctatttggaa tcccagtggg ggccttgctc 16500
tgtcccatcc cttttcatat tactgtctaa tagttaattg catttttgtc ttaaattgtt 16560
ttatttcacc cttcatcagg gaaaaatcac caaagactat gaaaaagtgc atgctacaat 16620
tttgcatttt acacagttga ggactccatt aggtgaaaac atttcagttc attttatctc 16680
agtcctgtgt gtgtgtgtgt gtgtatctgt gcttgtgcaa acacatgtgt ggatgtgtgt 16740
atgtatgtgc acatgcatgc gtgtgcatgt gtgtacatgt gtgagtgagt gtgtgtgcct 16800
gtgtttgtga gtgtacatgt gtgtgcacat gcgcatacat gggcatgcat gcttgcattc 16860
gtgcatgtgt atgtgtgtgt gttcaagtag agccataaag taactcagac tggaagtgaa 16920
agagttttac attctgtttc ttaaagagaa gtcacatcga cagaaggcaa gaagtacagt 16980
atgaggcata aatttgtttc ctgccatctt aagcccttct ttgtgtcaga tttcatttgt 17040
ttagtgagat gtaatgtgga acaaaatctg gagccaagaa acttggtcaa ctccacccac 17100
accgttcgaa taccttaaaa tatttattgt ggttttgttg ttgatattta ttgctaggtt 17160
ctcattgttt tgtttggttg ttgtttgttc tcccatagag acatcatgcc tagccatagg 17220
cattaattca ttttggggaa aacatttaaa attcacacgt tgattatgag tgccatttca 17280
gcagactcct agatttccgt taatgattta tttatttatc tgtatgtgtg tggagagggc 17340
actgggtcac agcacatacg tgaaggtcag agtggacttt gaagttcttt cttcacacac 17400
gattctttat gtggggatca gactcaggtc tacaggcttg tgggaggcga gcaccttacc 17460
ctgagccatc ttgctggccc aaatttaaga catgaaatac cacctgtatt cagaaacaaa 17520
aagatttggg gtggggggag ataatccaca agaatacaaa atattataat aataaattaa 17580
ctccataagt attaagatta aatactaaga ttaaactaat cttcctaaga gtgtcccaaa 17640
gtgaacgatg agagcccaag gcagtgtgag tcctcgctct gactgtgctg tgagagagat 17700
actagttaac ttctcctgtg gacaaaggga gacttgctaa ccacctttaa aattgcttcc 17760
agtccttcac taacagtcag agacccagag cacccgtcca ccactcatgc aatcatgttt 17820
tgtttgtttt tcaatgacag ggtttcactg tgtaactctg gctactttgt ggaccaggct 17880
ggcctcagac tcatagagat ccacctgcct cttcctccca agtgctggga ttagagttgc 17940
atgcctccca tatccagaat acgctcattg tttttatgtg ctggggacat cctcctccgc 18000
tcagccctta gacattgtca gggtaggata ggtgattgct tccgcaacta tgtagctcag 18060
agcagcctgc atttttgctg gactttggtt taagagtgag ttacttgccg ggcgtggtgg 18120
cgcatgcctt taattccagc acttaggagg cagaggcagg cggatttctg agttcaaggc 18180
cagcctagtc tacaaagtga gttccaggac agccagggct ataacaaagg aaccctgtct 18240
cgaaaaacaa aacaaaacaa aacaaaacaa aacaaaacca agagtgagtt acttaacatt 18300
tttaaaaatt gaatccagtt gctttgtttt gctttttgag tctcatctag ccctgggtgg 18360
cctcaaactt actatgtagc caatgatgac cttgaacttc tgaccatgcc tcctgtctct 18420
tgtttccaaa aggctggggt cacaggtgtg cacattacac ctggtcaact taatatagtt 18480
taaaaatctg attacaaatg agccataaat tcagaaaaca catatttagg aggattggat 18540
tttccaatga tacaagccaa gaatagaagt ttatttttgt gttcacagtc agtttttgca 18600
gggcaatttt tgaaatttat tttcttttaa gaccttttct tttaaaaata agtctattca 18660
catatatctt gctgcaagca ttgagggtag atctgctgat ggacaggaag agtcacctag 18720
cgggagtttt acctgttgac tttgttccct gtttctaaaa agggcaatgt caaaaaccca 18780
ttgaacacag aagagatttc agggcaagcg gatgagtgtt tgaccctaga tagcaggctc 18840
agtgtttatc tcaatggagg ctttgctcaa gggctcatgc ctagcctttg aggctccgat 18900
ggctgaaaga ccgtgtctga gccttgccct gtttgttctt cctactaggt tggtagagat 18960
gttcaaacta acaaaaggta gcaggaattt ggtttgtcaa taagcaacca ggaaagcaca 19020
gctctcagca aattaggtag agaaagaacc tttcgggtca aaaaaaatca tgaatgttta 19080
acttctccag ggtcactatt atcggaaatc actctttctg accttactgt caactgattt 19140
tgaaagtgta taatgtggca ccctacaagt gaagatctca cagtgggcat tgctattaga 19200
agtgtaaaag gtccagggag gtggatggtc gggatcacac aactagccag catcaaaggg 19260
gatataaaaa cacttcaatt taagtagtgt aaatgatagc tagccttttt tttaactttc 19320
ccatctttaa atcatgtgtt gtagtgtaga gtatagtgga gagctggaat ttaattgacc 19380
tagaaaacag atgaggggtt ttccttcttc cttccttcct tccttccttc cttccttcct 19440
tccttccttc cttccttcct tccttccttc ccattcctgc acagaaatgc tttaaatccc 19500
ctttgccatt cagggcagtc acttgaaggt ggaccctgtc atcatcttag gggcctggag 19560
agctgagagc tcagaggttg tagtccctac gcagtttaat tcccatccct cccattagac 19620
agcacaattg ctgaaccttc agctcagggg acccatgcct ctgtctcctg ccggcacccg 19680
tactctctca tatgtaggca ttttaaaaat taaaattaaa aataatggga tttcagatct 19740
gcgctgaaag gctgagaaag gaaatgaagt tctgagtcac ttgggttaac cattgcgagc 19800
atctttccct ccctcccttt cccgcgtctt ctgtcaccct tgtgaacaca gggtttgatg 19860
actggacaga cagtaaatgt catttatatt ctcttaataa tagatttatc aaggagattt 19920
agttatcaca agttttccag cctcaaattc agtaaataag atgcatgaga catgtctatc 19980
tacctgagag attatactag gatttttcta aaacagcaat atttaacagc cttatgcaga 20040
ttgtcactaa taacataagg tctgttttta ctgattcata tgaaacctct ttaaatagtg 20100
tttgaaagaa atgtttttaa tgtatttgta tttgtgaggc tcttcatcta tggaaggagc 20160
tattccagag ggctgtgcaa tggacttgag ttgattaatg ggacaaccaa cctgtgtggc 20220
gcgtgggtcc tatgcccctt aggatgcaaa gatgagaatt ttgacatttc agcttgtagc 20280
attaagtgaa atcaagactc aatgaatatg tgttagtctt caacaagctg agttattccc 20340
aatgaagaag ttgagttcaa aatcttttga ggtcacataa atatgtaagt tacatattta 20400
ttctgctaaa gaagattttg cttttaaaga atttagaagc ttaagaccat aattaaatct 20460
gaaagtcaat atattttttc caagagcact cagaaatcgc aggtagtgta gagaactcct 20520
ttatcagcat gcagaatttt cttctgtctc acagagcatc agtgagaact ttgtgtctta 20580
ggtttttgta aggactttgt acaaatggat tttgactgac aaagaattag agagaagata 20640
aatttccatt ctgtaaacag agtttttgat aaaatttcat tattatccta aatggaatct 20700
actatattaa aaaattgatt cccttctctt attttgcctt ttttttcccc ccaaggaaaa 20760
aacctgaatc tatcttaaat tttgttaata acagtcatat caagatctga aaatactgaa 20820
ttttaaatat atgctttcaa atgtcatttc aattgatgat tgcttaaaaa gatttttttt 20880
ttgaacaatt cgctcacagt ggctttaaga gtgtacttaa gtaaatgtaa aacgaacaaa 20940
caaacaaaaa cactaaagga gagaaggctt agactgatgg ggaaataaac cttgggcttt 21000
aattattacc tctgtctgtt tgtccggatt cagccccatt tagaaatgtt tgttttgtgt 21060
cacgccgtaa ggccttggga tcattgcttc tgagcagagt cctctgtccc gaaagcctcc 21120
atgattcgga atttgtctta caagagcctt catgtaatta gcacatgagg tctgtattct 21180
gagctacatt cttcgtgtta aggaaatttc acagttgtcc cacgtcttac tttgaaagcc 21240
agagaagaag gcaagctatg agacactgga gtggtttctc tcgtatttat tagaaaaaga 21300
attctaattg cttttcttat gggaaaggca atgattacca ggtcaaatca gactgtgctt 21360
tttcttcagc taatgtcaca atgtagaagg tttaactaga ctctttgccc acatttcccg 21420
agaagcgaaa agtctttaag gatggacatc catgttttgt aaaactttaa gaccacacaa 21480
gctaaagaga tggcatgttt tcattttcag gcacaactgg acctgtccaa gtaattatca 21540
cggagacccc cagccagccc aattcccacc ccatccagtg gaatgccccg gagccttcac 21600
acatcaccaa gtacattctc agatggagac ctgtgagtaa tagctccgca gccttggact 21660
ctgacccctg acctgatggg actaggatgt gttgccctct gggtttgtta ctgcttttga 21720
gtcgacagat ctgatgccat gtcgaacagt gctgacattt attttcttag tgtctagcca 21780
atatgtagtt agtcgaatca acatgtagat tcagggtttt ttgattgttt ttggtttttt 21840
tgttttgata tgtagaagaa attaaattag gcctttggct taggaaaatc ttagaagcca 21900
taatgctaac aactattctc atccaatgtg gaaagaaaat ttgaaatttt ggtatccatt 21960
tgcaatgtca ttaaaattaa aatcacattt tcaagttatt tccagagttt aaaaccagct 22020
aaatgaacat cgttcttttg actcaactca gttgtcctgt agtcctcttg agttgtgtag 22080
acagaaggga atgaggtatt gagagaagga ggagcgggga agggtttata tttggtttct 22140
aaaaggaccc ccaaacccta gcgttttcta accatccaga tgccaaaacc atagcaagga 22200
gtctctcata ttagtctatt aacccttgat gtctcgtccc ttctcagact tgccctcttc 22260
catctccaaa gtttatgaca gaatttaaaa ccactacttc agaaaggaga aatgcacttt 22320
taaaaatcaa atctactcaa ttgaactatt attaatccta gactacaaca acctgtctga 22380
cttaggacgt caactcactc ggtcgaattt aaactcttgg ggaattccat tctgctgagc 22440
tcactctttt ccttcagccg tcccatgttg tcactacaaa tgaggcattt ataaataggt 22500
ttcgaaatac acattgagtt gaggcgtctt cacatttgat taaactctca gcaaacattt 22560
tagcttcggt tttgttgtgt ttcgttttga gatgatgacc ccattaggcc aagactgact 22620
tcatattctt acgtagctca cgttgatctc cctgctgagt gcttgattat aggttcagct 22680
cccccttggt atgtgatgct agggactgaa ctcaggactt tggccacctt taggcaagtg 22740
ctctgccaac cgagccgcat ccatggctct gaaaatttaa aaagaatttc tgttgtttcg 22800
tttttttaaa tgtaggccat ctgagagttt atattctcat attttcttct gatggccaat 22860
tgctaatttt taagctaaca aaatggctaa cttcaatttc tttcagcata tttgagctaa 22920
aactaaagat taaagagaac ttgcttggat cacttttatt tatctccaaa ataaaaaacc 22980
gggcattaga acatttgaag tatgtacaaa cttgattaga taacattaaa aaaaaaaatc 23040
actgggcatt aaccatgtat ttgatattta aaccgcttta gaatatttac acttaaaagg 23100
atttcttgtt tgaagtctgg gtgtttcttt tccacacaat ctattgcaat gagttctgtg 23160
gtccatgaca tattaatgaa gctggacagg atataaaaat gtaaactgga gggggaagat 23220
taaacaaacc gaaccctatt cttctgcagt ctttcccaga gttggctaac gactcttgat 23280
gggtcgttca tttccaagga tgagtcacgc caccagacac gttgaacctt gtttgtgatg 23340
gccccaggat ctgagtccag gcaatgttat tatacttttc agtgtctcgc gaggcaagaa 23400
gcttgaaatg tatcccacca agttgaaaga tagagcgtga ggccttttct cacttcagaa 23460
gagagacgtg cctctgttta ccacaaaagt ctagaggctg aattgatggc gctggtctta 23520
aatgattcga ggcctcaagt gtgtaacttt gaaaacctca tttctccacc tgtaaagtgc 23580
agtgaggcac ttcacttccg gcaggaaggt gaagatcagg gggagaaaca aacaagcaaa 23640
acagccctga gtgcttggtc aaccacttgg acgaataatt aattaacatc gacaaactgt 23700
agaggccctg ttcccagtca ggttttccac catctttctt ccaaaacaga gcctcgagaa 23760
tcctatctat cctccattct tctttgaaga tgactaacca ccacgttttt tttcctttta 23820
catattcaga aaacctctac gggtcgctgg aaggaagcta ccattcctgg ccaccttaac 23880
tcctatacca tcaaaggcct gaccccaggt gtgatctatg agggacagct catcagcatc 23940
cagcagtatg gccacagaga agtgacacgc ttcgacttca ccaccagcgc cagcacccct 24000
gtgaccagta cgtagccagc atctgttggg gctgtgcctg cactgctcag acgtgggttc 24060
cccagagaag gttctgtcct tagctgcttc tttgctcgga tggtgaacat cctctgaaca 24120
cagagagcgt gggtattcca gataatcaaa ggctcttgtc ccctgctccc attcctctag 24180
gcaacacggt gaccggagag actgcgccct actctcctgt tgtggccact tctgaatctg 24240
taactgaaat cacagccagc agctttgtgg tctcatgggt ctcagcctcc gacaccgtgt 24300
caggcttccg ggtggagtat gagctgagcg aggagggaga tgaaccacag taccttggta 24360
agtagaatgt ctggcttcct cggctcgtgt ttctagatac ttacttggct cgcaggagtt 24420
ttgattccgg aacgcctcca cagttcaaac ggaagacggt ccctttcatc agagccagga 24480
gagaggtgac tcctctctgg ccaggctggg attccctggg cacctttgtg gcctctggtg 24540
ctgtgtattt ctcatagcca tggaaggggg accaggatga ggcctatggc tgacaatgtt 24600
atcctttagg ggtgcggagt taccttcttg tttactttta aaatagccca gtgatgaggg 24660
ggtctttaaa aatatttgct ggtgccagtg aggcggctca gtgagtaaag gccctcaccc 24720
ctaagcctta taacccaagt tcaccctcca gtctgacctc catcacgtgt gtacgccccc 24780
cccccaccaa tgtaataatg agaagatact gaacatacat gtgaatagga cccagatcat 24840
aaaaatgaat ctccttccaa cccctgccct gtcatccttc cttccaccat ggctactact 24900
ctgatatcta atgacagctc tgttttaaaa aacaaaaaaa cagagagatg ttattaaaaa 24960
ttatacatct tcgggggtgg gggaaagtgg aaaatgaaag aacttactta cattggaaat 25020
tgcaggctat tcactagaac atttctcgtg ggctttcacc ctctgagtat agcgctctta 25080
gaagccgtgg aagattggtt tgctcaggcc actaaccttt gccctgtatt ttaaagatct 25140
cccaagcacg gccacttccg tgaacattcc tgacctgctc ccgggcagaa agtacattgt 25200
caatgtctat cagatatctg aggagggaaa acagagcttg atcctgtcta cctcacagac 25260
tacaggtatg tgggcaccca gccatgataa aagcaacttt aggtatgggg tatggtggta 25320
tggtgggtga tacgatacat acatacatca taatcacaca tacttacact catacataca 25380
gctttgggat gctgagggta gagatccagg ctagcctgca gtaagaacca ctgttttaaa 25440
aaacaaattt ttgaagactc tttttgtttt tctgtaacgc gtgggcttgt agcaacactg 25500
actgatttcc tttcttcttc tttcagcacc tgacgctcct ccagacccta ccgtggacca 25560
ggttgatgat acttccattg ttgttcggtg gagtagaccc caggcaccta tcacaggtca 25620
tccttggctt ctgtgtttct tttgatgtat agatgtggaa ggggaaaatt ctgatcacac 25680
tggtaccacc ttaaatcttc cattttaagt ggttggaggt gtgtgtgcat gtgtgtgcat 25740
gtgtgagtgc gtgcgtgggt gtgtccactt caaatcttcc agggattctt cgtttttgat 25800
tcgttttcct tcaagtctgt tcacacgccc ccattcctaa tacctgcatc tgcaacctat 25860
aaggccagcc ccgctgttca ctgcagtggg cagttcccgg gctgtacagg tgggtgattc 25920
ctgcagagct gctgctcact gctgaagagg gagctgagtc gccgctctag cttcaccagt 25980
gaagttccca aaggtgcaaa cactgctcag gctgattcca ttcctctgct ccgagaaggg 26040
aaagccgcta gtactatgaa tgtctcacgt catggcatca cttactgaca ttcattaagg 26100
atctctgggt tcaaggatgc tatttgatta ttaaaagctt cctatcaact tattcttatt 26160
tctgtgcccg tcaggcatta tcagaggaag tggtaacatt gaaagacccg gaaagaatct 26220
tgctgattct tagccatgag aaaggagagt tataatttgt ctagcctccg cttctgaaga 26280
ccatgtgtct aaacgctgtt ctcctaaacc tgcagggtat agaattgtct attcaccttc 26340
agtagaaggc agtagcacag agctcaacct ccctgaaacg gccaactccg tcaccctcag 26400
cgacctgcag cccggtgttc agtacaacat cactatctat gctgtggagg agaaccagga 26460
gagcacaccc gttttcatcc aacaagagac cactggcacc ccaagatctg gtaacttaaa 26520
aacagcccat tccctgatgt ctgatctctt aggactagac cagagagccg ctctaacctt 26580
ccaggggaag ataaagccca cgtggattag actcattctt tagccttcag ggaggactga 26640
ggtgcaggtc acgtgggtga cagatccctg agagggagct gtttttgtct ttgccagctc 26700
tttctatgtc ccccatcacc caaatcaatg gctctcaccc ttcctaatgc tgtggtgacc 26760
cccaactata aaattagtgt catgctgctc tatagccaca ctgtcgtgaa tcataatgta 26820
agtatctgtg tagaattctg atggtcttag gtgacccctg tgaaagggtc atctgccacc 26880
aaaggggtct caactcacag gttgagaact accgagttaa atgctaaaat gtcagcactt 26940
ggaaggaatt tatttatcca aggcaactat tgggttttct ggttaaaaac tcacagcatc 27000
tcctctttct tttcctggga ggcttaagaa ttactgttct cttaactacc attttcttaa 27060
gaaaatctgt tctcttaact accataaaat gagtcagtta aacaaacaca ccagctgtct 27120
tgtaaagtga aaacatttat ttttgtatat tattttaact tggttttatg ttataacatg 27180
cctatctata gatactaaat agagattcca atatcagttt gactaaccat gagtatacac 27240
acacacacac acacacacac acacacacac acacacacac atttattttt tgattaagag 27300
gcaaagccca gtattggcct agaatgagtg ggtctaagag atggcggaat tgttcaggga 27360
gctaacttct agcatcaacc ttcagtggga attgtgactg actgactcat cgctcttgtc 27420
tgctagataa cgtcccccct ccgacggacc tacagtttgt ggaactgact gatgtgaaag 27480
tcaccatcat gtggacccct cctgatagtg tggtgtctgg ataccgtgtg gaggtcctgc 27540
ctgtcagcct gcccggggaa catgggcaga ggctgcctgt caacagaaat acctttgctg 27600
aaatcactgg gctgtcccct ggggtcacgt acctcttcaa agtctttgct gtgcaccagg 27660
gcagggaaag caatcctctg acggcacaac agaccaccag tacgttccag gcctgcctgc 27720
ctgtcttgtg gccccctcct tccagctctg aaccctcagc tctacctggg ataactccat 27780
agcatgctgc tcactcccag gttcacagct cagcagttag ggaacatcga gttgaaagga 27840
atgttgaagg tggaatgaaa ctagcgttct gagaatgctg actccaacat acatgcttcc 27900
aacacgcatg tcatgtccaa catgctcact gctggagtta gagttttctt tgctaatgga 27960
gatgcaattt cagtgctttt gtctctctgt ttcccctccc ttcttccctc ctccttccct 28020
cttttttctt ccttccctcc ctccctttct ccctcccttc ccttccctta accttccttt 28080
ctttaagctg tgaatcaaaa aatgctctac cactatacaa catccccagc ccttaagtgc 28140
atttttaaaa aatatatggc cgggcgtggt ggtgcacgcc tttaatccca gcactcggga 28200
ggcagaggca ggcggatttc tgagttggag gccagcctgg tctacaaagt gagttccagg 28260
acagccaggg ctacacagag aaaccctgtc tcgaaaaacc aaagggaaaa aaaaatatat 28320
gtagttagat atagtagaat tcatttgagg ctagcagttg ccaggcagca gggtgtgtaa 28380
atgtatgtct gggatgtgtg aggccctggg ttctctctct agcaccacac aacgagttga 28440
taccttaagt aattcatcct aaacatttag tggccctggg cagcgaggta tcatctattt 28500
agctctttat cagcagaacc tggctggctc ttaagtcttt agctgacatg tgcaaaggga 28560
aatgctactt ctgttggatg tgggaagaga cctaaggtct tccctgagga agtgacagtg 28620
gtttggattc caaagctcat gtatgttctc aattacactc gaccacctct ggaaggttct 28680
ttctatcaaa gatgttctaa cttcctatgg gaggcccagt tatcatcctt agaaagaaga 28740
aaaatggtga tctatgtgat tctttctgat actccatggg actggggttc tgcccatctg 28800
ttttagttat tgtaattaga tccatgtgag gcagctttta tttctccagc agaggttagg 28860
tcagccaatg aacatacacg ttagcatatt gcctgcagga cccatggagc ttttcttgcc 28920
ctaactctgt tggacttagc cccctccctt aacctttctg gcccaaaaca aattgtgggg 28980
tttgcaaaat gtttgttttg ctttagaaaa aaaaaagtaa tactgttatt ataatgtgac 29040
tataatttcc aagggtggtg ggtaaatctt tactgggaaa agtagccttt ccaaaggatg 29100
atagacaagt gaaaagggtc aacgaatttt cataactgat aaagtttcgg caaaattcta 29160
cactatcctg agtctcccag agccccacgg tatccagggc tgtggctctg actttagttc 29220
caaccttgag taagggagct tgggatgctt aatcaagcgg gaggatttcc gcatggctgt 29280
tactgatcta aacgtttctt gacacatttc atcttatttt ttccccagaa ctcgacgctc 29340
ccactaacct ccagtttgtc aatgaaactg acagaacagt tctggtaacg tggactccac 29400
ctcgagcccg tatagcaggc taccgactga ccgcgggcct gacccgagga ggccagccca 29460
agcagtacaa tgtgggaccc ttggcctcca agtatcccct gagaaatctg cagcctgggt 29520
ctgagtacac cgtgaccttg gtggctgtga aagggaacca gcagagtccc aaagccaccg 29580
gagtctttac tacccgtaag ctaaaattca aatgccttgc tttcgtgaag ctagagttct 29640
caattaactc ttggcttttt ctgtcctttt gcttttcaaa agtgaaccta aaaagccctg 29700
gtgcaccatt taaagccgcc ccattgaagg tgtgccccat ggacaggctg gtgttctctg 29760
agtatttctt gctggtctgc tgtaacatac acagctttgc cagcgtgggc agcacagttc 29820
gtggcctttg cccgggctga taagtgcttg atgaagataa cagtgtgtta atttgcaggt 29880
atttccaggt tctttctatc tttctgggct aacactatga gtcaggagga cttgggaggt 29940
agctcagtgg ataaaacaag tgcggctaac acatgagggc cagagttcgg atccctggca 30000
tggacataaa aggccaggtg ctttggtgga taattgtaat cctagcactg agagacagag 30060
acaagaggat ctggaggctc acagccagtg ttgctgatca gtagctccag gttctccaaa 30120
aatccaccgc cgaggctggt gtggcggcgt acgcttttat tcattcatcc cagcaagtgg 30180
gaggcaaaag caggcggatc tctgagtttg agaccagcct ggtctacata gcgagttcca 30240
gaacagtcag gactatatag aaagacccta tctcaaacaa acaaacaaac aaacaaaaat 30300
acacaaacaa gaaacaaaaa agaaagaaag aaggaaaagg aaatatggtg gagactggtt 30360
aaggaagtca cacgaatcca tgggcgcata gactgaatac aaagtagaaa aggctgagta 30420
aatactagta gacagaatct aacccatatg catagctcca tcacatcact ctctagacat 30480
caactgagag tcatatatgt ttaaaaaaaa tccacccatg gactgaacag acatcagcaa 30540
atggaaagag aggttaagta tgtgacttcc ttgagagcct ggaccgcccg ccgaaggcta 30600
ccgtccttca cagcagagcc tggtttcctc ttccttaact ttctcttcca catcttccac 30660
acagaggaaa aagacaaggg ttttgggtat gactagcctt tgactcaata ttttagagga 30720
aatggcctta actctcttat ttatccacat tcccataaac tcctgtcttc acaagctgct 30780
ttcctcctac gtacactcca tttacatgac agagagctct gagacttatt tcttgctgag 30840
tacttgttat ttttttgact tgcgggtttg aattatagga ggacctaaca ataagcatgc 30900
tttgggcatt tatggccgtc tacctctggt tcccagcttt ccaggagctt tcagcaagtc 30960
ttgtttgcat taaaaagtaa tctaagccct gcatggtagc acatacctgc ctttagtgct 31020
atcacttggt aggtagactc aggtggatct ctctgagttc aaggccactc tggtcattag 31080
tgaggtctag aacagctagg gctaagcaaa gaggccctgt ctcaaaaaca aacaaataaa 31140
taaataagca acaatttaga aaaactgtca actgttcccc acaggaatct attgtttacc 31200
acaaacttct ttgcatgcac atttggtaat gtgaggttga acaccgaagg cctgtttttt 31260
cctacgaaac tgttcaccag caaatgaagt ctgctttcta gtttgcagac ttctttttaa 31320
atgtttggta tttgacattg cccagttttg agaaagtcta agatccactc ttacagaact 31380
agtatccttg tttttcttgc aaaacccatt tcttggagct gtcccttaaa ttaatgagca 31440
tggagtttct gtgcacacag cctcttactt ggcctcgtac ccgaggcttc tgggtgtaac 31500
agtaaaactg tatttgctga ccattaatta acataccgaa ttgcgtggag tatcctttcc 31560
aacacggtag ggtaggtgac tgaaagacaa atgagcagct caccgtggct cagatttaaa 31620
taaaccagtg gaaccaagga gttaagcaaa tccatttgga cctcagatag tcttggtata 31680
aacatgagca gggcctagga actttggttt ctgatgcttt accaaaatta agttttggaa 31740
acaaccagtt ttctgacttt tatatctcat gctaaattct taagagcaac tgtgagaaaa 31800
gtggggggaa taagttattt atagaggagg aatccagcct ccttctgttt gggggcgtat 31860
gtcatttctc aacagccagg ttgttcctta cctaacaagc cctgccagag cccataattc 31920
atacttacag gcacatcctt tgtttgacaa cactttgtgg gtttgtggct tggtgatttt 31980
cctgtaatgg tcttgtctag gcaagagaat attgtctcaa acatggggca agatttagct 32040
gcttggctga cgcaatagaa aatgcctagg tgtgaaaatg gacagttctg aattgcagga 32100
gcagtatttg gtcctaattg ctgaacattc tctccaggct gttaaaaagt tagaattttc 32160
agccgggcat tggtggcgca cgcctttaat cccagcactc gggaggcaga ggcaggcgga 32220
tttctgagtt cgaggccagc ctggtctata gagtgagttc caggacagcc aggggctaca 32280
cagagaaact ctgtctcgaa aaaacaaaaa caaaacaaaa caaaaaaagt tagaattttc 32340
agtagaagaa atgatggtgg tgtcaggata ctagaatacc aagcatacta gttataattt 32400
ctatgtctag tggtcaggta ttaagtgtct gtagcatttt tgtttgaatg atcaaccaca 32460
tgttggagga atggatcttt gatgttgatg ataagatccc caaatcatga aaagatacag 32520
atcataaggc ccaagaaatt aaaaggagct tccattgagg tgagcgagcc cctctttcta 32580
ctacctgtga gtgacaggtc tctgccagaa attcaagccc cagcccaaac aaagctggac 32640
ctgcagaatc accaccctcg gcccccttcc cgggtctcac caggtcctgg gtgccttgaa 32700
gcagttcaac ttcttagccg atgaatgcac cttagctaca ttctctgtgt acttactggt 32760
tagaccaaag ctctgtttac aatgctcgtt aatctgcagt cctggcctac acctatgcgc 32820
ctaacgttga acctcatgtt ggttaatttg cagtgcagcc tctgcgctcc attccacctt 32880
acaacaccga ggtgacagag accacaattg tgatcacctg gacccccgct ccaaggattg 32940
gcttcaaggt gagtttcaga tgcacctctc atgatccagc ccaggggtgt ctttccattc 33000
ccactacact ttacagacct gggtttttaa agttctatgc tcatactcca ggaccttctg 33060
agagcaaagc ctgcattgag gcttctctgt gttgcaaggg aagaaaacca tgagccatgg 33120
aactgtagtg ttgttctgtt ttctgtcctt ctccccaggg aactccattt taaaataaaa 33180
gtatagccaa acctcatttg atgtgttgct ctaaatgggt gtcgagaagc ttatgaaaac 33240
caatttggga agaccaatta aactgagagt cacttaaaaa tcacattttt atccaatcag 33300
tttcatctca acttgttcaa agccctgtgg gtgaatttct taatagaagt taaaattgag 33360
gtcttcgctt tagatatcca gagtcatgtt ctttaaagca gtgataccag ggacgtgatg 33420
gatacaaatg aatatgtttt ttaaaaagaa tcccatcctt aggcatccag aggataaaaa 33480
aaaaagagac acttattatg tctggaatca aagcctgatt gtttaaaaga gagaaaaaag 33540
aaatagaccg agggtcactc tgctttttag tatgcaaata gccatcttga tgagtgggct 33600
gctcaggtac agaggggacc tttatgaaga ccgccacggc acctttttag tttcccttaa 33660
taatgtcgtt cagagtttta gaagccacag agaatctgaa gggtttctct ggagctgagt 33720
actgtttgat aatgtcacct aagcttttgt agttaggaac acacggacgt cttcgtggga 33780
atgtgttttt catttccgtg tgtcaaagtg gctgcagata acttattaaa gagagagcct 33840
agagcatttc ttccctgtgt actgctggta tgcaccagaa gggtttgtgt caaacagtta 33900
tactgacatt tctctagaac ctttctatta taaaggaccc tagtaccaaa ggaagatacc 33960
tccagctaat tgcaagatca ctaaagtgag ccctcaatgt gttatccacc cagtaaatgc 34020
agtgtggagt tgtaacggac ttccccctgt gtaaatctac aacctctcgg gatctctgga 34080
atattcatcc ttcatgctga ttttgctgtc ttccttccag ctgggtgtac gaccgagcca 34140
gggaggtgag gcaccccgag aagtgacttc agactctggg agcattgttg tgtctggctt 34200
gactccaggc gtggaataca cttacaccat ccaagtcctg cgagatggcc aggagagaga 34260
tgcaccgatt gtcaacagag tagtgacacg tgaggagagc cttccttctt cttttaactt 34320
gtaaactatt ttaaaagatt gccaaagcca ggtgtggtag ggtgtgcctt taatcctagt 34380
gcttgggaaa gttaagaatg atgatgggag ttcaagacca gccaaaaact ggaggcggag 34440
ctgggtttta taatacacac ctctagtccc agtacttagg aagcagagag aggcagatat 34500
tggagaattt atggctagcc tggtctacat agtaagttct aggccaacca acagtgagag 34560
cctgtccccc caaaaaagaa acatattcct ctaattattt gaatgttagc gtcccagctt 34620
tcttttgaga cagaacaagg gaagaacctc tctcttattt atatcagcag agtcttcaga 34680
actggatgta gtttagctgg tgtcatgcag gccacagaat tagaagtgtt ccttccatgt 34740
caaaagtctt ccaaactggc aagatgaaac aatttcagta gtgaattaca atagcgttaa 34800
tcctagagac cacctatcgg ggttactgtc gcctgtattt ttatagaata ctttattttc 34860
ccagtcctag agggaaggga taaagaaagg caaaaaagga gggaggtgcg aggaaagaag 34920
ggtggagaga gggcgtagag gaaacatttc acaggccacg tgttctgtgt tcagtttaac 34980
ttttaagttt tcttttctgt tgtgtagcgc tgtctccacc gaccaacttg catctggagg 35040
caaaccctga cactggagtg cttactgtct cctgggagag gagcactacc ccaggtaaca 35100
aaggggagca ccaccctagg gaagcgtggg gcggatctga gagccgcgta cacataaggc 35160
tttcccaaga cagatttgga ttccattcag agaaagagag aaagcaagtg ctctgctctc 35220
catgagtgac agaggagaat gagagagttc atgaactacg tgtaaacacg gctgcatctt 35280
ttcttaactc gcaggaaaga gaacaatcaa atgctaggct gtgggggcgg gggagactaa 35340
cgtttatact acagggaatt ttgagaggat tagatggaaa gaagattttg ttcagctcgt 35400
taaaaatgcc caaactgggg ctggagggat ggctcagcag ttcagagccc cagctgcctt 35460
tttcagagaa ccctggttca attcccagca cccacatggc agctcacaac tgtctgtaac 35520
tccagtttcc aggggatctg aaaccctcac acatgtaggc acaacacgca tgcacataat 35580
aaataaacaa acaagcaaat aacaaataaa taacaagtaa ataaatgaca aataaataaa 35640
taaatttaaa gcccaatttt aaaggctgaa atcatagtct atagtccata aatcttaagt 35700
tgactgttta ctgaagtttg acagatcgct tggtatctgg gtggggctgg cttcagggtt 35760
cccattgatt ccaaactctg tagctgctca gccaattgca taaaatggtg ttgtgcttgc 35820
gtataaccta tacattgctt gcatacttca actatctgta ggttacttgt agcctaatag 35880
attgcaaatg ctgtggaagt cattgtccca ctggattgtt ttggggacag taacaagaaa 35940
gagtgcatgc atagcataga tccaaattat cttcaaccag tattttcttt taatccatgt 36000
tggttcagta tgcacatctg taacctatga atatgtaatg aattgaacca taagatgtat 36060
gagagacagg gatgggcaga ggctcacatg gggaagaaca tttgatgtgc atgcagaagg 36120
acatagttca tccccagcca ctaggcaaaa agctgggcgt ggctacacga gcagctatga 36180
ttcccctggg agacccgctg ccacaccttg ctacttgaga acatggtcaa tgggagccaa 36240
ctagttggag caatattttt agttcattat ttgattgttg ctaattttac tcattgatca 36300
tttttttttt tgagacaggg tttctctgta tagccctggc tgtcctggaa ctcactctat 36360
agaccaggct ggcctcaaac tcagaaatcc accttcctct gcctcccaag tgctgggatt 36420
aaaggcgtga gccaccatcg cccggtgata atggttttct aaaagtaacg tcaccccaac 36480
actaaggctg aggcaggagg attagcctgg tatatacagc aagtcttaat gctagcctgg 36540
agtcatagtg tgggctatgt cttgacaaaa ctatataaac tatatctgca tctatctcta 36600
tatattatat acatacacat atataatatc atcttaaagt acctttgtat gatggatgca 36660
tgcctacatg cattttcatg tgtctaagtt caggtggtac agtgtgtgta tggaggtcag 36720
aggataacct tcagtatacg tgactgcctt ccatcttctt taagacagtg agaccaatag 36780
cttctgggaa ctctcctgtc ttcacttccc aatgctctct agcaacattg gggatttcag 36840
acacgctctc gtgtctggct ttatgtggat tctggagata ggaactcagt caggtcctca 36900
tgagtacgtg gccaacagct tatccaccga gccaaatctt tagtctataa tttgtagcta 36960
taatctctta cactgttctt acccttgctc gggcgtaggt gtcaagcagt tatctataaa 37020
tgtgtgtgat tatagtcaca caaaataaaa ctagtttaaa atactccttt taatctcctt 37080
ttgaaataga cagactgagt gatgtttcct tctctgtggc aatgtattgt ataatgtgac 37140
agctacagtg tttccagata agtttctctg ggtttgaaac ttgaagctga caagttcttg 37200
cttctgggca gctggatcat caatctttgg tttcagtggc ctgcccattc aatggtcagg 37260
cgtaaagcaa atgaccgaaa tgttattgac ttcccatccc actgggtttc ctagcacata 37320
acacgttaat gttcaccttc tccccactga caggatatac cctcattccc tgttctcagt 37380
gggtcagtct tgttctgtct tcttccagcc tggccctgca gagctctggc cactactaga 37440
tttattgata tctcctttcc tttaatgcct tcactgccca attttcatga ttctgaagtc 37500
ttctatgatt aatatttgtt ttcgagaatg agcatctaca cttctgtgtt ctgtgccctc 37560
cagcccctac cccccccccc ccccgttccc atagttcaaa cttttacact cttcggagaa 37620
tgtttaagtg gaaagcaacc tcagagcatt caaaaaaaaa aatgtagatt tcctagctct 37680
cccacaggtc gcccattaag gaaaaacagg ataaaatagt aaaaagaggc tggaatttgt 37740
agacaggaaa ctctcaggtc ttctctaaga tttccttatc tttgttaaag gtcccatgat 37800
tttactttgt agttaacaca tttatatggg ttgtaagatc gcccaatgga tgcaatgtag 37860
aatgatcgag ttagcatttc catctaaaac attcatgtct aagtgctgga cactctcaga 37920
ctctagttat tatgaaatta tcataagttg ctgtggacta gtcacccggc agagtaattc 37980
ctactttctg actgttggta cattacagcc ctgccccttg gtcccacctt ttcctctcta 38040
ggtccatcat tggtgtacag tttaatatac cctgagtcac attggttctg tatggtaact 38100
tcctctctgc atttactcca gatatcactg gctacagaat aactactacc cccacgaacg 38160
ggcagcaggg gacctctctg gaagaagtgg tccatgctga tcagagttcc tgcacttttg 38220
agaacctgaa tcctggcctg gagtacaacg tcagtgttta cactgtcaaa gatgacaagg 38280
aaagtgcccc tatctctgat accgttgtcc caggtaatag aaaaataagc tgttatcctt 38340
agagtggcag ttttgagtag cgatggggat aagcatctta atccgagata gctgagtgtg 38400
tcagatacag ttgggattta atgccaacct cccagggcgc tctccaaaac cacaaagcca 38460
aaaagcaact gtttggatga aggctttcct gtttcctctg cttcactatc tgtgcttccc 38520
tgggatgctg tttgttgcca tgggtacctg atgagtgcgg ccacggcatt aactctgtac 38580
tgtttgctca cacggaaaga ttactaaaca gtgtcgcgtg tctgtaccca gtgctgacag 38640
gctaaaagta atgtggtaaa tgcatccctt tggggctttt gtgcccgggt tttacagtcc 38700
atctccacct ccaactgtta tctagaaaac agcctttgtc tccatatgtg agcactgaaa 38760
cacacttggt tgacaatcca aatctttatc ttgcagcttc aaatcctttt taaaattgca 38820
agtggggtga aaaaccacag aaaggaaaga agtaaaggcc aggcccccca tggcttgctt 38880
tcttctgaat tgaaagacag cgtcacaaag gcctgtctag ggataggttc attgtttgtc 38940
cccagtcttc tgtagattga aagccctggt cagactctct taccctctgc agtattttgc 39000
tatgcattta tgaatactaa ttaaattaca tgaattaaaa tgttggcagt ggagtgggct 39060
cagggctctg tgctggctgg ccttggcctg actgtgcatt tgagtggcac attcacaaca 39120
tagattaata ccatggtcat gatgccatca tggcttttga acatggaaaa taagtcaatt 39180
agccagccaa ttttttttta aaaaaccttt ggaagatttt attttcttac taaaggtttt 39240
gtgttctccc cactcccaac cccccacccc gccaacattg ctagtgtctt ttatagatca 39300
gttcaggctc tgagaatgat tttgacattg taaatgggtt tatgattaat tttttttaac 39360
acttgagaag ttaaaactgt accattcagg gacattttct aaatgggagg aagcccctga 39420
aagaatgtgg taacctgcat tagtctccca ggggagcaaa ttactcatga tgcttgggac 39480
gtcttttcag ataatttggg atacattgca tataccatca ttgcttgagc attccgtcaa 39540
tttcactacc ggtcacctga tgtacactgc tttatttttt cctttgtttt ttgcctctac 39600
ttttcttttg cctcctcttt gcttcgtaac tcaatagagg tgccccagct cactgaccta 39660
agctttgttg atataactga ttcaagcatc ggcctgaggt ggaccccgct aaactcttcc 39720
accattatcg ggtaccgaat cacagtagtt gcggcaggag aagggatccc tatttttgaa 39780
gattttgtgg actcctcagt aggatactac acagttacag ggctggagcc tggcattgac 39840
tatgacatca gcgttatcac tctcattaat ggcggagaga gtgcccctac tacactgaca 39900
cagcaaacgg gtgaatcttg aagtcttctg tgtttgagac atggatggtg ttgcatgctg 39960
ctcagtcgct gtggttaaat ctggatgttt ccaagccagt gattggctac ggagatgaag 40020
acggggcccg ctcagagata agggatacat tagtctggtt gcatgaaagt atgcgtaaat 40080
agtctcaagc actttcagtc aaagcacaaa cagatgtgaa ggggaagagc tctagatctc 40140
tgatttatga aatgcaaagg agattacatt tgcagatctt gagggtgttt gttttttttt 40200
aaagtatgac tatcaaactg aacaatgagc actcatttac actaagacag gcctccaaag 40260
tgtgccactg cgtgcttcct cttaccttga taagctcctt ttgtagctaa taaaacacct 40320
accaaaaatg agtgtggaac agaaggggag atctcagggt aggatgacga cgagccgtag 40380
ggctttctgg atagtgctgc tctacagggt aaagaaactc ctctttaacc acagtctaga 40440
gacgagcatg caacatctta aaggttctct gccctgcatg gtaagaaaca ttgctgagaa 40500
ccactgtgca tgaatccctc acttgtaagt agagttcact gaatggaatt atggcaatgc 40560
agtagtgtgt agatatctca ctccggggaa actgaggacc ccttgtcttt tttgtcttcg 40620
tgcatgtgtt tcttcggaaa gtactgctat gtgtctttgc tgtgtggcaa cttaagcctc 40680
ttcagcctgg gagaaacatc ttccgtggta tcgatgtact aaaacggcaa tagcagccac 40740
caaaaaaaaa gcctacctat ttgaaaagta gactaaaatt cttttaaaat gcattgatca 40800
tggcagaaag gttaaagggg cctaacagtg ttctctatag tgttttgttt atttttttaa 40860
cagtagcgtg tcatgattta gattagatta gattagactg tttgcatggt tgtaactgtt 40920
tcttttctgc atgaaatact ggtttttacc ttttcagcta tttttttttt ttagctttga 40980
ctttaaaatc gcattaactc aatcctcctt atttgatatc agctgtccct cctcccacgg 41040
atctgcgatt caccaatatc ggtccagaca cgatgcgggt cacttgggcc ccgcctccgt 41100
ccatcgagct gaccaacctc ttggtgcgct actcacccgt gaagaatgaa gaggacgttg 41160
cagagctatc catttcacct tcagacaatg ccgtggtcct aacaagtaag ccctcaaaca 41220
tagcttgtcc cgtagatacg cagatccgta gatctggagc acaaggcatg gatcctgagt 41280
tttcctggag gaccacctaa gagaaaggag aactgtgacc gagagacacg ctctccaagt 41340
tcagtaggcg gctctgtaaa ctgtgaaaga tgtaatgatt ctgccggagt ggcagacctt 41400
tgatcgctac aaatcgtagt cgaaggcacg gtctgtgaag caccaaggtg tcagacattc 41460
tctaatcagt gcacaaaaga tacgtgactc ccaagtgaat tctgtaacta aggcaagagt 41520
gagaaacatg gagatcagcg catctggttt attgtccttt cttgtgtgag atctaccacc 41580
accaggggat ctatttagca ctagaaaact tagaatggct tttgcgtgga gacaggcaga 41640
cgtttagttc atatttcaga aagcacgtgt ttgcaccatt tccctgaagc tgggagagtt 41700
tagaaagcaa ctgacatgta ttagacaagt tatagaaatt gtttcttccc gagtcctact 41760
ggaagaggat actttgaatt aaagagaaca agagcttgca acattgtagg aaattgtata 41820
agtacagggg ttctacagga gaggaaagta gttacattca ggcccatttc caaatagggt 41880
cagaaaacat cctctgctct tcagatacgg ctcagaaagc taactacaaa gaggcagcag 41940
cagcagctct cacttggtgg ctaaagacca gaggacccag atacttaacc cgagtgtgga 42000
aatgtctgtc cagtcagtag gaaccacatt gtccaatata ctagacccat cgccacctgt 42060
tggcaccggt ttagccaaac cgtgtcacat gttaattatg tatcttaaag agtcctaatg 42120
ctagaagaaa ctccccctta gagaagtcat tattacccta ttttaaaaat taagcagttt 42180
gagggcagtg gagtgagtcc aggggcacta ggtatgttca ttgtcttgaa tacattcatg 42240
gccccaacaa ggacacatgt caaattttgt ccaactgtac atcttgacat tgcatagcat 42300
ggaagctgct gaccacctca tgtggttgtt gtgatgggta gatggtaatg tagactccca 42360
caaaagttac atcagtggcc ctcacagatg ccctttcaaa tggacgggag agatagtaac 42420
atcccgtgtt tacacttgac tgagttccat ttatacctgt ggagctgggg cttacagaca 42480
ggacagagcg gcccttattt acagattatg tccagacaga catactcact tagccacagg 42540
taggctatgg gactgaacgc ttggatgttt tatcagatga cggagtcccg gggagcgtta 42600
tgctttctca aagtctcaat caagtttaaa gcaaatccca ctttgcctct tcagatctcc 42660
tgcctgggac agaatactta gtcagtgtct ccagtgtcta cgaacaacat gagagcatcc 42720
ctctccgggg aaggcagaaa acaggtgagc cacgttagct accaacgtta agcaacaaaa 42780
tgataggttg agtctatagt tgcatctcca ccttttgtgg cattgataca ttacttttaa 42840
tttattaatt aatttatgat gacaataatt aattacaact aattaataat taattttagt 42900
tattgtagag tagtggtttt gccatggtat tttcacatgc tctgttgatg ttcctcttcc 42960
gttcctctcc ttgccccctg tcatccttcc tggtcccctt tctccctgta gtaatgtaca 43020
gccccgtttt cactctcgtc atcttgtcac ctctatccta tgaccctttt cactttctac 43080
cctctccgcc ttaaagcacc ttctcttctc cccacattcc tttttctagt ttcaggacct 43140
ttgctctgca catacatgta gatgctctat acacacatat gaaaaattaa agctaggatc 43200
caggtaccag aaaactccac ttgtctttct gagactggat tgctttgttt aacataataa 43260
tgttactttg tttaacataa caatagagtt ccctggtttc cttgtgaatt tcactggttt 43320
cttgtcttag ttaaggttgt tgtgatattt gtgaggaaac accatgatca atagcaaact 43380
ggggagggaa gggtttattc gacttacact tccacactgt agtccatcac tgcagggaaa 43440
ccaggacagg aactcaagca gggcaggaac ttggaggcag gagctgatac ccggggccat 43500
ggaggagtgc tgcttactga ctggcttcta ccatgacctg ctcagcctgg tttcttatag 43560
aatccaggac catgagccca gagaaggcac tgtcccgccc acagtgggca gggccctgcc 43620
ctgtcaatca ctgataaaga gaaagcccta caagcttgcc tagatcttac agaggcattt 43680
tcttaattaa cgactccttc ctcttagata actttagctt ggtcaagttt atgatataaa 43740
gctacccaga acaacgctga agccctcaga agtatcagtg tttcggtata atgtagaaat 43800
cggctataat tttacatatt gtttcaatta cttttaaaag gaaaaaaaga aagaaatgct 43860
tgtgtaagct gattgcggtc agctatcagt cccgtataac agtgtcagtt gcgttcccca 43920
catcctccat cctcgatgtc taagctcgtg gttgttgtct tttgctcccc tccttgggtg 43980
ggaaaaacag gtctcgattc cccaactggt tttgattctt ctgatatcac cgccaactca 44040
ttcactgtcc actgggtggc tcctcgggcc cccatcaccg gctacatcat ccgccatcac 44100
gccgagcatt ctgtcggaag acccaggcag gatcgagtgc cgccctcgcg gaattccatc 44160
accctcacca accttaatcc gggcaccgag tacgttgtca gcatcattgc tgttaatggc 44220
agagaggaga gcccgccact gattggccag caagccacag gtaattttgt ttttttaatc 44280
cgcaaagaaa tcccttggtg tggactttgt ataggtttgg tgtagactgt gaaaaagctt 44340
catgttagac acaaagagca gtggtggagc caggcgcagc tgtgcgcgct catgcacgca 44400
ggcacgcgcg cacacacgcg cacacacaca cacacgcacg cgtacgcaca cacacgcacg 44460
cacgcctttg atcccagcgc ttggaggcag gtggatttct ggattggagg tcagcttggt 44520
ctacagagtg agttccagac tagccagagc tacacaacaa gatcttatct caataaaaag 44580
ggaaagagga cagtgataga ctgtgtggta aacatttctc cctctaaaaa catatttatt 44640
tctctgagag attgtcacct ggttcagcta tgttctggtg tttttgctgg tcagtcttta 44700
tttatgatgg tttgagagag cgtcatagcc cagactgact cagaagctgg ctctgtagcc 44760
caagcttatc taagatactt cgccttgact tgtgagtgct ggagttacag gcatgagcta 44820
ctactactca tggatattta ctggttttta agaaggtttc atacaaaacc ataatatggt 44880
accaaagtta ctgtaaacct atgatttttg tttcgttagc tgggcttggt agcacagatg 44940
tgtaatccca ggtacttggg aggctggagc aagaaggcca tcctgggcta ctgtgagttc 45000
aaagttagcc tgtgcaattc agtgaggctc atctcaaagt aaataaaagt tttttaaagg 45060
ggtgcagtgg atgtagtgta gtggtggagt gctctgtgtg gcgtgagtca agccctagat 45120
tttggcttta agcacagata gatatatttt cagtgacaat gactgggaga cctgttatca 45180
gaacaatctg tagcttagct gtgaataggg gcgtgtgtga ccactatttc caaataacac 45240
atagttaagg gtgcatgggg tgggatctct gtgagttcca ggccagcctg gtctacaaag 45300
cgagttccag gacagacagg gctgttataa cacacagaga aaccctgtct tcaaaaacca 45360
aaagaaaaaa gaaaagtgca tggtgagtgc tgctgtagtt tttataactt ctgtgattta 45420
aattatttcc caaagagact gttgaggaaa aaaggaattc acaattggga tggtctccat 45480
agccccttcc cttgacctcg ccatagaatt taactctgct aattcagtgt tgcatttaga 45540
tttttgtttg aagaggatgt gtgtaatcgt tatctgggaa aggacaaagt gaacctgagc 45600
tttctttgga agttatacat gtgaagtttt cctgtgattt ttttttttct agtttctgat 45660
attccgagag atctggaggt cattgcctcc acccccacca gcctgctcat cagttgggaa 45720
ccccctgccg tctctgtgcg ctattacaga atcacctacg gagagacagg tctgttcatt 45780
ttgggccatt tcacccttag aggatcaggg ttcgggtggg taacttggaa atctgacagt 45840
gggaacagga ttaaatgcaa acaggcccat ttagaaaacc cccctccttc cctccctccn 45900
tcccnctccc ctcccctccc cctctttctt tctttctttc tttctttctt tctttctttc 45960
tttctttctt tctttctttc tttttctgtc caaaaatgca tgggagctac atttaattga 46020
ttgtaatgaa gttcaaaggt ggtttataca ctacagcaag ggtgggaagc agagctgaga 46080
aaaaaaagtt tatatattta caaatattac cattggtaat tcttactatt ctttcttttc 46140
agtgttctct aaatttaaca aatattctgt taaccctttt gtaaagactt cattccattt 46200
taggttgagt gagccacatt cttgtcccct ttttctattt aatttaaaca attaattaaa 46260
tataattaca tgatttcctc cttccctttc ctcttccaaa ctatcccaca cccctctcgc 46320
tccacttcct ctcagtttct tggcttcttt gtcttactgt tacacacaca cacacacaca 46380
cacacacaca cacacacaca cacagagtgc atgtgcatcc aacaaataag tataaataca 46440
acccaccgag tctgcttact gttgcttata tggacatggt ttcagggctg actgcttggt 46500
atttattatc aaccagggag ctcatttctg gggatttctt caccttttgc ctgttaatct 46560
gcaactcagt gacattttaa cccagggatg ttaatatggc attagcttga gagttctcct 46620
ggtttttata tacttctcag ggcttactac acacataaat acacttgtct gtcaggttgg 46680
gttaaagcag ccactcctta tgatggaacc agcaagctgc agtgacttac ataccgcttt 46740
cgatgtgtta ataatattgg agtaactcct agctcctcaa attctatgct aactcctttc 46800
gtacaggagg aaatagccct gtccaggagt tcactgtgcc cggaagcaag tccacagcca 46860
ccatcaacaa cattaaacca ggagcagact acaccatcac cctgtatgct gtcactggcc 46920
gtggggacag tccagcaagc agcaagccag tttccatcaa ttataaaaca ggtacaaatt 46980
tctcttgggg taacacgggg ttatttatga agatggttat ccctgtattc gtccaaggta 47040
ttgtcttcac tacacagttg attttccttt agttttgtgt ggtgctgggg accaaaccca 47100
gcatctcata aatatatata tgctgtacca ctgaactaca cccttgaccc tgatttattt 47160
ttcttttttt ttttccgaga cagggtttct ctgtgtacaa aagcctgtag ctaacaacac 47220
cttcaagtaa tagagtcttg agacaaatgt acaaagaaga ccccaagagc agacattttt 47280
gtctgtgttt ttaactgcta ccgctatgta tctacattag acacaagcca gagagtgttt 47340
ataaatacct gtagaaaatg actggatggg ttgactatta ggagacaaag gcctacctga 47400
gatgtaatgc tttgtttgtg gaatgaaaga atcaggttgt aaatagttgt aatagtgact 47460
ggatgcatgg ctttccttct tcaagctaac accctttatt cttgtcaaaa gaaacatttg 47520
caatacatta atagaagcaa gagaacattc gcatacacac tggaactaaa ggccagggct 47580
tgtccagccc tccccccaca ctgggacatc actgctttct tttgtactta cagaaattga 47640
caagccgtcc cagatgcagg tgacagatgt ccaggacaac agcatcagtg tcaggtggct 47700
gccttcaact tctcctgtga caggctacag agtgaccacc actcccaaaa atggcctagg 47760
accatcaaaa actaaaactg ccagtccagg taaggataac cacaaggcca cacctagcaa 47820
gagaaacact gtaggagctc agaagttgcc atttgaagtg agtgtcctat gtggtgtgtg 47880
tatgctactc ccattcatag gcttggcacc agctcagtat tggtatccgt gtatctcggg 47940
ttttattttt ttttaatact gtcttgtgta gtaggaagag aaggatatac tgatgttata 48000
gatccttcta gatctgatgt tcttatatga aatggcttgc aaggtctcaa gccagtttct 48060
taagatcaat tttcatttct ttcttgaaat ttttcaagaa tagcctcatt aattttgggg 48120
gatggggcat catgttaagt tagttgtaaa gcttattctt gaatatgatt ttacttcagt 48180
atgctagatt ttgttttgag atgggggtct catgaagtct gtgctggcct tcactgcact 48240
acgtaggcaa ggatggcgtt aaacttctga tcttgttgtc agtatctcct gagtgctaga 48300
actatagata cgcacacagt ttactgtgcc gcttggttat ctaagcctgg gtttgttcat 48360
gggaacagca ttctaccaac taagccgagc tccccagccc cagttttggt accagtgaac 48420
aagttgtcct gagaggaaac aggcatctga ctttcccaag tggaatgggt gtttcatggt 48480
tattctgcaa atgaaaatta taggctcagc atctgcttct cattgagtcc ttaggagtgg 48540
cttgggtggc tctatagacc tgcaattaat tgcttctccc tccttttcag atcaaacaga 48600
aatgaccatt gaaggtttgc aacccactgt ggagtacgtg gttagtgttt atgctcagaa 48660
ccggaacgga gaaagccagc ccctggttca aactgcagtg accagtacgt aaccaatgct 48720
cggtttccta cttccaaagt catattgtcc tcaggtgtct ctcgatgccc accgcacatc 48780
ttgtgccatt gtatacacac agggaaaggc aatgtgtcag ctggttcata tcttgagatg 48840
agcccttggc ctacatttct tggcgccaaa gcgagcttgc aggaaaaatc actgtagtgt 48900
tgccatcaat ggctgctgtg ctttgaatct cctttgctta aacagcctca gcaaaatctt 48960
atttgctttt agcaaatcta tgaaagatct ctccaggacc tactttttct atgactggat 49020
ggtaatgttg actgtagtgt gccccaagaa gtggttatgg ttgaaggact gtggctgggt 49080
cagccttgtt tttttttcct ttttaaagat tttatttttt tcatctatat gagtacactg 49140
tcactgtctt cagacacacc agaagagggc atcggatccc attacagatg gttgtgagcc 49200
accatgtggt tgctaggaat tgaactcagg acctctggaa gagcagtcag tgctcctaac 49260
ctctgagcca tctctccagc ccagggtcag cctttttaaa tataaagact taagagaggg 49320
gaaaaaagaa gaacctaaga caaattatga cttgaggaaa aaaaaaatca actttaccat 49380
ttccaagata tagaaaatcc aggtccttga gactaacatc acattgcaga atcaaatcta 49440
gaatatcttt aaattgatat aaataaattt ccttggtgga gatttttttc ttcagggtgt 49500
ctacatacct tacacacact tgtgtcttaa taagcaacgt gacactgcat atgctaaatc 49560
tcaaaaaaaa aaaaaaagcc ttttaagcag atgtcaagca actttctgtt ttaatagtgt 49620
gataattgga acttaattca tcaaagacaa gagttatctg cagaactgct ttgcatggta 49680
tggaaatatg cttgtttcac aacttgcttt tcacataacc tcttaccatt aatttgccta 49740
acagacattg atcgccctaa aggactggca ttcactgatg tggatgtcga ttccatcaaa 49800
attgcttggg aaagcccaca ggggcaagtt tccaggtaca gggtgaccta ctcgagccct 49860
gaggatggaa tccgggagct tttccctgca cctgatggtg aagacgacac tgcagagctg 49920
cagggcctca ggccggggtc tgagtacaca gtcagtgtgg ttgccttgca cgatgatatg 49980
gagagccagc ccctgattgg aatccagtcc acaggtatat cgttaaccgc acccaccacc 50040
cgggtgcttc tgggaacagt ggctttatgc cttgctggcg ttatacttta ctgggctatt 50100
gagtcccatg taagggagag tagaaaaatg ccttcaaact cttagtaaag aaaggccctc 50160
tttaatgagg aatggttgtg aacaatgaaa gtcaggtgat gtttaggtaa ctaagtctag 50220
gaaagagaaa tttaaagtag ctaagcacag acgtgcaaac atatgaaata tataaatatt 50280
taaagattat gaagcaagac atttgaaggt actaaattac ggattgtttc ctaagtgaga 50340
cacctcggtg gtgaccctcc ctctccacac atggaggaaa gaagtctaga atcatagagc 50400
ttactctgag aattgaccct cttaagccag gcattttctt gcaacatgat caaagaatac 50460
atgggtaaga cctcccctgg ctagctctcc tgtgctgggc cttcatttgc ttaaaggatg 50520
atgatgcaga tgcacaggac agcgtcatta ggaccagtgc ttcttaccag cctcttatgc 50580
ttttaccgct ggagcaagat tggaatgctc aaagcataca gaggtgacag tctgtggaac 50640
tgctctctgc ttctctctcc tgcctctatt gtaaaccaat tttcttctta tgctacgccg 50700
cagagaatac ttcaaattta gcagtgctat ctgccgtggg gtccaaataa aagagacaaa 50760
taaaaacaat tctatctcta ggatggaata gtctgtgaaa ttgtttcctg tacaaagata 50820
atttatatag aaaaaggggc cattgctcat ctttttcata caaatggaaa aaaaatcaat 50880
tctaatgact aataagggaa ttcaactctt ggcttctaaa ggcgtagggt agggagataa 50940
gacccaaagt ctctcggaac cctggtgttt atgcagatgt ttgcagtggt tctgagagtt 51000
gctggtataa atactcctct cgtttttatt atctgtttgt gcagactctc ctgggagtct 51060
ccagggagtc caccagtccc tacgaggacc atccattctc cttcttcaag tttgctttct 51120
ttccccgttc ctcgttccct ataagataac cttttaacca atgaccatcc tgacagccat 51180
tcctgcgccc accaatctga agttcagtca ggtgacaccc accagcttta ctgcccagtg 51240
gatagcaccc agtgttcagc tcactggcta ccgggtgcgg gtgaacccga aagagaagac 51300
aggaccaatg aaagaaatca acctttctcc agacagctca tcggtgattg tgtcaggact 51360
catggtaaga agtgagcttc cctctgcaga gtaaggcagg aggtcatttc atagagttca 51420
taggtgcaat ctcataataa acctagtgtt ctttgcttct accatcaaat agggttgtca 51480
caaatgtgta caatagaatt cttttatgta gacctaggat tttctagata ccctaagatg 51540
actattggat tagaatggtg taaatagctt tggatttcgt gcaggtcttt gacagaagta 51600
ttccacttat ttaaaagaag tggtattcgg tagggagcaa tttatataca cacacacaca 51660
cacacacaca cacacactct ggctgagttt atggctttta tgagtgatgt ttccctggca 51720
agacgcattc tccagttagt accagcctaa cttgacacta cccccattaa aacatttgac 51780
aatcagccag ctgtgcttta atcttgggag gcagaataag caggtggatt tctgagttcg 51840
agcccagctt ggtctacaag aatgagttcc aggacagcca gagatacaca aagagaccct 51900
gccgcaaaca agcaagcaag tagtatttaa aactttttct agccatgcag aaattagcta 51960
ggatcctata agggcttaat gcacatctta acacaaggcc aattcttaga gaagtagcag 52020
tagaatagaa gctttctctt gctttttttg tgatcaggaa aaaagcaaaa cctgatttat 52080
atctgtcata tcataaaggc aaaaaaaaaa aaaggctaag actgatttct ttcttattct 52140
ttttttgctg ctccttgtgg attgtggact taacccctga gaacatttta aaattcactt 52200
aatttaaatg taaatgtatt gtcactcata ggtaacagtg aagttgctct gggaacctgg 52260
gggtttgggg tttgctgggc tatgcagatg gtcttttata atcaccgcat ttctctaatg 52320
ctttggtaag aactccgggc atcatgcaac accattgcca aagtttctgg tacctctgct 52380
tccaggtggc cactaaatac gaagtcagtg tctatgctct caaggacaca ctgacaagca 52440
gaccagccca gggagtcatc actactctgg agagtgagta atccgatgag tgacatgttt 52500
taatcctgac acaccctgag tggaagtcaa aagaaaagat ctttacattt aagccactga 52560
cttagcaata gaatttggaa gttgatagaa cagcttgtcg tttcgggaat ccatccagga 52620
aatgacctgc cgaaacaaaa tggaatcact tcactgtgtt gtgttggtgc tggtgggtta 52680
aaactcacag ctggcttatg cggtactggt gagggtctgt attcgtaggg ttcaatgtgg 52740
ggaagatgaa ctggcttcca ccatagggaa tgtggggcta aattagatct gtggtctagt 52800
ctgttgatgt ttcatcacct atggaatgat taacacgtga agccttatag aaatgaccga 52860
agattcgcca cccagacaga cgttattact aattgtctgt gttataattc ctaccataca 52920
tccttacata ttagtaaagt aatcattgtc acacttgttt gacatagctc tagacactag 52980
agagtcaacc ctgggcacca ctgatagtat ttagaaagct tttctgttta gtgaacattt 53040
ccatatttcc tcaataccgt taacccatct ttctgtaacc tccacattac tttttagtgt 53100
atttcctgaa gtggatgtat ttgcataatg aggactcttt ttaaaatatc caaaccttac 53160
atgtatgagc caagcgtgct ttaatctctg gctctgctcc tacacagatg ttagccctcc 53220
aagaagggcc cgtgtgacgg acgctacaga gaccaccatc actattagct ggagaacaaa 53280
gacagagaca atcactggct tccaagtcga tgccatccca gccaatggcc agaccccagt 53340
tcagaggagc atcagcccgg atgttagaag ctacaccatt acaggtcagt gtactcgtgg 53400
tctgcctgtg tgcgcccgca ggagaccctg gctcggtaga tagtctggtc tggtattgag 53460
aatgtgggca ccattccacg atctgttggc ttcctgatgt ttgcttgacc tataaatctc 53520
attcattgaa tttgttgttt tataaatgct cattcattat tgtctaatga aaatctgcac 53580
actgtagtca taggcaggag tctgaggcag gaggatgtga gtttgagact agacatagtg 53640
aaaccctact ttttttaaag ttaatataga gaacataaag atacaaaata gtaaaattag 53700
catgcctaga ttttaaaagg cataatgaaa tttatgatta caaacagcat tatgtataat 53760
aaaaccggaa actgtaatca gagacgattc agtattggga cataagtgag gtgcttttga 53820
gatgagtttt tcattagtag tgacctgtcc accccgtgaa gccctttact cttccctgta 53880
actgcttctg ccagtatagg agtcaaggaa actgtaggca agcatgagaa ctcgcctagt 53940
aaagtaggag tggattaaac aggcgtcttt ttaacttcca ggtttacagc caggcactga 54000
ctacaagatc cacctgtaca ctctgaacga caatgcccgg agctcgcccg tgatcatcga 54060
tgcctccacc ggtaactatg ctttctatgg aggaaatgtc agctgctgca tattgtaatc 54120
agccgcgtca agtttagaaa cagttaggga gctggaattt ccatgttctg gctcccggga 54180
ctctctgatt ctctctctcc tcctctgttc gctagggctg ggctcaactg tgagaatgga 54240
cattcatttt tctaaggtgt cactttgctt gcctttcagc catcgacgca ccatccaacc 54300
tgcggttcct gaccaccaca cccaactcct tgctggtgtc atggcaggcg ccccgtgcca 54360
ggattactgg ctacattatc aagtatgaga agcctggatc ccctcccaga gaagtggtcc 54420
ctcggccccg ccctggtgtc acggaggcca ccattactgg tattgcttcc acactgtgat 54480
ttttttcccc ccttaatcat agatgcccca agtccataat actccccaat tgtgtctttg 54540
atgctatttc atgagaatga ggtgcccagc actctagatg ttctgtttag ggacagtagt 54600
tttctcaaga gatatgagca actgagcatg caatttcagt gccgtcctat gacacagctg 54660
tgatgtatta cactctggtg taaattcttc attattcccc cctcccccat aggataaatt 54720
gtgtgtatag attctcctgg atgttgaagt ctctaaaaca cacagatata aggagatcac 54780
agcttctttg ttgcatttat tgaagaagaa aataagagtc tgatatggga agacttaagc 54840
agaagacatc ctaatttttg ctctgtcact gacagctgtc tgagattaga cctaaataga 54900
agtctgaagt ctctgatggc ctctcccaaa tacatatttc attgtcggcc cacagtatag 54960
atagtttatc tacaggctga aagaatcctc taggaaggtt gccatgaaac tgctcattca 55020
agtatcagct gtggttgtga aatgactaac tagccaaggg gctttggggt tcgcagagta 55080
gataaacaag gagtgaagct gaaagacttc acaggcagct ggcaggaatg cctgctcccc 55140
agtcgcctct gctgagccaa tcactggccg tgcccgccaa cgtgagtgaa acggccgcgt 55200
ttcccatcag gtctggagcc aggaaccgag tacaccatct acgtcattgc cctgaagaac 55260
aatcagaaga gtgagcccct gattgggagg aagaagacag gtaaagactc ataaccagtg 55320
gttgctttgc agggtgaagt ctctacattt ccacacatca cacatctctc acggattttt 55380
tttatttccc tagcagagtg gcttatatat tttactcttt gacaggaatc acctaacatg 55440
ctctaaaaat gtctgattta tttctttttc tacaacctta agcttcgttt accttgcaga 55500
gattcaaact agatagtttg aattggaagg ggggggaagc tttataatgg tgggagtaaa 55560
acctttctga tttgggtcga tttatttatt atttgatttc tgaacttcaa acacttcagt 55620
tcgttgcaaa gccttaattg gagcagagat ggctttctgt ggggctcagc ggttcaaagc 55680
tttgtctgta tgagaattca tactaacttt tttttttttc tgtctgaact ataaagaaat 55740
ctgtgagaaa aaaaaaatca cgatttcttt ctctaagagt gttttgtgat ctgagaaccg 55800
ctggttgtgt gggagctctg atcgggttga taaacagttg ttgcctgggt tgacagtgat 55860
tggttgcttc ttcttcgagc ttaacttttg cgctttgctt ttttggctct aacctctctt 55920
ggctagatga gcttccccaa ctggttaccc ttccacaccc caatcttcat ggaccagaga 55980
tcttggatgt tccctccaca gttcaaaaga cccccttcat caccaaccct gggtatgaca 56040
ccgaaaatgg tattcagctt cctggcacaa cccaccagca acccagtgtt gggcaacaaa 56100
tgatctttga ggaacatggc tttaggcgga caacgccacc cactgcggcc acccccgtca 56160
ggcttaggcc aagaccatac ctgccgaatg tagatgagga ggtccaaatc ggtcatgttc 56220
ccaggggaga cgtagactac cacctctatc ctcatgttcc gggcctcaat ccaaatgcct 56280
ctacaggaca ggaagctctc tctcagacaa ccatctcttg gacgccgttc caggagagtt 56340
ctgagtacat catttcatgc caaccagttg gcaccgacga agagccctta caggtacatg 56400
acagcccttg caaagtgtct ctctatgtaa ctgtgtcttc agaaacaacc acagcttcat 56460
gtctgatgcc cactgtctta gtcagggttt ctattcctgc acaaatatca tgaccaagaa 56520
gcaagttggg gaggaaaggg tttattcggc ttacacttcc atactgctgt tcatcaccaa 56580
aggaagtcag gactgcaatt caagcaggtc aggaagcagg agctgatgca gaagccatgg 56640
agggatgttc cttactggct tgcttcccct ggcttgctca gcctgctctc ttatagaacc 56700
caagtctacc agcccagaga tggtcccacc cacaaggggc ctttgcccct tgatcactaa 56760
ttgagaaaat accccatagc tggatctcat ggaggcattt cccccaacta aagctccttt 56820
ctttgtgata accccagcct gtgtcaagtt gacacataac accagccagt atacccaccc 56880
tcccagggca gaggctacga ctctgactgg aggttgtttg actcagagag catcactgag 56940
cgtcacgcag tagagaaaac gaaattcttt ttattattct catacactgg agactactta 57000
gtgagatgga tgaaacaatt atcttaggaa gtagaggaaa agtaatttat atgaagtttg 57060
aaatgccacc tttggcgtct gtccttgaag aggcacgctg ttacgtgtct aggaagacga 57120
ggtgaaccgt tggggaccag ctgttatgag agatcgattc tccaaaactc tcttctttaa 57180
tttgtcccac aggtgctaga atcaattttt attgtgttat ttttagaaag tggcagaaat 57240
tttaaaattg actgtaccct aggacattta ttagcttaga aactttagtc tggggatgtg 57300
ccggtatttt aggaaaaccc aagttctact gtgttggcac cttacatggc acatgttgtc 57360
tgtctgtggc actcatgttt atgaaggggc tttttttcca ggagttctag tggccacagg 57420
attcagagga agctggtata gctgagggtt tctgggaatt gtggaacacc taggtagaaa 57480
aatctagcag aaatgatttt tttttaagtt actcttttaa taatttttta tgtaccttgg 57540
tgttttgtct gcatgtatgt cagggtgagg atgtcagaag ctctggaact ggagttacag 57600
atggttgtga gccaccatgt ggctgctggg aattgaaccc aggtcctctg gaagagcatt 57660
tagtgctctt aaccactgag ccatctcccc aatcttaaaa cgatggtttt ttgcactcat 57720
ttaatatctc atcttgacta ggtgggagtc ctatacagcc ctgttctctc ccttcgtctg 57780
tttttaaatg ggagtggggg attgctcata gactaaggaa gctcatgccg attcatcatt 57840
gaaatgcttt ctccctgctt tggatgtata gttccaagtt cctggaactt ctaccagtgc 57900
gactctgact ggccttacca gaggggtcac ctacaacatc atagtggagg cactgcagaa 57960
ccagaggagg cacaaggttc gggaagaggt tgtgactgtg ggcaacgctg gtaggtacac 58020
tgctggcctg ttgaggcaca cgcttcttgc tggatcagcc cagagaagac ttggtctgtc 58080
gttctttgtt ggctttaaac ttaggaaaat gagattgcac aacagtcaga gatgtcccct 58140
tatgtaaccc atatgttcac caacacatat tgacaggatg ccaggcctgg gagggacatg 58200
aatattattt actctaatac atttttcccc tcctgttgag gatccagttg acagaggcaa 58260
tggttttttg taccttttac tattctctca tcccatactg tggtccactt aagcgttcct 58320
aacccgaacc gaacacctat aaacagtcct ccttggcaat cttaagtgat gacttaggtt 58380
ttgtacctaa tgtaaaatgt taccaatatt gccctttgct ttcctaagag cttcccattc 58440
caaatttcaa ctttatatac ttctttgttt tcttcttctt tagatttacg tattttaatg 58500
ttatgtgtac gggtgttttg cctgcatgta tgtgtgcaac atgcattcag cacccatgga 58560
ggccagaaga ggacaccggg tcctctggaa ctggacttat agagggttgt tagtgactat 58620
gtgggtgcta gaacctatgt aatgtcctgt ggaagaggag ccagtgacat aactcctgag 58680
ccatctctcc agccccttta tatgtgtctt aatacataaa ttatatatgt catgttatat 58740
acatgcaagc tcttaaaggt taaatggcca tcatacaaac gtaataaaga tgaaacgacc 58800
cccatgcagc cttttaataa aggttaaatg accagcatgc aacatcttaa taaaggttaa 58860
ataaatttaa tcctgaaaat ttttgataaa ggttgaatga ccctgactct gagaagcctt 58920
ttgaagccag tgatgtgtca tttggcttaa gttgcaatag ctaaagattc accaaggagc 58980
atgagttaag ggctaactga gactggatcc cgagtcctct taccctggaa gggctaactc 59040
ccactttttc cagggagcag gacttctggg taggaccact gccttctttt cagccttctt 59100
cctcttagcg aagactgcta ttatttgact cttcagttaa gcagttgcat gtctggcaat 59160
gcagaagtgg gcagatcttc tgtgttccat ccacagtaat tagcatttgc cttttgtggt 59220
ttcactagta aaatgccact tgaaagggat ttttttcaaa agcatagggg ttttgtggtt 59280
ttccacatca ttttcttgaa ggtgtgtgtg tggtgtgttt cagacagtcc tactgtattg 59340
tatgctgttt gtatatagtg tgctagactg aactgctatg tagcccaggc tcctaatgtt 59400
agggcagacc tcctagatat tttaaaatag tgaaccccca tgagagtttt agcccctttg 59460
ttttctttcc gactcctgtc tttaccaggt cctcttggtt tcaaaacatt ttggatagac 59520
tttttagttc ttccagaatg atggcttttg aaatattagg catttcaaat attgatttca 59580
tttgcacttt tgatttttac actattaaaa gaagctatcc acaagtagga tttttttttt 59640
cctgagacag ggtttctctg tatatagccc tggctgtcct ggaactcact ctgtagacta 59700
ggctggcttc gaactcagaa atccgcctgc ctctgcctcc caagtacggg gatgaaatct 59760
tgggaaaccc actgcagctt ttctacttat tcctaactgc acggtggtga tttctcttac 59820
ttgaaaatca ggtcttatct agttttacag taaccataag catctaggtt ttcaaactat 59880
ttagcaaaag aaaagctaca atgtaagtaa agattgtgtt ataatgctat ataaagatgc 59940
taagacattg actacagcaa agacgtatct aacaataatt gttaattatt gagtaacagt 60000
agttagtaag tcatctctgc atagtgatac tggtccagag ctttgattcc tcagtttcat 60060
gtagccttta caagatccaa aaaagtgggg ctagttatat tattatcccg taatagatga 60120
gagaagagag acagacaaat gttaattggc tccatgtact caggtgtctt ggggaagcac 60180
cactgcccat attctcagct agttaaaatg cctgacgatc tgcttcatgt catgagaaac 60240
agaagacggg aatgaaggaa gacgtccttt gaccctgctg tgacaagtgc ctactgactg 60300
catcaaagtg ttgccgatga gaacgtctgt gttgttagtg ctgattaggt cacaatatac 60360
agtatggccg tttccccatc aataaccgtc aataaaatgt cttctccttt ttttcctttc 60420
tccttctttt cttcatagtc agcgaaggcc tgaaccagcc tacagatgac tcatgctttg 60480
acccttacac ggtttcccat tacgccattg gagaggagtg ggagcggttg tctgacgctg 60540
gctttaagct cacatgccag tgcttgggct ttggcagtgg tcatttcaga tgcgattcat 60600
ctagtgagta gcttgcgttc cccaccctct cactcctcca tctcttctgg tctcatgcgt 60660
tcgcactagg tggccacgga aacatgtttg gcagactcgg gctcttccaa acatgatgca 60720
aacagaagta gactgtttga ctccaagtaa cattttgcat catagaagga tgatgggaaa 60780
ttttacttgt gcaatatgac tgcatttcaa gagttgtgta ctaatctaac tattccttac 60840
aaatatatct gtagtgttga tatgctcctt gtagtgttta gctctatgta aattgaagtt 60900
aaaaaatatc tcattagagt ttggtttaat tgagacaggc aggcagagac tccaaattct 60960
tttcagtctt tagtattgag taaggacaga ggtgaacatt tatactcaca aacaccactt 61020
tttcagcata accagatata catgcacaca tcacacacac acatacacac acacacatct 61080
cacaacccag atatcccaaa cattgctcgt ataaaggaaa atgtctctct gtatagccct 61140
ggctgtcctg gaagtcactt tgtagaccag gtcggcctca aactcagaaa tctgcctgcc 61200
tctgccttct gagtgctggg attaaaggcg tgtgccacca cgcctagttt gcattctaca 61260
tttaaggatc aagttcaggg ctggtgagct aggctaggca tcccatccct ggaacccagg 61320
tggtgccagt ccccacaaat tgtcccttga ccttcacata ttcctggggg gacactaagg 61380
cccatatgta catacatatg tacacacaca tgcaaatcaa taaatctaat aaatgttaag 61440
atcaactttg actgaaaaat aatttgattt tcaaatctta aagaggttaa aatttcaaat 61500
tattagtgaa aatgatccta tgagttatct atgtttctag agatttagta ttggagtata 61560
taaccattca ttctttgttt ttagagctat aattattatt agctttttaa tgtgcttttt 61620
ttatgtgttc atcatatatc atagatatcc acaggcctat ggacaattat aggtcccata 61680
ttccatggaa tgacatttaa tagatctcta aagttttttg tgtaacattt tcctttcctt 61740
tacatgaaat agcaaaatcc agactggttt caatgtgtgt tgttgggtag agcccagtgg 61800
gcaatatacc atgctgggga caggagggac accatttggc cttgaccagg tgctttttca 61860
gagagtgaac tgcactgaag tttgcatgtt tttcataact cagtacaaat gtggacgtat 61920
acaatgattt ttatccgtga gcctctgact caccagtctt tgctggatat gtcataactg 61980
ccttatacat ttgctcatcg tttaaggaag gctgaattgt taaagtggaa gaatcactgc 62040
cctggatgag ggtcgtaagt gaactctgtt tagtataaat cttagaggtt aaagggcatt 62100
tttacatctg ccattagaca cagctcgtgg tgacttctta ggacttgtct atttgtacaa 62160
caagcctgat tcatttcatt tgtctttatt ttgttggctg ttatattcgt tcgttcttca 62220
cttatatgaa tcaggtgaca ccagctgttt ttctctttaa tcttcttgtt tgtttttgtt 62280
tgtttgcttt tgtcgttgtt tcatgagaca gggtttctct gtgtgtccct ggatgtggta 62340
cactcagtct gtagacaggg ctgtcctcaa actcagagat ctgcctgcct ctgcctccct 62400
aatgctggga gcaaattcgt gcacgacgac gcctgccctc tctttaatgt ttaattaaac 62460
tattttgtat ctaggatctc tgcgaaccta aaatatatat tttttaattc tccaatccca 62520
ttttaatttt ccatatttgt aaaatttaaa aggagctgaa tgaatcactg gttggtcctc 62580
tgaaatgatc ttggtggtag tgttaagtct taacactggc ctggaagata ttaaatgtta 62640
tgatgaagaa atgcttcatc attagaaatg tgatcttgga cttcctgctc tgtatggatt 62700
ttcgtcctgt tccagtgttc tgcccatcct gtgagtcaga acacagagta actctctgcc 62760
tgcgatgtcc ctaccttcca gaatggtgcc atgacaacgg tgtcaactac aagatcggag 62820
agaagtggga tcggcaggga gaaaatggcc agcggatgag ctgcacatgc ctcgggaatg 62880
gaaagggaga attcaagtgt gatccccgta cgtcatccta aaaatgcttt ctagactttt 62940
taagtactcc catgttccta actgagccga aacacccatt tacaggctgg gctggacgtg 63000
gtgggcttgt cagtctgtgg ttggtaagtc agtagcttgc ttcagaaagt gaatcatgac 63060
tgaatggcac gtctaagcac tttagcactt tcacaacttg agcactttgg tcatctgcag 63120
tgaagtgcta tgtagactca gtttttaaaa cataacttca aagccaagca gtggtggcac 63180
atgtctttaa tcccagcact tgggaggcag aggcaggagg atttctgagt tggaggacag 63240
cttggtctac acagagagaa cctgtctcaa aaaaccaaaa aaaaaaaaag acttcaatcg 63300
ttccatctgg cctagtctac caaggctttg gaacatctcc ttgtgattca cctaagttga 63360
tgagatttgg cccgtgctca ttcaggtcga gggcagatgc atcaacttga gtgtacctga 63420
ttgtccttgg tcttacaact gttcctttct gctctgtgcc cacgtgcaga tgaagcaacg 63480
tgctatgacg atgggaagac ctaccatgta ggagaacagt ggcagaaaga atatctcgga 63540
gccatttgct cctgcacgtg tttcggaggc cagcgggtaa gcctggttgg cgtttagata 63600
aagcacttag gaggttgcag catggatatg ctttgtgcac aggagccttg ccttttagga 63660
agagtctcta agatgggtgt ctcagttagg gtttgcgttg ctttgaagag acaccatgac 63720
caaggtaact tttataaggg acaatattta attggggctg gcttacagtt tcagaggttc 63780
agtccattat catcatggca ggaagcttgg cagtgtgcag gcagacatgg tactctagaa 63840
agagctgagt gttctgcatc ttgaactgac aaagacagct agaagaaagc tttcttcttc 63900
attgggtaga gcttgaacat aggacctcaa agcccacccc cacagtgact cacttcctct 63960
aacaaagagt gccacttccc atggaccaag catattcaaa ccaccacaat gggtctgtcc 64020
ctcccagttg ataatagctt cagcaccttc tcccatgact aaaattctca ggctgccctg 64080
tttgtcctcg cctggagtgt agcactaagg ccccagctct gagctgatgg actagcatct 64140
gagtattgtt cacattttta ataatactgt gatctaagaa aatttaacta tttttgagcc 64200
tttgttcaat ctaaaaatta ttatcactct aatactgagc taagtaacaa tagacacaca 64260
gggaagggtg gccgttgctc ttgaggatat acttggaggc agcaaattag cataccctgc 64320
caagccaagc taatcacagg agattttgac gaatacagtt ctggatggcc tgcaatcagc 64380
aagaaggctt cctagaaaag agaaacataa accagccgcc tggggtttag gatagctatc 64440
attaagtggg gagggaagga agcagagact acatacttcc tggcctaggg agagctggcc 64500
cagcgaggca gtccttccgc tggaatcttt tggtaagaaa ttagatttga ggaggagact 64560
catggaaagc tgggaaagcc atcatttaag acagtaattc tcagtcatgt ctaacgtggg 64620
cccttcttca atataacaac aacttccact ccatctttta ataagtgaaa tatcaaaatg 64680
acttttaact taaatgtaat agggggctgg agatggtggc acatcccttt aatcccagca 64740
ctcagagtag tcagaggcag gtagatctct tgagtacgag ggcagcctgg tccacaaagc 64800
aagttccagg acagccaggg ctacacagag aaaccctgat tcataaaaac gaaacaaaca 64860
aaaaaagaaa atgatcgggc aggtcccaca agtttccctt tgacctccac acattttggg 64920
cacatgtgta tacatacaca tatgtaaata aatgtgctta attttttagg aattaaattg 64980
ttatgtaaag ggcttgacct taaagggtcc cagaaatctg gggcacaagg aataatgccc 65040
ctcaccccca cagtgaagtt cacccattaa tgctattggc attcatcaat gattaaaagt 65100
agcataatgg acaataacct tttaaaaaaa tgaatctggg agctggagaa atggctcagt 65160
gcttaatggg actcactgtt ctcctgggga cctggacttg gtttctctcc tcacatggtc 65220
cataaccacc attcccagaa gaactgacgt cctcatctgg cttccttgag catcatgcac 65280
acatggtgca cagacataca cacaggcaag cacttatcac ataaaataaa aacatatgat 65340
aaatcctttt taaaagaaga agggcagtta atgtggccac aagaaagact ctatgtatca 65400
tcacaacctt cttaggtctg ggcagccggc aggattgaca atctcgtttt atctgttatt 65460
catggagtgg actgtctgtc cctctgtctc tctgtctctt tctcagacac acagaagcag 65520
atcatatgac tcagtcatca tggtctgaat gagtggcttt gttgggaggc agattttagt 65580
ctttcttcac tccattcttg ttccctatga acgggaatct ctttgggtaa tgcctgtctc 65640
taaagttctg aaacatggtg gcggttgcta tggtctttga gaatcgttat tgattctgca 65700
agcaggccct ctgggaaata ggctcctaaa tggagaaata cgtcaaagat gtttaaatga 65760
ttctataaga aagtgattgt aggatttatt tatttttgag acagagtcta gtagccctga 65820
ctatcctgga acttgctatg tagagcaggc tggccttcag ctcacagaga tctacctgcc 65880
tctgggtgtg tgccaccact ctccagcctg gccttatttc ttcattttgt tgttgttgtt 65940
gttgttgttt tcaaccctaa atgtaaagtc ttgctagtta ggcaaaagat ggctaccaac 66000
atgaactccc ccattctgtg aacttcaagg actactttgc cccaagagtg cgcctctctc 66060
tgtgtccccc tagtgtccat ttctgtgtcc cctggggctt ctgctaatgg tgccatcgtt 66120
caccacatca gctccagatc ttcctcctcc cagctcagga gtgatgagaa agcaaatgtg 66180
tgccagcaaa actcaggaag aagcacaggc ccgctgtggt gtcttcctgt acccagcccc 66240
acctctggcc agagctaagg ctatatagta taggttaggg aggttttaga agggactgga 66300
aagagaatgt ggccaggtac ccagttctac ctgggaccca cggcgtcctt tctggttcct 66360
tccaagtcat tcctctcctt caccagaaag tgatggcatt tgtccccaca ctctcaagtc 66420
actgtgactg atttcgcagc cctaggggtc tgtgagaaat cttccaccta gagcagaaag 66480
cctaccaagg aggaaggtag gaccaaagat gagaagagca aaagaagtga ggaggatatt 66540
tcagcggaaa ggaaagcata tgtagacaga tgaataagcc aagatctatt gtaagagtta 66600
cgactgtaca caggcatcat tgcagtctcc tgattaactg cttgtactgc tgatgggcaa 66660
gagctgaaac tcagtcatga taccctcagg ttatcctaaa ccccatttaa cttcgtgtct 66720
ttcctctcag ggctggcgct gtgacaactg ccgtagacct ggggctgctg aacccagtcc 66780
cgatggcacc accggccaca cctacaacca gtatacacag agatacaatc agagaacaaa 66840
cactgtaagt gtacacatat ccccacccac ccccaccacc gtgactctcc ctgcatgcag 66900
ccaggggcag gtggatagat gcttttcttg aatgaaccaa atgagtttta tttggagata 66960
agtcttttgc tcatgagtcc agtcctcagg acccatccat gtaaaagagc taggcgctac 67020
agcaagtgct tataatctcc tcactgagga ggtagaaata gggtgtgggt ggtgtccctg 67080
gggctgtctg gccagccact gtagccttgt taatgaactt caggctcatg aacaaagcag 67140
acagcatttg cttgattaaa gttaactctt ggctccttat acacacaaag tcatgaatta 67200
attataactc gttataattt actaaatccc taagcattgt ctattgctca gtacattgct 67260
agtcttttga aactatttat ccttcctata aaacacctgt gacacaaatc tccactcaac 67320
cctccccgaa acacacacac ttttggtttt ccgagtattt gctactaatg tttgtcttct 67380
attttgacag aacgtaaatt gccccattga gtgcttcatg ccgctagatg tgcaagctga 67440
cagagacgat tctcgagagt aatctttcca gccccaccct acaagtgtct ctctaccaag 67500
gtcaatccac accccagtga tgttagcaga ccctccatct ttgagtggtc ctttcaccct 67560
taagcctttt gctctggagc catgttctca gcttcagcac aatttacagc ttctccaagc 67620
atcgccccgt gggatgtttt gagacttctc tcctcaatgg tgacagttgg tcaccctgtt 67680
ctgcttcagg gtttcagtac tgctcagtgt tgtttaagag aatcaaaagt tcttatggtt 67740
tggtctggga tcaataggga aacacaggta gccaactagg aggaaatgta ctgaatgcta 67800
gtacccaaga ccttgagcag gaaagtcacc cagacacctc tgctttcttt tgccatctga 67860
cctgcagcac tgtcaggaca tggcctgtgg ctgtgtgttc aaacacccct cccacaggac 67920
tcactttgtc ccaacaattc agattgccta gaaatacctt tctcttacct gtttgttatt 67980
tatcaatttt tcccagtatt tttatacgga aaaaattgta ttgaagacac tttgtatgca 68040
gttgataaga ggaattcagt ataattatgg ttggtgatta tttttataag cacatgccaa 68100
cgctttacta ctgtggaaag acaagtgttt taataaaaag atttacattc catgatgtgg 68160
acgtcatttc tttttttttt taacatcatg tgtttggaga gaaaaattgt cttcatgcat 68220
gtcctttttc ttttcgatgc tacaagcatg tgaagaggca ctgtgttggg ctggggtggt 68280
ttctgcacat gagcgcctgc ctggccttac agaagcactg atactttgcg tcattttgtg 68340
tcctcacttg tggttctgcc ttatcagatt taaatggatt caaatgtggg ctaagcttgc 68400
tagctagcac gttaggagta taaaggaaat aagattcgtg tgtgtgtgtg tgtgtgtgtg 68460
tacatacata caagtgtgtg tgtagctgct catgaaaatc aggaggccag aaggggatgc 68520
tgggtccctt agagctggat acaagtgttt gtgagataga tactgggatt tgaactcata 68580
acagagcggc aaatgccctc acctctccag ccctatagtt ctgtttaatc atcacaggcc 68640
tttgcttctt t 68651
<210> SEQ ID NO 30
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 30
gtaagaggtt atgtg 15
<210> SEQ ID NO 31
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 31
ttaatggtaa gaggt 15
<210> SEQ ID NO 32
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 32
aatgtctgtt aggcaaat 18
<210> SEQ ID NO 33
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 33
caatgtctgt taggcaaa 18
<210> SEQ ID NO 34
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 34
tcaatgtctg ttaggcaa 18
<210> SEQ ID NO 35
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 35
aatgtctgtt aggca 15
<210> SEQ ID NO 36
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 36
atcaatgtct gttaggca 18
<210> SEQ ID NO 37
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 37
caatgtctgt taggc 15
<210> SEQ ID NO 38
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 38
cgatcaatgt ctgttagg 18
<210> SEQ ID NO 39
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 39
atcaatgtct gttag 15
<210> SEQ ID NO 40
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 40
gcgatcaatg tctgttag 18
<210> SEQ ID NO 41
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 41
gatcaatgtc tgtta 15
<210> SEQ ID NO 42
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 42
ggcgatcaat gtctgtta 18
<210> SEQ ID NO 43
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 43
gccagtcctt taggg 15
<210> SEQ ID NO 44
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 44
gtgaatgcca gtcct 15
<210> SEQ ID NO 45
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 45
acatcagtga atgcc 15
<210> SEQ ID NO 46
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 46
acatccacat cagtg 15
<210> SEQ ID NO 47
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 47
gaatcgacat ccaca 15
<210> SEQ ID NO 48
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 48
ttgatggaat cgaca 15
<210> SEQ ID NO 49
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 49
gcaattttga tggaa 15
<210> SEQ ID NO 50
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 50
tcccaagcaa ttttg 15
<210> SEQ ID NO 51
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 51
gggctttccc aagca 15
<210> SEQ ID NO 52
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 52
ccctgtgggc tttcc 15
<210> SEQ ID NO 53
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 53
acttgcccct gtggg 15
<210> SEQ ID NO 54
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 54
ctggaaactt gcccc 15
<210> SEQ ID NO 55
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 55
ctgtacctgg aaact 15
<210> SEQ ID NO 56
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 56
gtcaccctgt acctg 15
<210> SEQ ID NO 57
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 57
gagtaggtca ccctg 15
<210> SEQ ID NO 58
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 58
gggctcgagt aggtc 15
<210> SEQ ID NO 59
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 59
tcctcagggc tcgag 15
<210> SEQ ID NO 60
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 60
attccatcct caggg 15
<210> SEQ ID NO 61
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 61
tcatggattc catcc 15
<210> SEQ ID NO 62
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 62
aatagctcat ggatt 15
<210> SEQ ID NO 63
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 63
gcagggaata gctca 15
<210> SEQ ID NO 64
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 64
tcaggtgcag ggaat 15
<210> SEQ ID NO 65
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 65
tcaccatcag gtgca 15
<210> SEQ ID NO 66
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 66
tcttcttcac catca 15
<210> SEQ ID NO 67
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 67
gcagtgtctt cttca 15
<210> SEQ ID NO 68
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 68
agctctgcag tgtct 15
<210> SEQ ID NO 69
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 69
ccttgcagct ctgca 15
<210> SEQ ID NO 70
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 70
ctgaggcctt gcagc 15
<210> SEQ ID NO 71
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 71
cccggtctga ggcct 15
<210> SEQ ID NO 72
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 72
tcagaacccg gtctg 15
<210> SEQ ID NO 73
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 73
gtgtactcag aaccc 15
<210> SEQ ID NO 74
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 74
ctgactgtgt actca 15
<210> SEQ ID NO 75
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 75
accacactga ctgtg 15
<210> SEQ ID NO 76
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 76
aaggcaacca cactg 15
<210> SEQ ID NO 77
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 77
tcgtgcaagg caacc 15
<210> SEQ ID NO 78
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 78
atatcatcgt gcaag 15
<210> SEQ ID NO 79
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 79
ctctccatat catcg 15
<210> SEQ ID NO 80
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 80
ggctggctct ccata 15
<210> SEQ ID NO 81
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 81
gattccaatc agggg 15
<210> SEQ ID NO 82
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 82
actggattcc aatca 15
<210> SEQ ID NO 83
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 83
tggactggat tccaa 15
<210> SEQ ID NO 84
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 84
cctgtggact ggattcca 18
<210> SEQ ID NO 85
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 85
ctgtggactg gattc 15
<210> SEQ ID NO 86
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 86
tacctgtgga ctgga 15
<210> SEQ ID NO 87
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 87
aacgatatac ctgtg 15
<210> SEQ ID NO 88
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 88
aattaatcat aaacc 15
<210> SEQ ID NO 89
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 89
ggtgcaatta accat 15
<210> SEQ ID NO 90
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 90
cctggtggtg caatt 15
<210> SEQ ID NO 91
<211> LENGTH: 20
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Primer
<400> SEQUENCE: 91
gccttgcacg atgatatgga 20
<210> SEQ ID NO 92
<211> LENGTH: 21
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Primer
<400> SEQUENCE: 92
tgtgggtgtg acctgagtga a 21
<210> SEQ ID NO 93
<211> LENGTH: 17
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Probe
<400> SEQUENCE: 93
attggaaccc agtccac 17
<210> SEQ ID NO 94
<211> LENGTH: 21
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Primer
<400> SEQUENCE: 94
gaatccaagc ggagagagtc a 21
<210> SEQ ID NO 95
<211> LENGTH: 23
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Primer
<400> SEQUENCE: 95
acatcagtga atgccagtcc ttt 23
<210> SEQ ID NO 96
<211> LENGTH: 30
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Probe
<400> SEQUENCE: 96
ttcagactgc agtaaccaac attgatcgcc 30
<210> SEQ ID NO 97
<211> LENGTH: 8374
<212> TYPE: DNA
<213> ORGANISM: Homo sapiens
<400> SEQUENCE: 97
gcccgcgccg gctgtgctgc acagggggag gagagggaac cccaggcgcg agcgggaaga 60
ggggacctgc agccacaact tctctggtcc tctgcatccc ttctgtccct ccacccgtcc 120
ccttccccac cctctggccc ccaccttctt ggaggcgaca acccccggga ggcattagaa 180
gggatttttc ccgcaggttg cgaagggaag caaacttggt ggcaacttgc ctcccggtgc 240
gggcgtctct cccccaccgt ctcaacatgc ttaggggtcc ggggcccggg ctgctgctgc 300
tggccgtcca gtgcctgggg acagcggtgc cctccacggg agcctcgaag agcaagaggc 360
aggctcagca aatggttcag ccccagtccc cggtggctgt cagtcaaagc aagcccggtt 420
gttatgacaa tggaaaacac tatcagataa atcaacagtg ggagcggacc tacctaggca 480
atgcgttggt ttgtacttgt tatggaggaa gccgaggttt taactgcgag agtaaacctg 540
aagctgaaga gacttgcttt gacaagtaca ctgggaacac ttaccgagtg ggtgacactt 600
atgagcgtcc taaagactcc atgatctggg actgtacctg catcggggct gggcgaggga 660
gaataagctg taccatcgca aaccgctgcc atgaaggggg tcagtcctac aagattggtg 720
acacctggag gagaccacat gagactggtg gttacatgtt agagtgtgtg tgtcttggta 780
atggaaaagg agaatggacc tgcaagccca tagctgagaa gtgttttgat catgctgctg 840
ggacttccta tgtggtcgga gaaacgtggg agaagcccta ccaaggctgg atgatggtag 900
attgtacttg cctgggagaa ggcagcggac gcatcacttg cacttctaga aatagatgca 960
acgatcagga cacaaggaca tcctatagaa ttggagacac ctggagcaag aaggataatc 1020
gaggaaacct gctccagtgc atctgcacag gcaacggccg aggagagtgg aagtgtgaga 1080
ggcacacctc tgtgcagacc acatcgagcg gatctggccc cttcaccgat gttcgtgcag 1140
ctgtttacca accgcagcct cacccccagc ctcctcccta tggccactgt gtcacagaca 1200
gtggtgtggt ctactctgtg gggatgcagt ggctgaagac acaaggaaat aagcaaatgc 1260
tttgcacgtg cctgggcaac ggagtcagct gccaagagac agctgtaacc cagacttacg 1320
gtggcaactc aaatggagag ccatgtgtct taccattcac ctacaatggc aggacgttct 1380
actcctgcac cacagaaggg cgacaggacg gacatctttg gtgcagcaca acttcgaatt 1440
atgagcagga ccagaaatac tctttctgca cagaccacac tgttttggtt cagactcgag 1500
gaggaaattc caatggtgcc ttgtgccact tccccttcct atacaacaac cacaattaca 1560
ctgattgcac ttctgagggc agaagagaca acatgaagtg gtgtgggacc acacagaact 1620
atgatgccga ccagaagttt gggttctgcc ccatggctgc ccacgaggaa atctgcacaa 1680
ccaatgaagg ggtcatgtac cgcattggag atcagtggga taagcagcat gacatgggtc 1740
acatgatgag gtgcacgtgt gttgggaatg gtcgtgggga atggacatgc attgcctact 1800
cgcagcttcg agatcagtgc attgttgatg acatcactta caatgtgaac gacacattcc 1860
acaagcgtca tgaagagggg cacatgctga actgtacatg cttcggtcag ggtcggggca 1920
ggtggaagtg tgatcccgtc gaccaatgcc aggattcaga gactgggacg ttttatcaaa 1980
ttggagattc atgggagaag tatgtgcatg gtgtcagata ccagtgctac tgctatggcc 2040
gtggcattgg ggagtggcat tgccaacctt tacagaccta tccaagctca agtggtcctg 2100
tcgaagtatt tatcactgag actccgagtc agcccaactc ccaccccatc cagtggaatg 2160
caccacagcc atctcacatt tccaagtaca ttctcaggtg gagacctaaa aattctgtag 2220
gccgttggaa ggaagctacc ataccaggcc acttaaactc ctacaccatc aaaggcctga 2280
agcctggtgt ggtatacgag ggccagctca tcagcatcca gcagtacggc caccaagaag 2340
tgactcgctt tgacttcacc accaccagca ccagcacacc tgtgaccagc aacaccgtga 2400
caggagagac gactcccttt tctcctcttg tggccacttc tgaatctgtg accgaaatca 2460
cagccagtag ctttgtggtc tcctgggtct cagcttccga caccgtgtcg ggattccggg 2520
tggaatatga gctgagtgag gagggagatg agccacagta cctggatctt ccaagcacag 2580
ccacttctgt gaacatccct gacctgcttc ctggccgaaa atacattgta aatgtctatc 2640
agatatctga ggatggggag cagagtttga tcctgtctac ttcacaaaca acagcgcctg 2700
atgcccctcc tgacccgact gtggaccaag ttgatgacac ctcaattgtt gttcgctgga 2760
gcagacccca ggctcccatc acagggtaca gaatagtcta ttcgccatca gtagaaggta 2820
gcagcacaga actcaacctt cctgaaactg caaactccgt caccctcagt gacttgcaac 2880
ctggtgttca gtataacatc actatctatg ctgtggaaga aaatcaagaa agtacacctg 2940
ttgtcattca acaagaaacc actggcaccc cacgctcaga tacagtgccc tctcccaggg 3000
acctgcagtt tgtggaagtg acagacgtga aggtcaccat catgtggaca ccgcctgaga 3060
gtgcagtgac cggctaccgt gtggatgtga tccccgtcaa cctgcctggc gagcacgggc 3120
agaggctgcc catcagcagg aacacctttg cagaagtcac cgggctgtcc cctggggtca 3180
cctattactt caaagtcttt gcagtgagcc atgggaggga gagcaagcct ctgactgctc 3240
aacagacaac caaactggat gctcccacta acctccagtt tgtcaatgaa actgattcta 3300
ctgtcctggt gagatggact ccacctcggg cccagataac aggataccga ctgaccgtgg 3360
gccttacccg aagaggacag cccaggcagt acaatgtggg tccctctgtc tccaagtacc 3420
cactgaggaa tctgcagcct gcatctgagt acaccgtatc cctcgtggcc ataaagggca 3480
accaagagag ccccaaagcc actggagtct ttaccacact gcagcctggg agctctattc 3540
caccttacaa caccgaggtg actgagacca ccattgtgat cacatggacg cctgctccaa 3600
gaattggttt taagctgggt gtacgaccaa gccagggagg agaggcacca cgagaagtga 3660
cttcagactc aggaagcatc gttgtgtccg gcttgactcc aggagtagaa tacgtctaca 3720
ccatccaagt cctgagagat ggacaggaaa gagatgcgcc aattgtaaac aaagtggtga 3780
caccattgtc tccaccaaca aacttgcatc tggaggcaaa ccctgacact ggagtgctca 3840
cagtctcctg ggagaggagc accaccccag acattactgg ttatagaatt accacaaccc 3900
ctacaaacgg ccagcaggga aattctttgg aagaagtggt ccatgctgat cagagctcct 3960
gcacttttga taacctgagt cccggcctgg agtacaatgt cagtgtttac actgtcaagg 4020
atgacaagga aagtgtccct atctctgata ccatcatccc agctgttcct cctcccactg 4080
acctgcgatt caccaacatt ggtccagaca ccatgcgtgt cacctgggct ccacccccat 4140
ccattgattt aaccaacttc ctggtgcgtt actcacctgt gaaaaatgag gaagatgttg 4200
cagagttgtc aatttctcct tcagacaatg cagtggtctt aacaaatctc ctgcctggta 4260
cagaatatgt agtgagtgtc tccagtgtct acgaacaaca tgagagcaca cctcttagag 4320
gaagacagaa aacaggtctt gattccccaa ctggcattga cttttctgat attactgcca 4380
actcttttac tgtgcactgg attgctcctc gagccaccat cactggctac aggatccgcc 4440
atcatcccga gcacttcagt gggagacctc gagaagatcg ggtgccccac tctcggaatt 4500
ccatcaccct caccaacctc actccaggca cagagtatgt ggtcagcatc gttgctctta 4560
atggcagaga ggaaagtccc ttattgattg gccaacaatc aacagtttct gatgttccga 4620
gggacctgga agttgttgct gcgaccccca ccagcctact gatcagctgg gatgctcctg 4680
ctgtcacagt gagatattac aggatcactt acggagagac aggaggaaat agccctgtcc 4740
aggagttcac tgtgcctggg agcaagtcta cagctaccat cagcggcctt aaacctggag 4800
ttgattatac catcactgtg tatgctgtca ctggccgtgg agacagcccc gcaagcagca 4860
agccaatttc cattaattac cgaacagaaa ttgacaaacc atcccagatg caagtgaccg 4920
atgttcagga caacagcatt agtgtcaagt ggctgccttc aagttcccct gttactggtt 4980
acagagtaac caccactccc aaaaatggac caggaccaac aaaaactaaa actgcaggtc 5040
cagatcaaac agaaatgact attgaaggct tgcagcccac agtggagtat gtggttagtg 5100
tctatgctca gaatccaagc ggagagagtc agcctctggt tcagactgca gtaaccaaca 5160
ttgatcgccc taaaggactg gcattcactg atgtggatgt cgattccatc aaaattgctt 5220
gggaaagccc acaggggcaa gtttccaggt acagggtgac ctactcgagc cctgaggatg 5280
gaatccatga gctattccct gcacctgatg gtgaagaaga cactgcagag ctgcaaggcc 5340
tcagaccggg ttctgagtac acagtcagtg tggttgcctt gcacgatgat atggagagcc 5400
agcccctgat tggaacccag tccacagcta ttcctgcacc aactgacctg aagttcactc 5460
aggtcacacc cacaagcctg agcgcccagt ggacaccacc caatgttcag ctcactggat 5520
atcgagtgcg ggtgaccccc aaggagaaga ccggaccaat gaaagaaatc aaccttgctc 5580
ctgacagctc atccgtggtt gtatcaggac ttatggtggc caccaaatat gaagtgagtg 5640
tctatgctct taaggacact ttgacaagca gaccagctca gggagttgtc accactctgg 5700
agaatgtcag cccaccaaga agggctcgtg tgacagatgc tactgagacc accatcacca 5760
ttagctggag aaccaagact gagacgatca ctggcttcca agttgatgcc gttccagcca 5820
atggccagac tccaatccag agaaccatca agccagatgt cagaagctac accatcacag 5880
gtttacaacc aggcactgac tacaagatct acctgtacac cttgaatgac aatgctcgga 5940
gctcccctgt ggtcatcgac gcctccactg ccattgatgc accatccaac ctgcgtttcc 6000
tggccaccac acccaattcc ttgctggtat catggcagcc gccacgtgcc aggattaccg 6060
gctacatcat caagtatgag aagcctgggt ctcctcccag agaagtggtc cctcggcccc 6120
gccctggtgt cacagaggct actattactg gcctggaacc gggaaccgaa tatacaattt 6180
atgtcattgc cctgaagaat aatcagaaga gcgagcccct gattggaagg aaaaagacag 6240
ttcaaaagac ccctttcgtc acccaccctg ggtatgacac tggaaatggt attcagcttc 6300
ctggcacttc tggtcagcaa cccagtgttg ggcaacaaat gatctttgag gaacatggtt 6360
ttaggcggac cacaccgccc acaacggcca cccccataag gcataggcca agaccatacc 6420
cgccgaatgt aggacaagaa gctctctctc agacaaccat ctcatgggcc ccattccagg 6480
acacttctga gtacatcatt tcatgtcatc ctgttggcac tgatgaagaa cccttacagt 6540
tcagggttcc tggaacttct accagtgcca ctctgacagg cctcaccaga ggtgccacct 6600
acaacatcat agtggaggca ctgaaagacc agcagaggca taaggttcgg gaagaggttg 6660
ttaccgtggg caactctgtc aacgaaggct tgaaccaacc tacggatgac tcgtgctttg 6720
acccctacac agtttcccat tatgccgttg gagatgagtg ggaacgaatg tctgaatcag 6780
gctttaaact gttgtgccag tgcttaggct ttggaagtgg tcatttcaga tgtgattcat 6840
ctagatggtg ccatgacaat ggtgtgaact acaagattgg agagaagtgg gaccgtcagg 6900
gagaaaatgg ccagatgatg agctgcacat gtcttgggaa cggaaaagga gaattcaagt 6960
gtgaccctca tgaggcaacg tgttatgatg atgggaagac ataccacgta ggagaacagt 7020
ggcagaagga atatctcggt gccatttgct cctgcacatg ctttggaggc cagcggggct 7080
ggcgctgtga caactgccgc agacctgggg gtgaacccag tcccgaaggc actactggcc 7140
agtcctacaa ccagtattct cagagatacc atcagagaac aaacactaat gttaattgcc 7200
caattgagtg cttcatgcct ttagatgtac aggctgacag agaagattcc cgagagtaaa 7260
tcatctttcc aatccagagg aacaagcatg tctctctgcc aagatccatc taaactggag 7320
tgatgttagc agacccagct tagagttctt ctttctttct taagcccttt gctctggagg 7380
aagttctcca gcttcagctc aactcacagc ttctccaagc atcaccctgg gagtttcctg 7440
agggttttct cataaatgag ggctgcacat tgcctgttct gcttcgaagt attcaatacc 7500
gctcagtatt ttaaatgaag tgattctaag atttggtttg ggatcaatag gaaagcatat 7560
gcagccaacc aagatgcaaa tgttttgaaa tgatatgacc aaaattttaa gtaggaaagt 7620
cacccaaaca cttctgcttt cacttaagtg tctggcccgc aatactgtag gaacaagcat 7680
gatcttgtta ctgtgatatt ttaaatatcc acagtactca ctttttccaa atgatcctag 7740
taattgccta gaaatatctt tctcttacct gttatttatc aatttttccc agtattttta 7800
tacggaaaaa attgtattga aaacacttag tatgcagttg ataagaggaa tttggtataa 7860
ttatggtggg tgattatttt ttatactgta tgtgccaaag ctttactact gtggaaagac 7920
aactgtttta ataaaagatt tacattccac aacttgaagt tcatctattt gatataagac 7980
accttcgggg gaaataattc ctgtgaatat tctttttcaa ttcagcaaac atttgaaaat 8040
ctatgatgtg caagtctaat tgttgatttc agtacaagat tttctaaatc agttgctaca 8100
aaaactgatt ggtttttgtc acttcatctc ttcactaatg gagatagctt tacactttct 8160
gctttaatag atttaagtgg accccaatat ttattaaaat tgctagttta ccgttcagaa 8220
gtataataga aataatcttt agttgctctt ttctaaccat tgtaattctt cccttcttcc 8280
ctccaccttt ccttcattga ataaacctct gttcaaagag attgcctgca agggaaataa 8340
aaatgactaa gatattaaaa aaaaaaaaaa aaaa 8374
<210> SEQ ID NO 98
<211> LENGTH: 24
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Primer
<400> SEQUENCE: 98
aaactgcagt gaccaacatt gatc 24
<210> SEQ ID NO 99
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Primer
<400> SEQUENCE: 99
cttgcccctg tgggcttt 18
<210> SEQ ID NO 100
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Probe
<400> SEQUENCE: 100
ctgatgtgga tgtcgatt 18
<210> SEQ ID NO 101
<211> LENGTH: 17
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Primer
<400> SEQUENCE: 101
gccagcccct gattgga 17
<210> SEQ ID NO 102
<211> LENGTH: 20
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Primer
<400> SEQUENCE: 102
ccggtagcca gtgagctgaa 20
<210> SEQ ID NO 103
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Probe
<400> SEQUENCE: 103
caccaatctg aagttc 16
<210> SEQ ID NO 104
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 104
gcaaattaat ggtaa 15
<210> SEQ ID NO 105
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 105
cgatcaatgt ctgtt 15
<210> SEQ ID NO 106
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 106
tccataccat gcaaa 15
<210> SEQ ID NO 107
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 107
atatttccat accat 15
<210> SEQ ID NO 108
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 108
caagcatatt tccat 15
<210> SEQ ID NO 109
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 109
tgaaacaagc atatt 15
<210> SEQ ID NO 110
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 110
agttgtgaaa caagc 15
<210> SEQ ID NO 111
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 111
aagcaagttg tgaaa 15
<210> SEQ ID NO 112
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 112
gtgaaaagca agttg 15
<210> SEQ ID NO 113
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 113
gttatgtgaa aagca 15
<210> SEQ ID NO 114
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 114
aagaggttat gtgaa 15
<210> SEQ ID NO 115
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 115
atggtaagag gttat 15
<210> SEQ ID NO 116
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 116
aattaatggt aagag 15
<210> SEQ ID NO 117
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 117
aggcaaatta atggt 15
<210> SEQ ID NO 118
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 118
ctgttaggca aatta 15
<210> SEQ ID NO 119
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 119
tagggcgatc aatgt 15
<210> SEQ ID NO 120
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 120
tcctttaggg cgatc 15
<210> SEQ ID NO 121
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 121
tgaatgccag tcctt 15
<210> SEQ ID NO 122
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 122
atcagtgaat gccag 15
<210> SEQ ID NO 123
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 123
tccacatcag tgaat 15
<210> SEQ ID NO 124
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 124
cgacatccac atcag 15
<210> SEQ ID NO 125
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 125
ggaatcgaca tccac 15
<210> SEQ ID NO 126
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 126
caattttgat ggaat 15
<210> SEQ ID NO 127
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 127
ccaagcaatt ttgat 15
<210> SEQ ID NO 128
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 128
ctttcccaag caatt 15
<210> SEQ ID NO 129
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 129
gtgggctttc ccaag 15
<210> SEQ ID NO 130
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 130
cccctgtggg ctttc 15
<210> SEQ ID NO 131
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 131
tggaaacttg cccct 15
<210> SEQ ID NO 132
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 132
gtacctggaa acttg 15
<210> SEQ ID NO 133
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 133
accctgtacc tggaa 15
<210> SEQ ID NO 134
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 134
aggtcaccct gtacc 15
<210> SEQ ID NO 135
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 135
cgagtaggtc accct 15
<210> SEQ ID NO 136
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 136
cctcagggct cgagt 15
<210> SEQ ID NO 137
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 137
tccatcctca gggct 15
<210> SEQ ID NO 138
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 138
cggattccat cctca 15
<210> SEQ ID NO 139
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 139
gctcccggat tccat 15
<210> SEQ ID NO 140
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 140
gaaaagctcc cggat 15
<210> SEQ ID NO 141
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 141
gcagggaaaa gctcc 15
<210> SEQ ID NO 142
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 142
caggtgcagg gaaaa 15
<210> SEQ ID NO 143
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 143
accatcaggt gcagg 15
<210> SEQ ID NO 144
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 144
tcttcaccat caggt 15
<210> SEQ ID NO 145
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 145
tgtcgtcttc accat 15
<210> SEQ ID NO 146
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 146
tgcagtgtcg tcttc 15
<210> SEQ ID NO 147
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 147
agctctgcag tgtcg 15
<210> SEQ ID NO 148
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 148
cctgcagctc tgcag 15
<210> SEQ ID NO 149
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 149
gaggccctgc agctc 15
<210> SEQ ID NO 150
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 150
ggcctgaggc cctgc 15
<210> SEQ ID NO 151
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 151
accccggcct gaggc 15
<210> SEQ ID NO 152
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 152
ctcagacccc ggcct 15
<210> SEQ ID NO 153
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 153
gtgtactcag acccc 15
<210> SEQ ID NO 154
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 154
tgactgtgta ctcag 15
<210> SEQ ID NO 155
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 155
cacactgact gtgta 15
<210> SEQ ID NO 156
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 156
gcaaccacac tgact 15
<210> SEQ ID NO 157
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 157
gcaaggcaac cacac 15
<210> SEQ ID NO 158
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 158
atcgtgcaag gcaac 15
<210> SEQ ID NO 159
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 159
tctccatatc atcgt 15
<210> SEQ ID NO 160
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 160
ctggctctcc atatc 15
<210> SEQ ID NO 161
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 161
gactggattc caatc 15
<210> SEQ ID NO 162
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 162
tatacctgtg gactg 15
<210> SEQ ID NO 163
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 163
cggttaacga tatac 15
<210> SEQ ID NO 164
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 164
gggtgcggtt aacga 15
<210> SEQ ID NO 165
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 165
gtggtgggtg cggtt 15
<210> SEQ ID NO 166
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 166
cccgggtggt gggtg 15
<210> SEQ ID NO 167
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 167
aagcacccgg gtggt 15
<210> SEQ ID NO 168
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 168
cccagaagca cccgg 15
<210> SEQ ID NO 169
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 169
ctgttcccag aagca 15
<210> SEQ ID NO 170
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 170
agccactgtt cccag 15
<210> SEQ ID NO 171
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 171
cataaagcca ctgtt 15
<210> SEQ ID NO 172
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 172
caaggcataa agcca 15
<210> SEQ ID NO 173
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 173
gccagcaagg cataa 15
<210> SEQ ID NO 174
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 174
ataacgccag caagg 15
<210> SEQ ID NO 175
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 175
aaagtataac gccag 15
<210> SEQ ID NO 176
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 176
ccagtaaagt ataac 15
<210> SEQ ID NO 177
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 177
gttaggcaaa ttaatggt 18
<210> SEQ ID NO 178
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 178
tgttaggcaa attaatgg 18
<210> SEQ ID NO 179
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 179
ctgttaggca aattaatg 18
<210> SEQ ID NO 180
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 180
tctgttaggc aaattaat 18
<210> SEQ ID NO 181
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 181
gtctgttagg caaattaa 18
<210> SEQ ID NO 182
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 182
tgtctgttag gcaaatta 18
<210> SEQ ID NO 183
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 183
atgtctgtta ggcaaatt 18
<210> SEQ ID NO 184
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 184
gatcaatgtc tgttaggc 18
<210> SEQ ID NO 185
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 185
gggcgatcaa tgtctgtt 18
<210> SEQ ID NO 186
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 186
agggcgatca atgtctgt 18
<210> SEQ ID NO 187
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 187
tagggcgatc aatgtctg 18
<210> SEQ ID NO 188
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 188
ttagggcgat caatgtct 18
<210> SEQ ID NO 189
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 189
tttagggcga tcaatgtc 18
<210> SEQ ID NO 190
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 190
ctttagggcg atcaatgt 18
<210> SEQ ID NO 191
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 191
cctttagggc gatcaatg 18
<210> SEQ ID NO 192
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 192
tcctttaggg cgatcaat 18
<210> SEQ ID NO 193
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 193
gtcctttagg gcgatcaa 18
<210> SEQ ID NO 194
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 194
agtcctttag ggcgatca 18
<210> SEQ ID NO 195
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 195
cagtccttta gggcgatc 18
<210> SEQ ID NO 196
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 196
ggaatcgaca tccacatc 18
<210> SEQ ID NO 197
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 197
tggaatcgac atccacat 18
<210> SEQ ID NO 198
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 198
atggaatcga catccaca 18
<210> SEQ ID NO 199
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 199
gatggaatcg acatccac 18
<210> SEQ ID NO 200
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 200
tgatggaatc gacatcca 18
<210> SEQ ID NO 201
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 201
ttgatggaat cgacatcc 18
<210> SEQ ID NO 202
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 202
tttgatggaa tcgacatc 18
<210> SEQ ID NO 203
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 203
caattttgat ggaatcga 18
<210> SEQ ID NO 204
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 204
gcaattttga tggaatcg 18
<210> SEQ ID NO 205
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 205
agcaattttg atggaatc 18
<210> SEQ ID NO 206
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 206
aagcaatttt gatggaat 18
<210> SEQ ID NO 207
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 207
caagcaattt tgatggaa 18
<210> SEQ ID NO 208
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 208
ccaagcaatt ttgatgga 18
<210> SEQ ID NO 209
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 209
cccaagcaat tttgatgg 18
<210> SEQ ID NO 210
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 210
gtcaccctgt acctggaa 18
<210> SEQ ID NO 211
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 211
ggtcaccctg tacctgga 18
<210> SEQ ID NO 212
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 212
aggtcaccct gtacctgg 18
<210> SEQ ID NO 213
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 213
taggtcaccc tgtacctg 18
<210> SEQ ID NO 214
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 214
gtaggtcacc ctgtacct 18
<210> SEQ ID NO 215
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 215
agtaggtcac cctgtacc 18
<210> SEQ ID NO 216
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 216
gagtaggtca ccctgtac 18
<210> SEQ ID NO 217
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 217
cgagtaggtc accctgta 18
<210> SEQ ID NO 218
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 218
tcgagtaggt caccctgt 18
<210> SEQ ID NO 219
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 219
ctcgagtagg tcaccctg 18
<210> SEQ ID NO 220
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 220
gctcgagtag gtcaccct 18
<210> SEQ ID NO 221
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 221
ggctcgagta ggtcaccc 18
<210> SEQ ID NO 222
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 222
gggctcgagt aggtcacc 18
<210> SEQ ID NO 223
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 223
agggctcgag taggtcac 18
<210> SEQ ID NO 224
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 224
cagggctcga gtaggtca 18
<210> SEQ ID NO 225
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 225
tcagggctcg agtaggtc 18
<210> SEQ ID NO 226
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 226
ctcagggctc gagtaggt 18
<210> SEQ ID NO 227
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 227
cctcagggct cgagtagg 18
<210> SEQ ID NO 228
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 228
tcctcagggc tcgagtag 18
<210> SEQ ID NO 229
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 229
atcctcaggg ctcgagta 18
<210> SEQ ID NO 230
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 230
catcctcagg gctcgagt 18
<210> SEQ ID NO 231
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 231
ccatcctcag ggctcgag 18
<210> SEQ ID NO 232
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 232
tccatcctca gggctcga 18
<210> SEQ ID NO 233
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 233
ttccatcctc agggctcg 18
<210> SEQ ID NO 234
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 234
attccatcct cagggctc 18
<210> SEQ ID NO 235
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 235
gattccatcc tcagggct 18
<210> SEQ ID NO 236
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 236
ggattccatc ctcagggc 18
<210> SEQ ID NO 237
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 237
cggattccat cctcaggg 18
<210> SEQ ID NO 238
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 238
ccggattcca tcctcagg 18
<210> SEQ ID NO 239
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 239
cccggattcc atcctcag 18
<210> SEQ ID NO 240
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 240
tcccggattc catcctca 18
<210> SEQ ID NO 241
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 241
ctcccggatt ccatcctc 18
<210> SEQ ID NO 242
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 242
gctcccggat tccatcct 18
<210> SEQ ID NO 243
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 243
agctcccgga ttccatcc 18
<210> SEQ ID NO 244
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 244
aagctcccgg attccatc 18
<210> SEQ ID NO 245
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 245
aaagctcccg gattccat 18
<210> SEQ ID NO 246
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 246
aaaagctccc ggattcca 18
<210> SEQ ID NO 247
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 247
gaaaagctcc cggattcc 18
<210> SEQ ID NO 248
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 248
ggaaaagctc ccggattc 18
<210> SEQ ID NO 249
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 249
gggaaaagct cccggatt 18
<210> SEQ ID NO 250
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 250
agggaaaagc tcccggat 18
<210> SEQ ID NO 251
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 251
cagggaaaag ctcccgga 18
<210> SEQ ID NO 252
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 252
gcagggaaaa gctcccgg 18
<210> SEQ ID NO 253
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 253
tgcagggaaa agctcccg 18
<210> SEQ ID NO 254
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 254
gtgcagggaa aagctccc 18
<210> SEQ ID NO 255
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 255
ggtgcaggga aaagctcc 18
<210> SEQ ID NO 256
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 256
aggtgcaggg aaaagctc 18
<210> SEQ ID NO 257
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 257
caggtgcagg gaaaagct 18
<210> SEQ ID NO 258
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 258
tcaggtgcag ggaaaagc 18
<210> SEQ ID NO 259
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 259
atcaggtgca gggaaaag 18
<210> SEQ ID NO 260
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 260
catcaggtgc agggaaaa 18
<210> SEQ ID NO 261
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 261
ccatcaggtg cagggaaa 18
<210> SEQ ID NO 262
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 262
accatcaggt gcagggaa 18
<210> SEQ ID NO 263
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 263
caccatcagg tgcaggga 18
<210> SEQ ID NO 264
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 264
tcaccatcag gtgcaggg 18
<210> SEQ ID NO 265
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 265
ttcaccatca ggtgcagg 18
<210> SEQ ID NO 266
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 266
cttcaccatc aggtgcag 18
<210> SEQ ID NO 267
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 267
tcttcaccat caggtgca 18
<210> SEQ ID NO 268
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 268
gtcttcacca tcaggtgc 18
<210> SEQ ID NO 269
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 269
cgtcttcacc atcaggtg 18
<210> SEQ ID NO 270
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 270
tcgtcttcac catcaggt 18
<210> SEQ ID NO 271
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 271
gtcgtcttca ccatcagg 18
<210> SEQ ID NO 272
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 272
tgtcgtcttc accatcag 18
<210> SEQ ID NO 273
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 273
gtgtcgtctt caccatca 18
<210> SEQ ID NO 274
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 274
agtgtcgtct tcaccatc 18
<210> SEQ ID NO 275
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 275
cagtgtcgtc ttcaccat 18
<210> SEQ ID NO 276
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 276
gcagtgtcgt cttcacca 18
<210> SEQ ID NO 277
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 277
tgcagtgtcg tcttcacc 18
<210> SEQ ID NO 278
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 278
ctgcagtgtc gtcttcac 18
<210> SEQ ID NO 279
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 279
tctgcagtgt cgtcttca 18
<210> SEQ ID NO 280
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 280
ctctgcagtg tcgtcttc 18
<210> SEQ ID NO 281
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 281
gctctgcagt gtcgtctt 18
<210> SEQ ID NO 282
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 282
agctctgcag tgtcgtct 18
<210> SEQ ID NO 283
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 283
cagctctgca gtgtcgtc 18
<210> SEQ ID NO 284
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 284
gcagctctgc agtgtcgt 18
<210> SEQ ID NO 285
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 285
tgcagctctg cagtgtcg 18
<210> SEQ ID NO 286
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 286
ctgcagctct gcagtgtc 18
<210> SEQ ID NO 287
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 287
cctgcagctc tgcagtgt 18
<210> SEQ ID NO 288
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 288
ccctgcagct ctgcagtg 18
<210> SEQ ID NO 289
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 289
gccctgcagc tctgcagt 18
<210> SEQ ID NO 290
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 290
ggccctgcag ctctgcag 18
<210> SEQ ID NO 291
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 291
aggccctgca gctctgca 18
<210> SEQ ID NO 292
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 292
gaggccctgc agctctgc 18
<210> SEQ ID NO 293
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 293
tgaggccctg cagctctg 18
<210> SEQ ID NO 294
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 294
ctgaggccct gcagctct 18
<210> SEQ ID NO 295
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 295
cctgaggccc tgcagctc 18
<210> SEQ ID NO 296
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 296
gcaaggcaac cacactga 18
<210> SEQ ID NO 297
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 297
tgcaaggcaa ccacactg 18
<210> SEQ ID NO 298
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 298
gtgcaaggca accacact 18
<210> SEQ ID NO 299
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 299
cgtgcaaggc aaccacac 18
<210> SEQ ID NO 300
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 300
tcgtgcaagg caaccaca 18
<210> SEQ ID NO 301
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 301
atcgtgcaag gcaaccac 18
<210> SEQ ID NO 302
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 302
catcgtgcaa ggcaacca 18
<210> SEQ ID NO 303
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 303
atatcatcgt gcaaggca 18
<210> SEQ ID NO 304
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 304
catatcatcg tgcaaggc 18
<210> SEQ ID NO 305
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 305
ccatatcatc gtgcaagg 18
<210> SEQ ID NO 306
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 306
tccatatcat cgtgcaag 18
<210> SEQ ID NO 307
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 307
ctccatatca tcgtgcaa 18
<210> SEQ ID NO 308
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 308
tctccatatc atcgtgca 18
<210> SEQ ID NO 309
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 309
ctctccatat catcgtgc 18
<210> SEQ ID NO 310
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 310
gctctccata tcatcgtg 18
<210> SEQ ID NO 311
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 311
ggctctccat atcatcgt 18
<210> SEQ ID NO 312
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 312
tggctctcca tatcatcg 18
<210> SEQ ID NO 313
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 313
ctggctctcc atatcatc 18
<210> SEQ ID NO 314
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 314
gctggctctc catatcat 18
<210> SEQ ID NO 315
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 315
atatacctgt ggactgga 18
<210> SEQ ID NO 316
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 316
gatatacctg tggactgg 18
<210> SEQ ID NO 317
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 317
cgatatacct gtggactg 18
<210> SEQ ID NO 318
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 318
acgatatacc tgtggact 18
<210> SEQ ID NO 319
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 319
aacgatatac ctgtggac 18
<210> SEQ ID NO 320
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 320
taacgatata cctgtgga 18
<210> SEQ ID NO 321
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 321
ttaacgatat acctgtgg 18
<210> SEQ ID NO 322
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 322
gttaacgata tacctgtg 18
<210> SEQ ID NO 323
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 323
ggttaacgat atacctgt 18
<210> SEQ ID NO 324
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 324
cggttaacga tatacctg 18
<210> SEQ ID NO 325
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 325
gcggttaacg atatacct 18
<210> SEQ ID NO 326
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 326
tgcggttaac gatatacc 18
<210> SEQ ID NO 327
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 327
gtgcggttaa cgatatac 18
<210> SEQ ID NO 328
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 328
ggtgcggtta acgatata 18
<210> SEQ ID NO 329
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 329
gggtgcggtt aacgatat 18
<210> SEQ ID NO 330
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 330
agggaaaagc tcccgg 16
<210> SEQ ID NO 331
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 331
gtcaccctgt acctgg 16
<210> SEQ ID NO 332
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 332
gtaggtcacc ctgtac 16
<210> SEQ ID NO 333
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 333
tcgagtaggt caccct 16
<210> SEQ ID NO 334
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 334
gggctcgagt aggtca 16
<210> SEQ ID NO 335
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 335
ctcagggctc gagtag 16
<210> SEQ ID NO 336
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 336
catcctcagg gctcga 16
<210> SEQ ID NO 337
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 337
attccatcct cagggc 16
<210> SEQ ID NO 338
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 338
ccggattcca tcctca 16
<210> SEQ ID NO 339
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 339
gctcccggat tccatc 16
<210> SEQ ID NO 340
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 340
aaaagctccc ggattc 16
<210> SEQ ID NO 341
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 341
gtgcagggaa aagctc 16
<210> SEQ ID NO 342
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 342
tcaggtgcag ggaaaa 16
<210> SEQ ID NO 343
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 343
accatcaggt gcaggg 16
<210> SEQ ID NO 344
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 344
cttcaccatc aggtgc 16
<210> SEQ ID NO 345
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 345
tcgtcttcac catcag 16
<210> SEQ ID NO 346
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 346
agtgtcgtct tcacca 16
<210> SEQ ID NO 347
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 347
ctgcagtgtc gtcttc 16
<210> SEQ ID NO 348
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 348
agctctgcag tgtcgt 16
<210> SEQ ID NO 349
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 349
ctgcagctct gcagtg 16
<210> SEQ ID NO 350
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 350
ggccctgcag ctctgc 16
<210> SEQ ID NO 351
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 351
ctgaggccct gcagct 16
<210> SEQ ID NO 352
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 352
cggcctgagg ccctgc 16
<210> SEQ ID NO 353
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 353
accccggcct gaggcc 16
<210> SEQ ID NO 354
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 354
tcagaccccg gcctga 16
<210> SEQ ID NO 355
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 355
gtactcagac cccggc 16
<210> SEQ ID NO 356
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 356
ctgtgtactc agaccc 16
<210> SEQ ID NO 357
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 357
ctgactgtgt actcag 16
<210> SEQ ID NO 358
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 358
cacactgact gtgtac 16
<210> SEQ ID NO 359
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 359
caaccacact gactgt 16
<210> SEQ ID NO 360
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 360
aaggcaacca cactga 16
<210> SEQ ID NO 361
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 361
gtgcaaggca accaca 16
<210> SEQ ID NO 362
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 362
catcgtgcaa ggcaac 16
<210> SEQ ID NO 363
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 363
atatcatcgt gcaagg 16
<210> SEQ ID NO 364
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 364
ctccatatca tcgtgc 16
<210> SEQ ID NO 365
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 365
ggctctccat atcatc 16
<210> SEQ ID NO 366
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 366
ggctggctct ccatat 16
<210> SEQ ID NO 367
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 367
ctggattcca atcagg 16
<210> SEQ ID NO 368
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 368
tggactggat tccaat 16
<210> SEQ ID NO 369
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 369
cctgtggact ggattc 16
<210> SEQ ID NO 370
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 370
tatacctgtg gactgg 16
<210> SEQ ID NO 371
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 371
acgatatacc tgtgga 16
<210> SEQ ID NO 372
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 372
gttaacgata tacctg 16
<210> SEQ ID NO 373
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 373
tgcggttaac gatata 16
<210> SEQ ID NO 374
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 374
tgggtgcggt taacga 16
<210> SEQ ID NO 375
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 375
aaattaatgg taagag 16
<210> SEQ ID NO 376
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 376
aggcaaatta atggta 16
<210> SEQ ID NO 377
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 377
tgttaggcaa attaat 16
<210> SEQ ID NO 378
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 378
tgtctgttag gcaaat 16
<210> SEQ ID NO 379
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 379
tcaatgtctg ttaggc 16
<210> SEQ ID NO 380
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 380
gcgatcaatg tctgtt 16
<210> SEQ ID NO 381
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 381
tagggcgatc aatgtc 16
<210> SEQ ID NO 382
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 382
cctttagggc gatcaa 16
<210> SEQ ID NO 383
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 383
cagtccttta gggcga 16
<210> SEQ ID NO 384
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 384
atgccagtcc tttagg 16
<210> SEQ ID NO 385
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 385
gtgaatgcca gtcctt 16
<210> SEQ ID NO 386
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 386
atcagtgaat gccagt 16
<210> SEQ ID NO 387
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 387
ccacatcagt gaatgc 16
<210> SEQ ID NO 388
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 388
acatccacat cagtga 16
<210> SEQ ID NO 389
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 389
atcgacatcc acatca 16
<210> SEQ ID NO 390
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 390
tggaatcgac atccac 16
<210> SEQ ID NO 391
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 391
ttgatggaat cgacat 16
<210> SEQ ID NO 392
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 392
aattttgatg gaatcg 16
<210> SEQ ID NO 393
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 393
aagcaatttt gatgga 16
<210> SEQ ID NO 394
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 394
tcccaagcaa ttttga 16
<210> SEQ ID NO 395
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 395
gctttcccaa gcaatt 16
<210> SEQ ID NO 396
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 396
gtgggctttc ccaagc 16
<210> SEQ ID NO 397
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 397
ccctgtgggc tttccc 16
<210> SEQ ID NO 398
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 398
ttgcccctgt gggctt 16
<210> SEQ ID NO 399
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 399
aaacttgccc ctgtgg 16
<210> SEQ ID NO 400
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 400
ctggaaactt gcccct 16
<210> SEQ ID NO 401
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 401
gtacctggaa acttgc 16
<210> SEQ ID NO 402
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 402
ccctgtacct ggaaac 16
<210> SEQ ID NO 403
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 403
gcctgaggcc ctgcagct 18
<210> SEQ ID NO 404
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 404
cccggcctga ggccctgc 18
<210> SEQ ID NO 405
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 405
agaccccggc ctgaggcc 18
<210> SEQ ID NO 406
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 406
actcagaccc cggcctga 18
<210> SEQ ID NO 407
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 407
gtgtactcag accccggc 18
<210> SEQ ID NO 408
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 408
gactgtgtac tcagaccc 18
<210> SEQ ID NO 409
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 409
cactgactgt gtactcag 18
<210> SEQ ID NO 410
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 410
accacactga ctgtgtac 18
<210> SEQ ID NO 411
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 411
ggcaaccaca ctgactgt 18
<210> SEQ ID NO 412
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 412
atcatcgtgc aaggcaac 18
<210> SEQ ID NO 413
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 413
gactggattc caatcagg 18
<210> SEQ ID NO 414
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 414
tgtggactgg attccaat 18
<210> SEQ ID NO 415
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 415
tacctgtgga ctggattc 18
<210> SEQ ID NO 416
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 416
ggtgggtgcg gttaacga 18
<210> SEQ ID NO 417
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 417
gcaaattaat ggtaagag 18
<210> SEQ ID NO 418
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 418
ttaggcaaat taatggta 18
<210> SEQ ID NO 419
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 419
gccagtcctt tagggcga 18
<210> SEQ ID NO 420
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 420
gaatgccagt cctttagg 18
<210> SEQ ID NO 421
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 421
cagtgaatgc cagtcctt 18
<210> SEQ ID NO 422
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 422
acatcagtga atgccagt 18
<210> SEQ ID NO 423
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 423
atccacatca gtgaatgc 18
<210> SEQ ID NO 424
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 424
cgacatccac atcagtga 18
<210> SEQ ID NO 425
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 425
gaatcgacat ccacatca 18
<210> SEQ ID NO 426
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 426
ttttgatgga atcgacat 18
<210> SEQ ID NO 427
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 427
tttcccaagc aattttga 18
<210> SEQ ID NO 428
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 428
gggctttccc aagcaatt 18
<210> SEQ ID NO 429
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 429
ctgtgggctt tcccaagc 18
<210> SEQ ID NO 430
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 430
gcccctgtgg gctttccc 18
<210> SEQ ID NO 431
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 431
acttgcccct gtgggctt 18
<210> SEQ ID NO 432
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 432
ggaaacttgc ccctgtgg 18
<210> SEQ ID NO 433
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 433
acctggaaac ttgcccct 18
<210> SEQ ID NO 434
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 434
ctgtacctgg aaacttgc 18
<210> SEQ ID NO 435
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 435
caccctgtac ctggaaac 18
1
SEQUENCE LISTING
<160> NUMBER OF SEQ ID NOS: 435
<210> SEQ ID NO 1
<211> LENGTH: 76208
<212> TYPE: DNA
<213> ORGANISM: Homo sapiens
<400> SEQUENCE: 1
tattttatgg gttttcttcc tcacaaaata cactcctata agcagagatt ccccccctcc 60
accccgaaga gaggtgacgc aatgtcctca aacactacca ccacccccaa taaaaaagaa 120
aagggaaggg ggagcgtctt gcaacccctt cgcttcacac aagtccagcc actccctttc 180
ctcccagccg cttcccatcc cttcccccat cccctaaaaa gtttgatgac cgcaaaggaa 240
accgaaaaaa agttgtcttg ccccagtcct ggcgggccat cagcatctct tttgttcgct 300
gcgaacccac agtcccccgt gacgtcaccc ggagcccggg ccaatcggcg cgcggtcggc 360
tgcggcggcc ggcgggcggg cgggcgggtg gggtggggcg gggcggggac agcccggcgg 420
gtctctcctc ccccgcgccc cgggcctcca gaggggcggg aggggaccgt cccatataag 480
ccccggctcc cggcgctcgg acgcccgcgc cggctgtgct gcacaggggg aggagaggga 540
accccaggcg cgagcgggaa gaggggacct gcagccacaa cttctctggt cctctgcatc 600
ccttctgtcc ctccacccgt ccccttcccc accctctggc ccccaccttc ttggaggcga 660
caacccccgg gaggcattag aagggatttt tcccgcaggt tgcgaaggga agcaaacttg 720
gtggcaactt gcctcccggt gcgggcgtct ctcccccacc gtctcaacat gcttaggggt 780
ccggggcccg ggctgctgct gctggccgtc cagtgcctgg ggacagcggt gccctccacg 840
ggagcctcga agagcaagag gcaggctcag caaatggttc agccccagtc cccggtggct 900
gtcagtcaaa gcaagcgtga gtactgaccg cgggctgaaa caggctgcct cagggatggg 960
accctaaagc cgaccaaagt tggggctgaa gttttgtgcg cgcgcgtgtg tgcgagtgtg 1020
tgcgcgcttt actgagagaa accagctgtg cacacaaaag gaccgagttt tgagcacgct 1080
ggttctgagg gcctgggatg ataagaccgt gcattggagg acgaggactc tgcgactttc 1140
ccgtgttcta ataaattctg cacgttcaga ttgtccttct aggaattaac caaaacttgc 1200
ctttaaagag aaaaatgatg catgtctata aattttccgt ctgggattag tgtggtcctt 1260
actgctactt atttccttct gttaaataat tggtcaaata ttttcaacat gggggtggaa 1320
agggggtatt gaaatagctg tcttgtttct aactaacttg gaagagatgt aattggttca 1380
gacctcttta gggccgctca ggatacttca ccaagaacag aggttggaat tctttccgtt 1440
tttcaaagac acaccctcct tttgctttga gaaagctgct taaagttgtc ctttttgact 1500
attactccaa aagaatattt aagttccttg catgttttaa aaatgtgact tcaattgtct 1560
gccttccaaa atgtttccaa cttttttatg tagacccctg gccagatgga aatgacatca 1620
ttgtatataa cttttagcaa agttaaaagg aaaaaaatat gtacgtcaat attcacatga 1680
agaaaattcc ataattttgg gaaaaggaga aatgcaaatg taacgttttc cttcaattat 1740
ttgcagccgg ttgttatgac aatggaaaac actatcagat aaatcaacag tgggagcgga 1800
cctacctagg caatgcgttg gtttgtactt gttatggagg aagccgaggt tttaactgcg 1860
agagtaaacc tgaaggtaag tgacaacaag ccccatagtt agtatctttt aatacatgaa 1920
gtggtaattg ttaaactttg cattagtaag taaaaataca tacaccattt ttctaataga 1980
attacctgtc atttcctctt aagtttaaaa actgcttata tttgcttttc acatgctttt 2040
acctttaaaa caaagaaacg aatctttccc aaattagttc ctagagtctt ctttttgctt 2100
tactctccca aagtttttga tgagaaaaat gaaagatttt gtgtgtcctc cgacaaaaaa 2160
aattgcttat aaaattttaa tttattagaa agcagtctca aatcttaaac tgttagttta 2220
tgagccagaa aacactttgg ggacttacat cgtaaaatga tttgtcagcg gcagttaaca 2280
caaaaccatt agccacttca aagttctcat tcctttagga ccaatgatat ttttctcata 2340
aattatagca actctgtcag agaagcactg atcaggggaa aatggaaatc ataggattaa 2400
caactgtcaa ggccttgtgg gaggtgggga tcttcgaatt gtttgtttgt ttttgttttg 2460
ttttgttttt gagacagagt cttgctctgt caccaggctg gagtgcagta gcactatctc 2520
agctcactgc aacctctgcc tccagggttc aagcaattct cctgcctcag cctcctgagt 2580
agctgggact acaggcacat gccaccacac ccagctaatt ttcatatttt tagtagagac 2640
ggggtttcac cgtattggtc agggtggtct cgaattcctg acctcaggtg atccacccgc 2700
ctcagcctcc caaagtgctg ggattacagg cgtgagccac tgtgcccggc caatcgtttg 2760
ctttttatgt gaaccttgct ttgactttct gagtcagaga ttggaatgtg aaacccttca 2820
caaatctagc tctgtcataa gttagtactt tatatggcct tttcctaaga gcctgagatt 2880
tttctacaat atgaataatt tacagaaaat ttgacaatat gtcaaggtca aaaaccatgg 2940
ccttattaga gcttaggata aaaatctgta tctctcactt cattttattc tttgaggtgt 3000
accatgttac ttgtggaata gagaagtggg ttttccttta gaggggatta gtgaactaga 3060
aaagcttgta cctaagtgag gctcacatgg actttccttt tcccctcagc tgaagagact 3120
tgctttgaca agtacactgg gaacacttac cgagtgggtg acacttatga gcgtcctaaa 3180
gactccatga tctgggactg tacctgcatc ggggctgggc gagggagaat aagctgtacc 3240
atcgcaagta aggaagagat tgtgtaaaat gatgccaaaa tatcaaatat gaatttctct 3300
gttaccatca ctgtcatttt ctgttatcca tgactggata ttccgaactt tgaggtttgc 3360
ccctggtgac caggtactct taagtggtca cccaactggt tcctgtgttt cttaaagacg 3420
ggtatgagca cagatggaat cagtgtttga tgtgtgtgcg tttatgagtg tgtgtgcatt 3480
tatgagtgtg tgtgtttctg tacatagtag aaccaagaga cctcttgggt tccatttcag 3540
taagacatgc ttaggggagt tgcccatttt aaatcacctg gatatcttca agctagacaa 3600
atcatgagac ttttctgcag tgactgggaa ggtgttcatg aagagtgaac cagccatgtg 3660
ttgtctggtc ttcatgtttg caatgcagag acctcttgca cctcacagaa acagtctggt 3720
ttcttggtga ccagtaggtt atacccagga agcagatgtc actattccta gggataatac 3780
aaaattatta acccaataga gtttgctaag gaactttggg aaccgggctg attctcaact 3840
ctagtttagc taaggcactc tttccagtat gattcactgg gttaccaata gattctatta 3900
agatagtatt taagtttttt aatccattct ttaaatataa gtcgtcttaa agacttctat 3960
tcaaaagaac aagtcccgtg tgaataggcc caatcaactt tccccatatt tcatgttagg 4020
gtttatccaa gttcacaggc aaatcgcaag aggcaagggt ccatagtgtt tacaatctag 4080
ttcagcattt gaatgtgcca ttgggcttaa caacttagaa aactaccagg atttccacac 4140
tttatatgca tatgtctgtt tgctttccac caaaatgaca tttctatcct agggtaaaat 4200
acaggctctc catgctccca aaagctggag tgctgtgcct gatgtggcct tttcactgaa 4260
ttagtctcag tcttagcctg ctgtgtatga gtgaagacca agcctcccag cctttctttt 4320
ctgcttagga cccaatttcc tgtgatctct ctgggaaagc aggattcatg acctcttcct 4380
tgccatccag atttctctgt ggttttccat tgtgttctaa gcaagacact taactgaatt 4440
gactccaagt gaccagacct gttaacgttt cccctgtctc tgatgggaaa gctgttgtct 4500
gtgtctctac tttagccaac ctaagtacct accatgggtg gaatatgaga ccaaaaaaaa 4560
aaatctgttc tgccctctcc taacattttc gttgtatctt caacagaccg ctgccatgaa 4620
gggggtcagt cctacaagat tggtgacacc tggaggagac cacatgagac tggtggttac 4680
atgttagagt gtgtgtgtct tggtaatgga aaaggagaat ggacctgcaa gcccataggt 4740
gtgtgagtct tagggctgag caagagctgg gatgcttagt tctaatgtgg ggttggacca 4800
gaatcacatc tacataggtc atagacctga attccagtga aaaccaataa agaaatggga 4860
attttgtttg aaataatgaa ttattatata atccatagtc ttcttacagg agttagatca 4920
aaaagtactg actacacata gaagtcttaa ctttgcttca aaagcataag gtagaattga 4980
aagatttaga atggagtcat ttcttttacc taatagctga tctcagattc ctccttcgtc 5040
aagatataat ttatttaaaa gaaaaaaaaa tgacactttg gacacatttc tatatggaat 5100
gtcctggacc gaaacatgaa atagtgtgtg cttgtcacac tctgctcatt tcttttcaaa 5160
ttaaaagttg ttgagcttct ttggatctca atcctcagtt gaattttgta agtacaagcc 5220
tgaaagtttc tggctataaa ttttactctg tttacttgtc ttctaattta gaggtttttg 5280
tcttgttttg tattgttttg ctttccaata tttaaaaata gctttctttg tcattgtatt 5340
taggccactc aaaattcata attggtcatt tataattaag attggaattt tgcatatgta 5400
gtctcccaca gactagatac atacatagat ccttgctact ggaaatgctg ctgggaagtt 5460
tggggctcgc tgaaaatatg tagtccatgt acttattagg agaatggaat ttctgcctgc 5520
caactcagct tgagctttct tttgccttgg ctacttactg tgtgcttaga tgctgggtgt 5580
gtcattcttt ctgaacagag tgccacttaa aaaaaatgtg gctgaatttt tgcttacaca 5640
ctacacttta aattacaggg agcttgcaca attcaaaata accttttttt cctgtttttc 5700
ttccaaattt ccctacagct gagaagtgtt ttgatcatgc tgctgggact tcctatgtgg 5760
tcggagaaac gtgggagaag ccctaccaag gctggatgat ggtagattgt acttgcctgg 5820
gagaaggcag cggacgcatc acttgcactt ctagaagtat gttttacatc tttatgttaa 5880
agattaagcc aggtattgtt ttctggattc ctagagagaa gggtaatact atgttactca 5940
gaacacatcc agtatatcag catgctttgg taacttctgg aagtcaagaa aactttcata 6000
accaacttat tccgcatctt cagagaagac tacataaata gaaaaacata tcactttgat 6060
aaggttcaat ctcagctcac tgccactgac atagagttga acaaaaggtt taggtttcct 6120
tctatgtttg aaatttaaat agggcacatt cacaggctaa attgataaaa ttaaaaagaa 6180
tttatcccat aaattaaaat gatttatcta ctctggagtt agggatagtg tctctgacct 6240
aacgcatttg attagtgctg taaagaagct ggcctctggt gtctttactg ctccttctaa 6300
gattgtcttg gggtcttaat tgttgccttt gggtttgaag gctccttttt tgatattgta 6360
aactaataac agctagagag tttgttgaag taaaacagcc attaactact ggtgttgtaa 6420
ataagtttaa aatcaaatcc aaataatttg aacctgtttt atttatctag ctgaacccat 6480
ttaactacct ttaacatagc catcatccaa attcaaattc tttgctaaca aaaataggtc 6540
tctcatgaaa agtggtaacc attttgacca aagctttccc agaaacttgc tggtttatta 6600
gatattttgc atttaaaatg ttactgtgat catcagactt ccaagatctt tgtggcaata 6660
ttttagctta agacaaatta gatgtctgat tcaaacctta tctgttattt agaactcttt 6720
aaatagcaag ttgggaaaag tttctcaaag agaagtcatt tattccagaa aattttataa 6780
ggacttactt tgttcaaggt attatagggg tgcagatatg aaatgaacat tagcccagcc 6840
ttcaaagagt acttaggggg tcagggagat gagaaagtct tatacatatt tatcatctgc 6900
aaaacacagt attaaagatt tcaacagaaa tactgaaagt agtgctatgg aggttcaggg 6960
gatgataata cttttcgctg gggatttggg aaaaagctct aatcagtaat tataccttca 7020
tgcaaacttc tattcttgtg gtagatggat gtgggtgtgt atttgtttga acctacatca 7080
actattaatt ttttttctct aacccaggag ttgcaacaat atccaattca caaagacatc 7140
agatcctcta tactcacatc gtggcacaga gcaaatttgg attataattt aaataatcta 7200
tttaccagat aaatgcacgc atagactaat ggtcatttag ttacaaatta tcattttatg 7260
ttgatcccac tcttccagtg gagggctaac actgaataat ttggggctat tttgctagtg 7320
atttttaaat actgtagatg tttgggtata ggggaaggga aaataatatt ttagtcaaag 7380
aaattgtgca tcctctacat tttttacata acaaatgaag aaagagatac taccaccttc 7440
ttatagcttc tttgtagcca ttggtgaaga ccctttgata cctgcttgcc tccccattgt 7500
tataagcttt tttttgtttg cttgtttttt ttgttttgtt ttgttttgtt ttgtttttga 7560
gacagtctca ccctgtcgcc caggctggag tgcaatggtg tgatctcagc tcattgcaac 7620
ctccacctcc cgggttcaag cgattctctt gcctcagctt cccgagtagc ttggattaca 7680
ggcgcccgcc accacagccg gctaattttt tttggtattt ttagtagaga cgggggtttc 7740
accatgttgc ccaggctggt cttgaactcc tgactgcagg tgatccaccc tcctaaagta 7800
ctaggattac aggcgtgagc caccgcgctt agcctgtttt tagttttcta aagcaaggtc 7860
cctattgaaa ggcaggccat aaacagtgat gactaagaaa aatcctggaa gagcctgaga 7920
aggaaaaaga tgaaatataa tgccagagaa tgaagttagt caaaggaaca gtgtgaaaac 7980
aataaataaa tagataaatg aaaatgttat ttgacagaga gatgaaacta gactaaacca 8040
ttcagctgcc tttccactgt aacaaatgta atttcatctt tcagaagtgt aataccttgc 8100
agcaccagag ctgaatatga acatattacc aaaaatagat taccaggcat agatagcatt 8160
ccttttttaa gtttgaattg accacttgcg actctcgacc tgatgtatgt atgtgcttcc 8220
tttgtgacac agatagatgc aacgatcagg acacaaggac atcctataga attggagaca 8280
cctggagcaa gaaggataat cgaggaaacc tgctccagtg catctgcaca ggcaacggcc 8340
gaggagagtg gaagtgtgag aggcacacct ctgtgcagac cacatcgagc ggtgaggcac 8400
aggacgagca ggggcgggaa atggggaagc aggtcaagaa atatttccgc aaatccatct 8460
ttcctttgac atgccatttg aggataattt gcagtgtttc agctaataac ctaagataat 8520
ttacacatta ttggttgtta aaactttttt taatgtcaag ttttaaattt ttcagaaaaa 8580
aagaaaaatg acatacaaat aaaccttagg gggaaaaaag ccagatttat ctccaaaaga 8640
taaaactgag ttttaaagaa tgctagcatc ataaaactta ccatggatag atcacgcaca 8700
cacgcacaca cacacgtatt ttgaatatcc aaagttcatt tgaaaggaaa tgagagttat 8760
aattaattat atgactacct ggttcttctg ctaggaaagg acaaaaaaag tgcatttgga 8820
ttttttgttt gtttgttttt gaatgaaata tacttccctg tcccgacatt gaactctttt 8880
tgtagtggaa accatccttt atatgtggtt tctatgctct ggcaaacttt gttacattct 8940
ataaagtaac acacaattat ttccttcatg tattggcatt cgaaatttta gaaattcaga 9000
gaggacttag agatggccat gaaagacatg atatctaagc attcttttta aaaaacaagt 9060
tttaatcatt tttggcatga gaaaaagatt tttacgtcat aaatgtttca taaaaatctg 9120
aagagagaaa tatggccaac aaggacgtgc actcctctca ttatttttaa tatgttttga 9180
ttaacttttt actatatgat gtgccaacat cattacgtag tgtctcagcc atccttcaat 9240
taaaaatatt aattgttcta atttttcttc ttttgatgag tttttgtctt gctttgagca 9300
cttatgaagg tgaacaagat tagatttgat aatatctttg agttatttta ttatcattaa 9360
taaaattgct actggccaaa aaaaattata aacatcggcc acgcgcggtg gctcacgcct 9420
gtaatcccag cactttggga ggccgaggca ggcggatcac gaggtcagga gatcaagacc 9480
atcctggcta acacggtgaa accccatctc tactaaaaat acaaaaaatt aaccaggcgt 9540
tgtggcgggc gcctgtagtc ccagctactc gggaggctga ggcaggagaa tggcatgaac 9600
ccgggaggtg gagtttgcag tgacccgaga tcgcaccact gcactccagc ctgggtgata 9660
cagcgagacc ccatctcaaa aaaataaaat aaaataaaaa ataaaaaaaa ttataaatgt 9720
cagtctacca aaatagatta aaagtgtagg tgggaattaa atggggataa acactcaata 9780
aatgttagct atatatgaat attgccaata ctgaaaagat tccattgttc aaaaaagttt 9840
gagaagcaat gggttaaaca aaatggaacc tgctctgcag aatctgtgtg ttcctttaca 9900
tcatactctc catggtagag tgtaggggat gggcgccatg tctccctagt acgtttgacc 9960
ttgggattct ttgtctgtga acatctttgg gttctagtgt tcagcagcac ttagggaggc 10020
actgaattca gtgtaccttt ggtctagcct cagccctgat tctgttctgc ggtgggccct 10080
ggccttcaag agaacagata tctaaaagtt gaaagaaaag atcggccggg cgcggtggct 10140
cacgcctgta atcccagcac tttgggaggc caaggcgggt ggatcacaag gtcaggagat 10200
cgagaccatc ctggctaaca cggtgaaacc ccgtctctac taaaaataca aaaaattagc 10260
cgggcgtggt ggcgggtgcc tgtagtccca gctactcggg aggctgaggc aggagaatgg 10320
cgtgaacccg ggaggcagag cttgcagtga gccgagattg cgccactgca ctccagcctg 10380
ggtgacagag tgagactccg tctcaaaaaa aaaaaaaaaa aaaaaaagaa aaaagaaaag 10440
atcaacacat cctgttgtgt tattctgaaa ggaaagctgt cttaagagga tcaattggtt 10500
ttagaaaaaa cacaatagaa tcacaaataa tccagaggag aaataaaatg tggaaggtgg 10560
aggtgacctc cagaaaatcc aggacagctg ctgaaggcac cctctgatga gctcggttac 10620
tcagaagagt gaggatgtgt tgaaggtatc tgctgtatgg agtggcagga tgatgtctgt 10680
gattgagaaa tataatcccg gccaggcgag gtggctcatg cctgtaatcc cagcactttg 10740
ggaggccgaa gcgggtggat cccctgaggt caggagtttg agacaggagt ttgaggtcag 10800
gagtttgcca acatggcaaa accccgtctc tactaaaaaa tacaaaaaaa atcagctggg 10860
catggtggtg cgtgcctgta attgcagcta cttgggaggt tgaggcagga gaatagcttg 10920
aacccaggag gcagaggttg cagtgagccg agaccgcgcc actgcactcc agcctgggca 10980
acagagtgag accccatctc aaaaacaacc caaaaaacca aaaaacaaac aaacaaaaag 11040
aaatataatc ccagtagccc cagctgagct ggaggatgga gaccacttgg tagacacttg 11100
tggattattt cctaggctaa atgcaaaagc tactgctgaa taagggacat ttttttccag 11160
tcccaggcca gtagcgacat agatttcaga gtgatctctg tgagatcctg aagatcctga 11220
ctgcagaaag tagtgaattg tcttctctca cccagttttg tgacattccc ttttcatgcc 11280
attaggatct ggccccttca ccgatgttcg tgcagctgtt taccaaccgc agcctcaccc 11340
ccagcctcct ccctatggcc actgtgtcac agacagtggt gtggtctact ctgtggggat 11400
gcagtggctg aagacacaag gaaataagca aatgctttgc acgtgcctgg gcaacggagt 11460
cagctgccaa gagacaggta tgcattatct ttttgaagaa taggactgat gactttatta 11520
tttagttttt gaaggacaat acattttcaa tgtgaaacaa taaaacaaac aagaagcctg 11580
taatcttacc accctgtgat aacaattagg gttggcattt gaaatagttt cttccaatct 11640
ttttaattta tgtattttct ttctggtcat ggatatcatg ggtaaaaatt ttattgtatt 11700
tatctgtcta aagtgttgtt acaagagagc tactttctga ataatcatca atgttttata 11760
ttctaaatct caaatttcag cagctttgtg atgtaaacat cttccaataa cctaatatat 11820
gtattctgca ctacaaacat ggtagtcact atggcaataa caattgctac acaattctcc 11880
cccagaatag tctcatatat taattttatg gcatagatat agtcataaat attatcccaa 11940
catccttaag cagcatcctt aattgacctg tataaatata gctttacaaa tagagaaact 12000
gaggcatggc agcagaagtg gtcatgaagg acatcagcag aagaactcag gtgtcgttct 12060
atccacagta gacatggatt cctgagtaat gcattttgac tgaaattaac gagatgatca 12120
tctatactca tagcttcttc ctttgagggc acaagctcag tatctcattg aagccataaa 12180
taagcagctg ctggtgggag ataaagcatc tctgtttact gacactcttt tgattatgat 12240
tgtagctgta acccagactt acggtggcaa ctcaaatgga gagccatgtg tcttaccatt 12300
cacctacaat ggcaggacgt tctactcctg caccacagaa gggcgacagg acggacatct 12360
ttggtgcagc acaacttcga attatgagca ggaccagaaa tactctttct gcacagacca 12420
cactggtgag tgtcccaagg gggagccaca gaagtgagaa aaactcactt tcatgcccta 12480
gttttatttg ccagcattct agccatttat tttgaacccg cccaagaagc atcgcttttg 12540
ttcagtttgg actcaagaga tcgcagcgct cacgtaacag ctgaggattc ttccatcttc 12600
cccagtactg ttgggaaatg acaccaaggg agtagccttc cagttcattt gatttaacac 12660
attgggatta tgatgtgatt aaagatactt gtattttgga atcagtagat gatcccacag 12720
ggctgaggaa tacaaaggat gaatgtttta gtgccttagc ttattttcca gttaaaacaa 12780
tgttttattc aaagctatca tttaatcttt tgtggggggg gtgctgggga aatgacagtg 12840
aaagtgggat ttaaacctgt tttgaaggtg tgaaggtaaa tatgctaaga agcttagaac 12900
tatattatca gacatttttt attctgagat agactgtctg tgaatgagct gcagaaacct 12960
ggctctctca gaccagtaat tctgtgtaca ttggaaagct cagcggtaat cttttccttc 13020
tttgttgtgt attgttcctg gcagttttgg ttcagactcg aggaggaaat tccaatggtg 13080
ccttgtgcca cttccccttc ctatacaaca accacaatta cactgattgc acttctgagg 13140
gcagaagaga caacatgaag tggtgtggga ccacacagaa ctatgatgcc gaccagaagt 13200
ttgggttctg ccccatggct ggtaagatga agcccttgtg ggttgtcttg tttgacaaca 13260
atttagggag tagagactaa agactagtgt ccagtttact cccatttcat tcattaacac 13320
aattttgaga caacagaaaa cttcatgtga agtgtgtttg tgtgtgtgtg tgtgtgtgtg 13380
tgtgtgtgtg atgttacatc atatacataa ggattgggaa gaataattag ataattattt 13440
atataatttt taaacctcat tgacatgatt taatgtcaaa aatataatta cttatttgta 13500
agtctggaaa tatgaatttg cacaggtttg tctttgtaaa gagcacacaa ctgagtagct 13560
tacaacattt aatatatgta tgacggcttt agtcacagag ctacaatatt gacacatggt 13620
tgtggtttga tgggcataag ctctatcact tattaataag tgccaaagtg actaaaactc 13680
aatgttttct aacaggtagg gaatctcact ctttttttaa aggtccccag tttgtataga 13740
tggcgaacaa atggaaacga atacctttta cttgttttca gatttcaaga accccataga 13800
ttccctttaa ttttccagtt gtagaaacaa gagcctgggc ggtaggcact gtcaagtgtg 13860
actatgagac aaagaaattg cttatacttt tatttctttc aacaaaagaa gatgctgagt 13920
ttagaagaaa aaacccactt ttgcttgtaa ttctatatcc aaacccatag tttttatttg 13980
atccagaata aactggaact gggaaaagtt atgaagctgt agttaaatcc aggcttctag 14040
aacagcaaga accctttgtg tggatgtgta gatattatct tagtttaaca tcccctaacc 14100
cttcctgtaa ctattttcta tgacacgttt ggactacgtt ttctgcctcc agggctcaaa 14160
aattctaccc cttcacctga cagcacttag atgtctttga tgcacacaaa gcttcttccc 14220
aagtgagaat tcttaggatg accaaactga actgatcctt ttgcacacat acatgtttag 14280
acctggtgat catttatcaa gtgcatttct tatccatttc caaacagccc acgaggaaat 14340
ctgcacaacc aatgaagggg tcatgtaccg cattggagat cagtgggata agcagcatga 14400
catgggtcac atgatgaggt gcacgtgtgt tgggaatggt cgtggggaat ggacatgcat 14460
tgcctactcg cagcttcgag gtatgctggc tgattaacaa aaatatttga gatggcaaaa 14520
ggtacagaaa gggacacttt tttttatgaa aacttgcact atgccaaaag caggggaaga 14580
aatatggaat gccacgtcat tcattagtct actgtgcatg gtaagataag cctgaaaggc 14640
ttagcaggca gcctgctaag acaagcggca tagcaatgct aatgttctga aacactccta 14700
gcatgtaagt acttaggctg agccaaaaag atggcttcaa aagtaagaat gaaacatttg 14760
atccattcag ctttaggcta tgccactgga ttcatgtcta gaaaagatag gataatttct 14820
gtaaagaaat gaagaccttg ctattctaaa atcagatcct tacagatcca gatttcagga 14880
aacaaataca taggggacta actttccttg ttcagattag tttttctcct ttgcacccag 14940
ctatataata tgaggaagta ttgacttttt aaaagtgttt tagttttcca tttctttgat 15000
atgaaaagta atatttcggg agaaccctga gctattaata atctatgtgg ctagtgcgta 15060
gatattggtc tgaatttgtt ctccttttgt ggtgtccagt gggtaacacc atccgggagt 15120
aataattaca tgtggtgttg cagaactgaa agagacctta ataacacata gagacctcac 15180
tctatataga tcaaggagct gagacccaaa aaggaaaaag taattttctc aggatctctc 15240
aaagagtgag caacagagtt ggcctaattt attttagcgt tgtgaatact gttgacattt 15300
tatttcccaa atctaagtat ctcctcccct tccccctatt ccagagacca gaccaccaca 15360
tcatgctggg tgttagataa atatgtttaa tcttcttctt atttatccta acaagcagat 15420
atttaaagga aattatcaac taagcaagaa attttcagaa agtaagacat gtatttgttc 15480
aaatactggc ttctcacagg aaagtgtatt ttaccacatt ctttacttga gcatactgta 15540
acctctgcaa aagttacaca ttttgggaag aaaaaaattt ttttggcaaa aattgtatta 15600
ctgaccaaac tttgaaaaaa atgttattct atgcttgtag aaaagttatt ttagtggaag 15660
gtgttgataa ttaagtggaa gtagttgtat gctttgagaa gcataccttt tttctttcat 15720
caatggaact ttaaaaagtt tctcactcac ccacctgttt cctaaacaga tcagtgcatt 15780
gttgatgaca tcacttacaa tgtgaacgac acattccaca agcgtcatga agaggggcac 15840
atgctgaact gtacatgctt cggtcagggt cggggcaggt ggaagtgtga tcccgtcggt 15900
gagtagccct atttccctag atgagtttgc acagggggaa tggttagcaa gtttcagata 15960
agaaaagcta tgtgaaatca catgactgaa gttggctcca gactttgatc agttgcttgc 16020
aaagaacttt gcaaagtctt ctctctaata ctggaccaaa atatctcgat attggtagtc 16080
gtctggtttt tgctgaattt ggtgacaaat ttaggcttat tttaattgaa tggaatttat 16140
tcttgggttt agaatcataa agataatcca tgctattaaa agtattcttt cctttttttt 16200
ttgtttgttt ttgtttttgt ttttgttttt ttgagagaga gtttcgctct tgttgcccag 16260
gctggagtgt atggcacaat ctcggctcac tgcaacctct gcttcctggg ttcaagcaat 16320
tctgctgcct cagcctcctg agtagctggg attacaggca tgcgccacca ggcccagcta 16380
attttgtatc tttagtagag atggggtttc tccatgtggg tcaggctggt ctcaaactca 16440
cttccttacc agctgtgtaa cagcatgagc aaagggtgta aatatcaccc accaaaacac 16500
tctaggtttt tttttggccg cccttcaaaa tagaactaag caaatagtga aggctgagcc 16560
ttaaaagagc tgtgttacca gcactacaaa gtttaaggtg atccattact atttctttac 16620
caaaagagac aggttgctca ctgagaaaac aaactgataa catccgtttg tttgacgtga 16680
gattaccaga actgagagag aagcctgaga ggttttctta gaagctgctc agcaggtata 16740
ctcgtaaagt ctagttcatt catttaaatg tcaaacagtt tctttaaatt ttgaagaagt 16800
aaggaaaatg aaattattgc agattttttt cttgctattt aaatgttaag ccagttatat 16860
taatatgggt aaaaataata actaatattt aaaattaatg tgtagattat caatatacac 16920
tgaaatctaa atctttacat ttttatttag aaatattacc ttttagaaaa ctaaatattc 16980
ctcctaatag gtactttggt ttttttttta ctacaaactg tcctgtaagg taaagaatgt 17040
gaacaaaata tttttttaac tgcatatatt tgtaagaaca attgcaaatt tctatttaag 17100
ctaaatgtat gctctagcac cctgaaatta aattcgtagt tataagtctt caaggctgtt 17160
tatcttttcc ttccatgtat tttagaccaa tgccaggatt cagagactgg gacgttttat 17220
caaattggag attcatggga gaagtatgtg catggtgtca gataccagtg ctactgctat 17280
ggccgtggca ttggggagtg gcattgccaa cctttacaga cctatccaag taagtagctc 17340
tattactgca agttgagaac tgccaattgg gttataacaa cagggcagtg attattaatg 17400
ctctcatgcc taagttgggg gtctcccctc tttcccaccc ttttctcttg ttattatcta 17460
ataatcaatt gaatttttga ttaaaataat ttttctctct tcctctatca agtaaaaggt 17520
agagaaggct atgaaaatgt gcctgtttat aattttactt cttaactctg taaaatattc 17580
tgttaggtta agacactctg gctaatttca tcttatatcc atacatggaa ataaaaacca 17640
ccaagtgagt tatgctggga gtaaaggttt ggggctttat attatgattc ttaacagaga 17700
agctgcatag agagatggca tgaaatgcag cataaggtac gtgttcattc aacatgtcat 17760
ctaagctccc tttgcatcaa acttttcatt tgtttgatca gttgccacca ggaacacagt 17820
atgttgggcc aagggttgag taacttggtc aactctctgc ccacacagtt caaacactct 17880
caaatgttta ttgctgggtt tttccaggtc acaaagacat catgcctagc tgtaggtgta 17940
attagttcat ttggggggaa aattgcattt aaatattcac tgagtgatta taataaaaca 18000
tgttaataaa acatgaaagg ctaattaaaa ggcatcagtt atttgagcaa ctgctgaggt 18060
gcaaagtctc caaagtcttc actaacgttt gactgaaaat atggcctaca ttcagaaaca 18120
aaagagtttc agggtgtcag aatctgcatg cgacagaaat taagattaac tctgtgataa 18180
aagattcact gtgacagaga acaagctatg ggaacaactt ggccaaaggt agtgttagcc 18240
aagcctcatt cctccatttc ctcatctgta atatgggaag attgtagctg attaccttta 18300
atgttccatc ctaaatacta aacacccaga tgcacctttt ctaggaactt ggaagattct 18360
gcttttccca accctcagac actgtcagtg ctggggaagg tgacttcact tttgaaggct 18420
tatagcacag attgaccaac ctcctaaatt gtatttcttg gaggatttag gtgtaggaat 18480
cacttaattt tttgtaactt aatatatatt taaatctgat tgtggaagta ctataagtat 18540
atgaatggtt tgtttgttta tatgatgcaa atgatactta aatggtagaa acttctaaaa 18600
aaatgctctg tggtttctat atttatgatt gttattggtg ttgcaatttg ctgaaaatga 18660
tttccttctg aatgattgag agagatcttc gtctctctca acataaggct gtccacatag 18720
ctgcttgctg gaagcattta ggtggacatg ttggagataa aatctggaaa ggaaggaatc 18780
cttgagtatt ggagtattac atgttgacct tactcctact ctttaaaaag gagaacagca 18840
agatcccact gagcatagag gtgatttcgg agggaagaga ttggaatttg acctcagata 18900
tgctctttgg tgcttatctg tatgtctggt ttgctccgtg gcctagcacg tagggcttta 18960
agagtgtggt gagaataagg gaacagcaga ttaccaacag attgtctctg agtcctgcct 19020
tgtttgttcc tcctacagag aacttggtag agttgttcaa actagcaaaa gataagaggc 19080
atttggtttg tcaataagca actagaaaag cacagatctc agcaaaataa atagagaaaa 19140
aaaggactga gtcaaaaaat cataaatgtt taacttctcc aaggacacta ctattggaaa 19200
ttattcattt agactttatt tgaaactaat tttaaaagtg tagacattgt actatctcct 19260
ttttttggta tcatctcaac tattttattg ttagtttatt catattgaat aagagaggga 19320
gtaaagattt cacaatggcg atagctagta tatgccaatt aagttaattt aaaaagttat 19380
accaactacc agtagcgaaa aaggactgtc aaaagtttaa atctaaataa tgtaaaagat 19440
gtcataattt ttaacttttc tgtctttaaa ggatacatag tataagctag agtaattata 19500
cgtagtataa gctagaatat aggaatttaa ttgatctaag aaataactga cacaaagtct 19560
ctttacttcc tgaacaaaaa catgctaaat tccatgctgt tcagtccatt tcctttaaag 19620
gtgggctatg ccacagggct agattttaaa acgtggaatt tcacaccagt gctcgaaatc 19680
ttatgaaagc aaaagggacc tctgtagttg tactccactt tggcttgagt aaaaaccact 19740
gctgtaccct ttttctttcc tttccctgcc catttttatc ctcctccttg tgtccttgtg 19800
gacatagaaa tatgattagg cttagaggtg aacagtaaag gtcatttatg ttatcttttc 19860
aaaacttaat agacatttat ccatcataag cttgtccccc ctcaaaatca tgattgacaa 19920
gactaaataa agtgtatatc aggtgtctct ttatggagga aattgtagta ggatttattt 19980
aaaggatcaa tatttaaata gccctatgcc aattatcata aataattaag gacatgatat 20040
tcctagcttt cctgatttac atggaagtac gttaaatagt cacatctcca aaatttttct 20100
tgaatagttg tctttaaaaa tgtgtttaca tttgtaagga tcttcataaa cagaaggggt 20160
aattcaaaga taggcatgga attgacttat gccaattgat taaaacaaac atcctgtgtg 20220
ttctgtgaaa tacatacaac tttaaaatga aaaactcata attttatgca tgaattttgg 20280
tgttcatgtg gcttggaaat atgtgcatta aatggaatta agattcaaag tatttgctaa 20340
tcttcaacca actttgaatt gttactggtg tggaagtgag catattgttt tagaatttct 20400
gaatctacat ggatatccaa gttatatatt ttttctgcta cagaaagctt tgttttccaa 20460
gagaatttaa tggcttagat aataaagttt gaaaatcaat gtattttttt tcctagaagc 20520
tttcagaaaa cttaaatctg ttaataatct ggtgaagtgc tttattacac atacaaaatt 20580
ttgctctgtt tgacagagtg tcagttagaa attcttgaaa aggttactat aagacacaat 20640
ttttatttct agtaatttaa acattgactg acatcataaa gatagtgttt taagaaaaga 20700
tagttttctg ttctgcaagc ataaattttc tagctatttc attattatct taaatggagt 20760
taacactact tagaaattga tgctacttcc cttattttcc ttttatttta aacaaaagaa 20820
ccaaaaccat actttaaatt ttgttgataa cagtgatata catcaaggtg tagaaatact 20880
gaatttagta tacacttcat aaagtcattt ctgttgacaa ctgattttgg aaaaaaaata 20940
aatttaatca cttaataatt tgatggatca atggtgtgat ttgggagtaa acttcttgaa 21000
taaaaataaa acttgatgtt ttttccaaac tgatagactg cttagactga tgagaaataa 21060
aactaggtct ttaattatta cctttgctat ttgtctaaga ttctaccccc atttagaaat 21120
gtgtttgttt tacatcatct catatggcct ttggaatgtt gtttccttct taggtagtag 21180
attcattctt gatgaaaacc ttccaaaatt agaatttgct ttaaaagagg ctcaatacaa 21240
taagtaaatg aagtctgtgt tctgtattac attatttttg taggatcgtt tcacaatttt 21300
ctcacaattc ttactttgat agtagagaaa ataaaagcaa gccaagagac ttttttttaa 21360
aaatatattt tatttgctat aaacaactat gatttgcatt tctcatgtga agaataataa 21420
ttatcggcta aaaatggatt tgctgcattg attttcaacg taaatattta aaagattaat 21480
gccagataat tttattatac tcacatttaa cgacaagcaa agctgtttat aatgatgact 21540
gtccatgtac acagttttaa gttgaagtga gtgaatattc aagataatta aatgctacat 21600
tttcattttc aggctcaagt ggtcctgtcg aagtatttat cactgagact ccgagtcagc 21660
ccaactccca ccccatccag tggaatgcac cacagccatc tcacatttcc aagtacattc 21720
tcaggtggag acctgtgagt atcccaccca gaaaccttgg atactgagtc tcctaatctt 21780
atcaattctg atggtttctt tttttcccag cttttgagcc aacaactctg attaactatt 21840
cctatagcat ttactatatt tgtttagtga acaaacaata tgtggtcaat taaattgact 21900
tgtagactga ggggattttg gttttggttt tgggttttgt ttttttgcgg tgggggggct 21960
ggtatttgga agaatttagc tctttatgtt acagaaatct tttttgcaag gacttagaaa 22020
tgataatgct taagattgtt cttgcccaat gtgggaagag aatctaaggt ttttatatgt 22080
cttgcaacct catcaaagga aaattactgg catcattttc ataatttgaa aaaaaaagcc 22140
aaattaatat atttcttttt tgattcactt tttaagtgat catttttaaa actttacttt 22200
tgacccactg aatttattta gatagaagga aaagagatga tgggagggaa gtttagataa 22260
aggatggaag ttggttttat ttaaacaata gccctgtgat ttcctaatga gaagtgacta 22320
gaaattgaag aaaccaaata aggaggatat tggtcaattt agctttagtt tctcttactc 22380
tctcaagcct gccctgttta actccaaagt tcatggctca taatttgaga aacactgttt 22440
taaacacagg agaaaaaaat gtccatttta aatcatagct attgaattct acaattacaa 22500
agaaacaaac aaacaaaatt tgaccaaccc aggcggttaa atttaaactc ttcaggaaaa 22560
atttaagctg ttaaaattat tctttttcta aatttctaaa gtggagggac agaatttttc 22620
agatttaaaa gggcctccta ggtgcccaga aaattagtgg aaagaaccac gtctagacgc 22680
atctttgatg tgtcagagtt ccaaggataa aaagaaactt ttaaagtctt ctatactcag 22740
ccaggttatc aatcaaatat gagggcaaaa taatattttc agacagattt taggcagttt 22800
atcttccata tatccttttc tttaagggta tttgtagata cactccagaa aaacaagagt 22860
gaaatatgaa ggaagttgtg gggtccagca aacagtgctt ccaaatcaga cccctgatag 22920
aggtggaaaa ctttgcaatg caacaactgc gtagctggct tagaggacag ccaatacaga 22980
tggaacagaa agatgaggat gggattgagg gatcagggat tgaggtctcc aagaataaaa 23040
agggacttca tggaaaaagt aggcttgtgg ataattaatc acaggggcaa ataatgcagt 23100
taaaataaca acatgacaat caggtggagg aatgtataat aaacccaaat gtggctgggt 23160
agagtggctc acacctgtaa tcccagcact ttgggaggcc aagccgggca gattacctga 23220
ggtcaggagt tcgagaccag cttggccaac atggcgaaac cccgtctcta ctaaaaatac 23280
aaaaattagc caggcttggg ggcgcacgcc tgtagtccca gctcctcagg agctgaggta 23340
ggagaatcac ttgaacccag gaggcaaagg ttgcagggag ttgagccaag atcgcgccat 23400
tgcaccctag cctgggcaac agagcgagat tctgtttcaa aaaaccccca agtgtattat 23460
aaggcaataa ttcctatacg aagcaaacta aaatgcagca atattaaggt ataaaaacaa 23520
agaggaataa ttccattgaa ccttgattct ggaaactttg atccacccag cagtcatgat 23580
gttagactca ttgaaaagaa tgtatttcta atgcatgatg cgatcggtct atagatgtgt 23640
catggaaact tggttgcaac ttcaagacaa aataaaaagt aaacatttac atgaaaaatg 23700
gtggatatgg aaggtggaga agagaggaga taacagcttt atctttcaaa atagagaatt 23760
gagagatggt accaaaagct gatgaagtaa aaaaaaaaaa aaaaaaaaaa gatacttaat 23820
ataatacttt aaattacaaa tataaacaca agaagaacaa atataatgat acaaatgtca 23880
gacactggga atgtccaaga ttctggaagg aaagggtggt attattgagc taaatcctca 23940
actttgtctg ggcacagtgg ctaaaaatta gccgggcatg gtagcatgca cctgtagtcc 24000
cagctacttg ggaggctgag gcggaaggat cgcttgagct tgagaggcgg aagttgcagt 24060
gagccaagat ggcactactg cactccagcc tgggagacag agaaagaccc tgtgtcaaca 24120
taaataaata tataaataaa tcatcaagtc tcatattaaa gactctgtaa atatgactta 24180
ttgttgacaa atgaaacaaa tagaggtgta agcatgttgt ctacatggag gcaagaccag 24240
aataatagaa aatggaaaca gattccctta aagaggggaa tcgtgtcttt ctcattggct 24300
caatgtagtc tccgtagagt ctagaatgct tcagcacctg gcacactgct taacaaatgg 24360
tgaatgaaaa aaaaaaaaag aaaagtcatt ctttttcttc tttcacccta tgtccataat 24420
ctggccattt gcagaacttg atgtccagtg atcgaaatca acagcatcag tgcatccaat 24480
atcttctagt ctctcatctt cttattacat cattaatttt atttacttta aaattaagga 24540
tatccaaagt attatgtgag accattgcaa tgggagactt aaaagtggta taaaatgtac 24600
tttgggccag gcgcagtggc tcacgcctgt aatcccagca ctttgggagg ccaaggtggg 24660
cggatcacga ggtcaagaga tcgagagcat cctggccaac atggtgaaac cccgtctcta 24720
ttaaaaatac aaaaaaatta gctgggcatg gtggcgcata cctgtaatcc cagctactcg 24780
ggaagctgag gcaggagaat cgcttgaaac cagaaggcgg aggttgcagt gagccaggat 24840
cacgccactg cactccagcc tgggcaacaa gagcgaaact ccatctcaaa aaaaaaaaaa 24900
aaaaagtaca ttgaattgga aagtcttcaa aaagcagcag tgatgaattt tttgagattt 24960
ttaacaatta caaaaattca gggttttttc taatggatgc cacctgagac tttattttct 25020
gttattttct tgtaataact aaccaaacaa gctcatgttg aaaaatgatt actaaatttg 25080
agctaattgc aatgactggt ttcaaaattt tccacagtgt atttgagtta aaatttcact 25140
gtgaagagta ctacgatcac tctcgcttat tccaaaaata taaatggaca cttgagtatt 25200
tgaattattg aggaaatggt tgactgggta atttttaaaa atcactgggc acaaaaaata 25260
tattttgact tatattagtt tagagtattt acacttgaaa gagtctcatc ttttctgaag 25320
ggtgtttctt tcatacacat tttattgcac tgagttttgt gacccatggc atattaatga 25380
agctgaacag gatgtgaaat ataaactgga agcaaaagat taaataaacc aaaattgcat 25440
tttttctgta gtcttgtcca aaattgggta accacttctg atggggtagc tcatatccaa 25500
gaatgagtca caaaaccaga ctcgttgaac ctggtatatg atgagtcaca aagcaacatt 25560
ctgcctttgt tttttcagga caagaaactt gaattgtatc ccactgagtt aaaagataaa 25620
atatatggca ttggcatttc tgtacttcag agaggaatat atctgtttgt ggtaggaata 25680
aaaaataagt gagagaggca aagcttaggt tcatcatatt atgttactga tataacacaa 25740
ttaacttggt aaaagtgaag gtgtgggtgg gcgtggtggc tcacgcttgt aatcccagca 25800
ctttgggagt ccgaggcggg tggatcacct gaggtcggga gttcgagacc agcctgacca 25860
acatggagaa accccatctc tactaaaaat ataaaattag ccaggcatgg tggcacacgc 25920
ctctaatccc agctactcgg gaggctgagg caggagaagc gcttaaacct gggaggtgga 25980
gtttgcagtg agctgagatt gagccactgc actctagcct gggcaacaag agcaaaactc 26040
tgtctcaaaa aaaaaaaaaa aaagtgaagg tgcccagtgt ctgcaactat gtcaccccgg 26100
gcatatcaca tatcactctg tttttccgtc tgtaaaacgg gagcaacaat gccattgcct 26160
tatcatcaga aggatatgga gactaaatgg gagaatgtag gtaaacagca cagagtatgg 26220
gtatcagtaa gtaaactgca gcagtttgtt gatgttaaca atagttagca ttatatctaa 26280
ctatatctaa cgatataacc attgggaatc cagttttcca tgattttcct ctagaatgga 26340
gctgcctaag tcctgcttaa gtcatttttc tttgaagatt actgaacatc atcttcaaat 26400
gttcatcctt gtaaacacgt gtgtgtgtgt gtgtgtgtgt taatttaaat tttcagaaaa 26460
attctgtagg ccgttggaag gaagctacca taccaggcca cttaaactcc tacaccatca 26520
aaggcctgaa gcctggtgtg gtatacgagg gccagctcat cagcatccag cagtacggcc 26580
accaagaagt gactcgcttt gacttcacca ccaccagcac cagcacacct gtgaccagta 26640
tgtacacaac caccctcatg cctcctaccc ccgaggttcc tagagctagg ctctcctgag 26700
gcaatgcttt ccttctcaat tcatattctt ccaggagggg caccaacgtt ttttaaaatg 26760
atgttggcga cgaggacggt aaattttcta gatgactgaa ggctgacttt cccctttctg 26820
tgactctcta ggcaacaccg tgacaggaga gacgactccc ttttctcctc ttgtggccac 26880
ttctgaatct gtgaccgaaa tcacagccag tagctttgtg gtctcctggg tctcagcttc 26940
cgacaccgtg tcgggattcc gggtggaata tgagctgagt gaggagggag atgagccaca 27000
gtacctgggt aagctcaata tgtcgctcaa gacaggttca gggcagctgc tggaaaactc 27060
tccttgtggg ggtgggtggc ctctaggcag gtggtatctg tggtttggaa ctggttgaca 27120
gctcagactg aacaaaccac cctctggcat gaggaaggga aggactgact ctttctaaga 27180
agtggccggg tttttcccaa gccactgtca catgttcctg gtccctgatg ccagctgcat 27240
catgcgccta cctgtgcaca agttcctaca gcaaaagctg tgttcttggt ggaagtaatt 27300
accaggactg cagctgacaa tgtgagcaca gtacggtcac tcatactttt caaattgtta 27360
tggtgagggg cctttaaaaa acttcattgg cgcactgaag tgtgtgccat cgtaagcact 27420
gagttcagtg aatttgaatt cttataaagt gaacacacca caagaccagc acccagatca 27480
aggaaaagaa tatctctcta ccctcacccc atcatcttcc gccaataatc actaccctga 27540
ctcttactgc agagagctat ttttaaaaat ttggcattcg attacaaaaa ttatacgtct 27600
ttagaaaaaa agttggaaaa atgaaaggaa gaaggaggag gaggagaaag gagaaagaca 27660
agaagtggtg ttttcccata gtacattaat aatcacagat taggtgggtg cggtggctaa 27720
ctcctataat ctcagcactt cgggaagctg aggctggtgg atcacttgag gccaggagtt 27780
cgagatcagc ctggccaaca tggtgaacct ccatctctaa taaaaatgca aaaaaaatag 27840
ccgggtgtgg tggtgtgcac ctgtaatccc agctactcgg gaggccgagg cagaagaatt 27900
gcttgaaccg gaaaggtaga ggatgcagtg agctgaaatt gtgccactgc actccagcct 27960
gggcaacaca gcaagactct gtgtaaaaat aataataata atcactgatt agctattagc 28020
acattacctt ctagtcgctt ttccctatga atatataatt cttaaaatat ccttcttata 28080
agctgtagag tcatttgagg gactagtttg ctctgattag ttaccttttc ttttcatttc 28140
aaagatcttc caagcacagc cacttctgtg aacatccctg acctgcttcc tggccgaaaa 28200
tacattgtaa atgtctatca gatatctgag gatggggagc agagtttgat cctgtctact 28260
tcacaaacaa caggtacatg tgtgctacat agtgttaaaa gaatcttttt ctgtaaaaca 28320
caggcctgta gtagcacttc ctgactgttt gccccacttt ctttctttct tagcgcctga 28380
tgcccctcct gacacgactg tggaccaagt tgatgacacc tcaattgttg ttcgctggag 28440
cagaccccag gctcccatca caggtcagct aagcgtcccc ctctttggct gctatgttaa 28500
tcttaatgac atcagcaggg agggcgcaga ttctgactgc ggacctgcat atcactttaa 28560
atctccaata taatttatgg gagaggggtt tgtgtgtgtg tgtgtgtgtg tgtgtggcgg 28620
gggtggggga gttattttct atggcacatt tccccttgaa accatttcac caactccctt 28680
atacacacac accacaacat acacacaacc tgtaaagcca gctcattggc ttattaaagc 28740
aagtgttccc agggttgaag aggtgtaatt tcctgaaaac gttgctctaa gatttatcct 28800
taaggagaaa gctgagctgt cgtcttagct cattaggtga ttcaactgcc tcatcactga 28860
agttccaaaa agacacacac agtgctagac aactctgctt aggctggttc attaattgct 28920
tccctcgtct ggagctcaaa gaggaaaaat cagcttaaca tgaatatttt cacctaatgg 28980
catctctaat tgacatttat taaggatgtc aggtcttcaa ggatgacatt tattattaaa 29040
aaggttcgca tgactgttct tattttatct tcgtgctgaa tagtcattat tagaagaagt 29100
ggcaatattc aaagagtcaa aaagtatcac tggctcttca ctaatcaagc aagatgctaa 29160
gggatattag aaaagggagg atttatggtg tttctaagcc tctgtctcaa agaaaacagt 29220
gcatcttact tttgctcatg aatctgcagg gtacagaata gtctattcgc catcagtaga 29280
aggtagcagc acagaactca accttcctga aactgcaaac tccgtcaccc tcagtgactt 29340
gcaacctggt gttcagtata acatcactat ctatgctgtg gaagaaaatc aagaaagtac 29400
acctgttgtc attcaacaag aaaccactgg caccccacgc tcaggtaact tttttaagaa 29460
gacacttcct atgttatctt atcaggattg ttcctgaagg agggttgttt tgtctctgtc 29520
aacagtcctc tcattcaaga aatcttatat attagttttt ccctaaactt ctgatattta 29580
gctgaaatgt cataagtaac ttatcaaagc tggctactgg cctttctgat taaaaactga 29640
caccataacg tccatctaca aattttcccc tagaagctta agggtcattt catttttgat 29700
tcttaagtat tataaaatga ttcagtaaaa caaaaactgt tacattattt tctgcagtta 29760
tttcaaaggc tttttctaaa aaatttttta gtatcttttc ttataaccct ctccccccac 29820
caccatatga cacttcatat gctggtaact cacttattac ctattttaga taaaaggttc 29880
aaatgtcata atttaagcac tatgactgga ccatgaaaat gtgatctgat taagagacaa 29940
aacttagcaa aactctcgaa tgagaggctc aatgaactgc ctaacatatc caagaaactg 30000
gcttcttaaa agtaatcttc agcagagaat gtgaatgacc agttgactct tgtctgtcag 30060
atacagtgcc ctctcccagg gacctgcagt ttgtggaagt gacagacgtg aaggtcacca 30120
tcatgtggac accgcctgag agtgcagtga ccggctaccg tgtggatgtg atccccgtca 30180
acctgcctgg cgagcacggg cagaggctgc ccatcagcag gaacaccttt gcagaagtca 30240
ccgggctgtc ccctggggtc acctattact tcaaagtctt tgcagtgagc catgggaggg 30300
agagcaagcc tctgactgct caacagacaa ccagtatgtc ttctcctatc tctatctccc 30360
ctccaaattc tccaccctca cttgcagcct gtgagaaagt gcagtaaacc attcactcag 30420
aggtgtatgg cttagagaga gggaaatacc cagccggcaa gggaatgcat agtgaacaca 30480
aagcacatta aacttgaaaa caaaactcag acaagctcca tggatgctaa gtggtaaccc 30540
atttctaaaa tacatgtacc agctgaaggg tactaagagg ggagaactga agagaatcta 30600
atttgagtgc atttttcgtg taactaaata tatctagatc aaagttaaaa tgcaggatca 30660
taacacttag agtagaattc atttaacaat agcaattgtc aagtgtctag tattactagc 30720
caccagctta tctgctcagt ttttacaagc attattctca tatttactct ttgttttgac 30780
cttaggaagg aaggtcttat tattattatt ttatttattt atttttttga gatggagtct 30840
cgctctgtcg ccagggctgg agtacagtgg caccatctca gctcactgga acctctacca 30900
cctgggttca agcaattctc ctgcctcagc ctcccgagta gctgggacta caggcgtgtg 30960
ccaccatgcc ctgctaattt ttgtgttttt agtagaaatg ggtttcgctg tgttggccaa 31020
gctggtctga aactcctgac ctcaagtgat ccacccactt tggcctccca aagtgctggg 31080
attacaggcg tgagccatcg tgcccagccg gaaggtctta ctagtatccg tattgaatac 31140
ttaaagaaac tgaggcttta aaaaagttct gcaacttgta gggtcacaga gataggaagg 31200
gatagagctg gctctataac ctatgtccga agcccatgct ctcaattatt atactcgact 31260
gcctcttaaa gatttcctct atttgaaagg taatttaaat ttcggtggga aaactgctgg 31320
ttattattct caagaataaa ctccacaact tatgtgattc tgatagtgca aactcaccag 31380
tatcctacca tgaatctgag gatacgttat cattactgta attactgtct aatctgaacc 31440
atgtgaaaat aacttttatt tctctagcaa agggctattc acagaatatt gcttttgacc 31500
catagagagc ttcttcttgc tgtcatttta ggaggcatat ccctttttcc ttaatctgtt 31560
tggctcagag ctaactgtga acttcagaag tgtttgtttt gcctttttaa aaataccatt 31620
gctttaatgt aactataatt tctgagactg atgcgaaagt cttgctggaa aattagactt 31680
cccaaaggat cacagtcaag caaaatggtt ccacaatttc tcatgactgg cagagttttg 31740
gcaaagtttt gtgtagcact caatctctta ctggctcagt ttttccaggg ttttgacttt 31800
cacatagtta caaccttgag gagagaaaac ttagacattc aatcaagttt caggacttga 31860
gttatgatca ttactgatct aaatatttct tggcatgttt catctttttt cctagaactg 31920
gatgctccca ctaacctcca gtttgtcaat gaaactgatt ctactgtcct ggtgagatgg 31980
actccacctc gggcccagat aacaggatac cgactgaccg tgggccttac ccgaagagga 32040
cagcccaggc agtacaatgt gggtccctct gtctccaagt acccactgag gaatctgcag 32100
cctgcatctg agtacaccgt atccctcgtg gccataaagg gcaaccaaga gagccccaaa 32160
gccactggag tctttaccac acgtaagctg aaaattaagt gccttttctt aactatattt 32220
acattctcta ttcttcatgc tttaaaacaa aacaaaacaa aacaaaaaaa acattaaaaa 32280
attagtacat aatttaaatc agtgatacta aaaatgtgct ccatagactg gctgctggcc 32340
cgttaattgt ttgctgctag tctgcaacaa gaaaaacggt tgtgccagaa cgtaaatcac 32400
aaagcacact gcttagtaca gctgagaatt tttctgaagc cagattttct tgatgaagga 32460
agcagtgtgt taatttgcac acattgccaa gctcgctctt tcctctaggg ccagcacttt 32520
gagtaacatg ggtttaaagc agtctgttat tagaaaaatt aaattcgatt acattaaatg 32580
aatttaccaa acactagtta acgcaagaaa aaattagcac ctatgtctac attctattac 32640
tttgggcatt gaatagtaac tataaatgca gaataaaaat atctatggat tgaatgggaa 32700
ccaactaatt gaacatgaag ccaaggaaat gatttcttta tgagtgttgg ctgcagaaga 32760
ttaaagtact tttgcagacg gaatcgctct tttcttaaat tactcttgaa attcctcaga 32820
ggagaaaaat actaacaata atttttggtc atgtctatcc ttttgctcaa cattttaaag 32880
gaagtggtct taaatctccc acatatctac atcacaataa caacctctat tcacaaaccg 32940
attcctatta aatacatttc catttacatt acagagaatt atgagactcc ttatttctag 33000
ctgaacatca tttgttattt tcaactcgac attttgaatt atagaagcac ctaacataag 33060
tactttttca gcatatattc taaccatgga ctagtttgca attttctaag agctttcaac 33120
aaatgttact cttcgactaa tttaaaagta tggatgttaa aaagcattca aaaagtccat 33180
acaagcctag tttgtaaata actatggaat tgatttccca aagaaaatac aaacttttcc 33240
ccataagaat tcatacttta agaaaaactt acttccattt aaatttactg tatgaagttt 33300
ggctcatgaa ggctttttcc taaataatag ttaatcgtaa gcaagtaaaa ttcactttta 33360
atttgcaaat aagcttactt gaaaatttgg ctaaaatttt acacggttct aagatagtct 33420
aagatctact ctcatgaaat taatgtcttt atatttcttg taaatattca tttcttataa 33480
atgtccttca gtgaattaga atggagattt cagtgaatgc gccctttcag tagatgtcgt 33540
cttttactaa aatgtagaat tctatagttg tcttgttcat tccttaacat gagacatatt 33600
ttatgtagtt tcttttgttg aacacagtgc ttataaaaga aaaagcattt ttaatgatgc 33660
taacaataat taagggaagg tggtgggcca agatatttca agtacttctg aagactgata 33720
tattggatat attattttat gctttgcata atacattcat ataaaatata atgattttaa 33780
ctgaagtact gatagccaaa actaatttta ttagataaag gttaacatag tgtctggaac 33840
attgtatgct ttcaaaaact atttggtgaa tagataattg agaaaggaat aataataaaa 33900
acagctaaat gaagcttata tttaaataaa ctaatgtaag cagggtattc tacaactcca 33960
tttgaacttt aagcactccc taaggctgta aacatccaca aggcttgcat gtttttgaaa 34020
ttactaaatt tctgtagttt tttactatct tactaagctg aattctggga gtaacttttc 34080
tgagttttat aacttgtgct aaattcttaa gagcaaatgt gagaaaagtt aggggaaaaa 34140
gctgtttctg gggaaaattc agcttagtct tatattgata gggcaaattt tatttcttta 34200
acagctgggc tgttcttccc taacaagacc tgccagaacc catagctcac acttagaatc 34260
acatcctttg tttgacatcg tttgtgggtt tgtggtttgg tgattttccc ataatggcct 34320
tcccaggcag agagcatcat cttaaacttg ggaagactct aggtggctgg ctcaagcaat 34380
agaaaatacc tagtcttaaa gcccaggaca gttgaggcga atataatttg taaaaaaagt 34440
tgtggttttc acagatgttc agtgaaagaa actgactgtt ctctgaattg ttttttgtgg 34500
gccattaaaa atggtcacac agggctggcc atggcatttt ggcacagtca ccagcagtca 34560
agtggtgtat aatttcagag gtactaaaag gcatcgggtc acccatccca gtcatgtccc 34620
cccacccccc accaaacacc atcaaaataa taacatacat agatgaaaca gcccactaaa 34680
ccagtagtac ctcaattcag ccattagagc tatcattatg aagtggccca cacatatatt 34740
tggctttttc tcacacaata tttttaaaat aaaaataaaa aatggctcct tagaatccag 34800
actgaaaaaa aaatgcgaga attgcgatgt tgattctaaa ttcccacatg gcaaagaaaa 34860
aaaaattgac tggagttgag ttgagactgg agtctgaaca ctttttaatc cctgtttgta 34920
taactctgga gactaattct ttgtcttgcc agccattcat aatttagtat aaatgcattc 34980
agaggttttt tcccaatggg aacaaaattt gattgagatg taaagagagg aagaattgtg 35040
gagatgtcaa acatgtgacc agagctatga acacacttga tacccttgaa cttaaactta 35100
cccaactcaa aatatctggc cttctgcgat cttacctttc tacatttata ataagatttg 35160
caaggttgtt ggaaatctct atcttaactt tatatataca tgcctctttc tttctttttc 35220
tttcctttcc tttccctttc tttctttctc tttccttcct tccttccttt ctctctctct 35280
cttttcttcc tttcctttcc tttccttcct ttctttcttc ctttctttct ttctttcttt 35340
ctttctttct ttctttcttt ctttctttct tttctttctt tctctctcac tctctctctc 35400
tttctttctt tcttattttt ggtgctaaaa cccaaaacaa atcttttatt taaaaataag 35460
attttttttt tttttggcca ggtgtgatgg ctcatgcctg taattccagc actttgggag 35520
gccgaggtgg gtagatcacc taaggtcagg agttcgagac tggcctggcc aacatagtga 35580
aaccccatct ttactaaaaa tacaaaaatt agctggatgt ggtggtgggc aactgtagtc 35640
ccagctactt gggagtctga ggcaggagaa tcacttgaac ccaggaggct gaggttacag 35700
tgagatgaga ttgcgccact gcactccagc ctgggtgaca gagcaagagt ccatctcaaa 35760
aaaaaaattg tttaagtaaa attttatttt ctttcttttt tttttttttt tttttttttg 35820
agatggagcc ttgctctctc accctggctg gagtgcagtg gtgtgatctt ggctcactga 35880
aacctccatc tcccaggttc aggtgattct cctgcctcag cttcccaagc agctaggatt 35940
acaggcatcc accatcacac ctggctaatt tttatatttt tagcagagac aaggtttcac 36000
catgttggcc aggttggtct tgaactcctg gcctcaagtg attcacctac atcagcctcc 36060
caaagtgctg ggattacagg catgagccac tgcgcctggc caaagtaata ttttcaataa 36120
gaaaaataac agtgatgtca ggatgctaga aaatgcaaaa taaatttgtt ataattcctg 36180
attctggtga taaaatacta aatttttgca gtattattct gaaagaataa tcacgtattt 36240
aaagtacaaa tctttagact tcaaagtgca tccatggtgg cagattttgt ttaactttta 36300
tatagcatct tttattgcaa ccaaaaatag ctgaccatta ttgtggaata attcagcgta 36360
aagctttttt tttttctttt tttgagacgg agtctcattc tgtcacccag gctggagtgc 36420
aatggcatga tctcggctca ctgcaacttc tatctccagg gttcaagcga ttcttgtgtc 36480
tcagcctccc aagaagctgg gactacaggc atgagccacc atgacagtta atttttcata 36540
tttttaatag agacagggtt tcaccatgtt tgccagcctg gtctcgaact cctgacctca 36600
agtgatccac ccacctcggc ttcccaaagt gctgggatta cagtcatgag ccaccgatcc 36660
ccgcccagca taaagctgtt tttagatcac cttctataat ttaccattgt tcttaaatta 36720
atggttaaga aacaatatga taatcagttt gtggtggcca gttttacatt ttataaggga 36780
ttttacactg acgatatagg gaaatttatt gtcatcaaag tcaaatccca acaatcataa 36840
aaagacatga attagattat ataatttcaa tgaaaggacc accttagcaa acatctaacc 36900
ccttgttact caggtatcat tcacgggcca gcagaattgg tattatctgt gtttgtcaga 36960
aatgcaaact ccctagtttt ttgttggacc tccagaaaca gaatctgcat tttagccaga 37020
ccccagatga tgtgtgtggc acattaaaga ttgagaagcc tgatcctctc ccaattctca 37080
cccaatgaaa aaatatgtta catcctctat ccactgcttg gttaaactga ggttctccat 37140
aaaaatactt gttatctata tgctatgcaa tcatctgtga gtttgagttt tgaatatgtg 37200
cattgattct ctctcacagt gcagcctggg agctctattc caccttacaa caccgaggtg 37260
actgagacca ccattgtgat cacatggacg cctgctccaa gaattggttt taaggtaaac 37320
tgcagatgtt cctaatctct gtgatacagc cctgagctgt ccttgtggtt cccatgtagt 37380
ggaaacaggg tgctcaggag tcaggagacc tgggttttgt cacctgcttc tgtccataca 37440
tctttgacta cattgtcagg gcctaacagt ccttccctgc ctacctcact gaattgttgg 37500
aagggtagat ggaggctgcg aaagtgtttt gcaaaggata aaacattagc acgaagctgc 37560
tgcttattgt tatcttattt tctctatcct ttcctgcagg gaattacatt tcaaaaaaac 37620
atgggaaaac tttatttgat gtgttgttct aaatgagtgt gaacaagttc acaaaagcca 37680
gtttagggag accagttaaa ctcagagtca cttaaaaatc gcattttcat ccaatcagtt 37740
tcatctccaa ctgttcaaag cactgagggt gaatctctta atagaagtta agattaaggt 37800
ttccctgtgg atatctggat tcatcttctt taaagtaatg atattaggga agcggtgaat 37860
acaaatgaat atgtttaaaa gaattccatt ctttggcatt tagtgtgaag agagaaatat 37920
ttgttatcgc tggaaatcat gactcaatcc ccttgatcgt ttaaaaaaat acaccaaaga 37980
taaagtttgt aaatggccat atttatgatt atgctactca aatatagaag aactttctga 38040
agagtgccag tatacctttt aattccctta ataatgtcat gctgactttc agaagcctta 38100
tgatgtgtga aggatctctc tagagttgaa cactattgga taacagtgtt acctaagttt 38160
ttgaaataga atcttaaaag gattttaaat tatgggcata gttattctaa ttcttctctt 38220
gtaatgtatc atcctgcagt tgaagctatg tacatatctc ttcaaaaggt gtgtttttgc 38280
aatacagttg ctacaggggc tggtgccttt aaatggcaac taaaaggtta attgaatgtg 38340
aataactcgt taaagggaga gctcagacat tccttctagc acacacacag aaaaatagaa 38400
atgaactacc atgtgaccca cagtccctgt atacgtctgg tttgtaacaa gagattcttt 38460
atcaagcaaa acagtatgta atgacatttc tctggaacct tccattacaa gccaccttaa 38520
tgcagtttgg aagatacctc ccccacctgg gggaatttcc agctaaagta tataaaagag 38580
tccccaaatc atttcccaat aaaagtacac tgtgcagttt ctgaagagtt tacactattt 38640
aaagcataat catagcctca cagcagtaac agtcctctgg aaatatttgt ccttggtgtt 38700
tactttgcat tccttcctct agctgggtgt acgaccaagc cagggaggag aggcaccacg 38760
agaagtgact tcagactcag gaagcatcgt tgtgtccggc ttgactccag gagtagaata 38820
cgtctacacc atccaagtcc tgagagatgg acaggaaaga gatgcgccaa ttgtaaacaa 38880
agtggtgaca cgtaagaaga attttttccc ttttctatta gtttttaaaa ctgttctact 38940
tttcgaaaaa agctagtgtc aatatcactt tttacttatg agaatggcac aggggagata 39000
tcttatcctt acttatatta ttaatgctat tcctgaattt ggagtagcag gttcaattca 39060
tgctttatat tttatggcat cagaaatgtt ctttccatgt caagaatatt tatgaactgg 39120
caagatgaaa ataatttcaa tagtattgca aaatcattaa tcataaagaa gtctttgtca 39180
gagaattact gctgtccatc atattttcat aatgtaacct atatttttat gggagggagg 39240
gagggaggga agaagcatgg aagagaggga ggtagggaag gaggaaagat tacacaggtc 39300
aagagctttg tgtcagcttt gacttttaaa atgttctttc tgcatagcat tgtctccacc 39360
aacaaacttg catctggagg caaaccctga cactggagtg ctcacagtct cctgggagag 39420
gagcaccacc ccaggtaagt ttgggatgga tcagagggca agtatacacc ataccttccc 39480
aagacaaaga ttttagaaac tgtgtttctt tcagagaaag aagggattca aattacaaat 39540
gcttagctct ccataaaaac tatagcagta catgatgtac atcatggagc agcctgcagg 39600
atgctttaat gcacgttgac ttcaatcaca ggaagcagaa caaccttaca ctagtctagg 39660
gggacaagac agatcctcac acagctgtag ggctgaagaa aagcactgtg gaaggtggct 39720
tttgctgagt gcattaaaaa ttgccaaaca aatggttgaa gtcatattac gtaatttccc 39780
ttttgtgagt tgttacagag cctaagttta ttattccctg aagttttatg aatgttttgt 39840
catgggttgc accacaaata tttaagggtg atgaaaggca gaaatacctt cattttacag 39900
aataagaaaa ctgagactta gaaaaaattg gcctactcat agtcacacat tttaaatgtt 39960
acaaaactgg gattgtaact taagtttgta gactccttct cacacccaat gtcacatatt 40020
tggaatgtaa ttttttttta attatattct atgcaaactg aaaattctga ttaaggggtt 40080
tcctgaccat ttttagagct ttaaatgaag catttgtcta aattccttgt tcacatatat 40140
ttgaaaatta tttataaaat gctaaaatgt ataaagatag ttgttaacaa tattcaaaca 40200
gcatgacgta ctatagcaat aacaggaaat tttagatacc cattactttt gccaaaacca 40260
catggaagtc tcaacaaacc tatggagaaa aatcttaaac aaaaataaaa gttccaatta 40320
atgttgattg cattcttacc tcatatactt gttaatttaa gggatatgtt taggttatta 40380
tttagctatt tctaatttta ctgtaaaatt cttgtgaaat ttttgtttaa aaaaaagtat 40440
tatatagttc ttatctttgc cggggcacag agctaaggct atcatctcta aatctgatta 40500
atgtatgcaa acacacagaa tgaaactagc tcagaatatc tcttttaatc tccctctgaa 40560
gtagagtgat tttggtaaag ttttcattat ctgcggaaac attgtttaag ccaaagctat 40620
acaatttcca gctgagttgc tctgaatttg aaactttaag ttgacaatct tcgtgcttgt 40680
tagcagcagg atcattaata tctcgtctca atggcccagc ccacacatat ggatgaccac 40740
tagcaagtgt aatgatctca atatttattt ctcattcagt tgggtttcct tgtatttgcc 40800
acattagtgt ttaccctgtt cctaatggca aaatattctg tcatctcctt gccttttata 40860
aagtttaata tactttctca ttttaatctg tccccacaga tctctagtca tcactgtttt 40920
tatttgaatg tctctcatcc ctctcaactc ttttactgcc caatttctgt gattcctgaa 40980
gacttcaaca atcaatactc tctttttttg tttgttttgt tttttttttt tgagacagag 41040
tctcactctg tcacccaggc ttggagtgca gtggcgccat ctcaactcac tgcaacctcc 41100
gtctcctggg ctcaagcgat tctcgtgcct cagcctcccc aagtagctgg gactacagac 41160
atgcgccacc aagcccagct attttttaga tttttagtag agacagggtt ttaccgtgtt 41220
ggccaggctg gtctcgaact cccaacctca ggtgatctgc ctgcctcaac ctcccaatca 41280
atactctttc tagaataagt atcagcactt ttgtttctca ccttttctcc tttcttggtt 41340
ctcttcctat aaatcccata gtttcagacc ttttaaatta ggagagctct ctggggaatg 41400
tgcttaaggt ggagagcgat tctatactag gcaggtagaa aggaatattc ctcagctgtc 41460
ttcaaatgat tcattaagga aaagcagggt acagtgatag gaccatgaga tttggaaaca 41520
aagaaagctt tggggaatca ctcccctggt tcaagatttc ctttaaagtg aggatcttgg 41580
cggaggttga agtgagccaa gatcacaccg ctgcactcca gcctgggtga tagagggaga 41640
ctgtctcaaa aaataaaaat aaaaaaataa agtgaggatc ttagtactgc ctgaaaggat 41700
tgttgcaagc attgaataac agtgacagtg gagtcctcag taaatgccaa gtcctgcatt 41760
ccgccctgtg aatccatcat tggagtctag ttaaatatgc tctggctcac agatcctctg 41820
tgcaataact tcccttttct tttttctcca gacattactg gttatagaat taccacaacc 41880
cctacaaacg gccagcaggg aaattctttg gaagaagtgg tccatgctga tcagagctcc 41940
tgcacttttg ataacctgag tcccggcctg gagtacaatg tcagtgttta cactgtcaag 42000
gatgacaagg aaagtgtccc tatctctgat accatcatcc caggtaatag aaaaataagc 42060
tgctatcctg agagtgacac ttccaataag agtggggatt agcatcttaa tccccagatg 42120
cttaagggtg tcaactatat ttgggattta attccgatct cccagctgca ctttccaaaa 42180
ccaagaagtc aaagcagcga tttggacaaa tgcttgctgt taacactgct ttactgtctg 42240
tgcttcactg ggatgctgtg tgttgcagcg agtatgtaat ggagtggcag ccatggcttt 42300
aactctgtat tgtctgctca catggaagta tgactaaaac actgtcacgt gtctgtactc 42360
agtactgata ggctcaaagt aatatggtaa atgcatccca tcagtacatt tctgcccgat 42420
tttacaatcc atatcaattt ccaacagctg cctataaaat agttttgtcc ctgtatgtga 42480
gcactgaaac agcatttggt tgacacatct agtttttcat cttgcagttt caaatccttc 42540
tttttgaaaa ttggatttta aaaaaaagaa gtaaaagtca caccttcagg gtgttctttc 42600
ttgtggcttg aaagacaaca ttgcaaaggc ctgtctaagg ataggcttgt ttgtccattg 42660
ggttataaca taatgaaagc attggacaga tcgtgtcccc ctttggactc ttcagtagaa 42720
tgcttttact aacgctaatt acatgttttg attatgaatg aactaaaata gtggcaatgg 42780
ccttaacctt aggcctgtct ttcctcagcc tgaatgtgct tttgaatggc acatttcaca 42840
ccatacattc ataatgcatt agcgttatgg ccatgatgtt gtcatgagtt ttgtatggga 42900
gaaaaaaaat caatttatca cccatttatt attttttaac cttcttcatg caagcttatt 42960
ttctactaaa acagttttgg aattattaaa agcattgctg atacttactt cagatattat 43020
gtctaggctc taagaatggt tttgacatcc taaacagcca tatgattttt aggaatctga 43080
acagttcaaa ttgtaccctt taaggatgtt ttcaaaatgt aaaaaatata tatatatata 43140
tattccctaa aagaatattc ctgtttattc ttctagggaa gcaaactgtt catgatgctt 43200
aggaagtctt ttcagagaat ttaaaacaga ttgcatatta ccatcattgc tttaacattc 43260
caccaatttt actactagta acctgatata cactgcttta ttttttcctc tttttttccc 43320
tctattttcc ttttgcctcc ccctcccttt gctttgtaac tcaatagagg tgccccaact 43380
cactgaccta agctttgttg atataaccga ttcaagcatc ggcctgaggt ggaccccgct 43440
aaactcttcc accattattg ggtaccgcat cacagtagtt gcggcaggag aaggtatccc 43500
tatttttgaa gattttgtgg actcctcagt aggatactac acagtcacag ggctggagcc 43560
gggcattgac tatgatatca gcgttatcac tctcattaat ggcggcgaga gtgcccctac 43620
tacactgaca caacaaacgg gtgaattttg aaaacttctg cgtttgagac atagatggtg 43680
ttgcatgctg ccaccagtta ctccggttaa atatggatgt ttcatggggg aagtcagcaa 43740
ttggccaaag attcagatag ggtggattgg ggggataagg aatcaaatgc atctgctaaa 43800
ctgattggag aaaaacacat gcaagtattc ttcagtacac tctcatttaa accacaagta 43860
gatataaagc tagagaaata cagatgtctg ctctgttaaa tataaaatag caaatgttca 43920
ttcaatttga agacctagaa tttttcgtct taaataccaa acacgaatac caaattgcgt 43980
aagtaccaat taattataag aaatatatca ccaaaatgta ccatcatgat cttccttcta 44040
ccctttgata aactctacca tgctccttct ttgtagctaa aaacccatca aaatttaggg 44100
tagagtggat gggcattgtt ttgaggtagg agaaaagtaa acttgggagc attctaggtt 44160
ttgttgctgt cactaggtaa agaaacacct ctttaaccac agtctgggga caagcatgca 44220
acattttaaa ggttctctgc tgtgcatggg aaaagaaaca tgctgagaac caatttgcat 44280
gaacatgttc acttgtaagt agaattcact gaatggaact gtagctctag atatctcaca 44340
tggggggaag tttaggaccc tcttgtcttt ttgtctgtgt gcatgtattt ctttgtaaag 44400
tactgctatg tttctctttg ctgtgtggca acttaagcct cttcggcctg ggataaaata 44460
atctgcagtg gtattaataa tgtacataaa gtcaacatat ttgaaagtag attaaaattt 44520
tttttaaata tatcaatgat ggcaaaaagg ttaaaggggg cctaacagta ctgtgtgtag 44580
tgttttattt ttaacagtag tacactataa cttaaaatag acttagatta gactgtttgc 44640
atgattatga ttctgtttcc tttatgcatg aaatattgat tttacctttc cagctacttc 44700
gttagcttta attttaaaat tacattaact gagtcttcct tcttgttcga aaccagctgt 44760
tcctcctccc actgacctgc gattcaccaa cattggtcca gacaccatgc gtgtcacctg 44820
ggctccaccc ccatccattg atttaaccaa cttcctggtg cgttactcac ctgtgaaaaa 44880
tgaggaagat gttgcagagt tgtcaatttc tccttcagac aatgcagtgg tcttaacaag 44940
taagcagttg aatgtatctg ttccataaat attaacctag agcatagcaa atgaattcta 45000
aattctcaag taggaggagc taagagcaag agagctgcaa ccaagctaca aactaaactc 45060
tgaattcaat gcacagctcc attaattttg aaagatgtaa tgtttgttgc tatcttaata 45120
tacttttgat atctacagct ttaaaaaaat catagtggaa aaacacctgc aggaaagttc 45180
catgacttca aacaaattct gcttctaaat aagcacgtaa aaataagtga atatcaagag 45240
aaattatatg actaaatcta aatctttaga gaaaaaaatg agaactgaaa atagtgtcac 45300
catatgtgct ttattctcat ttttataaaa aaagtgtcag cagttgattg atttaggatt 45360
tgaatactta gaaaagtgac tgattgtttg gtctagatta gaatgttgtt gtgaagagag 45420
tcagaagttt aatttgtact tcaaaaagaa tctgttagaa ggatttctca gaagactgag 45480
agcttagaaa aaaaactgac attaaataaa taacaacaat ttatggaaat tgtctctttc 45540
tagtcccaac cattatagaa tagacatctt ttgttaaaga ataaaacagt aggctgcaag 45600
atggtgctgt gtttcacata aacagtgctt tttattattt tcactgtaat agtcaaatat 45660
ataacaacag caaaagattc tacataaggg aaaaatagct tacatttagg tacattacca 45720
agtattagtc tgaaaacatc tacctttcaa acataattta gataatgaaa cacaaagaag 45780
agcagctcag cgtgaccata atcttggttt cttactttgt ggctgagggc aagaatatct 45840
ttatattggc atatccacca ccccagggct gttgcttctg ttctagagca ccctggaatc 45900
actaattaca gcatcaccca gtatacaagc ccctgcatca caatgtctgt cccttagccg 45960
tagacctgtc acatgctaat catgtgttct aagaccttat tataatccta atgctacaga 46020
tgacctcagg gtagcccctc tccctcctag caaagtcatt attatcctct tttaaagatg 46080
aagcaaacca gtgcagtggc tctcgcctgt ataatcccag cactttggga ggctgaggtg 46140
ggccaattgc ttgagcccag gagttcgaga ccagcctggg caacacagtg agaccaagtc 46200
tctacaaaaa atacaaaaat tagccgggca tggtggtgca cacctgtggt ctcagctatg 46260
taggaagttg aggtaggagg atcacctgag cctggggagg ttgaggctgc agcaagccat 46320
gatcgtgcca ctgcactcca gcctgggtga cagagtgaga ccctgtctca aaaaaataaa 46380
caaacaaata aacatgaagc cgtcgaggtc cccagcagtt aagtaaattg ccactggcca 46440
gctagtatgg tggaaatgga atccaggcat ctggtcctcc attctggcac ttttccaaac 46500
ttttgtaggg ggctttatag aaacgctgaa gggcaaatgg tgtgcagggg aatgagggtt 46560
tagtgagtag gagttccaaa tttagaaacc tcactctctg tatcttttag atatacaaat 46620
atttaccata tattacagtt gcctctagtg ttcagtacag taacatgctg cacaggctca 46680
tagcctagga gcaataggct agaccacata gcttatagct taggtgtgtc aaaggctcta 46740
ccatctaggt tttttgtttt gttttgtttt gttttgtttt tgagacggag tctccctctg 46800
ttgcccagga tggagtgcag tggcacgatc tgggctcact gcaacctcca ccaccaaggc 46860
tcaagtgatt ctcctgcctc agcctcccga gtagctggga ttacaggcgt gagccaccac 46920
gcccagctaa tttttttgta tttttagtag acgaggggtt tcaccatgtt ggccaggctg 46980
gtttcaaact cctgacctca agtgatccac cctcctcggc ctcccaaagt gctgggatta 47040
caagcccatc taggtttgtg taggtacact ctatgatgct tacacaataa aatcaccaaa 47100
tcacacactt atcaaaatgt atctccacca ttaagctatg cctgactgtg tatcaaaatg 47160
gaagaagaag ctgggcacag tggctcacgc ctgtaatccc agcactttga gaggccaagg 47220
cgggtggatc acaaggtcag gatttccagt ccaagcctgg ttaacacggt gaagccccgt 47280
ctctattaaa aatacaaaaa ttagccaggc atggtggcag gcacctgtaa tcccagctac 47340
tcaggagtct gaggcaggag aatcacttga acccaggagg cagaggtttc agtgagccaa 47400
gatcacacca ctgcactccg gcctgggcaa cagagtaaaa cctcgtcaaa aagaaaaaat 47460
aataaaaata aaaaaaaatg gaacaagata ctcagggatg tatatttaat tttttaaaaa 47520
atattctgct ctcattttaa tatggcagaa ccgattgctt tctaagtgtg gcttttttcc 47580
agtaaaggtt aattattaag accactagtc ctggcctggg tcaatcccag tatgatcctg 47640
ggcaagtaaa ttaaagaaga taacttctct gtgcctcagt ttttttttgt tttgtttttt 47700
gttttttcat ttacaaaatg gagataattg tagtaaatca aatttttaga ggtgataggt 47760
ttgttcattt cttgaatgcg gtgatggtct cccaagtcac acatatgtaa aaacccatca 47820
ctttaaagat atgcagtacg ttgtatgaca agaaattgct tttaaaagga gcaaactacc 47880
ttccagggtt gttgtgaggc ataaatggca atccacagca ccacagcaag gattatcatg 47940
tgccctccag agacatactc tcaggtggat gcgagaaata tccagctgtt gcagcaactt 48000
catcccactc gaaatccagc tgagtcacac tcacaggtgg aatggagggc ttcgagaggc 48060
catggggcaa ggtgaccctt ccttatcatc taattacaga ccttctcaag gtctgttcac 48120
tgaacacttc gctgtagtgt tcacttaggt gtaagtaggc tataggactg gacatttgga 48180
tatttcatca gttcaaatag tcctgggcgt gctttagttt ctcatgcttt tgagcagagt 48240
tttaaaataa gccccatttg cccctacaga tctcctgcct ggtacagaat atgtagtgag 48300
tgtctccagt gtctacgaac aacatgagag cacacctctt agaggaagac agaaaacagg 48360
tgagtggtgt tggcagtatg actatccagt agcttttgcc tatcaattct gtataacaaa 48420
tgaaatgcta cttctaaaaa tacatctcca ttttttgttg tcatggtgtg tgtacctttg 48480
tcatcacagt atgattttat cgctggtctc aaaaactaaa agatacctta ctcaacaatc 48540
acctagactt tcagtcacta acaaattaag aaatttgttg tctgtccttt taaaaaacat 48600
tttctaagaa gatctttgtt atttagattt agcagacatt ccttttcatt aggcagctct 48660
gtctaatggc tgacccaaca ctcattgtca tctatttgtc ttcctttact aagccagcaa 48720
gtttacattt tctttttact taataaaata tgcatttact agaaggaagt tgaattgaat 48780
ctcataaata ttacatactt aaatatgaat gcttttaatt ttttctttca aaaggtacac 48840
tttagtgtat tcattaattt atttatagtc cacttgcttc caaaaaggac ttatgatatc 48900
ttagtttggt ttcttattga aaagaactag taaatgctgt aactgaaaca gaaatttgct 48960
ggaagtccca gagactaagt gatttgaatt tgcaacaaac tctgaatttt tgtgcatttt 49020
tgaaaaatgc atttttcaaa actgtcaatt cacgaggaat tatcagcatt gtaatttgtc 49080
tgggataatg tctttagttt cagaaagttt tgtgtttggc atcattacca ctctgttgac 49140
atataaattt cctcttgagc ttaggaggct tctctgagag tcaaacattt actttgagag 49200
tgggcagatc ttgctttact tggaaggata cacttacagg atagaaacac agaatacttg 49260
aacactgaag aatttgaaaa tgtcaattct cagaagatct tgaacactta tctccaaatg 49320
tgacacagaa acttactgta ataaccccta aaatctgctt gaattactta gcacaagaaa 49380
aaaatgaatg cttgagctgg ctattttgaa ttgagtcaat ttaagatttt aaaattcata 49440
tgtagcttag aatcagtaca tcttactctt tggtttatgg caaatcatgg tattgatgag 49500
acaggaacga aatgttggat gtacgttaat ttcccctaca ccttcctcac ttcctaaact 49560
ggtggtgtct tttctttttt ttttctcttc ctcccccggg tgggaaaaac aggtcttgat 49620
tccccaactg gcattgactt ttctgatatt actgccaact cttttactgt gcactggatt 49680
gctcctcgag ccaccatcac tggctacagg atccgccatc atcccgagca cttcagtggg 49740
agacctcgag aagatcgggt gccccactct cggaattcca tcaccctcac caacctcact 49800
ccaggcacag agtatgtggt cagcatcgtt gctcttaatg gcagagagga aagtccctta 49860
ttgattggcc aacaatcaac aggtaacttt tcttgtctgc aaagaaactc agaagacttt 49920
cctacccagt tggtagattc tgtaaagtag cttgctgttg tctgtcatca gctctcaaaa 49980
aaaaaaaaaa aaaaaaaaaa aatagatcat tgtcatggta catggagagg gaagtgagaa 50040
aatgtggaga aacatcttcc ttagaatatg gtaaagaagc ccgggcgtgg tggcagtaaa 50100
gaagataatt tttttcctct caagaaattt ctcacctgat ttgggtattt atgcatttct 50160
aataacacaa gttttgttga aaatgtagaa aattggccgg acggggtggc tcacgtcagt 50220
aatctcagca ctttgggagg ccgaaatggg cagatcactt gaggtcagaa gttcaagacc 50280
agcctggcca acatagtgaa accccatctc tactaaatat acaaaaatta gcaaggtgtg 50340
gtggcatgca cctgtaatcc cagctactgg ggaggctgag gcaggagaat ctttgaacct 50400
gggaggcgaa ggttgcagtg agctgagatc aggccattgc actccaacct gggtgacaga 50460
gcaagaccct gtctcaaaaa aaaaaaaaaa aaaagggcca ggcgcaatgg ctcacgcttg 50520
taatcccagc actttgggag gccaaggcgg gtggatcacg aggtcaagag atcgagacca 50580
tcctggccaa catgatgaaa cctcgtctct actaaaaata caaaaattag ctgggcgtgg 50640
tggcatgcac ctgtagtccc agctactcag gaggctgagg caggagaatt gcttgaaccc 50700
aggaggcgga ggttgcagta agccaagatt gtgtcactgc actccagcct ggtgacagag 50760
ggagactctg tctcaaaaaa aaaaaaaaaa aaggtggaaa actgaacact gtttcaaagt 50820
acctttaaaa atataatttt agggtaatag tgtcattgtt cttagcagat agaggctgaa 50880
gtacttacgg gaacagtagc atcatgttat ctgtatttta gtctcaagtc gtcaagccag 50940
agacaaatac ctaagggaag ggtatatagg tgttcattgt attacttttt tttttttttt 51000
tttcttcctg aaatggagtc ttgctctgtc gcccaggctg gagtgcaatg gtgggatctt 51060
ggctcactgc aacctctgcc tcccaggctc gagcaattct cttgcctcag cctcccaagt 51120
agctgggact acaggtgccc gccaccacgc ccggctaatt tttgtatttt tagtagagat 51180
gggattttac catgttggcc aggctggttt tgaactcctg acctcaaatg atccacccgc 51240
ctcggcctcc caaagtgctg ggattacagg cgtgagccac cacgcccggc cttgtatcac 51300
tttttttttt tttttttttt ttaacttttc tgtagttttg aaatttttcc aaataaaatg 51360
ttgagggaaa aaaactcttc cccaaatttg aaataatcat tttatcacaa tttgaatggg 51420
ctctgtaacc ccttatcttg aattcgtcat aatataaaat tctgctaatt acacgtagta 51480
tttacatgat tgtatggaag aatcattaag acaattatct ggaaaatgaa caaacagtaa 51540
atctgaatat tgtttgaaaa ttacggatgt gaaaagtttc cctttttttt ctagtttctg 51600
atgttccgag ggacctggaa gttgttgctg cgacccccac cagcctactg atcagctggg 51660
atgctcctgc tgtcacagtg agatattaca ggatcactta cggagagaca ggtacagcag 51720
taaaatgcta ttttacactc tgattaaatc agattctgtt gtggataacc tgaaagccca 51780
acagtgaaca aagaattaaa gaaactttgg caagtccatt caacggagcc cttgtttttt 51840
ccaagaaaat acgtaagata tagatgatat aatttgttct aaaacccaaa taaaaagttg 51900
tttatatact acaactagag ggggaacggc agagctgagg aaataaaagg attgtaaatt 51960
cacaaacata ttatcagtgg tggaaataag tgatttttat tttttcttct ctttactttt 52020
ctgtattttc caaattttat ttaaaaggaa tgtattctgt taaaagtttt aaaaaggaca 52080
caatgcatgc aatcctgggt tgagggctta ccttctccca cttctaatgc tactctacta 52140
ctcagtgaca ttttaaagct gaaatgttaa aacagcgcta actgtaattt tctctcaatg 52200
tttatacact taccaaggtt tgctacatgc ataaataccc ctttctgttc aagatagcgc 52260
tctttaaaag ggaataagca agaagatgtg atttacatgc tgctataaat gtggtaattc 52320
aattaatcag taatacccaa gtagctctaa acccctcaca ctctgaacta accctttttc 52380
atacaggagg aaatagccct gtccaggagt tcactgtgcc tgggagcaag tctacagcta 52440
ccatcagcgg ccttaaacct ggagttgatt ataccatcac tgtgtatgct gtcactggcc 52500
gtggagacag ccccgcaagc agcaagccaa tttccattaa ttaccgaaca ggtacaaact 52560
tctactctgg ggtgacacca gcttttactt attcagatac tgttttgcaa tgttctccca 52620
aggtattttt ctaattgtag aatagatttt cctttttaat gagcaacaac ctgcagctag 52680
cacctgcagc gaacagagtt ttgagccaga taaagaagga agcaccccaa gggcaggaag 52740
ttcagtcagt tttgtcgata tattccgcat gtctgcaata cgacaggcat agagagtgtt 52800
cagtaagtat ttgtgggaaa agaatggatg agttgataaa gtaggaagag acacctgctt 52860
gtggaatgta gcttctttgt gaatgaagca accatctcaa aaataggaaa tggtattgag 52920
atgcctgccc catccctcta aaagctctct ctgtattctt tcgagaagaa atacctttct 52980
catgtaagcg atcattcgaa tatgtaccag acctagagag gaggacttgt ccaatcttgt 53040
ctccaaggac tggggcttca ctggtttctc cctgctttta tttgtagaaa ttgacaaacc 53100
atcccagatg caagtgaccg atgttcagga caacagcatt agtgtcaagt ggctgccttc 53160
aagttcccct gttactggtt acagagtaac caccactccc aaaaatggac caggaccaac 53220
aaaaactaaa actgcaggtc caggtaagaa tcatctgcat ctcggccagg tgcggtggct 53280
cactcctata atcccagaac tttgggaggc tgatgcgggc agatcacttg aggttaggag 53340
ttcgagacca gcctggccaa tatggcgaaa ccccgtctgt actaaaaaat acaaaaaaat 53400
tagctgggca tggtggcttg tgcctgtaat cccagctact caggaggctg aggcaggaga 53460
atggcttgaa gtctggaggc agaggttgca gtgagccaag atagccccac tgcactccag 53520
cctgggtgac agagtgagag actccatctc agggaaaaaa aaaaaaaaag agtaatctgc 53580
atctcatata caacaggata gatggggtag gaccacctaa tattcttttt tatataaatg 53640
gctaccttgt tgtgagtact atgtattttt ttgtcctatg tcatcattgt ccccattcat 53700
gagttcaggg ctcaagatca ttatcaaccc ttttcacagt agaagtctta agtgcatttc 53760
tgtttttaca tggatagttc tatttagtga tatggacatc ttaaattact agattcaccc 53820
ttctggtttt gtttatcatt cacactaaga agagataaat ggcctaactg actttttcag 53880
ctctttttag ctatgttgtc tttgttttta aatagaatac ttgtgaaatt aggatcttaa 53940
ggcaatttat tagagtcaag ttaattttca ttttttctga gagcagtatc actaattgtt 54000
gggggcatca tattaagttt tagatcttat ccttgagtgt gacttcactc ccatatggta 54060
atttgtatta gcaatgaaca ggtttgtcca agaggaaatc aaagtctgac tctccatatt 54120
tttgttacaa ttctgcaaat aaaaattcta ggccaccata tgtttactac caaactctag 54180
acgccacttg aggactttat agtggatgac gtggatgttg catttgcttt tcactccctt 54240
tgcagatcaa acagaaatga ctattgaagg cttgcagccc acagtggagt atgtggttag 54300
tgtctatgct cagaatccaa gcggagagag tcagcctctg gttcagactg cagtaaccag 54360
tacgtaacca ctgcttggtt tccattttca aagtcaaatt ttgttcttgg gtgtctgaat 54420
gcccacgaca tgtcttttgc aattacacat agggaaagtg aacttgttgg ttagtttatg 54480
tcttgagctg agccctttac gaacatcttt tttccttctc agtgccaagc gaggaattta 54540
cagagaaaga agttgtgaaa ccaccatagt tagttgctgt gctttgaatt tcttttgctc 54600
aaatggcctc agcgaaatct tatttgccta tagcaaatct acaaaaaatt ttcctagacc 54660
gtcttttcta caactggatg gtaaagttga ttgaagtgtg cctcatgtag ctttatgttt 54720
ggggcatttg aagggctatg gctggaccag agtgtaatat aaatgcttaa tagagagggg 54780
aaaagaagag tgtaagaacc attatagggc tgggctcacg cctgtaatcc cagcattttg 54840
ggaggctgag gcaggcggat cacgaggtca ggagttcgag accagcctga ccaacatggt 54900
gaaaccccat ctctactaaa aatacaaaaa ttagccagtc gcggtggcac gtgcctgtaa 54960
tcccagctac tcaggaggct gaggcagaag aatcacttgg acccaggagg cagaagttgc 55020
agtgagccaa gatcatgcct ctgcacccca gcctaggtga tagagtgaga ctccatctca 55080
aaaaaaaaca aaacaaaaca attataacaa tttgaatctg acattgcaaa tcagctttac 55140
cacttccaag gtatagaaaa tccaggtcta tgagactaac atcacattgt aaaaatcaaa 55200
tcgtggtaga atatctttaa attaatataa atacatcccc attgtgggga cattttgcag 55260
ggtatctgct tatctcacat acacctatgt tttaataagt gatgcaacat tgcatatttt 55320
ctaaaccaag aaaaattaag caagtgttta agtgattttt ccttttgata gtgggttaat 55380
tggacttcat caaagaaaat ggtatctgca aaactgcttt gcatgttata aaaatgctta 55440
tttcacaact tgcttttcac ataacctctt accattaatt tgcctaacag acattgatcg 55500
ccctaaagga ctggcattca ctgatgtgga tgtcgattcc atcaaaattg cttgggaaag 55560
cccacagggg caagtttcca ggtacagggt gacctactcg agccctgagg atggaatcca 55620
tgagctattc cctgcacctg atggtgaaga agacactgca gagctgcaag gcctcagacc 55680
gggttctgag tacacagtca gtgtggttgc cttgcacgat gatatggaga gccagcccct 55740
gattggaacc cagtccacag gtatatggtt aattgcacca ccaggtgccc atgggagcag 55800
cggctttatg ccctactgaa tgaattatgc ttcactgggc tattgattcc cgtgtaaggg 55860
tgaaaaagaa ttattaggaa agatcctctt taaagaggaa tggtaagaaa caataaaact 55920
taggtgatat ttaaggaaac aagtctgatt aaaagaaatt ttggagtatc ctggcttata 55980
cacaagacca taaagcaaga catttgaaga ggatactaaa gttgtggatt atttcctaag 56040
ctctgactcc ctgtgattac cctcactatg tataaagaaa agaagtttgg cattacagag 56100
cttacttata aaaaggaacc caaactcggg catttcatag cagcatgatt ctgagcacac 56160
gtgggtaaga cctttcttct ctggttagat atcatatgct ggtgtataat tagcttaaat 56220
gattgtgatt tagacaccta ggaaataatc aatagggcaa ttgctttcca taatacttta 56280
tcttcttgtg ctttatttct gaagcagagt agaatgctaa agatgtatcc tagtgacagc 56340
ataaacccta gaggtgacag tctgtattat tgcttttcgc ttctcttttc tgcttctgtt 56400
gggagccagt tttcttctta cgccgcatta cagagagaac gtcaaattta gcagccatat 56460
ctgccatagg gtccaaataa agagacaata aaaacattat tctctctttt ttggatggaa 56520
tactgcgtga aatggttatc catacaaaga tactttatgt agaatagaaa aaggaggccg 56580
ggtgcagtgg ctcacacatg taatcctagt gctttgggag gctaagccgg gagcactgat 56640
tgaggccagg agttcatgat cagcctgggc aatgaagtga gaccccgtct ctacaaaaaa 56700
atatgaaaaa attagcgagg tgtggtgaca catgcctgta gtcccagcta ctcaagaggc 56760
tgaggtagag gatcacttga gcctacgagt tcaaggctgc agtgagctat gataactcca 56820
ctgcactgcc gcctggatga cacagagaga ccgtttctaa attaattaat taacaatttt 56880
aagaaagaaa aagggccatt gcttattttt ccatacaaaa gtaaaataaa tcataatggc 56940
caataagcca atgtaacttt tttttttaag ggaaagcaaa acttgtaaaa cctaaaatct 57000
cttagagttt tggcatttac ccaaatgttt tcagtgattc tgagaattgg tggatataaa 57060
acacatttct cagcaaacac tttcttcatt ttgcatccct tactgtacgt actttcttgt 57120
actgaatctt tgcttgacca gggaacccac ctagcccaac aagaacaatc cattctactt 57180
cttggaactc actttatttt ccttttcccc catttcctat aagataacct ctaaccaatg 57240
acaatctcga cagctattcc tgcaccaact gacctgaagt tcactcaggt cacacccaca 57300
agcctgagcg cccagtggac accacccaat gttcagctca ctggatatcg agtgcgggtg 57360
acccccaagg agaagaccgg accaatgaaa gaaatcaacc ttgctcctga cagctcatcc 57420
gtggttgtat caggacttat ggtaagacat gaccgttgtt cattggaata aagatggaga 57480
tcatctctaa cacagtttct aaggtggtga aaatataata tcataataaa tctaactgtt 57540
cttttcctct gcatcaaata atcttattgt aattttatat caacggaatt cctttatgtt 57600
gacctaagtt ttccagatga ctattgggac agaattttat aaatagcttt ggattttgtg 57660
cagctctttt agatgtattg tgcttatttt aaaaggttgt ggggggcaat ttacatatcc 57720
attggttgaa tgcataaatc gacttagtta tgcattttct gagctctgtt accttggtaa 57780
agaatatttt acagtttgta ccagtctacc ttgagcctac cctcattaaa acattttaaa 57840
atccttccag acatacatgc agaaaactgc taggaaccta ggggactgat gtacctctta 57900
acataaggcc aatttcaggg gaaactacag aaagagggtt cagagacaaa atggaacatt 57960
ctctttgcct ctctatgata aggaaaaaat tatgatttac acctgtcaga tcataaaaaa 58020
gaaaaatacg ctaataccca cttttctcat tttttttacc agcttagttt aagtatataa 58080
tctatggctt acttaagctt aaccgctaag agcattttaa aattgataaa tacatttatc 58140
acctgcactg taggaatgaa attaatctag gaattttcaa ggttgtgggt tttgctggtt 58200
tgtttatttt ttattttcta accattgcat ttacctaatg ctgtagtgaa actccttggg 58260
tttcagttga ggacgttgct aaagctcacc atgcccttat ttctctaggt ggccaccaaa 58320
tatgaagtga gtgtctatgc tcttaaggac actttgacaa gcagaccagc tcagggagtt 58380
gtcaccactc tggagagtaa gtaacaaaat gtcttcatat ggacaaacct tctgtataga 58440
caaaaattaa agaatggtaa atcagtgggg ttcagtggct catgtctaaa atccaagcac 58500
tttgggaagc tgaggcggga gcgtcacttg aggccaggag tttgagacct acccgggcaa 58560
atagcaaggc cctgtctctt aaaaaaaata aaataaataa aataaataat tttttagatt 58620
tatatgttaa cagtggaatg agtcctaatt tgaaaatcaa tttgattgcc tttttgacgc 58680
atgactgtca tcttttatac tccttcagaa aggggtctac tgacccataa aatggaatca 58740
cttcataagc ttataatgtt gatattatgg actatgactg acatctagtt tatgctctac 58800
ttgttagaat ttgttttcat agagctaagc ttggggagac cccactggct tctgctatat 58860
cttaacaatg catattaggc cattcttgca ttactataaa gaaataccgg agactgggta 58920
atttctaaag aaaagaggct taattggccc acaggccagc aggctttaca ggaagcatgg 58980
tgctggtatc ttcttggctt ctagggaggc cttgggaagc ttactcatgg tggaaggcca 59040
agggggagca ggcacatcac atggctgtgg caaaagcaag accgagagag agagagagtt 59100
ggggggggag gaccttatac atttaaatga cccagtctct tgagaactca ctgtcataaa 59160
gagggcacca agccacaagg gatctgcccc catgatccaa acacctctca ccaggcccca 59220
cctccagcat tggagattac aactcaacag agatttggac agggacaaat atccaaatta 59280
tatcacagca cagtaaccat tggaccaaat caggcttaga ttctagtctt ctgttatatc 59340
aataccttga tgtatgcctt ttcaaaagtc aggtaaagtg tcaaagtttt atcatttata 59400
aaagagggat ggcattgtac ctgttgagag aaaatacaaa atacttgccg taatattaga 59460
cacacacaca cacacacaca cacacacact ctctctctct ctcacacaca catacacaca 59520
cacacacaca aaattgttag ctggccatgt tattgtaact cctaccacac atatttttac 59580
attataatac attaataatt ttaatattta ttgaagtatt tgtagatact ataaagccag 59640
ccctgggaac cactggtagt atctataaag cttttcagct cttcaaaata aaatgtctga 59700
gaggtagata ttttcctatt ttctaattac agttgacctt tctctctgaa tgccaaagga 59760
gataatctac acattactag ttatatattt cttgaaatgg atgaatttga tatataccaa 59820
ggaaacgttt taaaatacca aaactttaca tggatgagcc aagcaggcac taatctctag 59880
ctatgctcct gtgcagatgt cagcccacca agaagggctc gtgtgacaga tgctactgag 59940
accaccatca ccattagctg gagaaccaag actgagacga tcactggctt ccaagttgat 60000
gccgttccag ccaatggcca gactccaatc cagagaacca tcaagccaga tgtcagaagc 60060
tacaccatca caggtcaggg aactcattgc actaaccaca tttgttaaca aatacccaca 60120
atgtaaacgg gcttattaac tgttctacga ctgacactga taaaatttat tttcagtgtt 60180
atcatcataa cccagtttta gaacgttatt ttcatgctat gatcagaaat agttttgtcc 60240
tttgaatgcc tgattttgtg taatatttgt catggaaatt gcgtaagtgt caatcaacaa 60300
gtttgatctt ccatcattgt gccctttctt atttaaaaaa ttgtaacata aggtttaaaa 60360
ctaaaagaaa taaaaaacag tgatgtatag atcttagcat taaaaagcat agttaatata 60420
aaagtaaaca ataccactta ataaaggcca aaattgtaac cgaagaatat tcaatatctg 60480
aggtcttttt tagcttttta aaattgtgat tccaaggctc aactattgac catctgatta 60540
cggtaaagag aaaacctcaa taagtggctg acccccattc tgcaagaggg cctcttccaa 60600
catagcattt ttgcattcca gaatttactt taccagtgtc cttgtctgta tcagtgattc 60660
actttcgaga tatgtttctt gttaacagtt aacatccata gcatgctcta ctttactgtt 60720
caaatgtgga ccactttggt agtctatata aatatgggat gatagaagaa cccagaaaaa 60780
ttgcaggcta gcttgagaat tctcctagta aaaagcaaga actgttaaaa atcatctctt 60840
ctcaaatccc aggtttacaa ccaggcactg actacaagat ctacctgtac accttgaatg 60900
acaatgctcg gagctcccct gtggtcatcg acgcctccac tggtaactat accttctact 60960
gaggaaatgc cattgacttg tatgcaatca gtttcatgaa ctcaaaaaac aaatgtgagg 61020
cgtatatttt tgtattatag attccagaga atcttgtttc cggtttacag tattctcaga 61080
ttcttttaag tgtgtttaga acggctcggg agaaaagtgt gggagtaatt ttcttggtta 61140
tttgccttct tagagactta attttgtttt ctttcagcca ttgatgcacc atccaacctg 61200
cgtttcctgg ccaccacacc caattccttg ctggtatcat ggcagccgcc acgtgccagg 61260
attaccggct acatcatcaa gtatgagaag cctgggtctc ctcccagaga agtggtccct 61320
cggccccgcc ctggtgtcac agaggctact attactggta ttgctgcttc catgctgtca 61380
ttttccttct tactacctag gacacatgaa gtccttagca aactcccaca gcgtctttga 61440
tactgtgtca tgagaatgcg aaactctgtt cctgataacc tcaaaaagca ttctctgtgt 61500
aggagtggta gagcctaata catcccaaaa ggcatgagtg aaggaaaatg caatttcaag 61560
actgtactaa tggcatgact agactcatgt tttcctttcg ctgcaagttt gccagatacc 61620
tgtcaattca gtcctggaga aagatatttt tcaaagcata ctagctgatt gtgattctgt 61680
cattacactc agctctctat agatatggca atcttgcagg acttgccagt gcaccacctg 61740
ccattgacct tgttgaccac tatcacagga taggtcttga ggcagagcag tcccaaccac 61800
ccacattgga agaatgcctg gaatggggaa taagagttgt ctaccttggt gggaaagact 61860
ataagcctct agtattattt ttgcccaaga gatgaaatat ttaaactatc tgtattagtc 61920
tgttttcata ctgctataaa gaggtttaat tgactcacag ttccgcatgg ctggggaggc 61980
ctcagaaaat gtacaatcat ggtggaagga aaagcaggca tgtcttacat ggcagcagga 62040
gagagaagca cacaggagga acttccagat acttacaaaa ctatcagatc ttgtgagaac 62100
tcactatcat gagaacagcc tgggggaacc accccatgat ccaatcacct cctctcctca 62160
atacatgggg attacaattc cagatgagat ttggatgcag acacagagcc aaaccatatc 62220
agtctgtata gagtatcacc tggactttaa aattcccaca gaacatacag acattagaag 62280
gagacactgg ctttttagaa ttggggggaa caggaaaata gaagcagaca tgagaggaat 62340
tgaactagac acttcccaca gaggctgcac aaacactggc caatctctcc tacccttcac 62400
ttgcctttag tttcactttt cattgatctg ccactgagga ctgcttggtt attaggccta 62460
agtagattca tgtatataat ctgcaggact ctctttcaaa tttatattcc agtggtggta 62520
tatgatgctg atagattttc ttaaattcaa aaaggcaaat aagaccacgt taaaagaata 62580
ccctggaaag gccaggcgcg gtggctcacg cctgtaatcc cagcactttg ggaggccgag 62640
gcaggcagat cacaaggtca ggagatcgag accatcctgg ctaacacggt gaaaccccat 62700
ctctactaaa aatacaaaaa caaaattagc caggcgtggt gatgggtgcc tgtagtccca 62760
gctactcggg tggctgaggc aggagaatgg ctgaacctgg gaagcggagc ttgcagtgag 62820
ccgagatagc accactgcac tccagcctgg gtgacagagc cagactccat ctcaaaaaaa 62880
aaaaaaaaaa aaaaaaaaag aataccctgg aaaagttagc caaaaaatgt ctattcaggc 62940
gtcagatatg atagtaagat aattagtttg cgatgcggac tttatatgca ggatatttgg 63000
gtgtttatgg aggaaaagtg aagtcgattt taccttcaag aggccaacag ccagctggag 63060
aggaagtgcc tgctcccagt agcgtctgct ggtgagaccg acttccactt gactagctga 63120
gcccattgac ataatgtgat ggttctattc tcccttcagg cctggaaccg ggaaccgaat 63180
atacaattta tgtcattgcc ctgaagaata atcagaagag cgagcccctg attggaagga 63240
aaaagacagg taagagtatc ttgcaggtaa caaggagaaa gataggacaa aactaataac 63300
aaatgagcaa tcttgcaata tgaaaaggtt ctccatgttt tgatgcattt cttgtgattt 63360
tttttatcta acagcatagt gtatatattg tattctttaa taggagaaat aatttaacat 63420
gcactgcaga gtttggtttt attttttttc tttactacag ccactcaata taaagccttg 63480
ttattcacct tttaaaaatt caaacaagat gttaaaatgt aaaagaagag ctatcattgc 63540
tcttctttta taccttctgt tgaattttaa aatgtttcct tttttaaagg agggagagaa 63600
acctctcaca tttatcttta tttggtttct acaacttaga gctaaataat gtcttacttt 63660
tgcatccagt ttcagttaat ttcaagaaaa tgtgtattcc tgatatagga aaatttcaaa 63720
aatgaacatg tgtgttttat ctatttttac catttcaaac catgaaaaac tgttgagcca 63780
aacctctgta attctcatac ttatgacact gatatgatta gtctggattc tacttcctac 63840
aacttgcttc tcaaatttaa aaaagaaaga gagaaagaga aagactgcac atttcagttc 63900
cattaggtct aatttgagca gaggcagctt ctacggggct cagcggttta aagctgtgtg 63960
tatgataaat tcatactaac acttttttct ttctaaacta taaagaaacc tttgagaaaa 64020
atcctaaaga tttctttctg gaaaaagtgt tttgtgatct cagaactgct cattttctgg 64080
tggcttttat caaattgatg aacagtcatt gttgcctgaa tcgattatta tcattgctgc 64140
tacttcctgg agcttaatgc gctttgcttt tttggctcta acctctctcg gctagacgag 64200
cttccccaac tggtaaccct tccacacccc aatcttcatg gaccagagat cttggatgtt 64260
ccttccacag ttcaaaagac ccctttcgtc acccaccctg ggtatgacac tggaaatggt 64320
attcagcttc ctggcacttc tggtcagcaa cccagtgttg ggcaacaaat gatctttgag 64380
gaacatggtt ttaggcggac cacaccgccc acaacggcca cccccataag gcataggcca 64440
agaccatacc cgccgaatgt aggtgaggaa atccaaattg gtcacatccc cagggaagat 64500
gtagactatc acctgtaccc acacggtccg ggactcaatc caaatgcctc tacaggacaa 64560
gaagctctct ctcagacaac catctcatgg gccccattcc aggacacttc tgagtacatc 64620
atttcatgtc atcctgttgg cactgatgaa gaacccttac aggtaattaa ttgttctctt 64680
cacttctcat ggggcagcac agaaaggaat aagttaggta actgaagtga ccagccctcg 64740
aataaaaagt ggcttcatgg ccgggtgtga tggctcacgc ctgtaatccc agcactttgg 64800
gaggccgagg caggtggatc atttgaggtt aggagttcaa gaccagcctg gccaacatgg 64860
tgaaacctcg tctcttgaaa aaaaaaaaaa aaaaaaagtg gctccacttt tagaacctct 64920
tagaagatgg cacatttaag ccctgctttt tttttttttt aaatcccaat atggctctac 64980
tttggaggac ataccagaga gtcactagct tttatttcat agagaaaatg aaactatttc 65040
tcttattctc acacatttga ggttcctttt tgagtaagat agatgattct agaaaagaaa 65100
gatattctac ctgaatttcc atttgtgtgc agaagtctaa aacactacct ttacgatttg 65160
tccttgaaga accccactat ctacaacata tctaaagaaa aaaaaaaaca ggcgaagctg 65220
tgcatagcag ctgataagtg attgattctc taaaacgtat attatttaat ttgtgttgac 65280
agtatccatt tttttttttc cccgagatgg agtcttgctc tatggccctg gctggagtgc 65340
agtggcgtga tctcggctca ctgcaacctc tgcctcccag gttcaagcaa ttctcctgcc 65400
tcagcctccc aaatagctgg gattacaggc atgtgccacc gcacccagct aatttttgta 65460
tttttagtag agacggggtt tcacgatgtt ggccaggatg gtctcgatct cctgacctcg 65520
tgatccgccc gccttggcct cccaaagtgc tgggactaca agcatgagcc acccactaca 65580
cccggcccac tgacagtatc aatttttatt gtgttgttac ttttagaaag tggcagaatt 65640
taaaaactga caacactgta ggaaatttat gagcttagaa acatgagttt gaggatttgc 65700
ccaactgttt taaggactcc acactggggt cagatgtcac ctggaggagc atgaccgtgt 65760
ctcccatata gcgcagtgtc caggttttat gtgaagcaaa catggccagg gcttccagag 65820
ggcttatgca gacctgcgac tgaagcaaga tcaatggcag gccgtctcta gtattgtcga 65880
gggctcctgt taactacgga gcacgtaggt agattgttgg caggaaaatc tggcaggaac 65940
gatggcccct atccttgttc catttctctc ctcagctggt taggaccact ataccctccc 66000
tctttttttt ttttttgttt tttgtttttt gtcttccttt gctttgttta aacagtgagg 66060
gttattggta agaggagagc ccgtgtcatt cctcactata atgctttctc tctgctttgg 66120
atgtaccgat aattgcagtt cagggttcct ggaacttcta ccagtgccac tctgacaggc 66180
ctcaccagag gtgccaccta caacgtcata gtggaggcac tgaaagacca gcagaggcat 66240
aaggttcggg aagaggttgt taccgtgggc aactctggta tgtaaacacg tactatttag 66300
acacaggctc ccctctgctg tacaccagag atgggctttt ctgttgactg tacctttgtt 66360
gccattgtct ttttatcttt gggatttaat gcaacacatc aacatgaaat aaatgagcaa 66420
ctttatatta aattaatctc tcccccacct cctgccatat cctgttgtct tcacaaaatg 66480
catacgtaat tgacagactc tcaaatggtg atatgattat agatctggaa gggatttcaa 66540
atattattta gtacaacact ctgagtcctt acttctgagt atctgagttg atatagggca 66600
caggtttcct gatgtctttt cccagaccct ctccatctca ccatgctgct gtcctcttga 66660
gtgattaaat actgaaacga ttacctataa agaaaatacc ccttctgcag acatggggac 66720
agttggcttt tgctcctgat ataaaatgct accaacattg tgcatttctg tctgcagaga 66780
atgttattcc aatgttattt ccattttttt ccaatgttat ttccattttt ttttctgact 66840
atacaggtta aaagcttcta tagaggttaa aagatcatta actcttcttt gtagcacctg 66900
ggaaatcctt ttaaatcaat agcgtgccac ctggctgctc aatttgcagc agctgaaaat 66960
tcaccaaggc acatgagata ggggataatc aaaaccgtga atccccaatc ttccaacagg 67020
agagttctct actccacacc aacagagagt gctaagtcct gtctatgcca agtgacagat 67080
tttattccta aggccagttg tttaatttta gccccttccc tcatctgata gaagactgtg 67140
ctactttaca tgtataaatt cctgtgaatt aagcagttga gcatttggct ggagagaggt 67200
tgggaggaga ttattttgtg tttgttgtat tacatatcca cagtaatgct tatctttgcc 67260
ttttgtggtt ttactagtag aatgccacgt gaacagaatt ttcaagagca aaaaggtctt 67320
tgtgcttttc taagtcattt tttttttttt tttttaaaga ttccatctct ttaactttag 67380
ttaggatgga atttgaactc ctggctcttt tgagtataga aacccctagt aacaatttaa 67440
gttccttcca tttttctttt aaactcctta ttcccagcag cagtattcta cattctaacc 67500
aggttctccc agctttgaga cgtctcagac ttaccagttc tccaaaacgc tattttcttt 67560
aagggtgaca ccttttaaaa attaggcacc tcaaatatct actgcttttg agcttttgag 67620
ttttgcactg taaaaagaaa aatacacagt gggattttaa gtcaaattag tttatctaat 67680
ttttagggaa taatttgaag catgctttgt ttgcatagat ttttttaaaa taagcttttc 67740
caaatcataa agagataaga tcttaggtaa catgaagaga ctcccttact tattcctaaa 67800
tcatctatat tccaagggca ttttcttatt tggaacagtt gacctcactg ataaagctgt 67860
ctcaccacta taataacaat gtccaaaatc taggctttct gcactattat gcaaaaatta 67920
caataataaa agtgaaaatt acattataat ggtatattaa aatgctaaga cttttgcatt 67980
ataagcaaaa gacagccttt aataattatt ctttatttag tgaacatttt ctaagtcttg 68040
gaaaagggtc aatgttttga attcatggcc ttatataatc ttcacaagat tccccaggag 68100
gtatagatat ttttattatt acgctagtat tgcagatgag ggaagcaagg cagagtggta 68160
ttaaatagct ggcccaaggt cactcaggta ccaatggaga ggcatcatta gtctttgcat 68220
cccactaaag ttctccacta gcttcaattg cctcaagatc tgttccatgt tctatgaagt 68280
agtttcaaca gaaatggcaa ttatcttaga agcaagggaa aaataaaaga tgggcttcct 68340
gtcgggtgcc tgtgacaggt gtcacatcta accatggttt tttagagcag ttaatgcctt 68400
gatagaacag atgaatgcct cttaatcctc ctggaattct tgttttagat taagtcattg 68460
tatacagtca ttcgattttc ttcttatggt ccaaatcgat taataagatg tctctttttg 68520
ctttttcttc cttttcttca tagtcaacga aggcttgaac caacctacgg atgactcgtg 68580
ctttgacccc tacacagttt cccattatgc cgttggagat gagtgggaac gaatgtctga 68640
atcaggcttt aaactgttgt gccagtgctt aggctttgga agtggtcatt tcagatgtga 68700
ttcatctagt gagtagttgc tttgtccatc cacttccgtg tttgtctcct caagttccat 68760
gcatgcactc atgtgccaag gaagcatgtt tggaagacac aggttcttcc aaacatgaag 68820
caaacaagag aatactgttt gactcgaagt aatattttgc atcatagaaa aatgatggga 68880
aattttactt gttggacatt gcttcatttc aagggttgta tgccaataca actattaatt 68940
acacataaga ttatggtgct aatttgattt ttgaaatttt ctgtgaaaac aaatggataa 69000
agacttttgg aaccaggtct atttaagagt attagagaca cagaaaaacc tcaaatctct 69060
tttaatcttc agtgttgaat gagatcagag gtgaacattt agactcaaaa acagcctcct 69120
tcaacataaa ccaaacatgc acatatcata gtacccatgc acacactttt gcgtcacaca 69180
catagcccag gtagcttgaa cgttgctaga aatatgaaag aaaaaacaga taatctgctt 69240
ttagatcatt aaaaatcaac ttgaattgat aaatgtttga ttttcaaatt ctaatacgtt 69300
ttaattttca aattttttaa gttaaaatgt gcctaggaaa tatctattat gctttgagat 69360
taggattaga atttataaac ctttcattta ttctttgtgt ttaggagatg tgatgattat 69420
tgacaattgg ttcattttta taggtgttga ccgttatgcc tataaataag cctcctatag 69480
acatacagaa atcatatcct gtggaattag aatataagac ttggtaaaag agattttcaa 69540
agtattttac ttaacttgta tacttgaaat catttaatcc agactgaagt tgtaaaagcc 69600
agccagtgtt ttcaatatag acttccatgt ttgaccatct gaaaatgaaa aacactaaaa 69660
acatcacatg ctgtttagga gctggaaatt ttaatatttg acttcaagta gatggttttt 69720
aactcctgaa atcgaactac gtttaagttt gtatgtttat tacctgtttg agcacttagg 69780
tgcaattgtg ggagcgggga tgtcaagttc atttatgtga ctctttggct caacttacat 69840
aatctttgtt ttgatatcac agttgtctaa ttattttact ttgtagctta aggcaggctg 69900
aattgttgat aaaatggaaa aagtagtata ttgttatata agcttctgag gtgtgttttg 69960
ttgtataagc cctggaggtt aaaaagtcat cccttatgta tagtagttaa aggcataaaa 70020
ctgtgacttt tagatattcc acagaaccag acttatttga tgtggataat aaccaatgat 70080
ttagcatttt gtttgctttt gttttatttt atccgggttc attttttact cttcccatgt 70140
acatgaaaca ggtggtggcg tgtagagatc agctgatcct tgttttatgg ttaattgaac 70200
tactttgtat ccagggtttc tgcaaatcca aaagtgattt ttcatctagg atctattcct 70260
aacagtctac tccaatccca ctttagtttt ccacaatttt aaatcttaat agtgagaatt 70320
caaatgaaag tcatttcatt tgactattct gatgacatga ttgtggcaga ataaattggg 70380
tcttaaaatg ccctagaaaa tggtaaatga taaaaaataa tattttaaaa ttcaaccaaa 70440
gaaatggccc attggccagg tgtggtggct cacacctgta atcccagcac ttttggaggc 70500
tgaggcgggt ggatcacctg agctcacgag tttgagacca gcctacccaa catggtaaaa 70560
ccccatctct acaaaaaata caaaaaaaaa aaaaaaaaaa aaaatagcac tgtggggagt 70620
gcctgtaatc ccagctactc aggaggctga ggcaggataa ctgcatgaac ccaggagatg 70680
gaggttacag tgagccgaga ttgcaccact tcactccagt ctgggcgaca gagaaagact 70740
ttgtctcaaa aaaaaaaaaa aaaataaaaa gtaaataaat aaataaaata aatggcccat 70800
tataggggtt tttatcttta acttgctatt tttccagatc atggttctga agaccctgtg 70860
acacgtccca gttcacctac tgtcttgtga gtcagaatat acaaataact ttttggtcct 70920
gactttcccc acccctacag gatggtgcca tgacaatggt gtgaactaca agattggaga 70980
gaagtgggac cgtcagggag aaaatggcca gatgatgagc tgcacatgtc ttgggaacgg 71040
aaaaggagaa ttcaagtgtg accctcgtat gtcatcacag atcattttta gtgccttatt 71100
aagcattctc actttcatta tcaggctgta actctcattc acagaaatga ttggagactt 71160
taggtctcct tgaggagtga acagtgggtt tcttaatctt ttgatttggg aaagtggaga 71220
caagcttcaa aaatgagtca tgatttaatg ttattacagg acactttagc acttgtccaa 71280
cctgagtatt ttgaccatta tctgcagtaa aatgctacaa agaagcttta ttggtctgta 71340
gattcaactt ttaaaatatg atttccatct tcccgttgga ccctttccag tgtattaggt 71400
ctaatttttg gaagtgccac cctaagatct gtatagcagt actgctctta gggatgattc 71460
acataaatat gtggtgtttg cgctgtgatg atacaaattt aggacagaaa tagaacccac 71520
ccctagatca agtctgcagt attgttctca gcttatgcgt gcatctgtct tgtgtctata 71580
tgcagatgag gcaacgtgtt atgatgatgg gaagacatac cacgtaggag aacagtggca 71640
gaaggaatat ctcggtgcca tttgctcctg cacatgcttt ggaggccagc gggtaagact 71700
ggatgtgcca ggctccctac aagttagata agataaaggg tgggctcctg caaggatgtg 71760
tcgtacacac aggaggggca gagacccttc ggaagtatta aaataccaca tttcctgttg 71820
gcatacaact gctgacatag agctctagag cagctctatg tctaccttac atgccattca 71880
ttctttctat tactcttagt agaaagaatg aatgaatggc atgtagagta ccaaaaacac 71940
aagtcttgag tcattcttaa tagcaacacc tgtcatttat atgatgttag aatcattttc 72000
ctaagctccc tagcatgtca gagatactat ttacactgaa aaatagtgaa gcagagatac 72060
tattcaaatt aattagtggt aaatagaatg tgtttcattt cagccggttc tccccatcct 72120
gggcagcctg agaccctccc ctcccctact attctcaggc tgcttctatt tttcagcaaa 72180
gtgttaagtg cagtgtagct ctaggcctcc aactccattc tgatggacag gtgtcccatg 72240
gcaacgttgt taaatatttt gaataatatc tcagatgtaa gaaaatgcca cttcttttaa 72300
cctctctctt gattcagaac agatgcttgt tataggtcta gcactgtgct aagtagtata 72360
ggaaaaacag aggaaatgag aaatggcttg gctcttaatg atatagttga agatgttaaa 72420
ttagcataca tttcaaagtc aagctaatta agttctaagt gggtctgaca aatacagttc 72480
tgggtaggct ggaattagca agaaagagaa gcatgaactg gctgaggttt acgatgacta 72540
aggtttagtt gggaggggag aaagcagaga gacacacccc ctgggataga aaggagctgg 72600
cccaggtggg ctttggtgag ccaaccctct gcctgctgtc ttctggtaag aaaatagatg 72660
ggaagaagtg gcttatggag ggccttggca acccattatt taagccagta cttctcaacc 72720
atttctaaaa tatgcccagt ataacaaaaa ataataagcc tttctctaat atgatttcaa 72780
atttcaaaat gaaattatgt gtaactcaaa agcaatggaa tgtgacagcc ctttgttttc 72840
aacgaagaca tgccctccca gcaactcccc aaatcctggt gggtgagggg catgcttcac 72900
actcaagggt gagactcatt ggttaatgcc aaatgcatta accaattaca ggtatccaag 72960
atgcaaagaa acatgatgga aaatagtctt tgggaaaatt aatctggcag caggggtgtt 73020
caggggcctg tcttggctcc accaggggca gcccatggaa actactatga tcttgtttca 73080
cccccagtga ttacatgggg agggaggtgc tcccaattct gatggaggag aattggagat 73140
tggaatttag attgaattca gtatctctct ctgtctctct ctctctctct ctcccattaa 73200
cacttacaac gactgtgatt gtatgacctt agaactcagt cattctggta tgaaattgtg 73260
tgatggagaa tgaatttgct gggaagttga ttttggtctc acttcagcat cttctcatta 73320
tttatgcaca tgaaaccttt catgtgcgac acttattcta ttctcaagtg ctaaatgaaa 73380
catttaagac aggagtggaa actgttcact ttctcatatg aaagcaagat tcagtgattc 73440
tgtaaggagg tagtcactgg tattgtgtta ggtattaagg ggcatatgtg cttaaacaga 73500
gaaatatgtc taaaatattt aaattctaat ataaaaaaga aagtgactgt attatttagg 73560
gctgcatttt agttgtaaga aaaaagtcca actcaagcaa aaatggccca cacaatggaa 73620
cagtcccagg acccaccggc ttcaggggct gctccagcaa tggcgcccgg actccctctt 73680
gctccgcgtg ccttcccatg cactggcttc gtgcttcagc ggggtctctg ctgatggtgc 73740
cattgatgac tgacctccat gagcttgctt taccccctgc cagcttaaga acagtagtga 73800
aagagaacat gtgtgtcctc ccatttccag taaaaacttc aggcaggagc ctcactggct 73860
cagcttggtc ccgtttccat ctcccatgcc atctccggcc aggtgacagg ctaccatgtc 73920
actgcctagg gaagtttagg aagagagtgg caaagtggtg cattagaaag aacatggcca 73980
ggtcacccca cctcctgggc ggcaggccca actccaccag tggtccactg tgtgacttcc 74040
ctgctccctc taagcaagtc actcctctcc tctgggtctc tgtttcctta cctataaaat 74100
gagaacgttt cttcatgtga tctcaagtcc cttttaaaat cgctaggatt ctttgaaaac 74160
cttttctatc atctagtgca gagaacttgt tgaggaagtt gggattggaa tgagcctcag 74220
cagatgggca aggtttgaat aggaagagaa gagacatttc aggagaaaga aacaacatag 74280
agagacagat gtaggtataa gatatggtaa taagccaaaa tgtattaaga gttataaatg 74340
catgaaatca tcatcaaagc ttgcttagtg attaactgct tatattttgc cagtgcatat 74400
gatgtgacat ttttctttaa ctcaaacact aaattacgat gtcctcaggt tatcataaac 74460
cccatttgac ttcatgcctc tactctctca gggctggcgc tgtgacaact gccgcagacc 74520
tgggggtgaa cccagtcccg aaggcactac tggccagtcc tacaaccagt attctcagag 74580
ataccatcag agaacaaaca ctgtaagtgc attagcagca caagtgtgtt ccctcatact 74640
agacagtctc tttctacagg tatctttctt cagaatgaac caagtgtttt aattaattaa 74700
aaaaaaaaac aactcataaa tgacttaagt gaaacactgt attccataat atagtttaag 74760
ttataattta tgtaactctt gaacatctcc tattgcccag tatgctgcta ggttcttgaa 74820
actaggaaga aatattatcc tatctataag cagctgtcat gagtccccac ctccccgcat 74880
ttttttttct gtacacttta cagtatttgc cactaatttt tttttccttc ttccttttta 74940
acagaatgtt aattgcccaa ttgagtgctt catgccttta gatgtacagg ctgacagaga 75000
agattcccga gagtaaatca tctttccaat ccagaggaac aagcatgtct ctctgccaag 75060
atccatctaa actggagtga tgttagcaga cccagcttag agttcttctt tctttcttaa 75120
gccctttgct ctggaggaag ttctccagct tcagctcaac tcacagcttc tccaagcatc 75180
accctgggag tttcctgagg gttttctcat aaatgagggc tgcacattgc ctgttctgct 75240
tcgaagtatt caataccgct cagtatttta aatgaagtga ttctaagatt tggtttggga 75300
tcaataggaa agcatatgca gccaaccaag atgcaaatgt tttgaaatga tatgaccaaa 75360
attttaagta ggaaagtcac ccaaacactt ctgctttcac ttaagtgtct ggcccgcaat 75420
actgtaggaa caagcatgat cttgttactg tgatatttta aatatccaca gtactcactt 75480
tttccaaatg atcctagtaa ttgcctagaa atatctttct cttacctgtt atttatcaat 75540
ttttcccagt atttttatac ggaaaaaatt gtattgaaaa cacttagtat gcagttgata 75600
agaggaattt ggtataatta tggtgggtga ttatttttta tactgtatgt gccaaagctt 75660
tactactgtg gaaagacaac tgttttaata aaagatttac attccacaac ttgaagttca 75720
tctatttgat ataagacacc ttcgggggaa ataattcctg tgaatattct ttttcaattc 75780
agcaaacatt tgaaaatcta tgatgtgcaa gtctaattgt tgatttcagt acaagatttt 75840
ctaaatcagt tgctacaaaa actgattggt ttttgtcact tcatctcttc actaatggag 75900
atagctttac actttctgct ttaatagatt taagtggacc ccaatattta ttaaaattgc 75960
tagtttaccg ttcagaagta taatagaaat aatctttagt tgctcttttc taaccattgt 76020
aattcttccc ttcttccctc cacctttcct tcattgaata aacctctgtt caaagagatt 76080
gcctgcaagg gaaataaaaa tgactaagat attaaaagta tttgaatagt ataatatgga 76140
ggagttttat cttagggaaa ccccatggta tgataacccc catctaacat gtcttacttt 76200
gggtcagc 76208
<210> SEQ ID NO 2
<211> LENGTH: 24
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Primer
<400> SEQUENCE: 2
ggagagagtc agcctctggt tcag 24
<210> SEQ ID NO 3
<211> LENGTH: 25
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Primer
<400> SEQUENCE: 3
tgtcaactgg gcgctcaggc ttgtg 25
<210> SEQ ID NO 4
<400> SEQUENCE: 4
000
<210> SEQ ID NO 5
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 5
gcaaattaat ggtaa 15
<210> SEQ ID NO 6
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 6
ttaggcaaat taatg 15
<210> SEQ ID NO 7
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 7
tctgttaggc aaatt 15
<210> SEQ ID NO 8
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 8
atgtctgtta ggcaa 15
<210> SEQ ID NO 9
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 9
tcaatgtctg ttagg 15
<210> SEQ ID NO 10
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 10
cgatcaatgt ctgtt 15
<210> SEQ ID NO 11
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 11
gggcgatcaa tgtct 15
<210> SEQ ID NO 12
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 12
tttagggcga tcaat 15
<210> SEQ ID NO 13
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 13
gtcctttagg gcgat 15
<210> SEQ ID NO 14
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 14
ccaatcaggg gctgg 15
<210> SEQ ID NO 15
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 15
ggttccaatc agggg 15
<210> SEQ ID NO 16
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 16
actgggttcc aatca 15
<210> SEQ ID NO 17
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 17
tggactgggt tccaa 15
<210> SEQ ID NO 18
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 18
ctgtggactg ggttc 15
<210> SEQ ID NO 19
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 19
tacctgtgga ctggg 15
<210> SEQ ID NO 20
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 20
atatacctgt ggact 15
<210> SEQ ID NO 21
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 21
aaccatatac ctgtg 15
<210> SEQ ID NO 22
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 22
aattaaccat atacc 15
<210> SEQ ID NO 23
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 23
gatcaatgtc tgttaggc 18
<210> SEQ ID NO 24
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 24
cctgtggact gggttcca 18
<210> SEQ ID NO 25
<211> LENGTH: 20
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 25
ccttccctga aggttcctcc 20
<210> SEQ ID NO 26
<211> LENGTH: 20
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Primer
<400> SEQUENCE: 26
gtaacccgtt gaaccccatt 20
<210> SEQ ID NO 27
<211> LENGTH: 20
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Primer
<400> SEQUENCE: 27
ccatccaatc ggtagtagcg 20
<210> SEQ ID NO 28
<400> SEQUENCE: 28
000
<210> SEQ ID NO 29
<211> LENGTH: 68651
<212> TYPE: DNA
<213> ORGANISM: Mus musculus
<220> FEATURE:
<221> NAME/KEY: misc_feature
<222> LOCATION: (45900)..(45900)
<223> OTHER INFORMATION: n is a, c, g, or t
<220> FEATURE:
<221> NAME/KEY: misc_feature
<222> LOCATION: (45905)..(45905)
<223> OTHER INFORMATION: n is a, c, g, or t
<400> SEQUENCE: 29
tttcccttcc cacaaaatac actctggtgt gcacagactt ttctcagagg tgacgcaatg 60
ttctcaaaca ccaccacagc caccaattta aaaaaaaaaa agttaagaga tgaggggggt 120
aagccttacc accccaggct tccttaggct ccagcccctc cctccctttc cttcgagtct 180
acatcacttt acagccgttt cccatcccta cccccaatcc tcctcccaaa agtttgacga 240
ccgcaaagga aaccagaaag gggaaaaaag ttctctagtc ccagacctgg cgggagatca 300
gcatctcttt tgttcggggc gaacccaccg taccccgtga cgtcacccgg actctgggcc 360
aataggcgcg cggtcggcgg cggctgcggc ggcaggaggg gcgggaggag tcggaccgga 420
ccctcctccc cggcgcgcag ggcctcgtgg ggggcgggaa ggtactgtcc catataagcc 480
tctgctcttg gggctcaacc gctcgcaccc gctgcgctgc acagggggag aaaaggagcc 540
cagggtgtga gccggacaac ttctggtcct ctccttccat ctccttaccg gcgtccccac 600
ctcaggactt ttcccgcagg ctgcgagggg acccacagtt cgtggccact tgcctcctgg 660
ggagggcgac tctcctccca tccactcaag atgctcaggg gtccgggacc cgggcggctg 720
ctgctgctgg cagtcctgtg cctggggacc tcggtgcgct gcaccgaagc cgggaagagc 780
aagaggcagg ctcagcaaat cgtgcagcct caatccccgg tggctgtcag tcagagcaag 840
cgtgagtacc gacagtctgg ttcaaaccgg ccggcggcag ggatgggttg gtcctcaagc 900
gcccgctcaa gttgtggcta aagtttttgc gcgcgtgcgt ggctgtgcga acgtgtgtga 960
gtgcgcgctt tatcgaggga aaccagctgt ggacacaaaa ggcttaggtc tgaacaggct 1020
ggttgctggt gaagtggagg tagggaccgt ctgttcttcc cctcaagtgc gctaacaaat 1080
tctacacctt cagttcgccc ttccaggaac caaaacgtgt gaaagagaaa agagacacga 1140
acttacaaat tttacatcag agattattgt ggttcccctg atccttattt tctttatcag 1200
caaatagctg gttaaatatt taacacgggg aggaggtgag actatctaaa taggtagttt 1260
cttaccaact tgaaagagat gttagttggc tcagtgcttt gggggggggg gggtagccta 1320
ggattctttc cccaagagca aggatagcca tttctcttcc agtttttcag agacacactc 1380
ttcctttatc ttgggctaga ggaaaattta aaagttctcc ctcctttttt tctttttctt 1440
ttcttttctt ttcttttctt ttttttttct tttttttttt tttttttttt ttttgccatg 1500
atctcacact gtagcctaag ctagcctggc attctcctgt gttgtccagg cttgtgtgtt 1560
caacttggga gcaattcttc tgcctcagtt tctacagagc tggggttatt ggcatagtca 1620
tcaagacacc caacttaagt tttctttctt gtctttttgt tgttgttgtt aagagtattg 1680
aagccctcag gatttaaaag taatttctat ttctggcctc tcagagtgtt tcaagtctgc 1740
tgaggtagtt cccctgccca taaggacatg acgtcattgt ataactttta cccaagttaa 1800
aagataagaa ggaaaaaacc cctaaacatc catctacata aacaatgctt aaatctttga 1860
ttagctagtt tccacatctg aactttagtg gaatattgct tttaagagtt tttttgtttg 1920
tgcaggctca ccaagtcagt tggcaaaatt cagtagtttt gtaggggaaa aaagagaggg 1980
agggatggaa ctgttaataa ctttccccat caattcttcg cagctggctg ttttgacaat 2040
gggaagcact atcagataaa tcagcagtgg gaacggacct acctaggcaa cgccctggtt 2100
tgtacctgct atggaggaag ccggggtttt aactgcgaga gcaagcctga gcgtaagtgg 2160
aaggcagtct gggccctggc agagatgatg ctctaagtaa aaccacattt gccttctcct 2220
cctccctgct ccagtcgctt gtaattccct cttattagac ttcttgcact ggcttttcac 2280
atgctcttac ctctaaaaca aatgtaatcc acacgagtct ccaaagccgc ctttttattc 2340
tcttggagct tttgattaga aaatgagagg ttttgcgtgt ctcccttcaa aaagaaaact 2400
tataaaagtt tgcttataaa agtttaattt attagaaagt gatctcggat cttttggctc 2460
ccaattatgg gccagaagtt gctttgaggc actgggttgt aaagtgattt gttagctgca 2520
gttccgtgaa aaaaacaaaa acaacaaccc actaccactt cggagactcc tgaagcccct 2580
tgatacgctt ccggtgagct acagcagtcc cttcagagag gctgctgagg gagggtacag 2640
gacaaatgtt tcagtggggc tgacaaaggc cagccactgc tgggaggccg gcaaccttca 2700
aactgtttgt gtcccttgtg acccttgaat tgatttccct ggtttgagac tggaatttgg 2760
aatctttcct ctgcaactca gctggtcaca gggtgtggct ttttcctggg aactctttac 2820
attataaata agggaaccgc tgagagctgg ccaaaggtca agagctctgg ttttattaaa 2880
gcctaactta aaaacttgtc tctcttaagt ttcagagtcg ccatgtatgt gtgtgagact 2940
cacatggact tttttttttt cccctttcca cagctgaaga gacttgcttt gacaaataca 3000
ctgggaacac ttacaaagtg ggtgacactt atgagcgccc taaagattcc atgatctggg 3060
actgtacctg catcggggct gggagaggca ggatcagctg taccattgca agtaagagag 3120
gccttctgtg gagttattga ggtcacatat acacacttcc ctctggcctg tccttgcctt 3180
ttcctgttat ccctgactga atagtgaata ctttttactt caatgaccaa accccatgtc 3240
gtcacccacc tagctcctct acatctggaa gatggatcta agcagagatg gaatctctct 3300
gtctctctct ctgtatgtgt gtgtgtgtgt gtgtgtgtgt gtggacagtg gaagatctct 3360
tggttctttt caataagata tgcccaaggg acctacctat tttaaattat ctgggcctct 3420
ttaagccaga ttgatcattt tatcctctgc agctatgagc cagaagggtt tttgctcttt 3480
gtcatggagt ctggttcttt gtgatgagta gattagattt ggggagaaaa ccttgcggtt 3540
ctcaaattca acacaggctg atgagcacag tgcatctcca aggaacttta ggtcctgggc 3600
tttctctcag gaagtctaca gctgcggcag tctttctcgt gtgactcatt gggttgccag 3660
tacgttctat taataagact ttctctctaa aaaccaactt ttaaatataa gtcctctgtc 3720
caaaagaacc aattagtccc ttctgaatag accaaatcaa tatttccaac atttaacatg 3780
agggtttttt ccaagtttcc tggcaaagcc caagagtcga tggtacactt gtgaccctgc 3840
gtacaattca gccattggat ttcacagcct aagaaagtat cagggtttcc aaccctcatg 3900
agtgtgtctg cttgctttct gccagagtgc tatttccacc ctggagtaga atgcaggctc 3960
tccgtcctcc aggagatcgg aatgctatgc ccaagtagct caccttgctg tctaggagga 4020
cagttccccc agctcttctc tgtctaggga acagattgcc tgtgatgtct ccggggaacc 4080
acaatttatg acttcttgcc attcagagtt ctccatggct ttcctttttg tgctttaacg 4140
attgacccaa agtgggctga tatggtgtta gccttctttc tgcttttttt tttttttttg 4200
gcaggagagc tgcctgccaa aaaaatccct caggattagg gattgcattt tggccaacat 4260
acatacttat ttatctcagg cagaacatga gatgagcacc ccctgaattc tctcaatccc 4320
ctaacgtttg cctttgatct gtaacagatc gctgccatga agggggtcag tcctacaaga 4380
ttggcgacaa gtggaggagg ccacatgaga ctggtggcta catgttagag tgtctgtgtc 4440
tgggaaatgg aaaaggggaa tggacctgca aacctatagg taagtggctc gtgtgtgtga 4500
tcgaggggaa cggagccaca agcagatagc ctaagcaaac cagtggccgg gatagctgaa 4560
tcacagcata aaaaccagtg aaatgtgctg cgagtcacca gccttaagga aatcagatcc 4620
tgaactatgg aacataaagg aatcttaatt ttgtttgaaa agcacaaggt ggagttaaaa 4680
tctttaggaa gaagtgattt cttttgttta tatactatgc tgtccccttg gtgaagaaga 4740
catgttattt aaaggaggaa aaattacact attgacacat ttcttgttgg aacacagttt 4800
gttaaagcac aaaatgccac gtggctccgg tcacaccttg gcaatttcct taaaaacaaa 4860
cattaaaggt tgtgggggat ttttgttggt ttgttttatt tattttttct gtttttttgt 4920
cttagccttg gttgtactct gaagcccaaa gttttgggtt ctctttctta gatctccaag 4980
tcagacgtgt gttttttcaa atttgttttg tttttgtttt ttacattagt ctaaaattta 5040
aagagcgctc ctctcattct ttgtaagtcg ttcatatttt atagtggttt agtttaggga 5100
cacacagatc agtggtagag agcacttgct gaggctaaca taaggttctg ggttcaattc 5160
ccaggactga attaatgagt taaaagagaa aggttgggat tttgcatagg gtcgtctccc 5220
acagggtaaa gacttgcatt tctttccact tgaaatgtta gtgggaagct tgggacaggc 5280
agaaaaatcc ggtctgtgta ctcattagga caacagaatt tacttgcagc aaggctgggg 5340
cttcctcttg ctccggcttc ttgctccgtg cttagctgca gggcgtgcct gctcatctga 5400
acagagtgcc actttaagaa atgtggctgg ggttttgatt ccatgctaca ctgtaaatta 5460
tagggagacg ctatcatttt aaatcgctct tcctcctttc tttttgcttt cccatttctt 5520
ctccagctga gaagtgtttt gatcatgctg ctgggacgtc ctacgtcgtg ggggagacct 5580
gggaaaagcc ctaccaaggc tggatgatgg tggactgtac ttgtctaggc gaaggcaatg 5640
gacgcatcac ctgtacctcc agaagtaggt ttagctcttt tctgttgaca atgcagccca 5700
ctgttgcttc tggatcccta gagagagttg tgatgccttg gtgactctgt ggtatcataa 5760
gatgtccaga aaaactgtat aaccatcacc ttctgcttct tcagaggaca ctcaataact 5820
aggaaaggca gttctcagtt caaccctgcc ttaggcagtc agctagtaaa aatgaaaaga 5880
gccttagtgg tattcgcttg ctggatgggt cttccttgat ctgggaatta tctcagagat 5940
acctttctgg taccgaggac aattaaatcc ctaaagtagc atgtaaatga atcctttgac 6000
ctgggggagc gattggaaat aaaaggctct accccatgtt cggatttcct tctatgtttg 6060
aagtttaaat aaggtttact gactctaaac aagaacctag tggaaatgag tccgtgccca 6120
gtattatcct tcaaatagga aagtggaatg aatttctgtg tgttgtttgt tcatcgattg 6180
ggcagagaga ctgttaaatt ataacccatc cttgctctta cgctacaatg tgggcagtaa 6240
gggtctaact ttgtgactta aatattgctg catttgcagt gtcaggaaaa aaaaatcaac 6300
cattgattca ggcaaatgca tagacacaca agaacagagg tccaagaccc cagctaacag 6360
tgttgtcaaa cctgaacctg ttttcagtat ctttgaatca gtatctcttg aaactcctaa 6420
tgctgagctt tgtaagtgat taatacatga gccttcctca tctttgacct actaagtgtt 6480
ctctgaaggc tgatgcccag ttcgtatttc cctccccata ttgccacata caaagtaagt 6540
acttataaaa ttttgttgat cacatgctat ttgtttgaga aactttgcat gctgtcagaa 6600
gggttttaaa tgataggtaa gagtctgaat tagatttctt tctacatgtg tttattttgt 6660
gtgtggaggt gggaggcaca cacgccacag tgtgcatgtg gagggcaaag gacagtttgg 6720
accgcgcagg gtgcagtgac ctcaggttgt caggtttggt ggcaaggttc tttactcact 6780
aagccagctc agtggctcag aattagatgt ctaatttgtc ttcaatgaaa atactgccac 6840
aaacgacttg gaagactgaa gctcatcaca gttttaaatc aaaagatcta aggatcctat 6900
aagtttgggg gaaacatttg atctttttcc atgacttatt tttgtgtggc aaagaatttg 6960
aacttgggtg gtatttttaa ttactagttt aagctggata aacaaaacac attcaagata 7020
tctagatttg actttttttt tttttgcatg cgttttaaaa ttcatgcttc agcaaattcc 7080
aaggctgttg ttagtttgaa attctaaatg gaactttgaa ggcagaagca gcaattaaga 7140
cttcaagaca atcttagaag cgggagggaa gaaggatgcc tggggccagc tttttacaag 7200
gataataaga gacagcatcc ttaactccag aagagacctt ttaaccgtgg gataagccat 7260
tttgtcgttg ctattggtta ttgtcactgt tattattaca attactatta tacagggagg 7320
attctcataa gcccaggctg gcctagaact tactgtgttg ctgagagaga ccttgggctc 7380
ttaacactcc tgctcctacc tcccagacgc tggggttaac cacgtgggtg actttgtaat 7440
tgtaaaacag gtggttttgg gtggggcaag aaaagagaac cttctagcca gagaagttgt 7500
ttttccacag gaatactttt acataacaag tggagagatt ggtgtggtta actttttagc 7560
ttccctgggg cagtcggaag agacctgcct ccttattgtt tattgaaagg agggccatgg 7620
gctgtaatta cagaaaaagg tctggaagac actgaggagt aaagagtaga ttgccagata 7680
attaattgag tcaaagaacc aatgtagaaa atcttaattt tttttaatca ataaaagaca 7740
ctgaatagta ttttttcttt ttttcctttg gcaaatggag aggtagggct gtactgtaac 7800
gaaccgggta tctgaatttt aatatatgca tcaccagcac tgggtaggat gtactaacac 7860
caacaacagc cactcagaag cattcaactg cagcattccc atcttagtgt ggatggctgc 7920
gtgtcggtta ctagataact tctatattca atgcttctct cctgaaacag acagatgcaa 7980
cgatcaggac acccggacat cctataggat tggagacacg tggagcaaga aggacaaccg 8040
aggaaacctg cttcagtgtg tctgcacagg caatggcaga ggggagtgga agtgtgagcg 8100
acatgctcta caaagtgctt cagccggtga ggcgctggga ccggggacag ctccacgcca 8160
gggtgattta tagcgtttca gctaagaagc tggaatcgtt cacataactg tttaaaaata 8220
ttcattctat attgtgaaca aagttgagtg gaatgaagtt gagacgtgcc tttagcacag 8280
agggctgggt tggaaagcat agtgtactct ggtcatggct ctattagtat aggctttggc 8340
ttatgagcat gagactcaga gttcagtcta gaaccaaagt aaatatccaa gtgtgatggt 8400
gttatcccag caccaagaag gtggaggcag gaggatacct ggggattaca gaccagccag 8460
cttacactac tttggaagtg tgggggtggt tccaggttag tgagatggtg tggctggcca 8520
gcccactttt cttgggggag ttgggggaag ttgtgttcta ggtttgtgaa agatggtgtc 8580
atagaaaaca agatggctct gggcataatc cctgccttct acatgcacaa gctctccaca 8640
cgcatgcgca catagataat gtgcatgcac cctccctcac atggacaagc aatagtgagt 8700
gaatgtgtgg tatgtacttg gaatcctcaa gccctgggtt cagttcccag caccctccca 8760
aaacacccca ataattatta tataaattta aaagaataac taaaacaaag aaaggtattt 8820
gtatgtatct tggatgcttg gtcagagtct gaggaagggg tcggagcact tgccaaccat 8880
gcgcaaagcc ctggttctgg ttccccatca ctaaataaaa ggagggtgtg ttgtgcctgc 8940
gattccaggg atcaggaagt agagggacgg aggatcagaa gtccagagtc agccttggct 9000
acgtagtgag ttctagtcaa acctgctcaa tgtggctcag tgggtaagag cacccaactg 9060
ctcttccgaa ggtccagagt tcaaatccca gcaaccacat ggtggctcac aaccacccgt 9120
aacgagatct gacgccctct tctggtgtgt ctgaagacag ctatggtgta cttacatgta 9180
ataaataaat aaatctttaa aaaaaaataa aaaaaaaaaa agatgctgtc tctcatgcac 9240
acacacatcg gaagaaggaa gtgcagctct tgtgggtggt accttcccgc tattgcgctc 9300
tgggtttcca tctagctttt actgtgtgat agtccagcct tgttacttag cctcttagca 9360
gtcagtcatt caggcaatag taattagatt tttttcccct tttgacgagt ttatctggac 9420
ctaattaatc cttgtgaaag caaacaaggt tacatttgat gatctctaca ttatccaatt 9480
atcatcgata aaaacagcta ttggccataa ggcagaggaa gaacagttac gaatgtcagt 9540
cgactgaact acatgaagga ttaactgagc taactgggat taaacaatac gtgttaacta 9600
tttttatggc atcactaata taccgaggtg tttcactatt aaagggtttg agaaacactg 9660
ttaaacgaaa caacctcttc taggagggcc ttgccgtcct tctgtatggt gggccttgac 9720
accattggcg tcctctgtct gagttctctt tgggtatttg tgctcgtcag cgctggggga 9780
agaggctaga ttcattctag aagctcttcc gctgccatac ggactctgac cttcaaaagc 9840
cagatttcta aaagagaagc tagcacaatc tgttgtgtta actatccgag gaaacttgtg 9900
aggattggtt gcttctagga aaacaaacag acatcctaag gaattctgct gagcaccgac 9960
acccaggaag agggataact taggaaatcc gtagctctcc agggtgtcct cctgagagcc 10020
aagttttaga gaaggcagga tatcccctgt gggtcttcag gggtctctca ggaagaggaa 10080
aggccacaca cagagcatat gagagctatg agggaagaca ggcaaggcag accatttcag 10140
atgagtgggg agccataggg agaaggcagg agcatggtac ccaggaatga tgagcagctc 10200
agtgggttga agcttagaac agggcaggga aggctagcag ccaggcggga ggggagagtg 10260
gtagaggggt gtggagctca cagatggatc gcttcctagc gtgactgaag gtttgtgaaa 10320
gataacctgt tgtgttgtgc ggcaggataa tgttgtcgct tagatgtgct gttcaggtgt 10380
ggctccgatg aggattatat gaggagtctt gtgaaccact tcttgggctg agtgcggaag 10440
ttccgggtca agccaagaag actctggact cattgacttc tcccttccag ttttataact 10500
ttttcattct cctgccctta ggatctggct ccttcactga tgtccgaaca gctatttacc 10560
aaccgcagac tcacccccag cccgctccct acggccactg tgtcaccgac agtggtgtgg 10620
tctactctgt gggaatgcag tggctgaagt cgcaaggaaa caagcaaatg ctgtgcacgt 10680
gcctgggcaa tggcgtcagc tgccaggaga caggtaggca ccatctgccc acggatgcca 10740
gaggacctac attcagtgtc tgcagtatct tagctgttcg taaaaaaaaa tgtaaaacca 10800
taaatccaga aaagtttata atcctgtgat aaaaatcata gtagctgaca ttttcttctc 10860
tggtcttttt tttttttttt ggttttttga gacagggttt ctctgtgtat ccctggctgt 10920
ggccttgaac tcagaaatcc ccctgcctct gcttcctgaa tgctgggatt aaaggcgtgt 10980
gccaccacgc ccggctcttc tctagtatta taacttgtat attttcttcc tatcatgagg 11040
atcaaactgc tttgtagtat ctgtatttgc cgaaagggat gctgcaagaa caccattttt 11100
ttcctgtttg tttttgtttt ttctcaacta gccaataatc tgtactctga gttcaatttg 11160
gaattataga tgtcttttag cagcacatgg cctcttctgg gtcaaacatg ctctctttta 11220
taattgtttt tctagagcag ccatatatac tgtttcttct gagaatgtaa gcaagcatgt 11280
atcgctctgt gccgtcttca aatcataata atttgtatta ataaagcttt acaagtgggg 11340
aaactgagtc acggtagcag aagtgtctcc caaagacatt aaaaggagaa ctctggctca 11400
cccttaacca gctgactaga cttttcatct tggcccttta gtagcacagt ttccatttaa 11460
attagaaatt tgtcaccact ggggtcagag gtgagggtgg gaaacaactg tactgactga 11520
gactcttggt tatgcttgta gccgtgaccc agacttatgg tggcaattca aacggggagc 11580
cctgtgtcct cccgttcacc tacaacggta ggaccttcta ttcctgcacc accgaagggc 11640
ggcaagacgg acatctgtgg tgtagcacaa cttccaatta cgaacaagac cagaagtatt 11700
ccttctgcac agaccatgcg ggtgagtgtc ctgggaggaa ccagagaggg cggtcgtctg 11760
tctgtccttg ccgtgcacac ccttctgtgt gccagcagtc agtcagtcat tccgaggctg 11820
cacgggaact atagctttga tctatttgaa cccacagcta atcccttagc agaggcaggc 11880
agtttccatg tcccttagcg ccactgggga aatgtcactg agggaaaagc cctatggttt 11940
gattatttcg acacatgggg attatgatgt gattaaagac actcaagtat tgaaatcagt 12000
ggatgatccc acagagccga tgaacacaca ggataaatgt caagggtgcc ggtacttatc 12060
ttctgtgtag agtcgaattt tacacaaagc tatcatttaa tctttttttt ccccccttgg 12120
ctgggaaaat gagaaaacat gagatttaaa tctattttga aagtgaagat gaaaatccac 12180
taagaagctt agggctgtat tatcagatat ctttttattt gtggataggc cctctgggac 12240
ttaacagccg gaacctggct ctgtctaagc ctgcggtagt ctctccttgt cgtacacaac 12300
acagctcagc tgtaatcttc gggtttgtgt gttgtcttgg gcagttttgg ttcagactcg 12360
aggcggaaat tccaatggtg ctctgtgcca cttccccttc ctgtacaaca accggaatta 12420
caccgactgt acttctgagg gtcgcaggga caacatgaaa tggtgcggca ccacccagaa 12480
ctacgatgcc gatcagaagt ttggattctg cccaatggct ggtaagagga agccctgtga 12540
gttatgggtg tggacccgct agcagcctgt tgatggtctg ggagagtacg atgtgcatct 12600
atgtattata tcttacattt gcaaattgag aaaactgtca atggcaatgt attctggcaa 12660
atacagagct gtcctcattt tacctggata cagaaagagg aatcagggat tgcttattgt 12720
ttttaagttt cgagagtccg gtagaagaca tcttttccag ttgtagaacc aatagcctga 12780
gggtcatgga gagtcatgtg ctcagacgca aggaaactac actttttgtt tttctcattt 12840
caacagaaga tgacattggg tttaagaggg acagtcactt ttacctggga ttttatgctc 12900
acagtttccc tttgaacttg agtgaaccag gtgaagtcac aaggctatag ttaaatccag 12960
tcctctagac aacgagaatc aatgagtata tgagattttc ctagtctaat cttcttcagc 13020
ccttttggta tttctctcca atctcctctg gaccggttct ttcctggaga gttcaaaact 13080
ccaccttcat ccagctacat gcatgcaagt cttcttccca aaggagagag aattgtcagg 13140
attatcaaac aagactgcta tcttcacata actatccatt tgtattccat ggctgtttac 13200
caagtgtttc tcctccattt ccaaccagcc cacgaggaga tctgcacaac caatgaaggg 13260
gtcatgtatc gcattgggga tcagtgggat aagcagcatg acctgggcca catgatgagg 13320
tgcacgtgtg tggggaacgg tcgtggagaa tgggcctgca tcccctactc ccagctccga 13380
ggtatgctgg tgtgttgacc agagagtttg tgtgaaagcc tgtagttgca aaagcagaga 13440
gggaagcatg cagtgtgtag ctatccactc acccgctgtg ctgaagaggt ctcttgattc 13500
caggagcccg ctgagaaaag ctggcgagtg agttgaatag ttctagggct ctggaaatat 13560
tctcaggatg taagcattta ggttgagcca aaaggatggc tttcccaaag agagatcaat 13620
atttgaaatc cttttagctc aaggttctgc ccgtgtttat gtctagagaa gatggtatca 13680
tttctccaag ccgggggtgg ggggggtggg gggggtggga ggggcgggaa tggatggata 13740
ttttctattt gtcaaattta aggtgatgaa tacatcacat cctcagacta atttcttttt 13800
ttcaaatcag ctttttttcc cctttggact cagatgtgtg ataggaggag ctgttaatgt 13860
attaaagcaa tttcagcttc tttgattgga aaagtaacat ttaggtggaa ctcagtgggt 13920
aaacagttcc catagccagt ccataaacag tgcgccctac attgattcct ttaatggtgt 13980
ccaatggcta gagatatctg ggagtcctct ttgttactta gaacattcca gagcaggagg 14040
aaaactaata agacatgcaa aacagccctt agtttgacag atgagaaaat ggggtcccaa 14100
agatagaatg taacttattc gggatttctc attgagtgag gaacagcatt gatttacatt 14160
ctaaaacttt ctgaacatca cagatgtcat tgtatttccc agatccaatt accttctgtc 14220
ttaggcttct attgctgtgg aacaccatga gcaaaaccaa accaaaccca accaaaccaa 14280
accatcttgg ggaggaaaag gttaatttta gcttacacct ttcaggccac agtccatcac 14340
tggggagagt cagggcagga agtcaaggca ggcatctgga ggtaggaact gaagcagcag 14400
aggccccaca gaccgaggag cccagcttac aggcttgctc tcccctgact tgttcaacct 14460
cctttgttat atagctcagg actacctgcc caggggtaac actacctgcc tgccatggac 14520
tgggtcctcc tccagttaac cactcatcaa atcagttcct cccagactgg cctgcaggcc 14580
agtgttgtgc agacagtttt ctcaatcgag attctctcat ctcagatctg tgtagattat 14640
gtcaagttgg taaaacccaa ccagcgcaca ctgctctcca tcccagaaag gagactacca 14700
catggtggtg tatgctatgt aaatttctct cttcgtctta gggtaacaac caaaaattta 14760
actaaaatca tcaactaaat gaggatgtta gaggaactaa ggcatgcctt tgttgagaaa 14820
ttagtttctc cacaggaaac tatattttac catggctttt agtttaatgg actgtaatcc 14880
ctgacaatta caagtctatt agtcagaata agaggggagt aaaaattaat attattaagc 14940
tttgaaaaaa agattattct gtgccagtag aaaatgtatt ttagcaggtg ttaaatccag 15000
cagtagaact gactgccttg aaaaaatgca gtttcttttg atttcattag tcaaagctta 15060
tcactcaccc aactgttccc tggacagacc agtgcatcgt tgatgacatt acttacaatg 15120
tgaacgacac gttccacaag cgtcacgagg agggacatat gctgaactgt acctgctttg 15180
gtcagggccg gggcagatgg aagtgtgacc ccattggtaa gtggccgcct ctgcttggtt 15240
ggttttcacc gaggacgttg gctggttggt tggttggttg gttggccact tgcagataag 15300
gaaagctatt tggtatcgcc agacttcctt ctctccaaac ctgcctcatc catcagtctg 15360
cagagagcct tgcaaatgtg ttggtaacaa gggtggcttt actgcagtga gtgagtgggg 15420
ttagctttgt tggttctgag tcatgacaaa ggaagtttcg ttactgactg cagaaaagaa 15480
acatgggtat aggactcagc cagtagatgc ctgcctccgg ccaaaacact tcagcttttg 15540
cctctctgta caataagtag ataaatagat agggctgggc catcactgag cgatcaacat 15600
taaaaggagc ctattcccca aatccaaagt ttaagataat cagttcttac tcctttactg 15660
aaggaggcag actgcttact gagacagcaa attgatccca gcagtttgtt cggcctgcga 15720
ttgtaaagcc gagaggtccc gggaggcttg cttagaaagc tgttcatgct ttaaatttag 15780
ctcattaatg taaagctacc tactgaattc cgaagaagta cacaaaatga aatcattgca 15840
aagttctttt cttattttac agatggcaag ttttaaaact tttaattggt atctagtttc 15900
ctaaaattaa ttttcagatt ttggctatat gctgaaattt taatctttac atttttttta 15960
aatttagcaa tgtttcccct gtaggacacc aaatatcctt cccaaaaggt acattttaat 16020
tttaacgact aattttccca taaggtaaat gacttgaata aaatattact ttaggactgg 16080
ggaaatggtt tcacacaaca tatgcacgta tctcacacac aagcacatat cacacacaca 16140
aacacataca cttataactt actttaacta tatttgtaag aactggaatt tttatattca 16200
tactttaaga atacacttca tcacactaca gtgatgtgtt tgaggctgtt ttaatctttt 16260
ctttgtgttt gttttagacc agtgccaaga ttcagagacc cggacatttt accagattgg 16320
tgactcctgg gagaagtttg tgcatggtgt ccgataccag tgttactgct acggccgtgg 16380
catcggggag tggcactgtc aacctctgca gacctaccca ggtaagtagc tctgagacag 16440
aagcagaccc atggatgcca gtctatgcta ctatttggaa tcccagtggg ggccttgctc 16500
tgtcccatcc cttttcatat tactgtctaa tagttaattg catttttgtc ttaaattgtt 16560
ttatttcacc cttcatcagg gaaaaatcac caaagactat gaaaaagtgc atgctacaat 16620
tttgcatttt acacagttga ggactccatt aggtgaaaac atttcagttc attttatctc 16680
agtcctgtgt gtgtgtgtgt gtgtatctgt gcttgtgcaa acacatgtgt ggatgtgtgt 16740
atgtatgtgc acatgcatgc gtgtgcatgt gtgtacatgt gtgagtgagt gtgtgtgcct 16800
gtgtttgtga gtgtacatgt gtgtgcacat gcgcatacat gggcatgcat gcttgcattc 16860
gtgcatgtgt atgtgtgtgt gttcaagtag agccataaag taactcagac tggaagtgaa 16920
agagttttac attctgtttc ttaaagagaa gtcacatcga cagaaggcaa gaagtacagt 16980
atgaggcata aatttgtttc ctgccatctt aagcccttct ttgtgtcaga tttcatttgt 17040
ttagtgagat gtaatgtgga acaaaatctg gagccaagaa acttggtcaa ctccacccac 17100
accgttcgaa taccttaaaa tatttattgt ggttttgttg ttgatattta ttgctaggtt 17160
ctcattgttt tgtttggttg ttgtttgttc tcccatagag acatcatgcc tagccatagg 17220
cattaattca ttttggggaa aacatttaaa attcacacgt tgattatgag tgccatttca 17280
gcagactcct agatttccgt taatgattta tttatttatc tgtatgtgtg tggagagggc 17340
actgggtcac agcacatacg tgaaggtcag agtggacttt gaagttcttt cttcacacac 17400
gattctttat gtggggatca gactcaggtc tacaggcttg tgggaggcga gcaccttacc 17460
ctgagccatc ttgctggccc aaatttaaga catgaaatac cacctgtatt cagaaacaaa 17520
aagatttggg gtggggggag ataatccaca agaatacaaa atattataat aataaattaa 17580
ctccataagt attaagatta aatactaaga ttaaactaat cttcctaaga gtgtcccaaa 17640
gtgaacgatg agagcccaag gcagtgtgag tcctcgctct gactgtgctg tgagagagat 17700
actagttaac ttctcctgtg gacaaaggga gacttgctaa ccacctttaa aattgcttcc 17760
agtccttcac taacagtcag agacccagag cacccgtcca ccactcatgc aatcatgttt 17820
tgtttgtttt tcaatgacag ggtttcactg tgtaactctg gctactttgt ggaccaggct 17880
ggcctcagac tcatagagat ccacctgcct cttcctccca agtgctggga ttagagttgc 17940
atgcctccca tatccagaat acgctcattg tttttatgtg ctggggacat cctcctccgc 18000
tcagccctta gacattgtca gggtaggata ggtgattgct tccgcaacta tgtagctcag 18060
agcagcctgc atttttgctg gactttggtt taagagtgag ttacttgccg ggcgtggtgg 18120
cgcatgcctt taattccagc acttaggagg cagaggcagg cggatttctg agttcaaggc 18180
cagcctagtc tacaaagtga gttccaggac agccagggct ataacaaagg aaccctgtct 18240
cgaaaaacaa aacaaaacaa aacaaaacaa aacaaaacca agagtgagtt acttaacatt 18300
tttaaaaatt gaatccagtt gctttgtttt gctttttgag tctcatctag ccctgggtgg 18360
cctcaaactt actatgtagc caatgatgac cttgaacttc tgaccatgcc tcctgtctct 18420
tgtttccaaa aggctggggt cacaggtgtg cacattacac ctggtcaact taatatagtt 18480
taaaaatctg attacaaatg agccataaat tcagaaaaca catatttagg aggattggat 18540
tttccaatga tacaagccaa gaatagaagt ttatttttgt gttcacagtc agtttttgca 18600
gggcaatttt tgaaatttat tttcttttaa gaccttttct tttaaaaata agtctattca 18660
catatatctt gctgcaagca ttgagggtag atctgctgat ggacaggaag agtcacctag 18720
cgggagtttt acctgttgac tttgttccct gtttctaaaa agggcaatgt caaaaaccca 18780
ttgaacacag aagagatttc agggcaagcg gatgagtgtt tgaccctaga tagcaggctc 18840
agtgtttatc tcaatggagg ctttgctcaa gggctcatgc ctagcctttg aggctccgat 18900
ggctgaaaga ccgtgtctga gccttgccct gtttgttctt cctactaggt tggtagagat 18960
gttcaaacta acaaaaggta gcaggaattt ggtttgtcaa taagcaacca ggaaagcaca 19020
gctctcagca aattaggtag agaaagaacc tttcgggtca aaaaaaatca tgaatgttta 19080
acttctccag ggtcactatt atcggaaatc actctttctg accttactgt caactgattt 19140
tgaaagtgta taatgtggca ccctacaagt gaagatctca cagtgggcat tgctattaga 19200
agtgtaaaag gtccagggag gtggatggtc gggatcacac aactagccag catcaaaggg 19260
gatataaaaa cacttcaatt taagtagtgt aaatgatagc tagccttttt tttaactttc 19320
ccatctttaa atcatgtgtt gtagtgtaga gtatagtgga gagctggaat ttaattgacc 19380
tagaaaacag atgaggggtt ttccttcttc cttccttcct tccttccttc cttccttcct 19440
tccttccttc cttccttcct tccttccttc ccattcctgc acagaaatgc tttaaatccc 19500
ctttgccatt cagggcagtc acttgaaggt ggaccctgtc atcatcttag gggcctggag 19560
agctgagagc tcagaggttg tagtccctac gcagtttaat tcccatccct cccattagac 19620
agcacaattg ctgaaccttc agctcagggg acccatgcct ctgtctcctg ccggcacccg 19680
tactctctca tatgtaggca ttttaaaaat taaaattaaa aataatggga tttcagatct 19740
gcgctgaaag gctgagaaag gaaatgaagt tctgagtcac ttgggttaac cattgcgagc 19800
atctttccct ccctcccttt cccgcgtctt ctgtcaccct tgtgaacaca gggtttgatg 19860
actggacaga cagtaaatgt catttatatt ctcttaataa tagatttatc aaggagattt 19920
agttatcaca agttttccag cctcaaattc agtaaataag atgcatgaga catgtctatc 19980
tacctgagag attatactag gatttttcta aaacagcaat atttaacagc cttatgcaga 20040
ttgtcactaa taacataagg tctgttttta ctgattcata tgaaacctct ttaaatagtg 20100
tttgaaagaa atgtttttaa tgtatttgta tttgtgaggc tcttcatcta tggaaggagc 20160
tattccagag ggctgtgcaa tggacttgag ttgattaatg ggacaaccaa cctgtgtggc 20220
gcgtgggtcc tatgcccctt aggatgcaaa gatgagaatt ttgacatttc agcttgtagc 20280
attaagtgaa atcaagactc aatgaatatg tgttagtctt caacaagctg agttattccc 20340
aatgaagaag ttgagttcaa aatcttttga ggtcacataa atatgtaagt tacatattta 20400
ttctgctaaa gaagattttg cttttaaaga atttagaagc ttaagaccat aattaaatct 20460
gaaagtcaat atattttttc caagagcact cagaaatcgc aggtagtgta gagaactcct 20520
ttatcagcat gcagaatttt cttctgtctc acagagcatc agtgagaact ttgtgtctta 20580
ggtttttgta aggactttgt acaaatggat tttgactgac aaagaattag agagaagata 20640
aatttccatt ctgtaaacag agtttttgat aaaatttcat tattatccta aatggaatct 20700
actatattaa aaaattgatt cccttctctt attttgcctt ttttttcccc ccaaggaaaa 20760
aacctgaatc tatcttaaat tttgttaata acagtcatat caagatctga aaatactgaa 20820
ttttaaatat atgctttcaa atgtcatttc aattgatgat tgcttaaaaa gatttttttt 20880
ttgaacaatt cgctcacagt ggctttaaga gtgtacttaa gtaaatgtaa aacgaacaaa 20940
caaacaaaaa cactaaagga gagaaggctt agactgatgg ggaaataaac cttgggcttt 21000
aattattacc tctgtctgtt tgtccggatt cagccccatt tagaaatgtt tgttttgtgt 21060
cacgccgtaa ggccttggga tcattgcttc tgagcagagt cctctgtccc gaaagcctcc 21120
atgattcgga atttgtctta caagagcctt catgtaatta gcacatgagg tctgtattct 21180
gagctacatt cttcgtgtta aggaaatttc acagttgtcc cacgtcttac tttgaaagcc 21240
agagaagaag gcaagctatg agacactgga gtggtttctc tcgtatttat tagaaaaaga 21300
attctaattg cttttcttat gggaaaggca atgattacca ggtcaaatca gactgtgctt 21360
tttcttcagc taatgtcaca atgtagaagg tttaactaga ctctttgccc acatttcccg 21420
agaagcgaaa agtctttaag gatggacatc catgttttgt aaaactttaa gaccacacaa 21480
gctaaagaga tggcatgttt tcattttcag gcacaactgg acctgtccaa gtaattatca 21540
cggagacccc cagccagccc aattcccacc ccatccagtg gaatgccccg gagccttcac 21600
acatcaccaa gtacattctc agatggagac ctgtgagtaa tagctccgca gccttggact 21660
ctgacccctg acctgatggg actaggatgt gttgccctct gggtttgtta ctgcttttga 21720
gtcgacagat ctgatgccat gtcgaacagt gctgacattt attttcttag tgtctagcca 21780
atatgtagtt agtcgaatca acatgtagat tcagggtttt ttgattgttt ttggtttttt 21840
tgttttgata tgtagaagaa attaaattag gcctttggct taggaaaatc ttagaagcca 21900
taatgctaac aactattctc atccaatgtg gaaagaaaat ttgaaatttt ggtatccatt 21960
tgcaatgtca ttaaaattaa aatcacattt tcaagttatt tccagagttt aaaaccagct 22020
aaatgaacat cgttcttttg actcaactca gttgtcctgt agtcctcttg agttgtgtag 22080
acagaaggga atgaggtatt gagagaagga ggagcgggga agggtttata tttggtttct 22140
aaaaggaccc ccaaacccta gcgttttcta accatccaga tgccaaaacc atagcaagga 22200
gtctctcata ttagtctatt aacccttgat gtctcgtccc ttctcagact tgccctcttc 22260
catctccaaa gtttatgaca gaatttaaaa ccactacttc agaaaggaga aatgcacttt 22320
taaaaatcaa atctactcaa ttgaactatt attaatccta gactacaaca acctgtctga 22380
cttaggacgt caactcactc ggtcgaattt aaactcttgg ggaattccat tctgctgagc 22440
tcactctttt ccttcagccg tcccatgttg tcactacaaa tgaggcattt ataaataggt 22500
ttcgaaatac acattgagtt gaggcgtctt cacatttgat taaactctca gcaaacattt 22560
tagcttcggt tttgttgtgt ttcgttttga gatgatgacc ccattaggcc aagactgact 22620
tcatattctt acgtagctca cgttgatctc cctgctgagt gcttgattat aggttcagct 22680
cccccttggt atgtgatgct agggactgaa ctcaggactt tggccacctt taggcaagtg 22740
ctctgccaac cgagccgcat ccatggctct gaaaatttaa aaagaatttc tgttgtttcg 22800
tttttttaaa tgtaggccat ctgagagttt atattctcat attttcttct gatggccaat 22860
tgctaatttt taagctaaca aaatggctaa cttcaatttc tttcagcata tttgagctaa 22920
aactaaagat taaagagaac ttgcttggat cacttttatt tatctccaaa ataaaaaacc 22980
gggcattaga acatttgaag tatgtacaaa cttgattaga taacattaaa aaaaaaaatc 23040
actgggcatt aaccatgtat ttgatattta aaccgcttta gaatatttac acttaaaagg 23100
atttcttgtt tgaagtctgg gtgtttcttt tccacacaat ctattgcaat gagttctgtg 23160
gtccatgaca tattaatgaa gctggacagg atataaaaat gtaaactgga gggggaagat 23220
taaacaaacc gaaccctatt cttctgcagt ctttcccaga gttggctaac gactcttgat 23280
gggtcgttca tttccaagga tgagtcacgc caccagacac gttgaacctt gtttgtgatg 23340
gccccaggat ctgagtccag gcaatgttat tatacttttc agtgtctcgc gaggcaagaa 23400
gcttgaaatg tatcccacca agttgaaaga tagagcgtga ggccttttct cacttcagaa 23460
gagagacgtg cctctgttta ccacaaaagt ctagaggctg aattgatggc gctggtctta 23520
aatgattcga ggcctcaagt gtgtaacttt gaaaacctca tttctccacc tgtaaagtgc 23580
agtgaggcac ttcacttccg gcaggaaggt gaagatcagg gggagaaaca aacaagcaaa 23640
acagccctga gtgcttggtc aaccacttgg acgaataatt aattaacatc gacaaactgt 23700
agaggccctg ttcccagtca ggttttccac catctttctt ccaaaacaga gcctcgagaa 23760
tcctatctat cctccattct tctttgaaga tgactaacca ccacgttttt tttcctttta 23820
catattcaga aaacctctac gggtcgctgg aaggaagcta ccattcctgg ccaccttaac 23880
tcctatacca tcaaaggcct gaccccaggt gtgatctatg agggacagct catcagcatc 23940
cagcagtatg gccacagaga agtgacacgc ttcgacttca ccaccagcgc cagcacccct 24000
gtgaccagta cgtagccagc atctgttggg gctgtgcctg cactgctcag acgtgggttc 24060
cccagagaag gttctgtcct tagctgcttc tttgctcgga tggtgaacat cctctgaaca 24120
cagagagcgt gggtattcca gataatcaaa ggctcttgtc ccctgctccc attcctctag 24180
gcaacacggt gaccggagag actgcgccct actctcctgt tgtggccact tctgaatctg 24240
taactgaaat cacagccagc agctttgtgg tctcatgggt ctcagcctcc gacaccgtgt 24300
caggcttccg ggtggagtat gagctgagcg aggagggaga tgaaccacag taccttggta 24360
agtagaatgt ctggcttcct cggctcgtgt ttctagatac ttacttggct cgcaggagtt 24420
ttgattccgg aacgcctcca cagttcaaac ggaagacggt ccctttcatc agagccagga 24480
gagaggtgac tcctctctgg ccaggctggg attccctggg cacctttgtg gcctctggtg 24540
ctgtgtattt ctcatagcca tggaaggggg accaggatga ggcctatggc tgacaatgtt 24600
atcctttagg ggtgcggagt taccttcttg tttactttta aaatagccca gtgatgaggg 24660
ggtctttaaa aatatttgct ggtgccagtg aggcggctca gtgagtaaag gccctcaccc 24720
ctaagcctta taacccaagt tcaccctcca gtctgacctc catcacgtgt gtacgccccc 24780
cccccaccaa tgtaataatg agaagatact gaacatacat gtgaatagga cccagatcat 24840
aaaaatgaat ctccttccaa cccctgccct gtcatccttc cttccaccat ggctactact 24900
ctgatatcta atgacagctc tgttttaaaa aacaaaaaaa cagagagatg ttattaaaaa 24960
ttatacatct tcgggggtgg gggaaagtgg aaaatgaaag aacttactta cattggaaat 25020
tgcaggctat tcactagaac atttctcgtg ggctttcacc ctctgagtat agcgctctta 25080
gaagccgtgg aagattggtt tgctcaggcc actaaccttt gccctgtatt ttaaagatct 25140
cccaagcacg gccacttccg tgaacattcc tgacctgctc ccgggcagaa agtacattgt 25200
caatgtctat cagatatctg aggagggaaa acagagcttg atcctgtcta cctcacagac 25260
tacaggtatg tgggcaccca gccatgataa aagcaacttt aggtatgggg tatggtggta 25320
tggtgggtga tacgatacat acatacatca taatcacaca tacttacact catacataca 25380
gctttgggat gctgagggta gagatccagg ctagcctgca gtaagaacca ctgttttaaa 25440
aaacaaattt ttgaagactc tttttgtttt tctgtaacgc gtgggcttgt agcaacactg 25500
actgatttcc tttcttcttc tttcagcacc tgacgctcct ccagacccta ccgtggacca 25560
ggttgatgat acttccattg ttgttcggtg gagtagaccc caggcaccta tcacaggtca 25620
tccttggctt ctgtgtttct tttgatgtat agatgtggaa ggggaaaatt ctgatcacac 25680
tggtaccacc ttaaatcttc cattttaagt ggttggaggt gtgtgtgcat gtgtgtgcat 25740
gtgtgagtgc gtgcgtgggt gtgtccactt caaatcttcc agggattctt cgtttttgat 25800
tcgttttcct tcaagtctgt tcacacgccc ccattcctaa tacctgcatc tgcaacctat 25860
aaggccagcc ccgctgttca ctgcagtggg cagttcccgg gctgtacagg tgggtgattc 25920
ctgcagagct gctgctcact gctgaagagg gagctgagtc gccgctctag cttcaccagt 25980
gaagttccca aaggtgcaaa cactgctcag gctgattcca ttcctctgct ccgagaaggg 26040
aaagccgcta gtactatgaa tgtctcacgt catggcatca cttactgaca ttcattaagg 26100
atctctgggt tcaaggatgc tatttgatta ttaaaagctt cctatcaact tattcttatt 26160
tctgtgcccg tcaggcatta tcagaggaag tggtaacatt gaaagacccg gaaagaatct 26220
tgctgattct tagccatgag aaaggagagt tataatttgt ctagcctccg cttctgaaga 26280
ccatgtgtct aaacgctgtt ctcctaaacc tgcagggtat agaattgtct attcaccttc 26340
agtagaaggc agtagcacag agctcaacct ccctgaaacg gccaactccg tcaccctcag 26400
cgacctgcag cccggtgttc agtacaacat cactatctat gctgtggagg agaaccagga 26460
gagcacaccc gttttcatcc aacaagagac cactggcacc ccaagatctg gtaacttaaa 26520
aacagcccat tccctgatgt ctgatctctt aggactagac cagagagccg ctctaacctt 26580
ccaggggaag ataaagccca cgtggattag actcattctt tagccttcag ggaggactga 26640
ggtgcaggtc acgtgggtga cagatccctg agagggagct gtttttgtct ttgccagctc 26700
tttctatgtc ccccatcacc caaatcaatg gctctcaccc ttcctaatgc tgtggtgacc 26760
cccaactata aaattagtgt catgctgctc tatagccaca ctgtcgtgaa tcataatgta 26820
agtatctgtg tagaattctg atggtcttag gtgacccctg tgaaagggtc atctgccacc 26880
aaaggggtct caactcacag gttgagaact accgagttaa atgctaaaat gtcagcactt 26940
ggaaggaatt tatttatcca aggcaactat tgggttttct ggttaaaaac tcacagcatc 27000
tcctctttct tttcctggga ggcttaagaa ttactgttct cttaactacc attttcttaa 27060
gaaaatctgt tctcttaact accataaaat gagtcagtta aacaaacaca ccagctgtct 27120
tgtaaagtga aaacatttat ttttgtatat tattttaact tggttttatg ttataacatg 27180
cctatctata gatactaaat agagattcca atatcagttt gactaaccat gagtatacac 27240
acacacacac acacacacac acacacacac acacacacac atttattttt tgattaagag 27300
gcaaagccca gtattggcct agaatgagtg ggtctaagag atggcggaat tgttcaggga 27360
gctaacttct agcatcaacc ttcagtggga attgtgactg actgactcat cgctcttgtc 27420
tgctagataa cgtcccccct ccgacggacc tacagtttgt ggaactgact gatgtgaaag 27480
tcaccatcat gtggacccct cctgatagtg tggtgtctgg ataccgtgtg gaggtcctgc 27540
ctgtcagcct gcccggggaa catgggcaga ggctgcctgt caacagaaat acctttgctg 27600
aaatcactgg gctgtcccct ggggtcacgt acctcttcaa agtctttgct gtgcaccagg 27660
gcagggaaag caatcctctg acggcacaac agaccaccag tacgttccag gcctgcctgc 27720
ctgtcttgtg gccccctcct tccagctctg aaccctcagc tctacctggg ataactccat 27780
agcatgctgc tcactcccag gttcacagct cagcagttag ggaacatcga gttgaaagga 27840
atgttgaagg tggaatgaaa ctagcgttct gagaatgctg actccaacat acatgcttcc 27900
aacacgcatg tcatgtccaa catgctcact gctggagtta gagttttctt tgctaatgga 27960
gatgcaattt cagtgctttt gtctctctgt ttcccctccc ttcttccctc ctccttccct 28020
cttttttctt ccttccctcc ctccctttct ccctcccttc ccttccctta accttccttt 28080
ctttaagctg tgaatcaaaa aatgctctac cactatacaa catccccagc ccttaagtgc 28140
atttttaaaa aatatatggc cgggcgtggt ggtgcacgcc tttaatccca gcactcggga 28200
ggcagaggca ggcggatttc tgagttggag gccagcctgg tctacaaagt gagttccagg 28260
acagccaggg ctacacagag aaaccctgtc tcgaaaaacc aaagggaaaa aaaaatatat 28320
gtagttagat atagtagaat tcatttgagg ctagcagttg ccaggcagca gggtgtgtaa 28380
atgtatgtct gggatgtgtg aggccctggg ttctctctct agcaccacac aacgagttga 28440
taccttaagt aattcatcct aaacatttag tggccctggg cagcgaggta tcatctattt 28500
agctctttat cagcagaacc tggctggctc ttaagtcttt agctgacatg tgcaaaggga 28560
aatgctactt ctgttggatg tgggaagaga cctaaggtct tccctgagga agtgacagtg 28620
gtttggattc caaagctcat gtatgttctc aattacactc gaccacctct ggaaggttct 28680
ttctatcaaa gatgttctaa cttcctatgg gaggcccagt tatcatcctt agaaagaaga 28740
aaaatggtga tctatgtgat tctttctgat actccatggg actggggttc tgcccatctg 28800
ttttagttat tgtaattaga tccatgtgag gcagctttta tttctccagc agaggttagg 28860
tcagccaatg aacatacacg ttagcatatt gcctgcagga cccatggagc ttttcttgcc 28920
ctaactctgt tggacttagc cccctccctt aacctttctg gcccaaaaca aattgtgggg 28980
tttgcaaaat gtttgttttg ctttagaaaa aaaaaagtaa tactgttatt ataatgtgac 29040
tataatttcc aagggtggtg ggtaaatctt tactgggaaa agtagccttt ccaaaggatg 29100
atagacaagt gaaaagggtc aacgaatttt cataactgat aaagtttcgg caaaattcta 29160
cactatcctg agtctcccag agccccacgg tatccagggc tgtggctctg actttagttc 29220
caaccttgag taagggagct tgggatgctt aatcaagcgg gaggatttcc gcatggctgt 29280
tactgatcta aacgtttctt gacacatttc atcttatttt ttccccagaa ctcgacgctc 29340
ccactaacct ccagtttgtc aatgaaactg acagaacagt tctggtaacg tggactccac 29400
ctcgagcccg tatagcaggc taccgactga ccgcgggcct gacccgagga ggccagccca 29460
agcagtacaa tgtgggaccc ttggcctcca agtatcccct gagaaatctg cagcctgggt 29520
ctgagtacac cgtgaccttg gtggctgtga aagggaacca gcagagtccc aaagccaccg 29580
gagtctttac tacccgtaag ctaaaattca aatgccttgc tttcgtgaag ctagagttct 29640
caattaactc ttggcttttt ctgtcctttt gcttttcaaa agtgaaccta aaaagccctg 29700
gtgcaccatt taaagccgcc ccattgaagg tgtgccccat ggacaggctg gtgttctctg 29760
agtatttctt gctggtctgc tgtaacatac acagctttgc cagcgtgggc agcacagttc 29820
gtggcctttg cccgggctga taagtgcttg atgaagataa cagtgtgtta atttgcaggt 29880
atttccaggt tctttctatc tttctgggct aacactatga gtcaggagga cttgggaggt 29940
agctcagtgg ataaaacaag tgcggctaac acatgagggc cagagttcgg atccctggca 30000
tggacataaa aggccaggtg ctttggtgga taattgtaat cctagcactg agagacagag 30060
acaagaggat ctggaggctc acagccagtg ttgctgatca gtagctccag gttctccaaa 30120
aatccaccgc cgaggctggt gtggcggcgt acgcttttat tcattcatcc cagcaagtgg 30180
gaggcaaaag caggcggatc tctgagtttg agaccagcct ggtctacata gcgagttcca 30240
gaacagtcag gactatatag aaagacccta tctcaaacaa acaaacaaac aaacaaaaat 30300
acacaaacaa gaaacaaaaa agaaagaaag aaggaaaagg aaatatggtg gagactggtt 30360
aaggaagtca cacgaatcca tgggcgcata gactgaatac aaagtagaaa aggctgagta 30420
aatactagta gacagaatct aacccatatg catagctcca tcacatcact ctctagacat 30480
caactgagag tcatatatgt ttaaaaaaaa tccacccatg gactgaacag acatcagcaa 30540
atggaaagag aggttaagta tgtgacttcc ttgagagcct ggaccgcccg ccgaaggcta 30600
ccgtccttca cagcagagcc tggtttcctc ttccttaact ttctcttcca catcttccac 30660
acagaggaaa aagacaaggg ttttgggtat gactagcctt tgactcaata ttttagagga 30720
aatggcctta actctcttat ttatccacat tcccataaac tcctgtcttc acaagctgct 30780
ttcctcctac gtacactcca tttacatgac agagagctct gagacttatt tcttgctgag 30840
tacttgttat ttttttgact tgcgggtttg aattatagga ggacctaaca ataagcatgc 30900
tttgggcatt tatggccgtc tacctctggt tcccagcttt ccaggagctt tcagcaagtc 30960
ttgtttgcat taaaaagtaa tctaagccct gcatggtagc acatacctgc ctttagtgct 31020
atcacttggt aggtagactc aggtggatct ctctgagttc aaggccactc tggtcattag 31080
tgaggtctag aacagctagg gctaagcaaa gaggccctgt ctcaaaaaca aacaaataaa 31140
taaataagca acaatttaga aaaactgtca actgttcccc acaggaatct attgtttacc 31200
acaaacttct ttgcatgcac atttggtaat gtgaggttga acaccgaagg cctgtttttt 31260
cctacgaaac tgttcaccag caaatgaagt ctgctttcta gtttgcagac ttctttttaa 31320
atgtttggta tttgacattg cccagttttg agaaagtcta agatccactc ttacagaact 31380
agtatccttg tttttcttgc aaaacccatt tcttggagct gtcccttaaa ttaatgagca 31440
tggagtttct gtgcacacag cctcttactt ggcctcgtac ccgaggcttc tgggtgtaac 31500
agtaaaactg tatttgctga ccattaatta acataccgaa ttgcgtggag tatcctttcc 31560
aacacggtag ggtaggtgac tgaaagacaa atgagcagct caccgtggct cagatttaaa 31620
taaaccagtg gaaccaagga gttaagcaaa tccatttgga cctcagatag tcttggtata 31680
aacatgagca gggcctagga actttggttt ctgatgcttt accaaaatta agttttggaa 31740
acaaccagtt ttctgacttt tatatctcat gctaaattct taagagcaac tgtgagaaaa 31800
gtggggggaa taagttattt atagaggagg aatccagcct ccttctgttt gggggcgtat 31860
gtcatttctc aacagccagg ttgttcctta cctaacaagc cctgccagag cccataattc 31920
atacttacag gcacatcctt tgtttgacaa cactttgtgg gtttgtggct tggtgatttt 31980
cctgtaatgg tcttgtctag gcaagagaat attgtctcaa acatggggca agatttagct 32040
gcttggctga cgcaatagaa aatgcctagg tgtgaaaatg gacagttctg aattgcagga 32100
gcagtatttg gtcctaattg ctgaacattc tctccaggct gttaaaaagt tagaattttc 32160
agccgggcat tggtggcgca cgcctttaat cccagcactc gggaggcaga ggcaggcgga 32220
tttctgagtt cgaggccagc ctggtctata gagtgagttc caggacagcc aggggctaca 32280
cagagaaact ctgtctcgaa aaaacaaaaa caaaacaaaa caaaaaaagt tagaattttc 32340
agtagaagaa atgatggtgg tgtcaggata ctagaatacc aagcatacta gttataattt 32400
ctatgtctag tggtcaggta ttaagtgtct gtagcatttt tgtttgaatg atcaaccaca 32460
tgttggagga atggatcttt gatgttgatg ataagatccc caaatcatga aaagatacag 32520
atcataaggc ccaagaaatt aaaaggagct tccattgagg tgagcgagcc cctctttcta 32580
ctacctgtga gtgacaggtc tctgccagaa attcaagccc cagcccaaac aaagctggac 32640
ctgcagaatc accaccctcg gcccccttcc cgggtctcac caggtcctgg gtgccttgaa 32700
gcagttcaac ttcttagccg atgaatgcac cttagctaca ttctctgtgt acttactggt 32760
tagaccaaag ctctgtttac aatgctcgtt aatctgcagt cctggcctac acctatgcgc 32820
ctaacgttga acctcatgtt ggttaatttg cagtgcagcc tctgcgctcc attccacctt 32880
acaacaccga ggtgacagag accacaattg tgatcacctg gacccccgct ccaaggattg 32940
gcttcaaggt gagtttcaga tgcacctctc atgatccagc ccaggggtgt ctttccattc 33000
ccactacact ttacagacct gggtttttaa agttctatgc tcatactcca ggaccttctg 33060
agagcaaagc ctgcattgag gcttctctgt gttgcaaggg aagaaaacca tgagccatgg 33120
aactgtagtg ttgttctgtt ttctgtcctt ctccccaggg aactccattt taaaataaaa 33180
gtatagccaa acctcatttg atgtgttgct ctaaatgggt gtcgagaagc ttatgaaaac 33240
caatttggga agaccaatta aactgagagt cacttaaaaa tcacattttt atccaatcag 33300
tttcatctca acttgttcaa agccctgtgg gtgaatttct taatagaagt taaaattgag 33360
gtcttcgctt tagatatcca gagtcatgtt ctttaaagca gtgataccag ggacgtgatg 33420
gatacaaatg aatatgtttt ttaaaaagaa tcccatcctt aggcatccag aggataaaaa 33480
aaaaagagac acttattatg tctggaatca aagcctgatt gtttaaaaga gagaaaaaag 33540
aaatagaccg agggtcactc tgctttttag tatgcaaata gccatcttga tgagtgggct 33600
gctcaggtac agaggggacc tttatgaaga ccgccacggc acctttttag tttcccttaa 33660
taatgtcgtt cagagtttta gaagccacag agaatctgaa gggtttctct ggagctgagt 33720
actgtttgat aatgtcacct aagcttttgt agttaggaac acacggacgt cttcgtggga 33780
atgtgttttt catttccgtg tgtcaaagtg gctgcagata acttattaaa gagagagcct 33840
agagcatttc ttccctgtgt actgctggta tgcaccagaa gggtttgtgt caaacagtta 33900
tactgacatt tctctagaac ctttctatta taaaggaccc tagtaccaaa ggaagatacc 33960
tccagctaat tgcaagatca ctaaagtgag ccctcaatgt gttatccacc cagtaaatgc 34020
agtgtggagt tgtaacggac ttccccctgt gtaaatctac aacctctcgg gatctctgga 34080
atattcatcc ttcatgctga ttttgctgtc ttccttccag ctgggtgtac gaccgagcca 34140
gggaggtgag gcaccccgag aagtgacttc agactctggg agcattgttg tgtctggctt 34200
gactccaggc gtggaataca cttacaccat ccaagtcctg cgagatggcc aggagagaga 34260
tgcaccgatt gtcaacagag tagtgacacg tgaggagagc cttccttctt cttttaactt 34320
gtaaactatt ttaaaagatt gccaaagcca ggtgtggtag ggtgtgcctt taatcctagt 34380
gcttgggaaa gttaagaatg atgatgggag ttcaagacca gccaaaaact ggaggcggag 34440
ctgggtttta taatacacac ctctagtccc agtacttagg aagcagagag aggcagatat 34500
tggagaattt atggctagcc tggtctacat agtaagttct aggccaacca acagtgagag 34560
cctgtccccc caaaaaagaa acatattcct ctaattattt gaatgttagc gtcccagctt 34620
tcttttgaga cagaacaagg gaagaacctc tctcttattt atatcagcag agtcttcaga 34680
actggatgta gtttagctgg tgtcatgcag gccacagaat tagaagtgtt ccttccatgt 34740
caaaagtctt ccaaactggc aagatgaaac aatttcagta gtgaattaca atagcgttaa 34800
tcctagagac cacctatcgg ggttactgtc gcctgtattt ttatagaata ctttattttc 34860
ccagtcctag agggaaggga taaagaaagg caaaaaagga gggaggtgcg aggaaagaag 34920
ggtggagaga gggcgtagag gaaacatttc acaggccacg tgttctgtgt tcagtttaac 34980
ttttaagttt tcttttctgt tgtgtagcgc tgtctccacc gaccaacttg catctggagg 35040
caaaccctga cactggagtg cttactgtct cctgggagag gagcactacc ccaggtaaca 35100
aaggggagca ccaccctagg gaagcgtggg gcggatctga gagccgcgta cacataaggc 35160
tttcccaaga cagatttgga ttccattcag agaaagagag aaagcaagtg ctctgctctc 35220
catgagtgac agaggagaat gagagagttc atgaactacg tgtaaacacg gctgcatctt 35280
ttcttaactc gcaggaaaga gaacaatcaa atgctaggct gtgggggcgg gggagactaa 35340
cgtttatact acagggaatt ttgagaggat tagatggaaa gaagattttg ttcagctcgt 35400
taaaaatgcc caaactgggg ctggagggat ggctcagcag ttcagagccc cagctgcctt 35460
tttcagagaa ccctggttca attcccagca cccacatggc agctcacaac tgtctgtaac 35520
tccagtttcc aggggatctg aaaccctcac acatgtaggc acaacacgca tgcacataat 35580
aaataaacaa acaagcaaat aacaaataaa taacaagtaa ataaatgaca aataaataaa 35640
taaatttaaa gcccaatttt aaaggctgaa atcatagtct atagtccata aatcttaagt 35700
tgactgttta ctgaagtttg acagatcgct tggtatctgg gtggggctgg cttcagggtt 35760
cccattgatt ccaaactctg tagctgctca gccaattgca taaaatggtg ttgtgcttgc 35820
gtataaccta tacattgctt gcatacttca actatctgta ggttacttgt agcctaatag 35880
attgcaaatg ctgtggaagt cattgtccca ctggattgtt ttggggacag taacaagaaa 35940
gagtgcatgc atagcataga tccaaattat cttcaaccag tattttcttt taatccatgt 36000
tggttcagta tgcacatctg taacctatga atatgtaatg aattgaacca taagatgtat 36060
gagagacagg gatgggcaga ggctcacatg gggaagaaca tttgatgtgc atgcagaagg 36120
acatagttca tccccagcca ctaggcaaaa agctgggcgt ggctacacga gcagctatga 36180
ttcccctggg agacccgctg ccacaccttg ctacttgaga acatggtcaa tgggagccaa 36240
ctagttggag caatattttt agttcattat ttgattgttg ctaattttac tcattgatca 36300
tttttttttt tgagacaggg tttctctgta tagccctggc tgtcctggaa ctcactctat 36360
agaccaggct ggcctcaaac tcagaaatcc accttcctct gcctcccaag tgctgggatt 36420
aaaggcgtga gccaccatcg cccggtgata atggttttct aaaagtaacg tcaccccaac 36480
actaaggctg aggcaggagg attagcctgg tatatacagc aagtcttaat gctagcctgg 36540
agtcatagtg tgggctatgt cttgacaaaa ctatataaac tatatctgca tctatctcta 36600
tatattatat acatacacat atataatatc atcttaaagt acctttgtat gatggatgca 36660
tgcctacatg cattttcatg tgtctaagtt caggtggtac agtgtgtgta tggaggtcag 36720
aggataacct tcagtatacg tgactgcctt ccatcttctt taagacagtg agaccaatag 36780
cttctgggaa ctctcctgtc ttcacttccc aatgctctct agcaacattg gggatttcag 36840
acacgctctc gtgtctggct ttatgtggat tctggagata ggaactcagt caggtcctca 36900
tgagtacgtg gccaacagct tatccaccga gccaaatctt tagtctataa tttgtagcta 36960
taatctctta cactgttctt acccttgctc gggcgtaggt gtcaagcagt tatctataaa 37020
tgtgtgtgat tatagtcaca caaaataaaa ctagtttaaa atactccttt taatctcctt 37080
ttgaaataga cagactgagt gatgtttcct tctctgtggc aatgtattgt ataatgtgac 37140
agctacagtg tttccagata agtttctctg ggtttgaaac ttgaagctga caagttcttg 37200
cttctgggca gctggatcat caatctttgg tttcagtggc ctgcccattc aatggtcagg 37260
cgtaaagcaa atgaccgaaa tgttattgac ttcccatccc actgggtttc ctagcacata 37320
acacgttaat gttcaccttc tccccactga caggatatac cctcattccc tgttctcagt 37380
gggtcagtct tgttctgtct tcttccagcc tggccctgca gagctctggc cactactaga 37440
tttattgata tctcctttcc tttaatgcct tcactgccca attttcatga ttctgaagtc 37500
ttctatgatt aatatttgtt ttcgagaatg agcatctaca cttctgtgtt ctgtgccctc 37560
cagcccctac cccccccccc ccccgttccc atagttcaaa cttttacact cttcggagaa 37620
tgtttaagtg gaaagcaacc tcagagcatt caaaaaaaaa aatgtagatt tcctagctct 37680
cccacaggtc gcccattaag gaaaaacagg ataaaatagt aaaaagaggc tggaatttgt 37740
agacaggaaa ctctcaggtc ttctctaaga tttccttatc tttgttaaag gtcccatgat 37800
tttactttgt agttaacaca tttatatggg ttgtaagatc gcccaatgga tgcaatgtag 37860
aatgatcgag ttagcatttc catctaaaac attcatgtct aagtgctgga cactctcaga 37920
ctctagttat tatgaaatta tcataagttg ctgtggacta gtcacccggc agagtaattc 37980
ctactttctg actgttggta cattacagcc ctgccccttg gtcccacctt ttcctctcta 38040
ggtccatcat tggtgtacag tttaatatac cctgagtcac attggttctg tatggtaact 38100
tcctctctgc atttactcca gatatcactg gctacagaat aactactacc cccacgaacg 38160
ggcagcaggg gacctctctg gaagaagtgg tccatgctga tcagagttcc tgcacttttg 38220
agaacctgaa tcctggcctg gagtacaacg tcagtgttta cactgtcaaa gatgacaagg 38280
aaagtgcccc tatctctgat accgttgtcc caggtaatag aaaaataagc tgttatcctt 38340
agagtggcag ttttgagtag cgatggggat aagcatctta atccgagata gctgagtgtg 38400
tcagatacag ttgggattta atgccaacct cccagggcgc tctccaaaac cacaaagcca 38460
aaaagcaact gtttggatga aggctttcct gtttcctctg cttcactatc tgtgcttccc 38520
tgggatgctg tttgttgcca tgggtacctg atgagtgcgg ccacggcatt aactctgtac 38580
tgtttgctca cacggaaaga ttactaaaca gtgtcgcgtg tctgtaccca gtgctgacag 38640
gctaaaagta atgtggtaaa tgcatccctt tggggctttt gtgcccgggt tttacagtcc 38700
atctccacct ccaactgtta tctagaaaac agcctttgtc tccatatgtg agcactgaaa 38760
cacacttggt tgacaatcca aatctttatc ttgcagcttc aaatcctttt taaaattgca 38820
agtggggtga aaaaccacag aaaggaaaga agtaaaggcc aggcccccca tggcttgctt 38880
tcttctgaat tgaaagacag cgtcacaaag gcctgtctag ggataggttc attgtttgtc 38940
cccagtcttc tgtagattga aagccctggt cagactctct taccctctgc agtattttgc 39000
tatgcattta tgaatactaa ttaaattaca tgaattaaaa tgttggcagt ggagtgggct 39060
cagggctctg tgctggctgg ccttggcctg actgtgcatt tgagtggcac attcacaaca 39120
tagattaata ccatggtcat gatgccatca tggcttttga acatggaaaa taagtcaatt 39180
agccagccaa ttttttttta aaaaaccttt ggaagatttt attttcttac taaaggtttt 39240
gtgttctccc cactcccaac cccccacccc gccaacattg ctagtgtctt ttatagatca 39300
gttcaggctc tgagaatgat tttgacattg taaatgggtt tatgattaat tttttttaac 39360
acttgagaag ttaaaactgt accattcagg gacattttct aaatgggagg aagcccctga 39420
aagaatgtgg taacctgcat tagtctccca ggggagcaaa ttactcatga tgcttgggac 39480
gtcttttcag ataatttggg atacattgca tataccatca ttgcttgagc attccgtcaa 39540
tttcactacc ggtcacctga tgtacactgc tttatttttt cctttgtttt ttgcctctac 39600
ttttcttttg cctcctcttt gcttcgtaac tcaatagagg tgccccagct cactgaccta 39660
agctttgttg atataactga ttcaagcatc ggcctgaggt ggaccccgct aaactcttcc 39720
accattatcg ggtaccgaat cacagtagtt gcggcaggag aagggatccc tatttttgaa 39780
gattttgtgg actcctcagt aggatactac acagttacag ggctggagcc tggcattgac 39840
tatgacatca gcgttatcac tctcattaat ggcggagaga gtgcccctac tacactgaca 39900
cagcaaacgg gtgaatcttg aagtcttctg tgtttgagac atggatggtg ttgcatgctg 39960
ctcagtcgct gtggttaaat ctggatgttt ccaagccagt gattggctac ggagatgaag 40020
acggggcccg ctcagagata agggatacat tagtctggtt gcatgaaagt atgcgtaaat 40080
agtctcaagc actttcagtc aaagcacaaa cagatgtgaa ggggaagagc tctagatctc 40140
tgatttatga aatgcaaagg agattacatt tgcagatctt gagggtgttt gttttttttt 40200
aaagtatgac tatcaaactg aacaatgagc actcatttac actaagacag gcctccaaag 40260
tgtgccactg cgtgcttcct cttaccttga taagctcctt ttgtagctaa taaaacacct 40320
accaaaaatg agtgtggaac agaaggggag atctcagggt aggatgacga cgagccgtag 40380
ggctttctgg atagtgctgc tctacagggt aaagaaactc ctctttaacc acagtctaga 40440
gacgagcatg caacatctta aaggttctct gccctgcatg gtaagaaaca ttgctgagaa 40500
ccactgtgca tgaatccctc acttgtaagt agagttcact gaatggaatt atggcaatgc 40560
agtagtgtgt agatatctca ctccggggaa actgaggacc ccttgtcttt tttgtcttcg 40620
tgcatgtgtt tcttcggaaa gtactgctat gtgtctttgc tgtgtggcaa cttaagcctc 40680
ttcagcctgg gagaaacatc ttccgtggta tcgatgtact aaaacggcaa tagcagccac 40740
caaaaaaaaa gcctacctat ttgaaaagta gactaaaatt cttttaaaat gcattgatca 40800
tggcagaaag gttaaagggg cctaacagtg ttctctatag tgttttgttt atttttttaa 40860
cagtagcgtg tcatgattta gattagatta gattagactg tttgcatggt tgtaactgtt 40920
tcttttctgc atgaaatact ggtttttacc ttttcagcta tttttttttt ttagctttga 40980
ctttaaaatc gcattaactc aatcctcctt atttgatatc agctgtccct cctcccacgg 41040
atctgcgatt caccaatatc ggtccagaca cgatgcgggt cacttgggcc ccgcctccgt 41100
ccatcgagct gaccaacctc ttggtgcgct actcacccgt gaagaatgaa gaggacgttg 41160
cagagctatc catttcacct tcagacaatg ccgtggtcct aacaagtaag ccctcaaaca 41220
tagcttgtcc cgtagatacg cagatccgta gatctggagc acaaggcatg gatcctgagt 41280
tttcctggag gaccacctaa gagaaaggag aactgtgacc gagagacacg ctctccaagt 41340
tcagtaggcg gctctgtaaa ctgtgaaaga tgtaatgatt ctgccggagt ggcagacctt 41400
tgatcgctac aaatcgtagt cgaaggcacg gtctgtgaag caccaaggtg tcagacattc 41460
tctaatcagt gcacaaaaga tacgtgactc ccaagtgaat tctgtaacta aggcaagagt 41520
gagaaacatg gagatcagcg catctggttt attgtccttt cttgtgtgag atctaccacc 41580
accaggggat ctatttagca ctagaaaact tagaatggct tttgcgtgga gacaggcaga 41640
cgtttagttc atatttcaga aagcacgtgt ttgcaccatt tccctgaagc tgggagagtt 41700
tagaaagcaa ctgacatgta ttagacaagt tatagaaatt gtttcttccc gagtcctact 41760
ggaagaggat actttgaatt aaagagaaca agagcttgca acattgtagg aaattgtata 41820
agtacagggg ttctacagga gaggaaagta gttacattca ggcccatttc caaatagggt 41880
cagaaaacat cctctgctct tcagatacgg ctcagaaagc taactacaaa gaggcagcag 41940
cagcagctct cacttggtgg ctaaagacca gaggacccag atacttaacc cgagtgtgga 42000
aatgtctgtc cagtcagtag gaaccacatt gtccaatata ctagacccat cgccacctgt 42060
tggcaccggt ttagccaaac cgtgtcacat gttaattatg tatcttaaag agtcctaatg 42120
ctagaagaaa ctccccctta gagaagtcat tattacccta ttttaaaaat taagcagttt 42180
gagggcagtg gagtgagtcc aggggcacta ggtatgttca ttgtcttgaa tacattcatg 42240
gccccaacaa ggacacatgt caaattttgt ccaactgtac atcttgacat tgcatagcat 42300
ggaagctgct gaccacctca tgtggttgtt gtgatgggta gatggtaatg tagactccca 42360
caaaagttac atcagtggcc ctcacagatg ccctttcaaa tggacgggag agatagtaac 42420
atcccgtgtt tacacttgac tgagttccat ttatacctgt ggagctgggg cttacagaca 42480
ggacagagcg gcccttattt acagattatg tccagacaga catactcact tagccacagg 42540
taggctatgg gactgaacgc ttggatgttt tatcagatga cggagtcccg gggagcgtta 42600
tgctttctca aagtctcaat caagtttaaa gcaaatccca ctttgcctct tcagatctcc 42660
tgcctgggac agaatactta gtcagtgtct ccagtgtcta cgaacaacat gagagcatcc 42720
ctctccgggg aaggcagaaa acaggtgagc cacgttagct accaacgtta agcaacaaaa 42780
tgataggttg agtctatagt tgcatctcca ccttttgtgg cattgataca ttacttttaa 42840
tttattaatt aatttatgat gacaataatt aattacaact aattaataat taattttagt 42900
tattgtagag tagtggtttt gccatggtat tttcacatgc tctgttgatg ttcctcttcc 42960
gttcctctcc ttgccccctg tcatccttcc tggtcccctt tctccctgta gtaatgtaca 43020
gccccgtttt cactctcgtc atcttgtcac ctctatccta tgaccctttt cactttctac 43080
cctctccgcc ttaaagcacc ttctcttctc cccacattcc tttttctagt ttcaggacct 43140
ttgctctgca catacatgta gatgctctat acacacatat gaaaaattaa agctaggatc 43200
caggtaccag aaaactccac ttgtctttct gagactggat tgctttgttt aacataataa 43260
tgttactttg tttaacataa caatagagtt ccctggtttc cttgtgaatt tcactggttt 43320
cttgtcttag ttaaggttgt tgtgatattt gtgaggaaac accatgatca atagcaaact 43380
ggggagggaa gggtttattc gacttacact tccacactgt agtccatcac tgcagggaaa 43440
ccaggacagg aactcaagca gggcaggaac ttggaggcag gagctgatac ccggggccat 43500
ggaggagtgc tgcttactga ctggcttcta ccatgacctg ctcagcctgg tttcttatag 43560
aatccaggac catgagccca gagaaggcac tgtcccgccc acagtgggca gggccctgcc 43620
ctgtcaatca ctgataaaga gaaagcccta caagcttgcc tagatcttac agaggcattt 43680
tcttaattaa cgactccttc ctcttagata actttagctt ggtcaagttt atgatataaa 43740
gctacccaga acaacgctga agccctcaga agtatcagtg tttcggtata atgtagaaat 43800
cggctataat tttacatatt gtttcaatta cttttaaaag gaaaaaaaga aagaaatgct 43860
tgtgtaagct gattgcggtc agctatcagt cccgtataac agtgtcagtt gcgttcccca 43920
catcctccat cctcgatgtc taagctcgtg gttgttgtct tttgctcccc tccttgggtg 43980
ggaaaaacag gtctcgattc cccaactggt tttgattctt ctgatatcac cgccaactca 44040
ttcactgtcc actgggtggc tcctcgggcc cccatcaccg gctacatcat ccgccatcac 44100
gccgagcatt ctgtcggaag acccaggcag gatcgagtgc cgccctcgcg gaattccatc 44160
accctcacca accttaatcc gggcaccgag tacgttgtca gcatcattgc tgttaatggc 44220
agagaggaga gcccgccact gattggccag caagccacag gtaattttgt ttttttaatc 44280
cgcaaagaaa tcccttggtg tggactttgt ataggtttgg tgtagactgt gaaaaagctt 44340
catgttagac acaaagagca gtggtggagc caggcgcagc tgtgcgcgct catgcacgca 44400
ggcacgcgcg cacacacgcg cacacacaca cacacgcacg cgtacgcaca cacacgcacg 44460
cacgcctttg atcccagcgc ttggaggcag gtggatttct ggattggagg tcagcttggt 44520
ctacagagtg agttccagac tagccagagc tacacaacaa gatcttatct caataaaaag 44580
ggaaagagga cagtgataga ctgtgtggta aacatttctc cctctaaaaa catatttatt 44640
tctctgagag attgtcacct ggttcagcta tgttctggtg tttttgctgg tcagtcttta 44700
tttatgatgg tttgagagag cgtcatagcc cagactgact cagaagctgg ctctgtagcc 44760
caagcttatc taagatactt cgccttgact tgtgagtgct ggagttacag gcatgagcta 44820
ctactactca tggatattta ctggttttta agaaggtttc atacaaaacc ataatatggt 44880
accaaagtta ctgtaaacct atgatttttg tttcgttagc tgggcttggt agcacagatg 44940
tgtaatccca ggtacttggg aggctggagc aagaaggcca tcctgggcta ctgtgagttc 45000
aaagttagcc tgtgcaattc agtgaggctc atctcaaagt aaataaaagt tttttaaagg 45060
ggtgcagtgg atgtagtgta gtggtggagt gctctgtgtg gcgtgagtca agccctagat 45120
tttggcttta agcacagata gatatatttt cagtgacaat gactgggaga cctgttatca 45180
gaacaatctg tagcttagct gtgaataggg gcgtgtgtga ccactatttc caaataacac 45240
atagttaagg gtgcatgggg tgggatctct gtgagttcca ggccagcctg gtctacaaag 45300
cgagttccag gacagacagg gctgttataa cacacagaga aaccctgtct tcaaaaacca 45360
aaagaaaaaa gaaaagtgca tggtgagtgc tgctgtagtt tttataactt ctgtgattta 45420
aattatttcc caaagagact gttgaggaaa aaaggaattc acaattggga tggtctccat 45480
agccccttcc cttgacctcg ccatagaatt taactctgct aattcagtgt tgcatttaga 45540
tttttgtttg aagaggatgt gtgtaatcgt tatctgggaa aggacaaagt gaacctgagc 45600
tttctttgga agttatacat gtgaagtttt cctgtgattt ttttttttct agtttctgat 45660
attccgagag atctggaggt cattgcctcc acccccacca gcctgctcat cagttgggaa 45720
ccccctgccg tctctgtgcg ctattacaga atcacctacg gagagacagg tctgttcatt 45780
ttgggccatt tcacccttag aggatcaggg ttcgggtggg taacttggaa atctgacagt 45840
gggaacagga ttaaatgcaa acaggcccat ttagaaaacc cccctccttc cctccctccn 45900
tcccnctccc ctcccctccc cctctttctt tctttctttc tttctttctt tctttctttc 45960
tttctttctt tctttctttc tttttctgtc caaaaatgca tgggagctac atttaattga 46020
ttgtaatgaa gttcaaaggt ggtttataca ctacagcaag ggtgggaagc agagctgaga 46080
aaaaaaagtt tatatattta caaatattac cattggtaat tcttactatt ctttcttttc 46140
agtgttctct aaatttaaca aatattctgt taaccctttt gtaaagactt cattccattt 46200
taggttgagt gagccacatt cttgtcccct ttttctattt aatttaaaca attaattaaa 46260
tataattaca tgatttcctc cttccctttc ctcttccaaa ctatcccaca cccctctcgc 46320
tccacttcct ctcagtttct tggcttcttt gtcttactgt tacacacaca cacacacaca 46380
cacacacaca cacacacaca cacagagtgc atgtgcatcc aacaaataag tataaataca 46440
acccaccgag tctgcttact gttgcttata tggacatggt ttcagggctg actgcttggt 46500
atttattatc aaccagggag ctcatttctg gggatttctt caccttttgc ctgttaatct 46560
gcaactcagt gacattttaa cccagggatg ttaatatggc attagcttga gagttctcct 46620
ggtttttata tacttctcag ggcttactac acacataaat acacttgtct gtcaggttgg 46680
gttaaagcag ccactcctta tgatggaacc agcaagctgc agtgacttac ataccgcttt 46740
cgatgtgtta ataatattgg agtaactcct agctcctcaa attctatgct aactcctttc 46800
gtacaggagg aaatagccct gtccaggagt tcactgtgcc cggaagcaag tccacagcca 46860
ccatcaacaa cattaaacca ggagcagact acaccatcac cctgtatgct gtcactggcc 46920
gtggggacag tccagcaagc agcaagccag tttccatcaa ttataaaaca ggtacaaatt 46980
tctcttgggg taacacgggg ttatttatga agatggttat ccctgtattc gtccaaggta 47040
ttgtcttcac tacacagttg attttccttt agttttgtgt ggtgctgggg accaaaccca 47100
gcatctcata aatatatata tgctgtacca ctgaactaca cccttgaccc tgatttattt 47160
ttcttttttt ttttccgaga cagggtttct ctgtgtacaa aagcctgtag ctaacaacac 47220
cttcaagtaa tagagtcttg agacaaatgt acaaagaaga ccccaagagc agacattttt 47280
gtctgtgttt ttaactgcta ccgctatgta tctacattag acacaagcca gagagtgttt 47340
ataaatacct gtagaaaatg actggatggg ttgactatta ggagacaaag gcctacctga 47400
gatgtaatgc tttgtttgtg gaatgaaaga atcaggttgt aaatagttgt aatagtgact 47460
ggatgcatgg ctttccttct tcaagctaac accctttatt cttgtcaaaa gaaacatttg 47520
caatacatta atagaagcaa gagaacattc gcatacacac tggaactaaa ggccagggct 47580
tgtccagccc tccccccaca ctgggacatc actgctttct tttgtactta cagaaattga 47640
caagccgtcc cagatgcagg tgacagatgt ccaggacaac agcatcagtg tcaggtggct 47700
gccttcaact tctcctgtga caggctacag agtgaccacc actcccaaaa atggcctagg 47760
accatcaaaa actaaaactg ccagtccagg taaggataac cacaaggcca cacctagcaa 47820
gagaaacact gtaggagctc agaagttgcc atttgaagtg agtgtcctat gtggtgtgtg 47880
tatgctactc ccattcatag gcttggcacc agctcagtat tggtatccgt gtatctcggg 47940
ttttattttt ttttaatact gtcttgtgta gtaggaagag aaggatatac tgatgttata 48000
gatccttcta gatctgatgt tcttatatga aatggcttgc aaggtctcaa gccagtttct 48060
taagatcaat tttcatttct ttcttgaaat ttttcaagaa tagcctcatt aattttgggg 48120
gatggggcat catgttaagt tagttgtaaa gcttattctt gaatatgatt ttacttcagt 48180
atgctagatt ttgttttgag atgggggtct catgaagtct gtgctggcct tcactgcact 48240
acgtaggcaa ggatggcgtt aaacttctga tcttgttgtc agtatctcct gagtgctaga 48300
actatagata cgcacacagt ttactgtgcc gcttggttat ctaagcctgg gtttgttcat 48360
gggaacagca ttctaccaac taagccgagc tccccagccc cagttttggt accagtgaac 48420
aagttgtcct gagaggaaac aggcatctga ctttcccaag tggaatgggt gtttcatggt 48480
tattctgcaa atgaaaatta taggctcagc atctgcttct cattgagtcc ttaggagtgg 48540
cttgggtggc tctatagacc tgcaattaat tgcttctccc tccttttcag atcaaacaga 48600
aatgaccatt gaaggtttgc aacccactgt ggagtacgtg gttagtgttt atgctcagaa 48660
ccggaacgga gaaagccagc ccctggttca aactgcagtg accagtacgt aaccaatgct 48720
cggtttccta cttccaaagt catattgtcc tcaggtgtct ctcgatgccc accgcacatc 48780
ttgtgccatt gtatacacac agggaaaggc aatgtgtcag ctggttcata tcttgagatg 48840
agcccttggc ctacatttct tggcgccaaa gcgagcttgc aggaaaaatc actgtagtgt 48900
tgccatcaat ggctgctgtg ctttgaatct cctttgctta aacagcctca gcaaaatctt 48960
atttgctttt agcaaatcta tgaaagatct ctccaggacc tactttttct atgactggat 49020
ggtaatgttg actgtagtgt gccccaagaa gtggttatgg ttgaaggact gtggctgggt 49080
cagccttgtt tttttttcct ttttaaagat tttatttttt tcatctatat gagtacactg 49140
tcactgtctt cagacacacc agaagagggc atcggatccc attacagatg gttgtgagcc 49200
accatgtggt tgctaggaat tgaactcagg acctctggaa gagcagtcag tgctcctaac 49260
ctctgagcca tctctccagc ccagggtcag cctttttaaa tataaagact taagagaggg 49320
gaaaaaagaa gaacctaaga caaattatga cttgaggaaa aaaaaaatca actttaccat 49380
ttccaagata tagaaaatcc aggtccttga gactaacatc acattgcaga atcaaatcta 49440
gaatatcttt aaattgatat aaataaattt ccttggtgga gatttttttc ttcagggtgt 49500
ctacatacct tacacacact tgtgtcttaa taagcaacgt gacactgcat atgctaaatc 49560
tcaaaaaaaa aaaaaaagcc ttttaagcag atgtcaagca actttctgtt ttaatagtgt 49620
gataattgga acttaattca tcaaagacaa gagttatctg cagaactgct ttgcatggta 49680
tggaaatatg cttgtttcac aacttgcttt tcacataacc tcttaccatt aatttgccta 49740
acagacattg atcgccctaa aggactggca ttcactgatg tggatgtcga ttccatcaaa 49800
attgcttggg aaagcccaca ggggcaagtt tccaggtaca gggtgaccta ctcgagccct 49860
gaggatggaa tccgggagct tttccctgca cctgatggtg aagacgacac tgcagagctg 49920
cagggcctca ggccggggtc tgagtacaca gtcagtgtgg ttgccttgca cgatgatatg 49980
gagagccagc ccctgattgg aatccagtcc acaggtatat cgttaaccgc acccaccacc 50040
cgggtgcttc tgggaacagt ggctttatgc cttgctggcg ttatacttta ctgggctatt 50100
gagtcccatg taagggagag tagaaaaatg ccttcaaact cttagtaaag aaaggccctc 50160
tttaatgagg aatggttgtg aacaatgaaa gtcaggtgat gtttaggtaa ctaagtctag 50220
gaaagagaaa tttaaagtag ctaagcacag acgtgcaaac atatgaaata tataaatatt 50280
taaagattat gaagcaagac atttgaaggt actaaattac ggattgtttc ctaagtgaga 50340
cacctcggtg gtgaccctcc ctctccacac atggaggaaa gaagtctaga atcatagagc 50400
ttactctgag aattgaccct cttaagccag gcattttctt gcaacatgat caaagaatac 50460
atgggtaaga cctcccctgg ctagctctcc tgtgctgggc cttcatttgc ttaaaggatg 50520
atgatgcaga tgcacaggac agcgtcatta ggaccagtgc ttcttaccag cctcttatgc 50580
ttttaccgct ggagcaagat tggaatgctc aaagcataca gaggtgacag tctgtggaac 50640
tgctctctgc ttctctctcc tgcctctatt gtaaaccaat tttcttctta tgctacgccg 50700
cagagaatac ttcaaattta gcagtgctat ctgccgtggg gtccaaataa aagagacaaa 50760
taaaaacaat tctatctcta ggatggaata gtctgtgaaa ttgtttcctg tacaaagata 50820
atttatatag aaaaaggggc cattgctcat ctttttcata caaatggaaa aaaaatcaat 50880
tctaatgact aataagggaa ttcaactctt ggcttctaaa ggcgtagggt agggagataa 50940
gacccaaagt ctctcggaac cctggtgttt atgcagatgt ttgcagtggt tctgagagtt 51000
gctggtataa atactcctct cgtttttatt atctgtttgt gcagactctc ctgggagtct 51060
ccagggagtc caccagtccc tacgaggacc atccattctc cttcttcaag tttgctttct 51120
ttccccgttc ctcgttccct ataagataac cttttaacca atgaccatcc tgacagccat 51180
tcctgcgccc accaatctga agttcagtca ggtgacaccc accagcttta ctgcccagtg 51240
gatagcaccc agtgttcagc tcactggcta ccgggtgcgg gtgaacccga aagagaagac 51300
aggaccaatg aaagaaatca acctttctcc agacagctca tcggtgattg tgtcaggact 51360
catggtaaga agtgagcttc cctctgcaga gtaaggcagg aggtcatttc atagagttca 51420
taggtgcaat ctcataataa acctagtgtt ctttgcttct accatcaaat agggttgtca 51480
caaatgtgta caatagaatt cttttatgta gacctaggat tttctagata ccctaagatg 51540
actattggat tagaatggtg taaatagctt tggatttcgt gcaggtcttt gacagaagta 51600
ttccacttat ttaaaagaag tggtattcgg tagggagcaa tttatataca cacacacaca 51660
cacacacaca cacacactct ggctgagttt atggctttta tgagtgatgt ttccctggca 51720
agacgcattc tccagttagt accagcctaa cttgacacta cccccattaa aacatttgac 51780
aatcagccag ctgtgcttta atcttgggag gcagaataag caggtggatt tctgagttcg 51840
agcccagctt ggtctacaag aatgagttcc aggacagcca gagatacaca aagagaccct 51900
gccgcaaaca agcaagcaag tagtatttaa aactttttct agccatgcag aaattagcta 51960
ggatcctata agggcttaat gcacatctta acacaaggcc aattcttaga gaagtagcag 52020
tagaatagaa gctttctctt gctttttttg tgatcaggaa aaaagcaaaa cctgatttat 52080
atctgtcata tcataaaggc aaaaaaaaaa aaaggctaag actgatttct ttcttattct 52140
ttttttgctg ctccttgtgg attgtggact taacccctga gaacatttta aaattcactt 52200
aatttaaatg taaatgtatt gtcactcata ggtaacagtg aagttgctct gggaacctgg 52260
gggtttgggg tttgctgggc tatgcagatg gtcttttata atcaccgcat ttctctaatg 52320
ctttggtaag aactccgggc atcatgcaac accattgcca aagtttctgg tacctctgct 52380
tccaggtggc cactaaatac gaagtcagtg tctatgctct caaggacaca ctgacaagca 52440
gaccagccca gggagtcatc actactctgg agagtgagta atccgatgag tgacatgttt 52500
taatcctgac acaccctgag tggaagtcaa aagaaaagat ctttacattt aagccactga 52560
cttagcaata gaatttggaa gttgatagaa cagcttgtcg tttcgggaat ccatccagga 52620
aatgacctgc cgaaacaaaa tggaatcact tcactgtgtt gtgttggtgc tggtgggtta 52680
aaactcacag ctggcttatg cggtactggt gagggtctgt attcgtaggg ttcaatgtgg 52740
ggaagatgaa ctggcttcca ccatagggaa tgtggggcta aattagatct gtggtctagt 52800
ctgttgatgt ttcatcacct atggaatgat taacacgtga agccttatag aaatgaccga 52860
agattcgcca cccagacaga cgttattact aattgtctgt gttataattc ctaccataca 52920
tccttacata ttagtaaagt aatcattgtc acacttgttt gacatagctc tagacactag 52980
agagtcaacc ctgggcacca ctgatagtat ttagaaagct tttctgttta gtgaacattt 53040
ccatatttcc tcaataccgt taacccatct ttctgtaacc tccacattac tttttagtgt 53100
atttcctgaa gtggatgtat ttgcataatg aggactcttt ttaaaatatc caaaccttac 53160
atgtatgagc caagcgtgct ttaatctctg gctctgctcc tacacagatg ttagccctcc 53220
aagaagggcc cgtgtgacgg acgctacaga gaccaccatc actattagct ggagaacaaa 53280
gacagagaca atcactggct tccaagtcga tgccatccca gccaatggcc agaccccagt 53340
tcagaggagc atcagcccgg atgttagaag ctacaccatt acaggtcagt gtactcgtgg 53400
tctgcctgtg tgcgcccgca ggagaccctg gctcggtaga tagtctggtc tggtattgag 53460
aatgtgggca ccattccacg atctgttggc ttcctgatgt ttgcttgacc tataaatctc 53520
attcattgaa tttgttgttt tataaatgct cattcattat tgtctaatga aaatctgcac 53580
actgtagtca taggcaggag tctgaggcag gaggatgtga gtttgagact agacatagtg 53640
aaaccctact ttttttaaag ttaatataga gaacataaag atacaaaata gtaaaattag 53700
catgcctaga ttttaaaagg cataatgaaa tttatgatta caaacagcat tatgtataat 53760
aaaaccggaa actgtaatca gagacgattc agtattggga cataagtgag gtgcttttga 53820
gatgagtttt tcattagtag tgacctgtcc accccgtgaa gccctttact cttccctgta 53880
actgcttctg ccagtatagg agtcaaggaa actgtaggca agcatgagaa ctcgcctagt 53940
aaagtaggag tggattaaac aggcgtcttt ttaacttcca ggtttacagc caggcactga 54000
ctacaagatc cacctgtaca ctctgaacga caatgcccgg agctcgcccg tgatcatcga 54060
tgcctccacc ggtaactatg ctttctatgg aggaaatgtc agctgctgca tattgtaatc 54120
agccgcgtca agtttagaaa cagttaggga gctggaattt ccatgttctg gctcccggga 54180
ctctctgatt ctctctctcc tcctctgttc gctagggctg ggctcaactg tgagaatgga 54240
cattcatttt tctaaggtgt cactttgctt gcctttcagc catcgacgca ccatccaacc 54300
tgcggttcct gaccaccaca cccaactcct tgctggtgtc atggcaggcg ccccgtgcca 54360
ggattactgg ctacattatc aagtatgaga agcctggatc ccctcccaga gaagtggtcc 54420
ctcggccccg ccctggtgtc acggaggcca ccattactgg tattgcttcc acactgtgat 54480
ttttttcccc ccttaatcat agatgcccca agtccataat actccccaat tgtgtctttg 54540
atgctatttc atgagaatga ggtgcccagc actctagatg ttctgtttag ggacagtagt 54600
tttctcaaga gatatgagca actgagcatg caatttcagt gccgtcctat gacacagctg 54660
tgatgtatta cactctggtg taaattcttc attattcccc cctcccccat aggataaatt 54720
gtgtgtatag attctcctgg atgttgaagt ctctaaaaca cacagatata aggagatcac 54780
agcttctttg ttgcatttat tgaagaagaa aataagagtc tgatatggga agacttaagc 54840
agaagacatc ctaatttttg ctctgtcact gacagctgtc tgagattaga cctaaataga 54900
agtctgaagt ctctgatggc ctctcccaaa tacatatttc attgtcggcc cacagtatag 54960
atagtttatc tacaggctga aagaatcctc taggaaggtt gccatgaaac tgctcattca 55020
agtatcagct gtggttgtga aatgactaac tagccaaggg gctttggggt tcgcagagta 55080
gataaacaag gagtgaagct gaaagacttc acaggcagct ggcaggaatg cctgctcccc 55140
agtcgcctct gctgagccaa tcactggccg tgcccgccaa cgtgagtgaa acggccgcgt 55200
ttcccatcag gtctggagcc aggaaccgag tacaccatct acgtcattgc cctgaagaac 55260
aatcagaaga gtgagcccct gattgggagg aagaagacag gtaaagactc ataaccagtg 55320
gttgctttgc agggtgaagt ctctacattt ccacacatca cacatctctc acggattttt 55380
tttatttccc tagcagagtg gcttatatat tttactcttt gacaggaatc acctaacatg 55440
ctctaaaaat gtctgattta tttctttttc tacaacctta agcttcgttt accttgcaga 55500
gattcaaact agatagtttg aattggaagg ggggggaagc tttataatgg tgggagtaaa 55560
acctttctga tttgggtcga tttatttatt atttgatttc tgaacttcaa acacttcagt 55620
tcgttgcaaa gccttaattg gagcagagat ggctttctgt ggggctcagc ggttcaaagc 55680
tttgtctgta tgagaattca tactaacttt tttttttttc tgtctgaact ataaagaaat 55740
ctgtgagaaa aaaaaaatca cgatttcttt ctctaagagt gttttgtgat ctgagaaccg 55800
ctggttgtgt gggagctctg atcgggttga taaacagttg ttgcctgggt tgacagtgat 55860
tggttgcttc ttcttcgagc ttaacttttg cgctttgctt ttttggctct aacctctctt 55920
ggctagatga gcttccccaa ctggttaccc ttccacaccc caatcttcat ggaccagaga 55980
tcttggatgt tccctccaca gttcaaaaga cccccttcat caccaaccct gggtatgaca 56040
ccgaaaatgg tattcagctt cctggcacaa cccaccagca acccagtgtt gggcaacaaa 56100
tgatctttga ggaacatggc tttaggcgga caacgccacc cactgcggcc acccccgtca 56160
ggcttaggcc aagaccatac ctgccgaatg tagatgagga ggtccaaatc ggtcatgttc 56220
ccaggggaga cgtagactac cacctctatc ctcatgttcc gggcctcaat ccaaatgcct 56280
ctacaggaca ggaagctctc tctcagacaa ccatctcttg gacgccgttc caggagagtt 56340
ctgagtacat catttcatgc caaccagttg gcaccgacga agagccctta caggtacatg 56400
acagcccttg caaagtgtct ctctatgtaa ctgtgtcttc agaaacaacc acagcttcat 56460
gtctgatgcc cactgtctta gtcagggttt ctattcctgc acaaatatca tgaccaagaa 56520
gcaagttggg gaggaaaggg tttattcggc ttacacttcc atactgctgt tcatcaccaa 56580
aggaagtcag gactgcaatt caagcaggtc aggaagcagg agctgatgca gaagccatgg 56640
agggatgttc cttactggct tgcttcccct ggcttgctca gcctgctctc ttatagaacc 56700
caagtctacc agcccagaga tggtcccacc cacaaggggc ctttgcccct tgatcactaa 56760
ttgagaaaat accccatagc tggatctcat ggaggcattt cccccaacta aagctccttt 56820
ctttgtgata accccagcct gtgtcaagtt gacacataac accagccagt atacccaccc 56880
tcccagggca gaggctacga ctctgactgg aggttgtttg actcagagag catcactgag 56940
cgtcacgcag tagagaaaac gaaattcttt ttattattct catacactgg agactactta 57000
gtgagatgga tgaaacaatt atcttaggaa gtagaggaaa agtaatttat atgaagtttg 57060
aaatgccacc tttggcgtct gtccttgaag aggcacgctg ttacgtgtct aggaagacga 57120
ggtgaaccgt tggggaccag ctgttatgag agatcgattc tccaaaactc tcttctttaa 57180
tttgtcccac aggtgctaga atcaattttt attgtgttat ttttagaaag tggcagaaat 57240
tttaaaattg actgtaccct aggacattta ttagcttaga aactttagtc tggggatgtg 57300
ccggtatttt aggaaaaccc aagttctact gtgttggcac cttacatggc acatgttgtc 57360
tgtctgtggc actcatgttt atgaaggggc tttttttcca ggagttctag tggccacagg 57420
attcagagga agctggtata gctgagggtt tctgggaatt gtggaacacc taggtagaaa 57480
aatctagcag aaatgatttt tttttaagtt actcttttaa taatttttta tgtaccttgg 57540
tgttttgtct gcatgtatgt cagggtgagg atgtcagaag ctctggaact ggagttacag 57600
atggttgtga gccaccatgt ggctgctggg aattgaaccc aggtcctctg gaagagcatt 57660
tagtgctctt aaccactgag ccatctcccc aatcttaaaa cgatggtttt ttgcactcat 57720
ttaatatctc atcttgacta ggtgggagtc ctatacagcc ctgttctctc ccttcgtctg 57780
tttttaaatg ggagtggggg attgctcata gactaaggaa gctcatgccg attcatcatt 57840
gaaatgcttt ctccctgctt tggatgtata gttccaagtt cctggaactt ctaccagtgc 57900
gactctgact ggccttacca gaggggtcac ctacaacatc atagtggagg cactgcagaa 57960
ccagaggagg cacaaggttc gggaagaggt tgtgactgtg ggcaacgctg gtaggtacac 58020
tgctggcctg ttgaggcaca cgcttcttgc tggatcagcc cagagaagac ttggtctgtc 58080
gttctttgtt ggctttaaac ttaggaaaat gagattgcac aacagtcaga gatgtcccct 58140
tatgtaaccc atatgttcac caacacatat tgacaggatg ccaggcctgg gagggacatg 58200
aatattattt actctaatac atttttcccc tcctgttgag gatccagttg acagaggcaa 58260
tggttttttg taccttttac tattctctca tcccatactg tggtccactt aagcgttcct 58320
aacccgaacc gaacacctat aaacagtcct ccttggcaat cttaagtgat gacttaggtt 58380
ttgtacctaa tgtaaaatgt taccaatatt gccctttgct ttcctaagag cttcccattc 58440
caaatttcaa ctttatatac ttctttgttt tcttcttctt tagatttacg tattttaatg 58500
ttatgtgtac gggtgttttg cctgcatgta tgtgtgcaac atgcattcag cacccatgga 58560
ggccagaaga ggacaccggg tcctctggaa ctggacttat agagggttgt tagtgactat 58620
gtgggtgcta gaacctatgt aatgtcctgt ggaagaggag ccagtgacat aactcctgag 58680
ccatctctcc agccccttta tatgtgtctt aatacataaa ttatatatgt catgttatat 58740
acatgcaagc tcttaaaggt taaatggcca tcatacaaac gtaataaaga tgaaacgacc 58800
cccatgcagc cttttaataa aggttaaatg accagcatgc aacatcttaa taaaggttaa 58860
ataaatttaa tcctgaaaat ttttgataaa ggttgaatga ccctgactct gagaagcctt 58920
ttgaagccag tgatgtgtca tttggcttaa gttgcaatag ctaaagattc accaaggagc 58980
atgagttaag ggctaactga gactggatcc cgagtcctct taccctggaa gggctaactc 59040
ccactttttc cagggagcag gacttctggg taggaccact gccttctttt cagccttctt 59100
cctcttagcg aagactgcta ttatttgact cttcagttaa gcagttgcat gtctggcaat 59160
gcagaagtgg gcagatcttc tgtgttccat ccacagtaat tagcatttgc cttttgtggt 59220
ttcactagta aaatgccact tgaaagggat ttttttcaaa agcatagggg ttttgtggtt 59280
ttccacatca ttttcttgaa ggtgtgtgtg tggtgtgttt cagacagtcc tactgtattg 59340
tatgctgttt gtatatagtg tgctagactg aactgctatg tagcccaggc tcctaatgtt 59400
agggcagacc tcctagatat tttaaaatag tgaaccccca tgagagtttt agcccctttg 59460
ttttctttcc gactcctgtc tttaccaggt cctcttggtt tcaaaacatt ttggatagac 59520
tttttagttc ttccagaatg atggcttttg aaatattagg catttcaaat attgatttca 59580
tttgcacttt tgatttttac actattaaaa gaagctatcc acaagtagga tttttttttt 59640
cctgagacag ggtttctctg tatatagccc tggctgtcct ggaactcact ctgtagacta 59700
ggctggcttc gaactcagaa atccgcctgc ctctgcctcc caagtacggg gatgaaatct 59760
tgggaaaccc actgcagctt ttctacttat tcctaactgc acggtggtga tttctcttac 59820
ttgaaaatca ggtcttatct agttttacag taaccataag catctaggtt ttcaaactat 59880
ttagcaaaag aaaagctaca atgtaagtaa agattgtgtt ataatgctat ataaagatgc 59940
taagacattg actacagcaa agacgtatct aacaataatt gttaattatt gagtaacagt 60000
agttagtaag tcatctctgc atagtgatac tggtccagag ctttgattcc tcagtttcat 60060
gtagccttta caagatccaa aaaagtgggg ctagttatat tattatcccg taatagatga 60120
gagaagagag acagacaaat gttaattggc tccatgtact caggtgtctt ggggaagcac 60180
cactgcccat attctcagct agttaaaatg cctgacgatc tgcttcatgt catgagaaac 60240
agaagacggg aatgaaggaa gacgtccttt gaccctgctg tgacaagtgc ctactgactg 60300
catcaaagtg ttgccgatga gaacgtctgt gttgttagtg ctgattaggt cacaatatac 60360
agtatggccg tttccccatc aataaccgtc aataaaatgt cttctccttt ttttcctttc 60420
tccttctttt cttcatagtc agcgaaggcc tgaaccagcc tacagatgac tcatgctttg 60480
acccttacac ggtttcccat tacgccattg gagaggagtg ggagcggttg tctgacgctg 60540
gctttaagct cacatgccag tgcttgggct ttggcagtgg tcatttcaga tgcgattcat 60600
ctagtgagta gcttgcgttc cccaccctct cactcctcca tctcttctgg tctcatgcgt 60660
tcgcactagg tggccacgga aacatgtttg gcagactcgg gctcttccaa acatgatgca 60720
aacagaagta gactgtttga ctccaagtaa cattttgcat catagaagga tgatgggaaa 60780
ttttacttgt gcaatatgac tgcatttcaa gagttgtgta ctaatctaac tattccttac 60840
aaatatatct gtagtgttga tatgctcctt gtagtgttta gctctatgta aattgaagtt 60900
aaaaaatatc tcattagagt ttggtttaat tgagacaggc aggcagagac tccaaattct 60960
tttcagtctt tagtattgag taaggacaga ggtgaacatt tatactcaca aacaccactt 61020
tttcagcata accagatata catgcacaca tcacacacac acatacacac acacacatct 61080
cacaacccag atatcccaaa cattgctcgt ataaaggaaa atgtctctct gtatagccct 61140
ggctgtcctg gaagtcactt tgtagaccag gtcggcctca aactcagaaa tctgcctgcc 61200
tctgccttct gagtgctggg attaaaggcg tgtgccacca cgcctagttt gcattctaca 61260
tttaaggatc aagttcaggg ctggtgagct aggctaggca tcccatccct ggaacccagg 61320
tggtgccagt ccccacaaat tgtcccttga ccttcacata ttcctggggg gacactaagg 61380
cccatatgta catacatatg tacacacaca tgcaaatcaa taaatctaat aaatgttaag 61440
atcaactttg actgaaaaat aatttgattt tcaaatctta aagaggttaa aatttcaaat 61500
tattagtgaa aatgatccta tgagttatct atgtttctag agatttagta ttggagtata 61560
taaccattca ttctttgttt ttagagctat aattattatt agctttttaa tgtgcttttt 61620
ttatgtgttc atcatatatc atagatatcc acaggcctat ggacaattat aggtcccata 61680
ttccatggaa tgacatttaa tagatctcta aagttttttg tgtaacattt tcctttcctt 61740
tacatgaaat agcaaaatcc agactggttt caatgtgtgt tgttgggtag agcccagtgg 61800
gcaatatacc atgctgggga caggagggac accatttggc cttgaccagg tgctttttca 61860
gagagtgaac tgcactgaag tttgcatgtt tttcataact cagtacaaat gtggacgtat 61920
acaatgattt ttatccgtga gcctctgact caccagtctt tgctggatat gtcataactg 61980
ccttatacat ttgctcatcg tttaaggaag gctgaattgt taaagtggaa gaatcactgc 62040
cctggatgag ggtcgtaagt gaactctgtt tagtataaat cttagaggtt aaagggcatt 62100
tttacatctg ccattagaca cagctcgtgg tgacttctta ggacttgtct atttgtacaa 62160
caagcctgat tcatttcatt tgtctttatt ttgttggctg ttatattcgt tcgttcttca 62220
cttatatgaa tcaggtgaca ccagctgttt ttctctttaa tcttcttgtt tgtttttgtt 62280
tgtttgcttt tgtcgttgtt tcatgagaca gggtttctct gtgtgtccct ggatgtggta 62340
cactcagtct gtagacaggg ctgtcctcaa actcagagat ctgcctgcct ctgcctccct 62400
aatgctggga gcaaattcgt gcacgacgac gcctgccctc tctttaatgt ttaattaaac 62460
tattttgtat ctaggatctc tgcgaaccta aaatatatat tttttaattc tccaatccca 62520
ttttaatttt ccatatttgt aaaatttaaa aggagctgaa tgaatcactg gttggtcctc 62580
tgaaatgatc ttggtggtag tgttaagtct taacactggc ctggaagata ttaaatgtta 62640
tgatgaagaa atgcttcatc attagaaatg tgatcttgga cttcctgctc tgtatggatt 62700
ttcgtcctgt tccagtgttc tgcccatcct gtgagtcaga acacagagta actctctgcc 62760
tgcgatgtcc ctaccttcca gaatggtgcc atgacaacgg tgtcaactac aagatcggag 62820
agaagtggga tcggcaggga gaaaatggcc agcggatgag ctgcacatgc ctcgggaatg 62880
gaaagggaga attcaagtgt gatccccgta cgtcatccta aaaatgcttt ctagactttt 62940
taagtactcc catgttccta actgagccga aacacccatt tacaggctgg gctggacgtg 63000
gtgggcttgt cagtctgtgg ttggtaagtc agtagcttgc ttcagaaagt gaatcatgac 63060
tgaatggcac gtctaagcac tttagcactt tcacaacttg agcactttgg tcatctgcag 63120
tgaagtgcta tgtagactca gtttttaaaa cataacttca aagccaagca gtggtggcac 63180
atgtctttaa tcccagcact tgggaggcag aggcaggagg atttctgagt tggaggacag 63240
cttggtctac acagagagaa cctgtctcaa aaaaccaaaa aaaaaaaaag acttcaatcg 63300
ttccatctgg cctagtctac caaggctttg gaacatctcc ttgtgattca cctaagttga 63360
tgagatttgg cccgtgctca ttcaggtcga gggcagatgc atcaacttga gtgtacctga 63420
ttgtccttgg tcttacaact gttcctttct gctctgtgcc cacgtgcaga tgaagcaacg 63480
tgctatgacg atgggaagac ctaccatgta ggagaacagt ggcagaaaga atatctcgga 63540
gccatttgct cctgcacgtg tttcggaggc cagcgggtaa gcctggttgg cgtttagata 63600
aagcacttag gaggttgcag catggatatg ctttgtgcac aggagccttg ccttttagga 63660
agagtctcta agatgggtgt ctcagttagg gtttgcgttg ctttgaagag acaccatgac 63720
caaggtaact tttataaggg acaatattta attggggctg gcttacagtt tcagaggttc 63780
agtccattat catcatggca ggaagcttgg cagtgtgcag gcagacatgg tactctagaa 63840
agagctgagt gttctgcatc ttgaactgac aaagacagct agaagaaagc tttcttcttc 63900
attgggtaga gcttgaacat aggacctcaa agcccacccc cacagtgact cacttcctct 63960
aacaaagagt gccacttccc atggaccaag catattcaaa ccaccacaat gggtctgtcc 64020
ctcccagttg ataatagctt cagcaccttc tcccatgact aaaattctca ggctgccctg 64080
tttgtcctcg cctggagtgt agcactaagg ccccagctct gagctgatgg actagcatct 64140
gagtattgtt cacattttta ataatactgt gatctaagaa aatttaacta tttttgagcc 64200
tttgttcaat ctaaaaatta ttatcactct aatactgagc taagtaacaa tagacacaca 64260
gggaagggtg gccgttgctc ttgaggatat acttggaggc agcaaattag cataccctgc 64320
caagccaagc taatcacagg agattttgac gaatacagtt ctggatggcc tgcaatcagc 64380
aagaaggctt cctagaaaag agaaacataa accagccgcc tggggtttag gatagctatc 64440
attaagtggg gagggaagga agcagagact acatacttcc tggcctaggg agagctggcc 64500
cagcgaggca gtccttccgc tggaatcttt tggtaagaaa ttagatttga ggaggagact 64560
catggaaagc tgggaaagcc atcatttaag acagtaattc tcagtcatgt ctaacgtggg 64620
cccttcttca atataacaac aacttccact ccatctttta ataagtgaaa tatcaaaatg 64680
acttttaact taaatgtaat agggggctgg agatggtggc acatcccttt aatcccagca 64740
ctcagagtag tcagaggcag gtagatctct tgagtacgag ggcagcctgg tccacaaagc 64800
aagttccagg acagccaggg ctacacagag aaaccctgat tcataaaaac gaaacaaaca 64860
aaaaaagaaa atgatcgggc aggtcccaca agtttccctt tgacctccac acattttggg 64920
cacatgtgta tacatacaca tatgtaaata aatgtgctta attttttagg aattaaattg 64980
ttatgtaaag ggcttgacct taaagggtcc cagaaatctg gggcacaagg aataatgccc 65040
ctcaccccca cagtgaagtt cacccattaa tgctattggc attcatcaat gattaaaagt 65100
agcataatgg acaataacct tttaaaaaaa tgaatctggg agctggagaa atggctcagt 65160
gcttaatggg actcactgtt ctcctgggga cctggacttg gtttctctcc tcacatggtc 65220
cataaccacc attcccagaa gaactgacgt cctcatctgg cttccttgag catcatgcac 65280
acatggtgca cagacataca cacaggcaag cacttatcac ataaaataaa aacatatgat 65340
aaatcctttt taaaagaaga agggcagtta atgtggccac aagaaagact ctatgtatca 65400
tcacaacctt cttaggtctg ggcagccggc aggattgaca atctcgtttt atctgttatt 65460
catggagtgg actgtctgtc cctctgtctc tctgtctctt tctcagacac acagaagcag 65520
atcatatgac tcagtcatca tggtctgaat gagtggcttt gttgggaggc agattttagt 65580
ctttcttcac tccattcttg ttccctatga acgggaatct ctttgggtaa tgcctgtctc 65640
taaagttctg aaacatggtg gcggttgcta tggtctttga gaatcgttat tgattctgca 65700
agcaggccct ctgggaaata ggctcctaaa tggagaaata cgtcaaagat gtttaaatga 65760
ttctataaga aagtgattgt aggatttatt tatttttgag acagagtcta gtagccctga 65820
ctatcctgga acttgctatg tagagcaggc tggccttcag ctcacagaga tctacctgcc 65880
tctgggtgtg tgccaccact ctccagcctg gccttatttc ttcattttgt tgttgttgtt 65940
gttgttgttt tcaaccctaa atgtaaagtc ttgctagtta ggcaaaagat ggctaccaac 66000
atgaactccc ccattctgtg aacttcaagg actactttgc cccaagagtg cgcctctctc 66060
tgtgtccccc tagtgtccat ttctgtgtcc cctggggctt ctgctaatgg tgccatcgtt 66120
caccacatca gctccagatc ttcctcctcc cagctcagga gtgatgagaa agcaaatgtg 66180
tgccagcaaa actcaggaag aagcacaggc ccgctgtggt gtcttcctgt acccagcccc 66240
acctctggcc agagctaagg ctatatagta taggttaggg aggttttaga agggactgga 66300
aagagaatgt ggccaggtac ccagttctac ctgggaccca cggcgtcctt tctggttcct 66360
tccaagtcat tcctctcctt caccagaaag tgatggcatt tgtccccaca ctctcaagtc 66420
actgtgactg atttcgcagc cctaggggtc tgtgagaaat cttccaccta gagcagaaag 66480
cctaccaagg aggaaggtag gaccaaagat gagaagagca aaagaagtga ggaggatatt 66540
tcagcggaaa ggaaagcata tgtagacaga tgaataagcc aagatctatt gtaagagtta 66600
cgactgtaca caggcatcat tgcagtctcc tgattaactg cttgtactgc tgatgggcaa 66660
gagctgaaac tcagtcatga taccctcagg ttatcctaaa ccccatttaa cttcgtgtct 66720
ttcctctcag ggctggcgct gtgacaactg ccgtagacct ggggctgctg aacccagtcc 66780
cgatggcacc accggccaca cctacaacca gtatacacag agatacaatc agagaacaaa 66840
cactgtaagt gtacacatat ccccacccac ccccaccacc gtgactctcc ctgcatgcag 66900
ccaggggcag gtggatagat gcttttcttg aatgaaccaa atgagtttta tttggagata 66960
agtcttttgc tcatgagtcc agtcctcagg acccatccat gtaaaagagc taggcgctac 67020
agcaagtgct tataatctcc tcactgagga ggtagaaata gggtgtgggt ggtgtccctg 67080
gggctgtctg gccagccact gtagccttgt taatgaactt caggctcatg aacaaagcag 67140
acagcatttg cttgattaaa gttaactctt ggctccttat acacacaaag tcatgaatta 67200
attataactc gttataattt actaaatccc taagcattgt ctattgctca gtacattgct 67260
agtcttttga aactatttat ccttcctata aaacacctgt gacacaaatc tccactcaac 67320
cctccccgaa acacacacac ttttggtttt ccgagtattt gctactaatg tttgtcttct 67380
attttgacag aacgtaaatt gccccattga gtgcttcatg ccgctagatg tgcaagctga 67440
cagagacgat tctcgagagt aatctttcca gccccaccct acaagtgtct ctctaccaag 67500
gtcaatccac accccagtga tgttagcaga ccctccatct ttgagtggtc ctttcaccct 67560
taagcctttt gctctggagc catgttctca gcttcagcac aatttacagc ttctccaagc 67620
atcgccccgt gggatgtttt gagacttctc tcctcaatgg tgacagttgg tcaccctgtt 67680
ctgcttcagg gtttcagtac tgctcagtgt tgtttaagag aatcaaaagt tcttatggtt 67740
tggtctggga tcaataggga aacacaggta gccaactagg aggaaatgta ctgaatgcta 67800
gtacccaaga ccttgagcag gaaagtcacc cagacacctc tgctttcttt tgccatctga 67860
cctgcagcac tgtcaggaca tggcctgtgg ctgtgtgttc aaacacccct cccacaggac 67920
tcactttgtc ccaacaattc agattgccta gaaatacctt tctcttacct gtttgttatt 67980
tatcaatttt tcccagtatt tttatacgga aaaaattgta ttgaagacac tttgtatgca 68040
gttgataaga ggaattcagt ataattatgg ttggtgatta tttttataag cacatgccaa 68100
cgctttacta ctgtggaaag acaagtgttt taataaaaag atttacattc catgatgtgg 68160
acgtcatttc tttttttttt taacatcatg tgtttggaga gaaaaattgt cttcatgcat 68220
gtcctttttc ttttcgatgc tacaagcatg tgaagaggca ctgtgttggg ctggggtggt 68280
ttctgcacat gagcgcctgc ctggccttac agaagcactg atactttgcg tcattttgtg 68340
tcctcacttg tggttctgcc ttatcagatt taaatggatt caaatgtggg ctaagcttgc 68400
tagctagcac gttaggagta taaaggaaat aagattcgtg tgtgtgtgtg tgtgtgtgtg 68460
tacatacata caagtgtgtg tgtagctgct catgaaaatc aggaggccag aaggggatgc 68520
tgggtccctt agagctggat acaagtgttt gtgagataga tactgggatt tgaactcata 68580
acagagcggc aaatgccctc acctctccag ccctatagtt ctgtttaatc atcacaggcc 68640
tttgcttctt t 68651
<210> SEQ ID NO 30
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 30
gtaagaggtt atgtg 15
<210> SEQ ID NO 31
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 31
ttaatggtaa gaggt 15
<210> SEQ ID NO 32
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 32
aatgtctgtt aggcaaat 18
<210> SEQ ID NO 33
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 33
caatgtctgt taggcaaa 18
<210> SEQ ID NO 34
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 34
tcaatgtctg ttaggcaa 18
<210> SEQ ID NO 35
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 35
aatgtctgtt aggca 15
<210> SEQ ID NO 36
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 36
atcaatgtct gttaggca 18
<210> SEQ ID NO 37
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 37
caatgtctgt taggc 15
<210> SEQ ID NO 38
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 38
cgatcaatgt ctgttagg 18
<210> SEQ ID NO 39
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 39
atcaatgtct gttag 15
<210> SEQ ID NO 40
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 40
gcgatcaatg tctgttag 18
<210> SEQ ID NO 41
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 41
gatcaatgtc tgtta 15
<210> SEQ ID NO 42
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 42
ggcgatcaat gtctgtta 18
<210> SEQ ID NO 43
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 43
gccagtcctt taggg 15
<210> SEQ ID NO 44
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 44
gtgaatgcca gtcct 15
<210> SEQ ID NO 45
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 45
acatcagtga atgcc 15
<210> SEQ ID NO 46
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 46
acatccacat cagtg 15
<210> SEQ ID NO 47
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 47
gaatcgacat ccaca 15
<210> SEQ ID NO 48
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 48
ttgatggaat cgaca 15
<210> SEQ ID NO 49
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 49
gcaattttga tggaa 15
<210> SEQ ID NO 50
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 50
tcccaagcaa ttttg 15
<210> SEQ ID NO 51
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 51
gggctttccc aagca 15
<210> SEQ ID NO 52
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 52
ccctgtgggc tttcc 15
<210> SEQ ID NO 53
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 53
acttgcccct gtggg 15
<210> SEQ ID NO 54
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 54
ctggaaactt gcccc 15
<210> SEQ ID NO 55
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 55
ctgtacctgg aaact 15
<210> SEQ ID NO 56
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 56
gtcaccctgt acctg 15
<210> SEQ ID NO 57
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 57
gagtaggtca ccctg 15
<210> SEQ ID NO 58
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 58
gggctcgagt aggtc 15
<210> SEQ ID NO 59
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 59
tcctcagggc tcgag 15
<210> SEQ ID NO 60
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 60
attccatcct caggg 15
<210> SEQ ID NO 61
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 61
tcatggattc catcc 15
<210> SEQ ID NO 62
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 62
aatagctcat ggatt 15
<210> SEQ ID NO 63
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 63
gcagggaata gctca 15
<210> SEQ ID NO 64
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 64
tcaggtgcag ggaat 15
<210> SEQ ID NO 65
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 65
tcaccatcag gtgca 15
<210> SEQ ID NO 66
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 66
tcttcttcac catca 15
<210> SEQ ID NO 67
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 67
gcagtgtctt cttca 15
<210> SEQ ID NO 68
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 68
agctctgcag tgtct 15
<210> SEQ ID NO 69
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 69
ccttgcagct ctgca 15
<210> SEQ ID NO 70
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 70
ctgaggcctt gcagc 15
<210> SEQ ID NO 71
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 71
cccggtctga ggcct 15
<210> SEQ ID NO 72
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 72
tcagaacccg gtctg 15
<210> SEQ ID NO 73
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 73
gtgtactcag aaccc 15
<210> SEQ ID NO 74
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 74
ctgactgtgt actca 15
<210> SEQ ID NO 75
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 75
accacactga ctgtg 15
<210> SEQ ID NO 76
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 76
aaggcaacca cactg 15
<210> SEQ ID NO 77
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 77
tcgtgcaagg caacc 15
<210> SEQ ID NO 78
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 78
atatcatcgt gcaag 15
<210> SEQ ID NO 79
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 79
ctctccatat catcg 15
<210> SEQ ID NO 80
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 80
ggctggctct ccata 15
<210> SEQ ID NO 81
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 81
gattccaatc agggg 15
<210> SEQ ID NO 82
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 82
actggattcc aatca 15
<210> SEQ ID NO 83
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 83
tggactggat tccaa 15
<210> SEQ ID NO 84
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 84
cctgtggact ggattcca 18
<210> SEQ ID NO 85
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 85
ctgtggactg gattc 15
<210> SEQ ID NO 86
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 86
tacctgtgga ctgga 15
<210> SEQ ID NO 87
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 87
aacgatatac ctgtg 15
<210> SEQ ID NO 88
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 88
aattaatcat aaacc 15
<210> SEQ ID NO 89
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 89
ggtgcaatta accat 15
<210> SEQ ID NO 90
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 90
cctggtggtg caatt 15
<210> SEQ ID NO 91
<211> LENGTH: 20
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Primer
<400> SEQUENCE: 91
gccttgcacg atgatatgga 20
<210> SEQ ID NO 92
<211> LENGTH: 21
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Primer
<400> SEQUENCE: 92
tgtgggtgtg acctgagtga a 21
<210> SEQ ID NO 93
<211> LENGTH: 17
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Probe
<400> SEQUENCE: 93
attggaaccc agtccac 17
<210> SEQ ID NO 94
<211> LENGTH: 21
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Primer
<400> SEQUENCE: 94
gaatccaagc ggagagagtc a 21
<210> SEQ ID NO 95
<211> LENGTH: 23
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Primer
<400> SEQUENCE: 95
acatcagtga atgccagtcc ttt 23
<210> SEQ ID NO 96
<211> LENGTH: 30
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Probe
<400> SEQUENCE: 96
ttcagactgc agtaaccaac attgatcgcc 30
<210> SEQ ID NO 97
<211> LENGTH: 8374
<212> TYPE: DNA
<213> ORGANISM: Homo sapiens
<400> SEQUENCE: 97
gcccgcgccg gctgtgctgc acagggggag gagagggaac cccaggcgcg agcgggaaga 60
ggggacctgc agccacaact tctctggtcc tctgcatccc ttctgtccct ccacccgtcc 120
ccttccccac cctctggccc ccaccttctt ggaggcgaca acccccggga ggcattagaa 180
gggatttttc ccgcaggttg cgaagggaag caaacttggt ggcaacttgc ctcccggtgc 240
gggcgtctct cccccaccgt ctcaacatgc ttaggggtcc ggggcccggg ctgctgctgc 300
tggccgtcca gtgcctgggg acagcggtgc cctccacggg agcctcgaag agcaagaggc 360
aggctcagca aatggttcag ccccagtccc cggtggctgt cagtcaaagc aagcccggtt 420
gttatgacaa tggaaaacac tatcagataa atcaacagtg ggagcggacc tacctaggca 480
atgcgttggt ttgtacttgt tatggaggaa gccgaggttt taactgcgag agtaaacctg 540
aagctgaaga gacttgcttt gacaagtaca ctgggaacac ttaccgagtg ggtgacactt 600
atgagcgtcc taaagactcc atgatctggg actgtacctg catcggggct gggcgaggga 660
gaataagctg taccatcgca aaccgctgcc atgaaggggg tcagtcctac aagattggtg 720
acacctggag gagaccacat gagactggtg gttacatgtt agagtgtgtg tgtcttggta 780
atggaaaagg agaatggacc tgcaagccca tagctgagaa gtgttttgat catgctgctg 840
ggacttccta tgtggtcgga gaaacgtggg agaagcccta ccaaggctgg atgatggtag 900
attgtacttg cctgggagaa ggcagcggac gcatcacttg cacttctaga aatagatgca 960
acgatcagga cacaaggaca tcctatagaa ttggagacac ctggagcaag aaggataatc 1020
gaggaaacct gctccagtgc atctgcacag gcaacggccg aggagagtgg aagtgtgaga 1080
ggcacacctc tgtgcagacc acatcgagcg gatctggccc cttcaccgat gttcgtgcag 1140
ctgtttacca accgcagcct cacccccagc ctcctcccta tggccactgt gtcacagaca 1200
gtggtgtggt ctactctgtg gggatgcagt ggctgaagac acaaggaaat aagcaaatgc 1260
tttgcacgtg cctgggcaac ggagtcagct gccaagagac agctgtaacc cagacttacg 1320
gtggcaactc aaatggagag ccatgtgtct taccattcac ctacaatggc aggacgttct 1380
actcctgcac cacagaaggg cgacaggacg gacatctttg gtgcagcaca acttcgaatt 1440
atgagcagga ccagaaatac tctttctgca cagaccacac tgttttggtt cagactcgag 1500
gaggaaattc caatggtgcc ttgtgccact tccccttcct atacaacaac cacaattaca 1560
ctgattgcac ttctgagggc agaagagaca acatgaagtg gtgtgggacc acacagaact 1620
atgatgccga ccagaagttt gggttctgcc ccatggctgc ccacgaggaa atctgcacaa 1680
ccaatgaagg ggtcatgtac cgcattggag atcagtggga taagcagcat gacatgggtc 1740
acatgatgag gtgcacgtgt gttgggaatg gtcgtgggga atggacatgc attgcctact 1800
cgcagcttcg agatcagtgc attgttgatg acatcactta caatgtgaac gacacattcc 1860
acaagcgtca tgaagagggg cacatgctga actgtacatg cttcggtcag ggtcggggca 1920
ggtggaagtg tgatcccgtc gaccaatgcc aggattcaga gactgggacg ttttatcaaa 1980
ttggagattc atgggagaag tatgtgcatg gtgtcagata ccagtgctac tgctatggcc 2040
gtggcattgg ggagtggcat tgccaacctt tacagaccta tccaagctca agtggtcctg 2100
tcgaagtatt tatcactgag actccgagtc agcccaactc ccaccccatc cagtggaatg 2160
caccacagcc atctcacatt tccaagtaca ttctcaggtg gagacctaaa aattctgtag 2220
gccgttggaa ggaagctacc ataccaggcc acttaaactc ctacaccatc aaaggcctga 2280
agcctggtgt ggtatacgag ggccagctca tcagcatcca gcagtacggc caccaagaag 2340
tgactcgctt tgacttcacc accaccagca ccagcacacc tgtgaccagc aacaccgtga 2400
caggagagac gactcccttt tctcctcttg tggccacttc tgaatctgtg accgaaatca 2460
cagccagtag ctttgtggtc tcctgggtct cagcttccga caccgtgtcg ggattccggg 2520
tggaatatga gctgagtgag gagggagatg agccacagta cctggatctt ccaagcacag 2580
ccacttctgt gaacatccct gacctgcttc ctggccgaaa atacattgta aatgtctatc 2640
agatatctga ggatggggag cagagtttga tcctgtctac ttcacaaaca acagcgcctg 2700
atgcccctcc tgacccgact gtggaccaag ttgatgacac ctcaattgtt gttcgctgga 2760
gcagacccca ggctcccatc acagggtaca gaatagtcta ttcgccatca gtagaaggta 2820
gcagcacaga actcaacctt cctgaaactg caaactccgt caccctcagt gacttgcaac 2880
ctggtgttca gtataacatc actatctatg ctgtggaaga aaatcaagaa agtacacctg 2940
ttgtcattca acaagaaacc actggcaccc cacgctcaga tacagtgccc tctcccaggg 3000
acctgcagtt tgtggaagtg acagacgtga aggtcaccat catgtggaca ccgcctgaga 3060
gtgcagtgac cggctaccgt gtggatgtga tccccgtcaa cctgcctggc gagcacgggc 3120
agaggctgcc catcagcagg aacacctttg cagaagtcac cgggctgtcc cctggggtca 3180
cctattactt caaagtcttt gcagtgagcc atgggaggga gagcaagcct ctgactgctc 3240
aacagacaac caaactggat gctcccacta acctccagtt tgtcaatgaa actgattcta 3300
ctgtcctggt gagatggact ccacctcggg cccagataac aggataccga ctgaccgtgg 3360
gccttacccg aagaggacag cccaggcagt acaatgtggg tccctctgtc tccaagtacc 3420
cactgaggaa tctgcagcct gcatctgagt acaccgtatc cctcgtggcc ataaagggca 3480
accaagagag ccccaaagcc actggagtct ttaccacact gcagcctggg agctctattc 3540
caccttacaa caccgaggtg actgagacca ccattgtgat cacatggacg cctgctccaa 3600
gaattggttt taagctgggt gtacgaccaa gccagggagg agaggcacca cgagaagtga 3660
cttcagactc aggaagcatc gttgtgtccg gcttgactcc aggagtagaa tacgtctaca 3720
ccatccaagt cctgagagat ggacaggaaa gagatgcgcc aattgtaaac aaagtggtga 3780
caccattgtc tccaccaaca aacttgcatc tggaggcaaa ccctgacact ggagtgctca 3840
cagtctcctg ggagaggagc accaccccag acattactgg ttatagaatt accacaaccc 3900
ctacaaacgg ccagcaggga aattctttgg aagaagtggt ccatgctgat cagagctcct 3960
gcacttttga taacctgagt cccggcctgg agtacaatgt cagtgtttac actgtcaagg 4020
atgacaagga aagtgtccct atctctgata ccatcatccc agctgttcct cctcccactg 4080
acctgcgatt caccaacatt ggtccagaca ccatgcgtgt cacctgggct ccacccccat 4140
ccattgattt aaccaacttc ctggtgcgtt actcacctgt gaaaaatgag gaagatgttg 4200
cagagttgtc aatttctcct tcagacaatg cagtggtctt aacaaatctc ctgcctggta 4260
cagaatatgt agtgagtgtc tccagtgtct acgaacaaca tgagagcaca cctcttagag 4320
gaagacagaa aacaggtctt gattccccaa ctggcattga cttttctgat attactgcca 4380
actcttttac tgtgcactgg attgctcctc gagccaccat cactggctac aggatccgcc 4440
atcatcccga gcacttcagt gggagacctc gagaagatcg ggtgccccac tctcggaatt 4500
ccatcaccct caccaacctc actccaggca cagagtatgt ggtcagcatc gttgctctta 4560
atggcagaga ggaaagtccc ttattgattg gccaacaatc aacagtttct gatgttccga 4620
gggacctgga agttgttgct gcgaccccca ccagcctact gatcagctgg gatgctcctg 4680
ctgtcacagt gagatattac aggatcactt acggagagac aggaggaaat agccctgtcc 4740
aggagttcac tgtgcctggg agcaagtcta cagctaccat cagcggcctt aaacctggag 4800
ttgattatac catcactgtg tatgctgtca ctggccgtgg agacagcccc gcaagcagca 4860
agccaatttc cattaattac cgaacagaaa ttgacaaacc atcccagatg caagtgaccg 4920
atgttcagga caacagcatt agtgtcaagt ggctgccttc aagttcccct gttactggtt 4980
acagagtaac caccactccc aaaaatggac caggaccaac aaaaactaaa actgcaggtc 5040
cagatcaaac agaaatgact attgaaggct tgcagcccac agtggagtat gtggttagtg 5100
tctatgctca gaatccaagc ggagagagtc agcctctggt tcagactgca gtaaccaaca 5160
ttgatcgccc taaaggactg gcattcactg atgtggatgt cgattccatc aaaattgctt 5220
gggaaagccc acaggggcaa gtttccaggt acagggtgac ctactcgagc cctgaggatg 5280
gaatccatga gctattccct gcacctgatg gtgaagaaga cactgcagag ctgcaaggcc 5340
tcagaccggg ttctgagtac acagtcagtg tggttgcctt gcacgatgat atggagagcc 5400
agcccctgat tggaacccag tccacagcta ttcctgcacc aactgacctg aagttcactc 5460
aggtcacacc cacaagcctg agcgcccagt ggacaccacc caatgttcag ctcactggat 5520
atcgagtgcg ggtgaccccc aaggagaaga ccggaccaat gaaagaaatc aaccttgctc 5580
ctgacagctc atccgtggtt gtatcaggac ttatggtggc caccaaatat gaagtgagtg 5640
tctatgctct taaggacact ttgacaagca gaccagctca gggagttgtc accactctgg 5700
agaatgtcag cccaccaaga agggctcgtg tgacagatgc tactgagacc accatcacca 5760
ttagctggag aaccaagact gagacgatca ctggcttcca agttgatgcc gttccagcca 5820
atggccagac tccaatccag agaaccatca agccagatgt cagaagctac accatcacag 5880
gtttacaacc aggcactgac tacaagatct acctgtacac cttgaatgac aatgctcgga 5940
gctcccctgt ggtcatcgac gcctccactg ccattgatgc accatccaac ctgcgtttcc 6000
tggccaccac acccaattcc ttgctggtat catggcagcc gccacgtgcc aggattaccg 6060
gctacatcat caagtatgag aagcctgggt ctcctcccag agaagtggtc cctcggcccc 6120
gccctggtgt cacagaggct actattactg gcctggaacc gggaaccgaa tatacaattt 6180
atgtcattgc cctgaagaat aatcagaaga gcgagcccct gattggaagg aaaaagacag 6240
ttcaaaagac ccctttcgtc acccaccctg ggtatgacac tggaaatggt attcagcttc 6300
ctggcacttc tggtcagcaa cccagtgttg ggcaacaaat gatctttgag gaacatggtt 6360
ttaggcggac cacaccgccc acaacggcca cccccataag gcataggcca agaccatacc 6420
cgccgaatgt aggacaagaa gctctctctc agacaaccat ctcatgggcc ccattccagg 6480
acacttctga gtacatcatt tcatgtcatc ctgttggcac tgatgaagaa cccttacagt 6540
tcagggttcc tggaacttct accagtgcca ctctgacagg cctcaccaga ggtgccacct 6600
acaacatcat agtggaggca ctgaaagacc agcagaggca taaggttcgg gaagaggttg 6660
ttaccgtggg caactctgtc aacgaaggct tgaaccaacc tacggatgac tcgtgctttg 6720
acccctacac agtttcccat tatgccgttg gagatgagtg ggaacgaatg tctgaatcag 6780
gctttaaact gttgtgccag tgcttaggct ttggaagtgg tcatttcaga tgtgattcat 6840
ctagatggtg ccatgacaat ggtgtgaact acaagattgg agagaagtgg gaccgtcagg 6900
gagaaaatgg ccagatgatg agctgcacat gtcttgggaa cggaaaagga gaattcaagt 6960
gtgaccctca tgaggcaacg tgttatgatg atgggaagac ataccacgta ggagaacagt 7020
ggcagaagga atatctcggt gccatttgct cctgcacatg ctttggaggc cagcggggct 7080
ggcgctgtga caactgccgc agacctgggg gtgaacccag tcccgaaggc actactggcc 7140
agtcctacaa ccagtattct cagagatacc atcagagaac aaacactaat gttaattgcc 7200
caattgagtg cttcatgcct ttagatgtac aggctgacag agaagattcc cgagagtaaa 7260
tcatctttcc aatccagagg aacaagcatg tctctctgcc aagatccatc taaactggag 7320
tgatgttagc agacccagct tagagttctt ctttctttct taagcccttt gctctggagg 7380
aagttctcca gcttcagctc aactcacagc ttctccaagc atcaccctgg gagtttcctg 7440
agggttttct cataaatgag ggctgcacat tgcctgttct gcttcgaagt attcaatacc 7500
gctcagtatt ttaaatgaag tgattctaag atttggtttg ggatcaatag gaaagcatat 7560
gcagccaacc aagatgcaaa tgttttgaaa tgatatgacc aaaattttaa gtaggaaagt 7620
cacccaaaca cttctgcttt cacttaagtg tctggcccgc aatactgtag gaacaagcat 7680
gatcttgtta ctgtgatatt ttaaatatcc acagtactca ctttttccaa atgatcctag 7740
taattgccta gaaatatctt tctcttacct gttatttatc aatttttccc agtattttta 7800
tacggaaaaa attgtattga aaacacttag tatgcagttg ataagaggaa tttggtataa 7860
ttatggtggg tgattatttt ttatactgta tgtgccaaag ctttactact gtggaaagac 7920
aactgtttta ataaaagatt tacattccac aacttgaagt tcatctattt gatataagac 7980
accttcgggg gaaataattc ctgtgaatat tctttttcaa ttcagcaaac atttgaaaat 8040
ctatgatgtg caagtctaat tgttgatttc agtacaagat tttctaaatc agttgctaca 8100
aaaactgatt ggtttttgtc acttcatctc ttcactaatg gagatagctt tacactttct 8160
gctttaatag atttaagtgg accccaatat ttattaaaat tgctagttta ccgttcagaa 8220
gtataataga aataatcttt agttgctctt ttctaaccat tgtaattctt cccttcttcc 8280
ctccaccttt ccttcattga ataaacctct gttcaaagag attgcctgca agggaaataa 8340
aaatgactaa gatattaaaa aaaaaaaaaa aaaa 8374
<210> SEQ ID NO 98
<211> LENGTH: 24
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Primer
<400> SEQUENCE: 98
aaactgcagt gaccaacatt gatc 24
<210> SEQ ID NO 99
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Primer
<400> SEQUENCE: 99
cttgcccctg tgggcttt 18
<210> SEQ ID NO 100
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Probe
<400> SEQUENCE: 100
ctgatgtgga tgtcgatt 18
<210> SEQ ID NO 101
<211> LENGTH: 17
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Primer
<400> SEQUENCE: 101
gccagcccct gattgga 17
<210> SEQ ID NO 102
<211> LENGTH: 20
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Primer
<400> SEQUENCE: 102
ccggtagcca gtgagctgaa 20
<210> SEQ ID NO 103
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Probe
<400> SEQUENCE: 103
caccaatctg aagttc 16
<210> SEQ ID NO 104
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 104
gcaaattaat ggtaa 15
<210> SEQ ID NO 105
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 105
cgatcaatgt ctgtt 15
<210> SEQ ID NO 106
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 106
tccataccat gcaaa 15
<210> SEQ ID NO 107
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 107
atatttccat accat 15
<210> SEQ ID NO 108
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 108
caagcatatt tccat 15
<210> SEQ ID NO 109
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 109
tgaaacaagc atatt 15
<210> SEQ ID NO 110
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 110
agttgtgaaa caagc 15
<210> SEQ ID NO 111
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 111
aagcaagttg tgaaa 15
<210> SEQ ID NO 112
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 112
gtgaaaagca agttg 15
<210> SEQ ID NO 113
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 113
gttatgtgaa aagca 15
<210> SEQ ID NO 114
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 114
aagaggttat gtgaa 15
<210> SEQ ID NO 115
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 115
atggtaagag gttat 15
<210> SEQ ID NO 116
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 116
aattaatggt aagag 15
<210> SEQ ID NO 117
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 117
aggcaaatta atggt 15
<210> SEQ ID NO 118
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 118
ctgttaggca aatta 15
<210> SEQ ID NO 119
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 119
tagggcgatc aatgt 15
<210> SEQ ID NO 120
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 120
tcctttaggg cgatc 15
<210> SEQ ID NO 121
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 121
tgaatgccag tcctt 15
<210> SEQ ID NO 122
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 122
atcagtgaat gccag 15
<210> SEQ ID NO 123
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 123
tccacatcag tgaat 15
<210> SEQ ID NO 124
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 124
cgacatccac atcag 15
<210> SEQ ID NO 125
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 125
ggaatcgaca tccac 15
<210> SEQ ID NO 126
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 126
caattttgat ggaat 15
<210> SEQ ID NO 127
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 127
ccaagcaatt ttgat 15
<210> SEQ ID NO 128
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 128
ctttcccaag caatt 15
<210> SEQ ID NO 129
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 129
gtgggctttc ccaag 15
<210> SEQ ID NO 130
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 130
cccctgtggg ctttc 15
<210> SEQ ID NO 131
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 131
tggaaacttg cccct 15
<210> SEQ ID NO 132
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 132
gtacctggaa acttg 15
<210> SEQ ID NO 133
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 133
accctgtacc tggaa 15
<210> SEQ ID NO 134
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 134
aggtcaccct gtacc 15
<210> SEQ ID NO 135
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 135
cgagtaggtc accct 15
<210> SEQ ID NO 136
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 136
cctcagggct cgagt 15
<210> SEQ ID NO 137
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 137
tccatcctca gggct 15
<210> SEQ ID NO 138
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 138
cggattccat cctca 15
<210> SEQ ID NO 139
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 139
gctcccggat tccat 15
<210> SEQ ID NO 140
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 140
gaaaagctcc cggat 15
<210> SEQ ID NO 141
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 141
gcagggaaaa gctcc 15
<210> SEQ ID NO 142
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 142
caggtgcagg gaaaa 15
<210> SEQ ID NO 143
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 143
accatcaggt gcagg 15
<210> SEQ ID NO 144
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 144
tcttcaccat caggt 15
<210> SEQ ID NO 145
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 145
tgtcgtcttc accat 15
<210> SEQ ID NO 146
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 146
tgcagtgtcg tcttc 15
<210> SEQ ID NO 147
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 147
agctctgcag tgtcg 15
<210> SEQ ID NO 148
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 148
cctgcagctc tgcag 15
<210> SEQ ID NO 149
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 149
gaggccctgc agctc 15
<210> SEQ ID NO 150
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 150
ggcctgaggc cctgc 15
<210> SEQ ID NO 151
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 151
accccggcct gaggc 15
<210> SEQ ID NO 152
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 152
ctcagacccc ggcct 15
<210> SEQ ID NO 153
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 153
gtgtactcag acccc 15
<210> SEQ ID NO 154
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 154
tgactgtgta ctcag 15
<210> SEQ ID NO 155
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 155
cacactgact gtgta 15
<210> SEQ ID NO 156
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 156
gcaaccacac tgact 15
<210> SEQ ID NO 157
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 157
gcaaggcaac cacac 15
<210> SEQ ID NO 158
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 158
atcgtgcaag gcaac 15
<210> SEQ ID NO 159
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 159
tctccatatc atcgt 15
<210> SEQ ID NO 160
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 160
ctggctctcc atatc 15
<210> SEQ ID NO 161
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 161
gactggattc caatc 15
<210> SEQ ID NO 162
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 162
tatacctgtg gactg 15
<210> SEQ ID NO 163
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 163
cggttaacga tatac 15
<210> SEQ ID NO 164
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 164
gggtgcggtt aacga 15
<210> SEQ ID NO 165
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 165
gtggtgggtg cggtt 15
<210> SEQ ID NO 166
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 166
cccgggtggt gggtg 15
<210> SEQ ID NO 167
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 167
aagcacccgg gtggt 15
<210> SEQ ID NO 168
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 168
cccagaagca cccgg 15
<210> SEQ ID NO 169
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 169
ctgttcccag aagca 15
<210> SEQ ID NO 170
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 170
agccactgtt cccag 15
<210> SEQ ID NO 171
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 171
cataaagcca ctgtt 15
<210> SEQ ID NO 172
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 172
caaggcataa agcca 15
<210> SEQ ID NO 173
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 173
gccagcaagg cataa 15
<210> SEQ ID NO 174
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 174
ataacgccag caagg 15
<210> SEQ ID NO 175
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 175
aaagtataac gccag 15
<210> SEQ ID NO 176
<211> LENGTH: 15
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 176
ccagtaaagt ataac 15
<210> SEQ ID NO 177
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 177
gttaggcaaa ttaatggt 18
<210> SEQ ID NO 178
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 178
tgttaggcaa attaatgg 18
<210> SEQ ID NO 179
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 179
ctgttaggca aattaatg 18
<210> SEQ ID NO 180
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 180
tctgttaggc aaattaat 18
<210> SEQ ID NO 181
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 181
gtctgttagg caaattaa 18
<210> SEQ ID NO 182
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 182
tgtctgttag gcaaatta 18
<210> SEQ ID NO 183
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 183
atgtctgtta ggcaaatt 18
<210> SEQ ID NO 184
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 184
gatcaatgtc tgttaggc 18
<210> SEQ ID NO 185
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 185
gggcgatcaa tgtctgtt 18
<210> SEQ ID NO 186
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 186
agggcgatca atgtctgt 18
<210> SEQ ID NO 187
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 187
tagggcgatc aatgtctg 18
<210> SEQ ID NO 188
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 188
ttagggcgat caatgtct 18
<210> SEQ ID NO 189
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 189
tttagggcga tcaatgtc 18
<210> SEQ ID NO 190
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 190
ctttagggcg atcaatgt 18
<210> SEQ ID NO 191
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 191
cctttagggc gatcaatg 18
<210> SEQ ID NO 192
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 192
tcctttaggg cgatcaat 18
<210> SEQ ID NO 193
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 193
gtcctttagg gcgatcaa 18
<210> SEQ ID NO 194
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 194
agtcctttag ggcgatca 18
<210> SEQ ID NO 195
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 195
cagtccttta gggcgatc 18
<210> SEQ ID NO 196
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 196
ggaatcgaca tccacatc 18
<210> SEQ ID NO 197
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 197
tggaatcgac atccacat 18
<210> SEQ ID NO 198
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 198
atggaatcga catccaca 18
<210> SEQ ID NO 199
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 199
gatggaatcg acatccac 18
<210> SEQ ID NO 200
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 200
tgatggaatc gacatcca 18
<210> SEQ ID NO 201
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 201
ttgatggaat cgacatcc 18
<210> SEQ ID NO 202
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 202
tttgatggaa tcgacatc 18
<210> SEQ ID NO 203
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 203
caattttgat ggaatcga 18
<210> SEQ ID NO 204
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 204
gcaattttga tggaatcg 18
<210> SEQ ID NO 205
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 205
agcaattttg atggaatc 18
<210> SEQ ID NO 206
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 206
aagcaatttt gatggaat 18
<210> SEQ ID NO 207
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 207
caagcaattt tgatggaa 18
<210> SEQ ID NO 208
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 208
ccaagcaatt ttgatgga 18
<210> SEQ ID NO 209
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 209
cccaagcaat tttgatgg 18
<210> SEQ ID NO 210
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 210
gtcaccctgt acctggaa 18
<210> SEQ ID NO 211
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 211
ggtcaccctg tacctgga 18
<210> SEQ ID NO 212
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 212
aggtcaccct gtacctgg 18
<210> SEQ ID NO 213
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 213
taggtcaccc tgtacctg 18
<210> SEQ ID NO 214
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 214
gtaggtcacc ctgtacct 18
<210> SEQ ID NO 215
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 215
agtaggtcac cctgtacc 18
<210> SEQ ID NO 216
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 216
gagtaggtca ccctgtac 18
<210> SEQ ID NO 217
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 217
cgagtaggtc accctgta 18
<210> SEQ ID NO 218
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 218
tcgagtaggt caccctgt 18
<210> SEQ ID NO 219
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 219
ctcgagtagg tcaccctg 18
<210> SEQ ID NO 220
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 220
gctcgagtag gtcaccct 18
<210> SEQ ID NO 221
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 221
ggctcgagta ggtcaccc 18
<210> SEQ ID NO 222
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 222
gggctcgagt aggtcacc 18
<210> SEQ ID NO 223
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 223
agggctcgag taggtcac 18
<210> SEQ ID NO 224
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 224
cagggctcga gtaggtca 18
<210> SEQ ID NO 225
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 225
tcagggctcg agtaggtc 18
<210> SEQ ID NO 226
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 226
ctcagggctc gagtaggt 18
<210> SEQ ID NO 227
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 227
cctcagggct cgagtagg 18
<210> SEQ ID NO 228
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 228
tcctcagggc tcgagtag 18
<210> SEQ ID NO 229
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 229
atcctcaggg ctcgagta 18
<210> SEQ ID NO 230
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 230
catcctcagg gctcgagt 18
<210> SEQ ID NO 231
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 231
ccatcctcag ggctcgag 18
<210> SEQ ID NO 232
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 232
tccatcctca gggctcga 18
<210> SEQ ID NO 233
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 233
ttccatcctc agggctcg 18
<210> SEQ ID NO 234
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 234
attccatcct cagggctc 18
<210> SEQ ID NO 235
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 235
gattccatcc tcagggct 18
<210> SEQ ID NO 236
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 236
ggattccatc ctcagggc 18
<210> SEQ ID NO 237
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 237
cggattccat cctcaggg 18
<210> SEQ ID NO 238
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 238
ccggattcca tcctcagg 18
<210> SEQ ID NO 239
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 239
cccggattcc atcctcag 18
<210> SEQ ID NO 240
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 240
tcccggattc catcctca 18
<210> SEQ ID NO 241
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 241
ctcccggatt ccatcctc 18
<210> SEQ ID NO 242
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 242
gctcccggat tccatcct 18
<210> SEQ ID NO 243
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 243
agctcccgga ttccatcc 18
<210> SEQ ID NO 244
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 244
aagctcccgg attccatc 18
<210> SEQ ID NO 245
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 245
aaagctcccg gattccat 18
<210> SEQ ID NO 246
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 246
aaaagctccc ggattcca 18
<210> SEQ ID NO 247
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 247
gaaaagctcc cggattcc 18
<210> SEQ ID NO 248
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 248
ggaaaagctc ccggattc 18
<210> SEQ ID NO 249
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 249
gggaaaagct cccggatt 18
<210> SEQ ID NO 250
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 250
agggaaaagc tcccggat 18
<210> SEQ ID NO 251
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 251
cagggaaaag ctcccgga 18
<210> SEQ ID NO 252
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 252
gcagggaaaa gctcccgg 18
<210> SEQ ID NO 253
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 253
tgcagggaaa agctcccg 18
<210> SEQ ID NO 254
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 254
gtgcagggaa aagctccc 18
<210> SEQ ID NO 255
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 255
ggtgcaggga aaagctcc 18
<210> SEQ ID NO 256
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 256
aggtgcaggg aaaagctc 18
<210> SEQ ID NO 257
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 257
caggtgcagg gaaaagct 18
<210> SEQ ID NO 258
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 258
tcaggtgcag ggaaaagc 18
<210> SEQ ID NO 259
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 259
atcaggtgca gggaaaag 18
<210> SEQ ID NO 260
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 260
catcaggtgc agggaaaa 18
<210> SEQ ID NO 261
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 261
ccatcaggtg cagggaaa 18
<210> SEQ ID NO 262
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 262
accatcaggt gcagggaa 18
<210> SEQ ID NO 263
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 263
caccatcagg tgcaggga 18
<210> SEQ ID NO 264
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 264
tcaccatcag gtgcaggg 18
<210> SEQ ID NO 265
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 265
ttcaccatca ggtgcagg 18
<210> SEQ ID NO 266
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 266
cttcaccatc aggtgcag 18
<210> SEQ ID NO 267
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 267
tcttcaccat caggtgca 18
<210> SEQ ID NO 268
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 268
gtcttcacca tcaggtgc 18
<210> SEQ ID NO 269
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 269
cgtcttcacc atcaggtg 18
<210> SEQ ID NO 270
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 270
tcgtcttcac catcaggt 18
<210> SEQ ID NO 271
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 271
gtcgtcttca ccatcagg 18
<210> SEQ ID NO 272
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 272
tgtcgtcttc accatcag 18
<210> SEQ ID NO 273
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 273
gtgtcgtctt caccatca 18
<210> SEQ ID NO 274
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 274
agtgtcgtct tcaccatc 18
<210> SEQ ID NO 275
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 275
cagtgtcgtc ttcaccat 18
<210> SEQ ID NO 276
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 276
gcagtgtcgt cttcacca 18
<210> SEQ ID NO 277
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 277
tgcagtgtcg tcttcacc 18
<210> SEQ ID NO 278
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 278
ctgcagtgtc gtcttcac 18
<210> SEQ ID NO 279
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 279
tctgcagtgt cgtcttca 18
<210> SEQ ID NO 280
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 280
ctctgcagtg tcgtcttc 18
<210> SEQ ID NO 281
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 281
gctctgcagt gtcgtctt 18
<210> SEQ ID NO 282
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 282
agctctgcag tgtcgtct 18
<210> SEQ ID NO 283
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 283
cagctctgca gtgtcgtc 18
<210> SEQ ID NO 284
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 284
gcagctctgc agtgtcgt 18
<210> SEQ ID NO 285
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 285
tgcagctctg cagtgtcg 18
<210> SEQ ID NO 286
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 286
ctgcagctct gcagtgtc 18
<210> SEQ ID NO 287
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 287
cctgcagctc tgcagtgt 18
<210> SEQ ID NO 288
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 288
ccctgcagct ctgcagtg 18
<210> SEQ ID NO 289
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 289
gccctgcagc tctgcagt 18
<210> SEQ ID NO 290
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 290
ggccctgcag ctctgcag 18
<210> SEQ ID NO 291
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 291
aggccctgca gctctgca 18
<210> SEQ ID NO 292
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 292
gaggccctgc agctctgc 18
<210> SEQ ID NO 293
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 293
tgaggccctg cagctctg 18
<210> SEQ ID NO 294
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 294
ctgaggccct gcagctct 18
<210> SEQ ID NO 295
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 295
cctgaggccc tgcagctc 18
<210> SEQ ID NO 296
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 296
gcaaggcaac cacactga 18
<210> SEQ ID NO 297
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 297
tgcaaggcaa ccacactg 18
<210> SEQ ID NO 298
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 298
gtgcaaggca accacact 18
<210> SEQ ID NO 299
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 299
cgtgcaaggc aaccacac 18
<210> SEQ ID NO 300
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 300
tcgtgcaagg caaccaca 18
<210> SEQ ID NO 301
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 301
atcgtgcaag gcaaccac 18
<210> SEQ ID NO 302
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 302
catcgtgcaa ggcaacca 18
<210> SEQ ID NO 303
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 303
atatcatcgt gcaaggca 18
<210> SEQ ID NO 304
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 304
catatcatcg tgcaaggc 18
<210> SEQ ID NO 305
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 305
ccatatcatc gtgcaagg 18
<210> SEQ ID NO 306
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 306
tccatatcat cgtgcaag 18
<210> SEQ ID NO 307
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 307
ctccatatca tcgtgcaa 18
<210> SEQ ID NO 308
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 308
tctccatatc atcgtgca 18
<210> SEQ ID NO 309
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 309
ctctccatat catcgtgc 18
<210> SEQ ID NO 310
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 310
gctctccata tcatcgtg 18
<210> SEQ ID NO 311
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 311
ggctctccat atcatcgt 18
<210> SEQ ID NO 312
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 312
tggctctcca tatcatcg 18
<210> SEQ ID NO 313
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 313
ctggctctcc atatcatc 18
<210> SEQ ID NO 314
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 314
gctggctctc catatcat 18
<210> SEQ ID NO 315
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 315
atatacctgt ggactgga 18
<210> SEQ ID NO 316
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 316
gatatacctg tggactgg 18
<210> SEQ ID NO 317
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 317
cgatatacct gtggactg 18
<210> SEQ ID NO 318
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 318
acgatatacc tgtggact 18
<210> SEQ ID NO 319
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 319
aacgatatac ctgtggac 18
<210> SEQ ID NO 320
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 320
taacgatata cctgtgga 18
<210> SEQ ID NO 321
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 321
ttaacgatat acctgtgg 18
<210> SEQ ID NO 322
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 322
gttaacgata tacctgtg 18
<210> SEQ ID NO 323
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 323
ggttaacgat atacctgt 18
<210> SEQ ID NO 324
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 324
cggttaacga tatacctg 18
<210> SEQ ID NO 325
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 325
gcggttaacg atatacct 18
<210> SEQ ID NO 326
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 326
tgcggttaac gatatacc 18
<210> SEQ ID NO 327
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 327
gtgcggttaa cgatatac 18
<210> SEQ ID NO 328
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 328
ggtgcggtta acgatata 18
<210> SEQ ID NO 329
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 329
gggtgcggtt aacgatat 18
<210> SEQ ID NO 330
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 330
agggaaaagc tcccgg 16
<210> SEQ ID NO 331
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 331
gtcaccctgt acctgg 16
<210> SEQ ID NO 332
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 332
gtaggtcacc ctgtac 16
<210> SEQ ID NO 333
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 333
tcgagtaggt caccct 16
<210> SEQ ID NO 334
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 334
gggctcgagt aggtca 16
<210> SEQ ID NO 335
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 335
ctcagggctc gagtag 16
<210> SEQ ID NO 336
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 336
catcctcagg gctcga 16
<210> SEQ ID NO 337
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 337
attccatcct cagggc 16
<210> SEQ ID NO 338
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 338
ccggattcca tcctca 16
<210> SEQ ID NO 339
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 339
gctcccggat tccatc 16
<210> SEQ ID NO 340
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 340
aaaagctccc ggattc 16
<210> SEQ ID NO 341
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 341
gtgcagggaa aagctc 16
<210> SEQ ID NO 342
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 342
tcaggtgcag ggaaaa 16
<210> SEQ ID NO 343
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 343
accatcaggt gcaggg 16
<210> SEQ ID NO 344
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 344
cttcaccatc aggtgc 16
<210> SEQ ID NO 345
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 345
tcgtcttcac catcag 16
<210> SEQ ID NO 346
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 346
agtgtcgtct tcacca 16
<210> SEQ ID NO 347
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 347
ctgcagtgtc gtcttc 16
<210> SEQ ID NO 348
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 348
agctctgcag tgtcgt 16
<210> SEQ ID NO 349
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 349
ctgcagctct gcagtg 16
<210> SEQ ID NO 350
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 350
ggccctgcag ctctgc 16
<210> SEQ ID NO 351
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 351
ctgaggccct gcagct 16
<210> SEQ ID NO 352
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 352
cggcctgagg ccctgc 16
<210> SEQ ID NO 353
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 353
accccggcct gaggcc 16
<210> SEQ ID NO 354
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 354
tcagaccccg gcctga 16
<210> SEQ ID NO 355
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 355
gtactcagac cccggc 16
<210> SEQ ID NO 356
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 356
ctgtgtactc agaccc 16
<210> SEQ ID NO 357
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 357
ctgactgtgt actcag 16
<210> SEQ ID NO 358
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 358
cacactgact gtgtac 16
<210> SEQ ID NO 359
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 359
caaccacact gactgt 16
<210> SEQ ID NO 360
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 360
aaggcaacca cactga 16
<210> SEQ ID NO 361
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 361
gtgcaaggca accaca 16
<210> SEQ ID NO 362
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 362
catcgtgcaa ggcaac 16
<210> SEQ ID NO 363
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 363
atatcatcgt gcaagg 16
<210> SEQ ID NO 364
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 364
ctccatatca tcgtgc 16
<210> SEQ ID NO 365
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 365
ggctctccat atcatc 16
<210> SEQ ID NO 366
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 366
ggctggctct ccatat 16
<210> SEQ ID NO 367
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 367
ctggattcca atcagg 16
<210> SEQ ID NO 368
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 368
tggactggat tccaat 16
<210> SEQ ID NO 369
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 369
cctgtggact ggattc 16
<210> SEQ ID NO 370
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 370
tatacctgtg gactgg 16
<210> SEQ ID NO 371
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 371
acgatatacc tgtgga 16
<210> SEQ ID NO 372
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 372
gttaacgata tacctg 16
<210> SEQ ID NO 373
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 373
tgcggttaac gatata 16
<210> SEQ ID NO 374
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 374
tgggtgcggt taacga 16
<210> SEQ ID NO 375
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 375
aaattaatgg taagag 16
<210> SEQ ID NO 376
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 376
aggcaaatta atggta 16
<210> SEQ ID NO 377
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 377
tgttaggcaa attaat 16
<210> SEQ ID NO 378
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 378
tgtctgttag gcaaat 16
<210> SEQ ID NO 379
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 379
tcaatgtctg ttaggc 16
<210> SEQ ID NO 380
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 380
gcgatcaatg tctgtt 16
<210> SEQ ID NO 381
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 381
tagggcgatc aatgtc 16
<210> SEQ ID NO 382
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 382
cctttagggc gatcaa 16
<210> SEQ ID NO 383
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 383
cagtccttta gggcga 16
<210> SEQ ID NO 384
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 384
atgccagtcc tttagg 16
<210> SEQ ID NO 385
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 385
gtgaatgcca gtcctt 16
<210> SEQ ID NO 386
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 386
atcagtgaat gccagt 16
<210> SEQ ID NO 387
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 387
ccacatcagt gaatgc 16
<210> SEQ ID NO 388
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 388
acatccacat cagtga 16
<210> SEQ ID NO 389
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 389
atcgacatcc acatca 16
<210> SEQ ID NO 390
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 390
tggaatcgac atccac 16
<210> SEQ ID NO 391
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 391
ttgatggaat cgacat 16
<210> SEQ ID NO 392
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 392
aattttgatg gaatcg 16
<210> SEQ ID NO 393
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 393
aagcaatttt gatgga 16
<210> SEQ ID NO 394
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 394
tcccaagcaa ttttga 16
<210> SEQ ID NO 395
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 395
gctttcccaa gcaatt 16
<210> SEQ ID NO 396
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 396
gtgggctttc ccaagc 16
<210> SEQ ID NO 397
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 397
ccctgtgggc tttccc 16
<210> SEQ ID NO 398
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 398
ttgcccctgt gggctt 16
<210> SEQ ID NO 399
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 399
aaacttgccc ctgtgg 16
<210> SEQ ID NO 400
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 400
ctggaaactt gcccct 16
<210> SEQ ID NO 401
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 401
gtacctggaa acttgc 16
<210> SEQ ID NO 402
<211> LENGTH: 16
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 402
ccctgtacct ggaaac 16
<210> SEQ ID NO 403
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 403
gcctgaggcc ctgcagct 18
<210> SEQ ID NO 404
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 404
cccggcctga ggccctgc 18
<210> SEQ ID NO 405
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 405
agaccccggc ctgaggcc 18
<210> SEQ ID NO 406
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 406
actcagaccc cggcctga 18
<210> SEQ ID NO 407
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 407
gtgtactcag accccggc 18
<210> SEQ ID NO 408
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 408
gactgtgtac tcagaccc 18
<210> SEQ ID NO 409
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 409
cactgactgt gtactcag 18
<210> SEQ ID NO 410
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 410
accacactga ctgtgtac 18
<210> SEQ ID NO 411
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 411
ggcaaccaca ctgactgt 18
<210> SEQ ID NO 412
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 412
atcatcgtgc aaggcaac 18
<210> SEQ ID NO 413
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 413
gactggattc caatcagg 18
<210> SEQ ID NO 414
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 414
tgtggactgg attccaat 18
<210> SEQ ID NO 415
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 415
tacctgtgga ctggattc 18
<210> SEQ ID NO 416
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 416
ggtgggtgcg gttaacga 18
<210> SEQ ID NO 417
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 417
gcaaattaat ggtaagag 18
<210> SEQ ID NO 418
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 418
ttaggcaaat taatggta 18
<210> SEQ ID NO 419
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 419
gccagtcctt tagggcga 18
<210> SEQ ID NO 420
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 420
gaatgccagt cctttagg 18
<210> SEQ ID NO 421
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 421
cagtgaatgc cagtcctt 18
<210> SEQ ID NO 422
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 422
acatcagtga atgccagt 18
<210> SEQ ID NO 423
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 423
atccacatca gtgaatgc 18
<210> SEQ ID NO 424
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 424
cgacatccac atcagtga 18
<210> SEQ ID NO 425
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 425
gaatcgacat ccacatca 18
<210> SEQ ID NO 426
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 426
ttttgatgga atcgacat 18
<210> SEQ ID NO 427
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 427
tttcccaagc aattttga 18
<210> SEQ ID NO 428
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 428
gggctttccc aagcaatt 18
<210> SEQ ID NO 429
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 429
ctgtgggctt tcccaagc 18
<210> SEQ ID NO 430
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 430
gcccctgtgg gctttccc 18
<210> SEQ ID NO 431
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 431
acttgcccct gtgggctt 18
<210> SEQ ID NO 432
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 432
ggaaacttgc ccctgtgg 18
<210> SEQ ID NO 433
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 433
acctggaaac ttgcccct 18
<210> SEQ ID NO 434
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 434
ctgtacctgg aaacttgc 18
<210> SEQ ID NO 435
<211> LENGTH: 18
<212> TYPE: DNA
<213> ORGANISM: Artificial sequence
<220> FEATURE:
<223> OTHER INFORMATION: Synthetic oligonucleotide
<400> SEQUENCE: 435
caccctgtac ctggaaac 18
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