MODULATION OF DYSTROPHIA MYOTONICA-PROTEIN KINASE (DMPK) EXPRESSION

Abstract

Provided herein are methods, compounds, and compositions for reducing expression of a DMPK mRNA and protein in an animal. Also provided herein are methods, compounds, and compositions for preferentially reducing CUGexp DMPK RNA, reducing myotonia or reducing spliceopathy in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate type 1 myotonic dystrophy, or a symptom thereof.

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 BIOL0134USC2SEQ.txt created Jul. 21, 2017, which is approximately 236 Kb in size. The information in the electronic format of the sequence listing is incorporated herein by reference in its entirety.

FIELD

[0002] Provided herein are methods, compounds, and compositions for reducing expression of DMPK mRNA and protein in an animal. Also, provided herein are methods, compounds, and compositions comprising a DMPK inhibitor for preferentially reducing CUGexp DMPK RNA, reducing myotonia, or reducing spliceopathy in an animal. Such methods, compounds, and compositions are useful, for example, to treat, prevent, or ameliorate type 1 myotonic dystrophy (DM1) in an animal.

BACKGROUND

[0003] Myotonic dystrophy type 1 (DM1) is the most common form of muscular dystrophy in adults with an estimated frequency of 1 in 7,500 (Harper P S., Myotonic Dystrophy. London: W.B. Saunders Company; 2001). DM1 is an autosomal dominant disorder caused by expansion of a non-coding CTG repeat in DMPK1. DMPK1 is a gene encoding a cytosolic serine/threonine kinase (Brook J D, et al., Cell., 1992, 68(4):799-808). The physiologic functions and substrates of this kinase have not been fully determined. The expanded CTG repeat is located in the 3' untranslated region (UTR) of DMPK1. This mutation leads to RNA dominance, a process in which expression of RNA containing an expanded CUG repeat (CUGexp) induces cell dysfunction (Osborne R J and Thornton C A., Human Molecular Genetics., 2006, 15(2): R162-R169).

[0004] The DMPK gene normally has 5-37 CTG repeats in the 3' untranslated region. In myotonic dystrophy type I, this number is significantly expanded and is, for example, in the range of 50 to greater than 3,500 (Harper, Myotonic Dystrophy (Saunders, London, ed. 3, 2001); Annu. Rev. Neurosci. 29: 259, 2006; EMBO J. 19: 4439, 2000; Curr Opin Neurol. 20: 572, 2007).

[0005] The CUGexp tract interacts with RNA binding proteins including muscleblind-like (MBNL) protein, a splicing factor, and causes the mutant transcript to be retained in nuclear foci. The toxicity of this RNA stems from sequestration of RNA binding proteins and activation of signaling pathways. Studies in animal models have shown that phenotypes of DM1 can be reversed if toxicity of CUGexp RNA is reduced (Wheeler T M, et al., Science., 2009, 325(5938):336-339; Mulders S A, et al., Proc Natl Acad Sci USA., 2009, 106(33):13915-13920).

[0006] In DM1, skeletal muscle is the most severely affected tissue, but the disease also has important effects on cardiac and smooth muscle, ocular lens, and brain. The cranial, distal limb, and diaphragm muscles are preferentially affected. Manual dexterity is compromised early, which causes several decades of severe disability. The median age at death is 55 years, usually from respiratory failure (de Die-Smulders C E, et al., Brain., 1998, 121 (Pt 8):1557-1563).

[0007] Antisense technology is emerging as an effective means for modulating expression of certain gene products and may therefore prove to be uniquely useful in a number of therapeutic, diagnostic, and research applications for the modulation of DMPK1. Intramuscular injection of fully modified oligonucleotides targeting with the CAG-repeat were shown in mice to block formation of CUGexp-MBNL1 complexes, disperse nuclear foci of CUGexp transcripts, enhance the nucleocytoplasmic transport and translation of CUGexp transcripts, release MBNL proteins to the nucleoplasm, normalize alternative splicing of MBNL-dependent exons, and eliminate myotonia in CUGexp-expressing transgenic mice (Wheeler T M, et al., Science., 2009, 325(5938):336-339; WO2008/036406).

[0008] Presently there is no treatment that can modify the course of DM1. The burden of disease, therefore, is significant. It is, therefore, an object herein to provide compounds, compositions, and methods for treating DM1

SUMMARY

[0009] Provided herein are methods, compounds, and compositions for inhibiting expression of DMPK and treating, preventing, delaying or ameliorating a DMPK related disease and or a symptom thereof. In certain embodiments, the compounds and compositions inhibit mutant DMPK or CUGexp DMPK.

[0010] Certain embodiments provide a method of reducing DMPK expression in an animal comprising administering to the animal a compound comprising a modified oligonucleotide as further described herein targeted to DMPK.

[0011] Certain embodiments provide a method of preferentially reducing CUGexp DMPK, reducing myotonia, or reducing spliceopathy in an animal comprising administering to the animal a compound comprising a modified oligonucleotide, as further described herein, targeted to CUGexp DMPK. CUGexp DMPK transcripts are believed to be particularly sensitive to antisense knockdown via nuclear ribonucleases, because of their longer residence time in the nucleus, and this sensitivity is thought to permit effective antisense inhibition of CUGexp DMPK transcripts in relevant tissues such as muscle despite the biodistribution barriers to tissue uptake of antisense oligonucleotides. Antisense mechanisms that do not elicit cleavage via nuclear ribonucleases, such as the CAG-repeat ASOs described in, for example, Wheeler T M, et al., Science., 2009, 325(5938):336-339 and WO2008/036406, do not provide the same therapeutic advantage.

[0012] Certain embodiments provide a method of treating an animal with type 1 myotonic dystrophy. In certain embodiments, the method includes administering to the animal a therapeutically effective amount of a compound comprising a modified oligonucleotide as further described herein targeted to DMPK. In certain embodiments, the method includes identifying an animal with type 1 myotonic dystrophy.

[0013] Certain embodiments provide a method of treating, preventing, delaying, or ameliorating symptoms and outcomes associated with development of DM1 including muscle stiffness, myotonia, disabling distal weakness, weakness in face and jaw muscles, difficulty in swallowing, drooping of the eyelids (ptosis), weakness of neck muscles, weakness in arm and leg muscles, persistent muscle pain, hypersomnia, muscle wasting, dysphagia, respiratory insufficiency, irregular heartbeat, heart muscle damage, apathy, insulin resistance, and cataracts. Certain embodiments provide a method of treating, preventing, delaying, or ameliorating symptoms and outcomes associated with development of DM1 in children, including, developmental delays, learning problems, language and speech issues, and personality development issues.

[0014] Certain embodiments provide a method of administering an antisense oligonucleotide to counteract RNA dominance by directing the cleavage of pathogenic transcripts.

[0015] In certain embodiments, the DMPK has a sequence as set forth in GenBank Accession No. NM_001081560.1 (incorporated herein as SEQ ID NO: 1). In certain embodiments, the DMPK has the sequence as set forth in GenBank Accession No. NT_011109.15 truncated from nucleotides 18540696 to 18555106 (incorporated herein as SEQ ID NO: 2). In certain embodiments, the DMPK has the sequence as set forth in GenBank Accession No. NT_039413.7 truncated from nucleotides 16666001 to 16681000 (incorporated herein as SEQ ID NO: 3). In certain embodiments, the DMPK has the sequence as set forth in GenBank Accession No. NM_032418.1 (incorporated herein as SEQ ID NO: 4). In certain embodiments, the DMPK has the sequence as set forth in GenBank Accession No. AI007148.1 (incorporated herein as SEQ ID NO: 5). In certain embodiments, the DMPK has the sequence as set forth in GenBank Accession No. AI304033.1 (incorporated herein as SEQ ID NO: 6). In certain embodiments, the DMPK has the sequence as set forth in GenBank Accession No. BC024150.1 (incorporated herein as SEQ ID NO: 7). In certain embodiments, the DMPK has the sequence as set forth in GenBank Accession No. BC056615.1 (incorporated herein as SEQ ID NO: 8). In certain embodiments, the DMPK has the sequence as set forth in GenBank Accession No. BC075715.1 (incorporated herein as SEQ ID NO: 793). In certain embodiments, the DMPK has the sequence as set forth in GenBank Accession No. BU519245.1 (incorporated herein as SEQ ID NO: 794). In certain embodiments, the DMPK has the sequence as set forth in GenBank Accession No. CB247909.1 (incorporated herein as SEQ ID NO: 795). In certain embodiments, the DMPK has the sequence as set forth in GenBank Accession No. CX208906.1 (incorporated herein as SEQ ID NO: 796). In certain embodiments, the DMPK has the sequence as set forth in GenBank Accession No. CX732022.1 (incorporated herein as SEQ ID NO: 797). In certain embodiments, the DMPK has the sequence as set forth in GenBank Accession No. S60315.1 (incorporated herein as SEQ ID NO: 798). In certain embodiments, the DMPK has the sequence as set forth in GenBank Accession No. S60316.1 (incorporated herein as SEQ ID NO: 799). In certain embodiments, the DMPK has the sequence as set forth in GenBank Accession No. NM_001081562.1 (incorporated herein as SEQ ID NO: 800). In certain embodiments, the DMPK has the sequence as set forth in GenBank Accession No. NM_001100.3 (incorporated herein as SEQ ID NO: 801).

DETAILED DESCRIPTION

[0016] It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention, as claimed. Herein, the use of the singular includes the plural unless specifically stated otherwise. Herein, the use of "or" means "and/or" unless stated otherwise. Furthermore, the use of the term "including" as well as other forms, such as "includes" and "included", is not limiting. Also, terms such as "element" or "component" encompass both elements and components comprising one unit and elements and components that comprise more than one subunit, unless specifically stated otherwise.

[0017] The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described. All documents, or portions of documents, cited in this application, including, but not limited to, patents, patent applications, articles, books, and treatises, are hereby expressly incorporated-by-reference for the portions of the document discussed herein, as well as in their entirety.

Definitions

[0018] Unless specific definitions are provided, the nomenclature utilized 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 can be used for chemical synthesis, and chemical analysis. Where permitted, all patents, applications, published applications and other publications, GENBANK Accession Numbers and associated sequence information obtainable through databases such as National Center for Biotechnology Information (NCBI) and other data referred to throughout in the disclosure herein are incorporated by reference for the portions of the document discussed herein, as well as in their entirety.

[0019] Unless otherwise indicated, the following terms have the following meanings:

[0020] "2'-O-methoxyethyl" (also 2'-MOE and 2'-O(CH.sub.2).sub.2--OCH.sub.3) refers to an O-methoxy-ethyl modification of the 2' position of a furanosyl ring. A 2'-O-methoxyethyl modified sugar is a modified sugar.

[0021] "2'-O-methoxyethyl nucleotide" means a nucleotide comprising a 2'-O-methoxyethyl modified sugar moiety.

[0022] "5-methylcytosine" means a cytosine modified with a methyl group attached to position 5. A 5-methylcytosine is a modified nucleobase.

[0023] "About" means within .+-.7% of a value. For example, if it is stated, "the compound affected at least 70% inhibition of DMPK", it is implied that the DMPK levels are inhibited within a range of 63% and 77%.

[0024] "Active pharmaceutical agent" means the substance or substances in a pharmaceutical composition that provide a therapeutic benefit when administered to an individual. For example, in certain embodiments an antisense oligonucleotide targeted to DMPK is an active pharmaceutical agent.

[0025] "Active target region" or "target region" means a region to which one or more active antisense compounds is targeted. "Active antisense compounds" means antisense compounds that reduce target nucleic acid levels or protein levels.

[0026] "Administered concomitantly" refers to the co-administration of two agents in any manner in which the pharmacological effects of both are manifest in the patient at the same time. Concomitant administration does not require that both agents be administered in a single pharmaceutical composition, in the same dosage form, or by the same route of administration. The effects of both agents need not manifest themselves at the same time. The effects need only be overlapping for a period of time and need not be coextensive.

[0027] "Administering" means providing an agent to an animal, and includes, but is not limited to, administering by a medical professional and self-administering.

[0028] "Agent" means an active substance that can provide a therapeutic benefit when administered to an animal. "First Agent" means a therapeutic compound of the invention. For example, a first agent can be an antisense oligonucleotide targeting DMPK. "Second agent" means a second therapeutic compound of the invention (e.g. a second antisense oligonucleotide targeting DMPK) and/or a non-DMPK therapeutic compound.

[0029] "Amelioration" refers to a lessening of at least one indicator, sign, or symptom of an associated disease, disorder, or condition. The severity of indicators can be determined by subjective or objective measures, which are known to those skilled in the art.

[0030] "Animal" refers to a human or non-human animal, including, but not limited to, mice, rats, rabbits, dogs, cats, pigs, and non-human primates, including, but not limited to, monkeys and chimpanzees.

[0031] "Antisense activity" means any detectable or measurable activity attributable to the hybridization of an antisense compound to its target nucleic acid. In certain embodiments, antisense activity is a decrease in the amount or expression of a target nucleic acid or protein encoded by such target nucleic acid.

[0032] "Antisense compound" means an oligomeric compound that is capable of undergoing hybridization to a target nucleic acid through hydrogen bonding. Examples of antisense compounds include single-stranded and double-stranded compounds, such as, antisense oligonucleotides, siRNAs, shRNAs, snoRNAs, miRNAs, and satellite repeats.

[0033] "Antisense inhibition" means reduction of target nucleic acid levels or target protein levels in the presence of an antisense compound complementary to a target nucleic acid compared to target nucleic acid levels or target protein levels in the absence of the antisense compound.

[0034] "Antisense oligonucleotide" means a single-stranded oligonucleotide having a nucleobase sequence that permits hybridization to a corresponding region or segment of a target nucleic acid.

[0035] "Bicyclic sugar" means a furanosyl ring modified by the bridging of two non-geminal carbon ring atoms. A bicyclic sugar is a modified sugar.

[0036] "Bicyclic nucleic acid" or "BNA" refers to a nucleoside or nucleotide wherein the furanose portion of the nucleoside or nucleotide includes a bridge connecting two carbon atoms on the furanose ring, thereby forming a bicyclic ring system.

[0037] "Cap structure" or "terminal cap moiety" means chemical modifications, which have been incorporated at either terminus of an antisense compound.

[0038] "Chemically distinct region" refers to a region of an antisense compound that is in some way chemically different than another region of the same antisense compound. For example, a region having 2'-O-methoxyethyl nucleotides is chemically distinct from a region having nucleotides without 2'-O-methoxyethyl modifications.

[0039] "Chimeric antisense compound" means an antisense compound that has at least two chemically distinct regions.

[0040] "Co-administration" means administration of two or more agents to an individual. The two or more agents can be in a single pharmaceutical composition, or can be in separate pharmaceutical compositions. Each of the two or more agents can be administered through the same or different routes of administration. Co-administration encompasses parallel or sequential administration.

[0041] "Complementarity" means the capacity for pairing between nucleobases of a first nucleic acid and a second nucleic acid.

[0042] "Contiguous nucleobases" means nucleobases immediately adjacent to each other.

[0043] "CUGexp DMPK" means mutant DMPK RNA containing an expanded CUG repeat (CUGexp). The wild-type DMPK gene has 5-37 CTG repeats in the 3' untranslated region. In a "CUGexp DMPK" (such as in a myotonic dystrophy type I patient) this number is significantly expanded and is, for example, in the range of 50 to greater than 3,500 (Harper, Myotonic Dystrophy (Saunders, London, ed. 3, 2001); Annu. Rev. Neurosci. 29: 259, 2006; EMBO J. 19: 4439, 2000; Curr Opin Neurol. 20: 572, 2007).

[0044] "Diluent" means an ingredient in a composition that lacks pharmacological activity, but is pharmaceutically necessary or desirable. For example, the diluent in an injected composition can be a liquid, e.g. saline solution.

[0045] "DMPK" means any nucleic acid or protein of DMPK. DMPK can be a mutant DMPK including CUGexp DMPK nucleic acid.

[0046] "DMPK expression" means the level of mRNA transcribed from the gene encoding DMPK or the level of protein translated from the mRNA. DMPK expression can be determined by art known methods such as a Northern or Western blot.

[0047] "DMPK nucleic acid" means any nucleic acid encoding DMPK. For example, in certain embodiments, a DMPK nucleic acid includes a DNA sequence encoding DMPK, an RNA sequence transcribed from DNA encoding DMPK (including genomic DNA comprising introns and exons), and an mRNA or pre-mRNA sequence encoding DMPK. "DMPK mRNA" means an mRNA encoding a DMPK protein.

[0048] "Dose" means a specified quantity of a pharmaceutical agent provided in a single administration, or in a specified time period. In certain embodiments, a dose can be administered in one, two, or more boluses, tablets, or injections. For example, in certain embodiments where subcutaneous administration is desired, the desired dose requires a volume not easily accommodated by a single injection, therefore, two or more injections can be used to achieve the desired dose. In certain embodiments, the pharmaceutical agent is administered by infusion over an extended period of time or continuously. Doses can be stated as the amount of pharmaceutical agent per hour, day, week, or month.

[0049] "Effective amount" or "therapeutically effective amount" means the amount of active pharmaceutical agent sufficient to effectuate a desired physiological outcome in an individual in need of the agent. The effective amount can vary among individuals depending on the health and physical condition of the individual to be treated, the taxonomic group of the individuals to be treated, the formulation of the composition, assessment of the individual's medical condition, and other relevant factors.

[0050] "Fully complementary" or "100% complementary" means each nucleobase of a nucleobase sequence of a first nucleic acid has a complementary nucleobase in a second nucleobase sequence of a second nucleic acid. In certain embodiments, a first nucleic acid is an antisense compound and a target nucleic acid is a second nucleic acid.

[0051] "Gapmer" means a chimeric antisense compound in which an internal region having a plurality of nucleosides that support RNase H cleavage is positioned between external regions having one or more nucleosides, wherein the nucleosides comprising the internal region are chemically distinct from the nucleoside or nucleosides comprising the external regions. The internal region can be referred to as a "gap segment" and the external regions can be referred to as "wing segments."

[0052] "Gap-widened" means a chimeric antisense compound having a gap segment of 12 or more contiguous 2'-deoxyribonucleosides positioned between and immediately adjacent to 5' and 3' wing segments having from one to six nucleosides.

[0053] "Hybridization" means the annealing of complementary nucleic acid molecules. In certain embodiments, complementary nucleic acid molecules include an antisense compound and a target nucleic acid.

[0054] "Identifying an animal with type 1 myotonic dystrophy" means identifying an animal having been diagnosed with a type 1 myotonic dystrophy, disorder or condition or identifying an animal predisposed to develop a type 1 myotonic dystrophy, disorder or condition. For example, individuals with a familial history can be predisposed to type 1 myotonic dystrophy, disorder or condition. Such identification can be accomplished by any method including evaluating an individual's medical history and standard clinical tests or assessments.

[0055] "Immediately adjacent" means there are no intervening elements between the immediately adjacent elements.

[0056] "Individual" means a human or non-human animal selected for treatment or therapy.

[0057] "Internucleoside linkage" refers to the chemical bond between nucleosides.

[0058] "Linked nucleosides" means adjacent nucleosides which are bonded or linked together by an internucleoside linkage.

[0059] "Mismatch" or "non-complementary nucleobase" refers to the case when a nucleobase of a first nucleic acid is not capable of pairing with the corresponding nucleobase of a second or target nucleic acid.

[0060] "Modified internucleoside linkage" refers to a substitution or any change from a naturally occurring internucleoside bond (i.e. a phosphodiester internucleoside bond).

[0061] "Modified nucleobase" refers to any nucleobase other than adenine, cytosine, guanine, thymidine, or uracil. An "unmodified nucleobase" means the purine bases adenine (A) and guanine (G), and the pyrimidine bases thymine (T), cytosine (C), and uracil (U).

[0062] "Modified nucleotide" means a nucleotide having, independently, a modified sugar moiety, modified internucleoside linkage, or modified nucleobase. A "modified nucleoside" means a nucleoside having, independently, a modified sugar moiety or modified nucleobase.

[0063] "Modified oligonucleotide" means an oligonucleotide comprising at least one modified nucleotide.

[0064] "Modified sugar" refers to a substitution or change from a natural sugar.

[0065] "Motif" means the pattern of chemically distinct regions in an antisense compound.

[0066] "Myotonia" means an abnormally slow relaxation of a muscle after voluntary contraction or electrical stimulation.

[0067] "Nuclear ribonuclease" means a ribonuclease found in the nucleus. Nuclear ribonucleases include, but are not limited to, RNase H including RNase H1 and RNase H2, the double stranded RNase drosha and other double stranded RNases.

[0068] "Naturally occurring internucleoside linkage" means a 3' to 5' phosphodiester linkage.

[0069] "Natural sugar moiety" means a sugar found in DNA (2'-H) or RNA (2'-OH).

[0070] "Nucleic acid" refers to molecules composed of monomeric nucleotides. A nucleic acid includes ribonucleic acids (RNA), deoxyribonucleic acids (DNA), single-stranded nucleic acids, double-stranded nucleic acids, small interfering ribonucleic acids (siRNA), and microRNAs (miRNA). A nucleic acid can also comprise a combination of these elements in a single molecule.

[0071] "Nucleobase" means a heterocyclic moiety capable of pairing with a base of another nucleic acid.

[0072] "Nucleobase sequence" means the order of contiguous nucleobases independent of any sugar, linkage, or nucleobase modification.

[0073] "Nucleoside" means a nucleobase linked to a sugar.

[0074] "Nucleoside mimetic" includes those structures used to replace the sugar or the sugar and the base and not necessarily the linkage at one or more positions of an oligomeric compound such as for example nucleoside mimetics having morpholino, cyclohexenyl, cyclohexyl, tetrahydropyranyl, bicyclo or tricyclo sugar mimetics e.g. non furanose sugar units.

[0075] "Nucleotide" means a nucleoside having a phosphate group covalently linked to the sugar portion of the nucleoside.

[0076] "Nucleotide mimetic" includes those structures used to replace the nucleoside and the linkage at one or more positions of an oligomeric compound such as for example peptide nucleic acids or morpholinos (morpholinos linked by --N(H)--C(.dbd.O)--O-- or other non-phosphodiester linkage).

[0077] "Oligomeric compound" or "oligomer" means a polymer of linked monomeric subunits which is capable of hybridizing to at least a region of a nucleic acid molecule.

[0078] "Oligonucleotide" means a polymer of linked nucleosides each of which can be modified or unmodified, independent one from another.

[0079] "Parenteral administration" means administration through injection or infusion. Parenteral administration includes subcutaneous administration, intravenous administration, intramuscular administration, intraarterial administration, intraperitoneal administration, or intracranial administration, e.g. intrathecal or intracerebroventricular administration. Administration can be continuous, or chronic, or short or intermittent.

[0080] "Peptide" means a molecule formed by linking at least two amino acids by amide bonds. Peptide refers to polypeptides and proteins.

[0081] "Pharmaceutical composition" means a mixture of substances suitable for administering to an individual. For example, a pharmaceutical composition can comprise one or more active agents and a sterile aqueous solution.

[0082] "Pharmaceutically acceptable salts" means physiologically and pharmaceutically acceptable salts of antisense compounds, i.e., salts that retain the desired biological activity of the parent oligonucleotide and do not impart undesired toxicological effects thereto.

[0083] "Phosphorothioate linkage" means a linkage between nucleosides where the phosphodiester bond is modified by replacing one of the non-bridging oxygen atoms with a sulfur atom. A phosphorothioate linkage is a modified internucleoside linkage.

[0084] "Portion" means a defined number of contiguous (i.e. linked) nucleobases of a nucleic acid. In certain embodiments, a portion is a defined number of contiguous nucleobases of a target nucleic acid. In certain embodiments, a portion is a defined number of contiguous nucleobases of an antisense compound.

[0085] "Preferentially reducing CUG exp DMPK RNA" refers to a preferential reduction of RNA transcripts from a CUGexp DMPK allele relative to RNA transcripts from a normal DMPK allele.

[0086] "Prevent" refers to delaying or forestalling the onset or development of a disease, disorder, or condition for a period of time from minutes to indefinitely. Prevent also means reducing risk of developing a disease, disorder, or condition.

[0087] "Prodrug" means a therapeutic agent that is prepared in an inactive form that is converted to an active form within the body or cells thereof by the action of endogenous enzymes or other chemicals or conditions.

[0088] "Side effects" means physiological responses attributable to a treatment other than the desired effects. In certain embodiments, side effects include injection site reactions, liver function test abnormalities, renal function abnormalities, liver toxicity, renal toxicity, central nervous system abnormalities, myopathies, and malaise. For example, increased aminotransferase levels in serum can indicate liver toxicity or liver function abnormality. For example, increased bilirubin can indicate liver toxicity or liver function abnormality.

[0089] "Single-stranded oligonucleotide" means an oligonucleotide which is not hybridized to a complementary strand.

[0090] "Specifically hybridizable" refers to an antisense compound having a sufficient degree of complementarity between an antisense oligonucleotide and a target nucleic acid to induce a desired effect, while exhibiting minimal or no effects on non-target nucleic acids under conditions in which specific binding is desired, i.e. under physiological conditions in the case of in vivo assays and therapeutic treatments.

[0091] "Spliceopathy" means a change in the alternative splicing of one or more RNAs that leads to the expression of altered splice products in a particular tissue.

[0092] "Subcutaneous administration" means administration just below the skin.

[0093] "Sugar surrogate" overlaps with the slightly broader term "nucleoside mimetic" but is intended to indicate replacement of the sugar unit (furanose ring) only. The tetrahydropyranyl rings provided herein are illustrative of an example of a sugar surrogate wherein the furanose sugar group has been replaced with a tetrahydropyranyl ring system.

[0094] "Targeting" or "targeted" means the process of design and selection of an antisense compound that will specifically hybridize to a target nucleic acid and induce a desired effect.

[0095] "Target nucleic acid," "target RNA," and "target RNA transcript" all refer to a nucleic acid capable of being targeted by antisense compounds.

[0096] "Target segment" means the sequence of nucleotides of a target nucleic acid to which an antisense compound is targeted. "5' target site" refers to the 5'-most nucleotide of a target segment. "3' target site" refers to the 3'-most nucleotide of a target segment.

[0097] "Therapeutically effective amount" means an amount of an agent that provides a therapeutic benefit to an individual.

[0098] "Treat" refers to administering a pharmaceutical composition to effect an alteration or improvement of a disease, disorder, or condition.

[0099] "Type 1 myotonic dystrophy" or "DM1" means an autosomal dominant disorder caused by expansion of a non-coding CTG repeat in DMPK. This mutation leads to RNA dominance, a process in which expression of RNA containing an expanded CUG repeat (CUGexp) induced cell dysfunction. The CUGexp tract interacts with RNA binding proteins and causes the mutant transcript to be retained in nuclear foci. The toxicity of this RNA stems from sequestration of RNA binding proteins and activation of signaling pathways.

[0100] "Unmodified nucleotide" means a nucleotide composed of naturally occurring nucleobases, sugar moieties, and internucleoside linkages. In certain embodiments, an unmodified nucleotide is an RNA nucleotide (i.e. .beta.-D-ribonucleosides) or a DNA nucleotide (i.e. .beta.-D-deoxyribonucleoside).

Certain Embodiments

[0101] Certain embodiments provide methods, compounds, and compositions for inhibiting DMPK expression.

[0102] Certain embodiments provide a method of reducing DMPK expression in an animal comprising administering to the animal a compound comprising a modified oligonucleotide targeting DMPK.

[0103] Certain embodiments provide a method of preferentially reducing CUGexp DMPK RNA, reducing myotonia or reducing spliceopathy in an animal comprising administering to the animal a compound comprising a modified oligonucleotide targeted to DMPK, wherein the modified oligonucleotide preferentially reduces CUGexp DMPK RNA, reduces myotonia or reduces spliceopathy in the animal.

[0104] Certain embodiments provide a method of administering an antisense oligonucleotide to counteract RNA dominance by directing the cleavage of pathogenic transcripts.

[0105] Certain embodiments provide a method of reducing spliceopathy of Serca1. In certain embodiments, methods provided herein result in exon 22 inclusion. In certain embodiments, the corrective splicing occurs in the tibialis anterior, gastrocnemius, and quadriceps muscles.

[0106] Certain embodiments provide a method of reducing spliceopathy of m-Titin. In certain embodiments, methods provided herein result in exon 5 inclusion. In certain embodiments, the corrective splicing occurs in the tibialis anterior, gastrocnemius, and quadriceps muscles.

[0107] Certain embodiments provide a method of reducing spliceopathy of Clcn1. In certain embodiments, methods provided herein result in exon 7a inclusion. In certain embodiments, the corrective splicing occurs in the tibialis anterior, gastrocnemius, and quadriceps muscles.

[0108] Certain embodiments provide a method of reducing spliceopathy of Zasp. In certain embodiments, methods provided herein result in exon 11 inclusion. In certain embodiments, the corrective splicing occurs in the tibialis anterior, gastrocnemius, and quadriceps muscles.

[0109] Certain embodiments provide a method for treating an animal with type 1 myotonic dystrophy comprising: a) identifying said animal with type 1 myotonic dystrophy, and b) administering to said animal a therapeutically effective amount of a compound comprising a modified oligonucleotide targeted to DMPK. In certain embodiments, the therapeutically effective amount of the compound administered to the animal preferentially reduces CUGexp DMPK RNA, reduces myotonia or reduces spliceopathy in the animal.

[0110] Certain embodiments provide a method of achieving a preferential reduction of CUGexp DMPK RNA, including administering to the subject suspected of having type 1 myotonic dystrophy or having a CUGexp DMPK RNA a modified antisense oligonucleotide complementary to a non-repeat region of said CUGexp DMPK RNA. The modified antisense oligonucleotide, when bound to said CUGexp DMPK RNA, achieves a preferential reduction of the CUGexp DMPK RNA.

[0111] Certain embodiments provide a method of achieving a preferential reduction of CUGexp DMPK RNA, including selecting a subject having type 1 myotonic dystrophy or having a CUGexp DMPK RNA and administering to said subject a modified antisense oligonucleotide complementary to a non-repeat region of said CUGexp DMPK RNA. The modified antisense oligonucleotide, when bound to the CUGexp DMPK RNA, activates a ribonuclease or nuclear ribonuclease, thereby achieving a preferential reduction of the CUGexp DMPK RNA in the nucleus.

[0112] Certain embodiments provide a method of achieving a preferential reduction of CUGexp DMPK RNA, including selecting a subject having type 1 myotonic dystrophy or having a mutant or CUGexp DMPK RNA and systemically administering to said subject a modified antisense oligonucleotide complementary to a non-repeat region of said CUGexp DMPK RNA. The modified antisense oligonucleotide, when bound to the mutant or CUGexp DMPK RNA, achieves a preferential reduction of the mutant or CUGexp DMPK RNA.

[0113] Certain embodiments provide a method of reducing myotonia in a subject in need thereof. The method includes administering to the subject a modified antisense oligonucleotide complementary to a non-repeat region of a DMPK RNA, wherein the modified antisense oligonucleotide, when bound to the DMPK RNA, activates a ribonuclease or nuclear ribonuclease, thereby reducing myotonia. In certain embodiments, the subject has or is suspected of having type 1 myotonic dystrophy or having a mutant DMPK RNA or CUGexp DMPK RNA. In certain embodiments, the DMPK RNA is nuclear retained.

[0114] Certain embodiments provide a method of reducing spliceopathy in a subject in need thereof. The method includes administering to the subject a modified antisense oligonucleotide complementary to a non-repeat region of a DMPK RNA, wherein the modified antisense oligonucleotide, when bound to the DMPK RNA, activates a ribonuclease or nuclear ribonuclease, thereby reducing spliceopathy. In certain embodiments, the subject has or is suspected of having type 1 myotonic dystrophy or having a nuclear retained CUGexp DMPK RNA. In certain embodiments, the DMPK RNA is nuclear retained. In certain embodiments, the spliceopathy is MBNL dependent spliceopathy.

[0115] In certain embodiments, the modified antisense oligonucleotide of the methods is chimeric. In certain embodiments, the modified antisense oligonucleotide of the methods is a gapmer.

[0116] In certain embodiments of the methods provided herein, the administering is subcutaneous. In certain embodiments, the administering is intravenous.

[0117] In certain embodiments, the modified antisense oligonucleotide of the methods targets a non-coding sequence within the non-repeat region of a DMPK RNA. In certain embodiments, the oligonucleotide targets a coding region, an intron, a 5'UTR, or a 3'UTR of the mutant DMPK RNA.

[0118] In certain embodiments of the methods provided herein, the nuclear ribonuclease is RNase H1.

[0119] In certain embodiments of the methods, the DMPK RNA is reduced in muscle tissue. In certain embodiments, the mutant DMPK RNA CUGexp DMPK RNA is preferentially reduced.

[0120] In certain embodiments, the DMPK has the sequence as set forth in GenBank Accession No. NM_001081560.1 (incorporated herein as SEQ ID NO: 1). In certain embodiments, the DMPK has the sequence as set forth in GenBank Accession No. NT_011109.15 truncated from nucleotides 18540696 to 18555106 (incorporated herein as SEQ ID NO: 2). In certain embodiments, the DMPK has the sequence as set forth in GenBank Accession No. NT_039413.7 truncated from nucleotides 16666001 to 16681000 (incorporated herein as SEQ ID NO: 3). In certain embodiments, the DMPK has the sequence as set forth in GenBank Accession No. NM_032418.1 (incorporated herein as SEQ ID NO: 4). In certain embodiments, the DMPK has the sequence as set forth in GenBank Accession No. AI007148.1 (incorporated herein as SEQ ID NO: 5). In certain embodiments, the DMPK has the sequence as set forth in GenBank Accession No. AI304033.1 (incorporated herein as SEQ ID NO: 6). In certain embodiments, the DMPK has the sequence as set forth in GenBank Accession No. BC024150.1 (incorporated herein as SEQ ID NO: 7). In certain embodiments, the DMPK has the sequence as set forth in GenBank Accession No. BC056615.1 (incorporated herein as SEQ ID NO: 8). In certain embodiments, the DMPK has the sequence as set forth in GenBank Accession No. BC075715.1 (incorporated herein as SEQ ID NO: 793). In certain embodiments, the DMPK has the sequence as set forth in GenBank Accession No. BU519245.1 (incorporated herein as SEQ ID NO: 794). In certain embodiments, the DMPK has the sequence as set forth in GenBank Accession No. CB247909.1 (incorporated herein as SEQ ID NO: 795). In certain embodiments, the DMPK has the sequence as set forth in GenBank Accession No. CX208906.1 (incorporated herein as SEQ ID NO: 796). In certain embodiments, the DMPK has the sequence as set forth in GenBank Accession No. CX732022.1 (incorporated herein as SEQ ID NO: 797). In certain embodiments, the DMPK has the sequence as set forth in GenBank Accession No. S60315.1 (incorporated herein as SEQ ID NO: 798). In certain embodiments, the DMPK has the sequence as set forth in GenBank Accession No. S60316.1 (incorporated herein as SEQ ID NO: 799). In certain embodiments, the DMPK has the sequence as set forth in GenBank Accession No. NM_001081562.1 (incorporated herein as SEQ ID NO: 800). In certain embodiments, the DMPK has the sequence as set forth in GenBank Accession No. NM_001100.3 (incorporated herein as SEQ ID NO: 801).

[0121] In certain embodiments, the modified oligonucleotide has a nucleobase sequence comprising at least 8 contiguous nucleobases of a nucleobase sequence recited in any one of SEQ ID NOs: 12-156, 160-770, and 774-792. In certain embodiments, the modified oligonucleotide has a nucleobase sequence comprising at least 9, at least 10, or at least 11, contiguous nucleobases of a nucleobase sequence recited in any one of SEQ ID NOs: 12-156, 160-770, and 774-792.

[0122] In certain embodiments, the modified oligonucleotide has a nucleobase sequence comprising at least 12 contiguous nucleobases of a nucleobase sequence recited in any one of SEQ ID NOs: 12-156, 160-770, and 774-792. In certain embodiments, the modified oligonucleotide has a nucleobase sequence comprising at least 13, or at least 14, contiguous nucleobases of a nucleobase sequence recited in any one of SEQ ID NOs: 12-156, 160-770, and 774-792.

[0123] In certain embodiments, the modified oligonucleotide has a nucleobase sequence comprising at least 15 contiguous nucleobases of a nucleobase sequence recited in any one of SEQ ID NOs: 12-156, 160-770, and 774-792. In certain embodiments, the modified oligonucleotide has a nucleobase sequence comprising at least 16, or at least 17, contiguous nucleobases of a nucleobase sequence recited in any one of SEQ ID NOs: 12-156, 160-770, and 774-792.

[0124] In certain embodiments, the modified oligonucleotide has a nucleobase sequence comprising at least 18 contiguous nucleobases of a nucleobase sequence recited in any one of SEQ ID NOs: 12-156, 160-770, and 774-792. In certain embodiments, the modified oligonucleotide has a nucleobase sequence comprising at least 19 contiguous nucleobases of a nucleobase sequence recited in any one of SEQ ID NOs: 12-156, 160-770, and 774-792.

[0125] In certain embodiments, the modified oligonucleotides provided herein are targeted to any one of the following regions of SEQ ID NO: 1: 1178-1206, 2159-2182, 2174-2196, 2426-2447, 2450-2518, 2679-2704, and 2697-2725.

[0126] In certain embodiments, the modified oligonucleotides provided herein are targeted to any one of the following regions of SEQ ID NO 1: 178-223, 232-253, 279-299, 366-399, 519-541, 923-975, 1073-1105, 1171-1196, 1215-1246, 1263-1324, 1706-1734, 1743-1763, 1932-1979, 1981-2003, 2077-2108, and 2152-2173.

[0127] In certain embodiments, the modified oligonucleotides provided herein are targeted to any one of the following regions of SEQ ID NO: 2: 1251-1303, 1305-1326, 1352-1372, 3762-3795, 4170-4192, 5800-5852, 6124-6149, 6168-6199, 6216-6277, 11979-12007, 12016-12036, 12993-13042, 13044-13066, 13140-13171, and 13215-13236.

[0128] In certain embodiments, the animal is a human.

[0129] In certain embodiments, the compounds or compositions of the invention are designated as a first agent and the methods of the invention further comprise administering a second agent. In certain embodiments, the first agent and the second agent are co-administered. In certain embodiments the first agent and the second agent are co-administered sequentially or concomitantly.

[0130] In certain embodiments, administration comprises parenteral administration.

[0131] In certain embodiments, the compound is a single-stranded modified oligonucleotide. In certain embodiments, the nucleobase sequence of the modified oligonucleotide is at least 95% complementary to any one of SEQ ID NOs: 1-8 and 793-801 as measured over the entirety of said modified oligonucleotide. In certain embodiments, the nucleobase sequence of the modified oligonucleotide is 100% complementary to any one of SEQ ID NOs: 1-8 and 793-801 as measured over the entirety of said modified oligonucleotide.

[0132] In certain embodiments, at least one internucleoside linkage of said modified oligonucleotide is a modified internucleoside linkage. In certain embodiments, each internucleoside linkage is a phosphorothioate internucleoside linkage.

[0133] In certain embodiments, at least one nucleoside of said modified oligonucleotide comprises a modified sugar. In certain embodiments, at least one modified sugar is a bicyclic sugar. In certain embodiments, at least one modified sugar comprises a 2'-O-methoxyethyl or a 4'-(CH.sub.2).sub.n--O-2' bridge, wherein n is 1 or 2.

[0134] In certain embodiments, at least one nucleoside of said modified oligonucleotide comprises a modified nucleobase. In certain embodiments, the modified nucleobase is a 5-methylcytosine.

[0135] In certain embodiments, the modified oligonucleotide comprises: a) a gap segment consisting of linked deoxynucleosides; b) a 5' wing segment consisting of linked nucleosides; and c) a 3' wing segment consisting of linked nucleosides. The gap segment is positioned between the 5' wing segment and the 3' wing segment and each nucleoside of each wing segment comprises a modified sugar.

[0136] In certain embodiments, the modified oligonucleotide comprises: a) a gap segment consisting of ten linked deoxynucleosides; b) a 5' wing segment consisting of five linked nucleosides; and c) a 3' wing segment consisting of five linked nucleosides. The gap segment is positioned between the 5' wing segment and the 3' wing segment, each nucleoside of each wing segment comprises a 2'-O-methoxyethyl sugar, each internucleoside linkage of said modified oligonucleotide is a phosphorothioate linkage, and each cytosine in said modified oligonucleotide is a 5'-methylcytosine.

[0137] In certain embodiments, the modified oligonucleotide consists of 20 linked nucleosides.

[0138] Certain embodiments provide a method of preferentially reducing CUGexp DMPK RNA, reducing myotonia or reducing spliceopathy in an animal comprising administering to the animal a compound comprising a modified oligonucleotide having a gap segment consisting of ten linked deoxynucleosides, a 5' wing segment consisting of five linked nucleosides and a 3' wing segment consisting of five linked nucleosides. The gap segment is positioned between the 5' wing segment and the 3' wing segment, each nucleoside of each wing segment comprises a 2'-O-methoxyethyl sugar, each internucleoside linkage of said modified oligonucleotide is a phosphorothioate linkage, each cytosine in said modified oligonucleotide is a 5'-methylcytosine.

[0139] Certain embodiments provide the use of any compound as described herein in the manufacture of a medicament for use in any of the therapeutic methods described herein. For example, certain embodiments provide the use of a compound as described herein in the manufacture of a medicament for treating, ameliorating, or preventing type 1 myotonic dystrophy. Certain embodiments provide the use of a compound as described herein in the manufacture of a medicament for inhibiting expression of DMPK and treating, preventing, delaying or ameliorating a DMPK related disease and or a symptom thereof. Certain embodiments provide the use of a compound as described herein in the manufacture of a medicament for reducing DMPK expression in an animal. Certain embodiments provide the use of a compound as described herein in the manufacture of a medicament for preferentially reducing CUGexp DMPK, reducing myotonia, or reducing spliceopathy in an animal. Certain embodiments provide the use of a compound as described herein in the manufacture of a medicament for treating an animal with type 1 myotonic dystrophy. Certain embodiments provide the use of a compound as described herein in the manufacture of a medicament for treating, preventing, delaying, or ameliorating symptoms and outcomes associated with development of DM1 including muscle stiffness, myotonia, disabling distal weakness, weakness in face and jaw muscles, difficulty in swallowing, drooping of the eyelids (ptosis), weakness of neck muscles, weakness in arm and leg muscles, persistent muscle pain, hypersomnia, muscle wasting, dysphagia, respiratory insufficiency, irregular heartbeat, heart muscle damage, apathy, insulin resistance, and cataracts. Certain embodiments provide the use of a compound as described herein in the manufacture of a medicament for counteracting RNA dominance by directing the cleavage of pathogenic transcripts.

[0140] Certain embodiments provide a kit for treating, preventing, or ameliorating type 1 myotonic dystrophy as described herein wherein the kit comprises: a) a compound as described herein; and optionally b) an additional agent or therapy as described herein. The kit can further include instructions or a label for using the kit to treat, prevent, or ameliorate type 1 myotonic dystrophy.

[0141] Certain embodiments provide any compound or composition as described herein, for use in any of the therapeutic methods described herein. For example, certain embodiments provide a compound or composition as described herein for inhibiting expression of DMPK and treating, preventing, delaying or ameliorating a DMPK related disease and or a symptom thereof. Certain embodiments provide a compound or composition as described herein for use in reducing DMPK expression in an animal. Certain embodiments provide a compound or composition as described herein for use in preferentially reducing CUGexp DMPK, reducing myotonia, or reducing spliceopathy in an animal. Certain embodiments provide a compound or composition as described herein for use in treating an animal with type 1 myotonic dystrophy. Certain embodiments provide a compound or composition as described herein for use in treating, preventing, delaying, or ameliorating symptoms and outcomes associated with development of DM1 including muscle stiffness, myotonia, disabling distal weakness, weakness in face and jaw muscles, difficulty in swallowing, drooping of the eyelids (ptosis), weakness of neck muscles, weakness in arm and leg muscles, persistent muscle pain, hypersomnia, muscle wasting, dysphagia, respiratory insufficiency, irregular heartbeat, heart muscle damage, apathy, insulin resistance, and cataracts. Certain embodiments provide a compound or composition as described herein for use in counteracting RNA dominance by directing the cleavage of pathogenic transcripts. Certain embodiments provide compounds comprising a modified oligonucleotide consisting of 12 to 30 linked nucleosides having a nucleobase sequence comprising at least 12 contiguous nucleobases of any of the nucleobase sequences of SEQ ID NOs: 12-156, 160-770, and 774-792.

[0142] Other compounds which can be used in the methods described herein are also provided.

[0143] For example, certain embodiments provide compounds comprising a modified oligonucleotide consisting of 10 to 80, 12 to 50, 12 to 30, 15 to 30, 18 to 24, 19 to 22, or 20 linked nucleosides having a nucleobase sequence comprising at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, or at least 19, contiguous nucleobases of any of the nucleobase sequences of SEQ ID NOs: 41, 44, 76, 109, 153, 320, 321, 322, 325, 329, 335, and 657.

[0144] Certain embodiments provide compounds comprising a modified oligonucleotide consisting of 10 to 80, 12 to 50, 12 to 30, 15 to 30, 18 to 24, 19 to 22, or 20, linked nucleosides having a nucleobase sequence comprising at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, contiguous nucleobases of any of the nucleobase sequences of SEQ ID NOs: 15, 73, 77, 79, 83, 85, 130, 602, 648, 655, 674, and 680.

[0145] Certain embodiments provide compounds comprising a modified oligonucleotide consisting of 10 to 80, 12 to 50, 12 to 30, 15 to 30, 18 to 24, 19 to 22, or 20, linked nucleosides having a nucleobase sequence comprising a portion of at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, or at least 19, or more, contiguous nucleobases complementary to an equal length portion of nucleobases 664-683, 773-792, 926-945, 927-946, 928-947, 931-950, 935-954, 941-960, 2089-2108, 2163-2182, 2490-2509, 2499-2518, 2676-2695, 2685-2704, 2676-2695, 2688-2707, 2697-2716, 2764-2783, and 2770-2789 of SEQ ID NO: 1, wherein the nucleobase sequence is complementary to SEQ ID NO: 1.

[0146] Certain embodiments provide compounds comprising a modified oligonucleotide consisting of 10 to 80, 12 to 50, 12 to 30, 15 to 30, 18 to 24, 19 to 22, or 20, linked nucleosides having a nucleobase sequence comprising a portion of at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, or at least 19, or more, contiguous nucleobases complementary to an equal length portion of nucleobases 812-831, 3629-3648, 4447-4466, 4613-4632, 5803-5822, 5804-5823, 5805-5824, 5808-5827, 5818-5837, 6794-6813, 12463-12482, 13152-13171, and 13553-13572 of SEQ ID NO: 2, wherein the nucleobase sequence is complementary to SEQ ID NO: 2.

[0147] In certain embodiments, the modified oligonucleotide is a single-stranded oligonucleotide.

[0148] In certain embodiments, the nucleobase sequence of the modified oligonucleotide is at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100%, complementary to any of SEQ ID NOs: 1-8 and 793-801.

[0149] In certain embodiments, at least one internucleoside linkage is a modified internucleoside linkage.

[0150] In certain embodiments, each internucleoside linkage is a phosphorothioate internucleoside linkage.

[0151] In certain embodiments, at least one nucleoside comprises a modified sugar.

[0152] In certain embodiments, at least one modified sugar is a bicyclic sugar.

[0153] In certain embodiments, at least one modified sugar comprises a 2'-O-methoxyethyl.

[0154] In certain embodiments, at least one nucleoside comprises a modified nucleobase.

[0155] In certain embodiments, the modified nucleobase is a 5-methylcytosine.

[0156] In certain embodiments, the modified oligonucleotide comprises:

[0157] a gap segment consisting of linked deoxynucleosides;

[0158] a 5' wing segment consisting of linked nucleosides; and

[0159] a 3' wing segment consisting of linked nucleosides;

[0160] wherein the gap segment is positioned between the 5' wing segment and the 3' wing segment and wherein each nucleoside of each wing segment comprises a modified sugar.

[0161] In certain embodiments, the modified oligonucleotide comprises:

[0162] a gap segment consisting of ten linked deoxynucleosides;

[0163] a 5' wing segment consisting of five linked nucleosides; and

[0164] a 3' wing segment consisting of five linked nucleosides;

[0165] wherein the gap segment is positioned between the 5' wing segment and the 3' wing segment, wherein each nucleoside of each wing segment comprises a 2'-O-methoxyethyl sugar; and wherein each internucleoside linkage is a phosphorothioate linkage.

[0166] In certain embodiments, the modified oligonucleotide consists of 14 linked nucleosides.

[0167] In certain embodiments, the modified oligonucleotide consists of 16 linked nucleosides.

[0168] In certain embodiments, the modified oligonucleotide consists of 20 linked nucleosides.

Antisense Compounds

[0169] Oligomeric compounds include, but are not limited to, oligonucleotides, oligonucleosides, oligonucleotide analogs, oligonucleotide mimetics, antisense compounds, antisense oligonucleotides, and siRNAs. An oligomeric compound can be "antisense" to a target nucleic acid, meaning that is capable of undergoing hybridization to a target nucleic acid through hydrogen bonding.

[0170] In certain embodiments, an antisense compound has a nucleobase sequence that, when written in the 5' to 3' direction, comprises the reverse complement of the target segment of a target nucleic acid to which it is targeted. In certain such embodiments, an antisense oligonucleotide has a nucleobase sequence that, when written in the 5' to 3' direction, comprises the reverse complement of the target segment of a target nucleic acid to which it is targeted.

[0171] In certain embodiments, an antisense compound targeted to DMPK as described herein is 10 to 30 nucleotides in length. In other words, the antisense compounds are in some embodiments from 10 to 30 linked nucleobases. In other embodiments, the antisense compound comprises a modified oligonucleotide consisting of 8 to 80, 10 to 80, 12 to 30, 12 to 50, 15 to 30, 18 to 24, 19 to 22, or 20 linked nucleobases. In certain such embodiments, the antisense compound comprises a modified oligonucleotide consisting of 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, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, or 80 linked nucleobases in length, or a range defined by any two of the above values. In certain embodiments, antisense compounds of any of these lengths contain at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, or at least 19, contiguous nucleobases of the nucleobase sequence of any of the exemplary antisense compounds described herein (e.g., at least 8 contiguous nucleobases of a nucleobase sequence recited in any one of SEQ ID NOs: 12-156, 160-770, and 774-792.

[0172] In certain embodiments, the antisense compound comprises a shortened or truncated modified oligonucleotide. The shortened or truncated modified oligonucleotide can have a single nucleoside deleted from the 5' end (5' truncation), or alternatively from the 3' end (3' truncation). A shortened or truncated oligonucleotide can have two nucleosides deleted from the 5' end, or alternatively can have two subunits deleted from the 3' end. Alternatively, the deleted nucleosides can be dispersed throughout the modified oligonucleotide, for example, in an antisense compound having one nucleoside deleted from the 5' end and one nucleoside deleted from the 3' end.

[0173] When a single additional nucleoside is present in a lengthened oligonucleotide, the additional nucleoside can be located at the 5' or 3' end of the oligonucleotide. When two or more additional nucleosides are present, the added nucleosides can be adjacent to each other, for example, in an oligonucleotide having two nucleosides added to the 5' end (5' addition), or alternatively to the 3' end (3' addition), of the oligonucleotide. Alternatively, the added nucleoside can be dispersed throughout the antisense compound, for example, in an oligonucleotide having one nucleoside added to the 5' end and one subunit added to the 3' end.

[0174] It is possible to increase or decrease the length of an antisense compound, such as an antisense oligonucleotide, and/or introduce mismatch bases without eliminating activity. For example, in Woolf et al. (Proc. Natl. Acad. Sci. USA 89:7305-7309, 1992), a series of antisense oligonucleotides 13-25 nucleobases in length were tested for their ability to induce cleavage of a target RNA in an oocyte injection model. Antisense oligonucleotides 25 nucleobases in length with 8 or 11 mismatch bases near the ends of the antisense oligonucleotides were able to direct specific cleavage of the target mRNA, albeit to a lesser extent than the antisense oligonucleotides that contained no mismatches. Similarly, target specific cleavage was achieved using 13 nucleobase antisense oligonucleotides, including those with 1 or 3 mismatches.

[0175] Gautschi et al (J. Natl. Cancer Inst. 93:463-471, March 2001) demonstrated the ability of an oligonucleotide having 100% complementarity to the bcl-2 mRNA and having 3 mismatches to the bcl-xL mRNA to reduce the expression of both bcl-2 and bcl-xL in vitro and in vivo. Furthermore, this oligonucleotide demonstrated potent anti-tumor activity in vivo.

[0176] Maher and Dolnick (Nuc. Acid. Res. 16:3341-3358, 1988) tested a series of tandem 14 nucleobase antisense oligonucleotides, and a 28 and 42 nucleobase antisense oligonucleotides comprised of the sequence of two or three of the tandem antisense oligonucleotides, respectively, for their ability to arrest translation of human DHFR in a rabbit reticulocyte assay. Each of the three 14 nucleobase antisense oligonucleotides alone was able to inhibit translation, albeit at a more modest level than the 28 or 42 nucleobase antisense oligonucleotides.

Antisense Compound Motifs

[0177] In certain embodiments, antisense compounds targeted to a DMPK nucleic acid have chemically modified subunits arranged in patterns, or motifs, to confer to the antisense compounds properties such as enhanced the inhibitory activity, increased binding affinity for a target nucleic acid, or resistance to degradation by in vivo nucleases.

[0178] Chimeric antisense compounds typically contain at least one region modified so as to confer increased resistance to nuclease degradation, increased cellular uptake, increased binding affinity for the target nucleic acid, and/or increased inhibitory activity. A second region of a chimeric antisense compound can optionally serve as a substrate for the cellular endonuclease RNase H, which cleaves the RNA strand of an RNA:DNA duplex.

[0179] Antisense compounds having a gapmer motif are considered chimeric antisense compounds. In a gapmer an internal region having a plurality of nucleotides that supports RNaseH cleavage is positioned between external regions having a plurality of nucleotides that are chemically distinct from the nucleosides of the internal region. In the case of an antisense oligonucleotide having a gapmer motif, the gap segment generally serves as the substrate for endonuclease cleavage, while the wing segments comprise modified nucleosides. In certain embodiments, the regions of a gapmer are differentiated by the types of sugar moieties comprising each distinct region. The types of sugar moieties that are used to differentiate the regions of a gapmer can in some embodiments include .beta.-D-ribonucleosides, .beta.-D-deoxyribonucleosides, 2'-modified nucleosides (such 2'-modified nucleosides can include 2'-MOE, and 2'-O--CH.sub.3, among others), and bicyclic sugar modified nucleosides (such bicyclic sugar modified nucleosides can include those having a 4'-(CH.sub.2).sub.n--O-2' bridge, where n=1 or n=2). Preferably, each distinct region comprises uniform sugar moieties. The wing-gap-wing motif is frequently described as "X-Y-Z", where "X" represents the length of the 5' wing region, "Y" represents the length of the gap region, and "Z" represents the length of the 3' wing region. As used herein, a gapmer described as "X-Y-Z" has a configuration such that the gap segment is positioned immediately adjacent each of the 5' wing segment and the 3' wing segment. Thus, no intervening nucleotides exist between the 5' wing segment and gap segment, or the gap segment and the 3' wing segment. Any of the antisense compounds described herein can have a gapmer motif. In some embodiments, X and Z are the same, in other embodiments they are different. In a preferred embodiment, Y is between 8 and 15 nucleotides. X, Y or Z can be any of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30 or more nucleotides. Thus, gapmers include, but are not limited to, for example 5-10-5, 4-8-4, 4-12-3, 4-12-4, 3-14-3, 2-13-5, 2-16-2, 1-18-1, 3-10-3, 2-10-2, 1-10-1, 2-8-2, 6-8-6, 5-8-5, 1-8-1, or 2-6-2.

[0180] In certain embodiments, the antisense compound as a "wingmer" motif, having a wing-gap or gap-wing configuration, i.e. an X-Y or Y-Z configuration as described above for the gapmer configuration. Thus, wingmer configurations include, but are not limited to, for example 5-10, 8-4, 4-12, 12-4, 3-14, 16-2, 18-1, 10-3, 2-10, 1-10, 8-2, 2-13, or 5-13.

[0181] In certain embodiments, antisense compounds targeted to a DMPK nucleic acid possess a 5-10-5 gapmer motif.

[0182] In certain embodiments, an antisense compound targeted to a DMPK nucleic acid has a gap-widened motif.

[0183] In certain embodiments, antisense compounds of any of these gapmer or wingmer motifs contain at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, or at least 19, contiguous nucleobases of the nucleobase sequence of any of the exemplary antisense compounds described herein (e.g., at least 8 contiguous nucleobases of a nucleobase sequence recited in any one of SEQ ID NOs: 12-156, 160-770, and 774-792.

Target Nucleic Acids, Target Regions and Nucleotide Sequences

[0184] Nucleotide sequences that encode DMPK include, without limitation, the following sequences as set forth in GenBank Accession No. NM_001081560.1 (incorporated herein as SEQ ID NO: 1), GenBank Accession No. NT_011109.15 truncated from nucleotides 18540696 to 18555106 (incorporated herein as SEQ ID NO: 2), GenBank Accession No. NT 039413.7 truncated from nucleotides 16666001 to 16681000 (incorporated herein as SEQ ID NO: 3), GenBank Accession No. NM_032418.1 (incorporated herein as SEQ ID NO: 4), GenBank Accession No. AI007148.1 (incorporated herein as SEQ ID NO: 5), GenBank Accession No. AI304033.1 (incorporated herein as SEQ ID NO: 6), GenBank Accession No. BC024150.1 (incorporated herein as SEQ ID NO: 7), GenBank Accession No. BC056615.1 (incorporated herein as SEQ ID NO: 8), GenBank Accession No. BC075715.1 (incorporated herein as SEQ ID NO: 793), GenBank Accession No. BU519245.1 (incorporated herein as SEQ ID NO: 794), GenBank Accession No. CB247909.1 (incorporated herein as SEQ ID NO: 795), GenBank Accession No. CX208906.1 (incorporated herein as SEQ ID NO: 796), GenBank Accession No. CX732022.1 (incorporated herein as SEQ ID NO: 797), GenBank Accession No. S60315.1 (incorporated herein as SEQ ID NO: 798), GenBank Accession No. S60316.1 (incorporated herein as SEQ ID NO: 799), GenBank Accession No. NM_001081562.1 (incorporated herein as SEQ ID NO: 800), and GenBank Accession No. NM_001100.3 (incorporated herein as SEQ ID NO: 801). It is understood that the sequence set forth in each SEQ ID NO in the Examples contained herein is independent of any modification to a sugar moiety, an internucleoside linkage, or a nucleobase. As such, antisense compounds defined by a SEQ ID NO can comprise, independently, one or more modifications to a sugar moiety, an internucleoside linkage, or a nucleobase. Antisense compounds described by Isis Number (Isis No) indicate a combination of nucleobase sequence and motif.

[0185] In certain embodiments, a target region is a structurally defined region of the target nucleic acid. For example, a target region can encompass a 3' UTR, a 5' UTR, an exon, an intron, an exon/intron junction, a coding region, a translation initiation region, translation termination region, or other defined nucleic acid region. The structurally defined regions for DMPK can be obtained by accession number from sequence databases such as NCBI and such information is incorporated herein by reference. In certain embodiments, a target region can encompass the sequence from a 5' target site of one target segment within the target region to a 3' target site of another target segment within the target region.

[0186] Targeting includes determination of at least one target segment to which an antisense compound hybridizes, such that a desired effect occurs. In certain embodiments, the desired effect is a reduction in mRNA target nucleic acid levels. In certain embodiments, the desired effect is reduction of levels of protein encoded by the target nucleic acid or a phenotypic change associated with the target nucleic acid.

[0187] A target region can contain one or more target segments. Multiple target segments within a target region can be overlapping. Alternatively, they can be non-overlapping. In certain embodiments, target segments within a target region are separated by no more than about 300 nucleotides. In certain embodiments, target segments within a target region are separated by a number of nucleotides that is, is about, is no more than, is no more than about, 250, 200, 150, 100, 90, 80, 70, 60, 50, 40, 30, 20, or 10 nucleotides on the target nucleic acid, or is a range defined by any two of the preceding values. In certain embodiments, target segments within a target region are separated by no more than, or no more than about, 5 nucleotides on the target nucleic acid. In certain embodiments, target segments are contiguous. Contemplated are target regions defined by a range having a starting nucleic acid that is any of the 5' target sites or 3' target sites listed herein.

[0188] Suitable target segments can be found within a 5' UTR, a coding region, a 3' UTR, an intron, an exon, or an exon/intron junction. Target segments containing a start codon or a stop codon are also suitable target segments. A suitable target segment can specifically exclude a certain structurally defined region such as the start codon or stop codon.

[0189] The determination of suitable target segments can include a comparison of the sequence of a target nucleic acid to other sequences throughout the genome. For example, the BLAST algorithm can be used to identify regions of similarity amongst different nucleic acids. This comparison can prevent the selection of antisense compound sequences that can hybridize in a non-specific manner to sequences other than a selected target nucleic acid (i.e., non-target or off-target sequences).

[0190] There can be variation in activity (e.g., as defined by percent reduction of target nucleic acid levels) of the antisense compounds within an active target region. In certain embodiments, reductions in DMPK mRNA levels are indicative of inhibition of DMPK protein expression. Reductions in levels of a DMPK protein are also indicative of inhibition of target mRNA expression. Further, phenotypic changes, such as a reducing myotonia or reducing spliceopathy, can be indicative of inhibition of DMPK mRNA and/or protein expression.

Hybridization

[0191] In some embodiments, hybridization occurs between an antisense compound disclosed herein and a DMPK nucleic acid. The most common mechanism of hybridization involves hydrogen bonding (e.g., Watson-Crick, Hoogsteen or reversed Hoogsteen hydrogen bonding) between complementary nucleobases of the nucleic acid molecules.

[0192] Hybridization can occur under varying conditions. Stringent conditions are sequence-dependent and are determined by the nature and composition of the nucleic acid molecules to be hybridized.

[0193] Methods of determining whether a sequence is specifically hybridizable to a target nucleic acid are well known in the art (Sambrooke and Russell, Molecular Cloning: A Laboratory Manual, 3.sup.rd Ed., 2001). In certain embodiments, the antisense compounds provided herein are specifically hybridizable with a DMPK nucleic acid.

Complementarity

[0194] An antisense compound and a target nucleic acid are complementary to each other when a sufficient number of nucleobases of the antisense compound can hydrogen bond with the corresponding nucleobases of the target nucleic acid, such that a desired effect will occur (e.g., antisense inhibition of a target nucleic acid, such as a DMPK nucleic acid).

[0195] An antisense compound can hybridize over one or more segments of a DMPK nucleic acid such that intervening or adjacent segments are not involved in the hybridization event (e.g., a loop structure, mismatch or hairpin structure).

[0196] In certain embodiments, the antisense compounds provided herein, or a specified portion thereof, are, or are at least, 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% complementary to a DMPK nucleic acid, a target region, target segment, or specified portion thereof. In certain embodiments, the antisense compounds are at least 70%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% complementary to a DMPK nucleic acid, a target region, target segment, or specified portion thereof, and contain at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, or at least 19, contiguous nucleobases of the nucleobase sequence of any of the exemplary antisense compounds described herein (e.g., at least 8 contiguous nucleobases of a nucleobase sequence recited in any one of SEQ ID NOs: 12-156, 160-770, and 774-792). Percent complementarity of an antisense compound with a target nucleic acid can be determined using routine methods, and is measured over the entirety of the antisense compound.

[0197] For example, an antisense compound in which 18 of 20 nucleobases of the antisense compound are complementary to a target region, and would therefore specifically hybridize, would represent 90 percent complementarity. In this example, the remaining noncomplementary nucleobases can be clustered or interspersed with complementary nucleobases and need not be contiguous to each other or to complementary nucleobases. As such, an antisense compound which is 18 nucleobases in length having 4 (four) noncomplementary nucleobases which are flanked by two regions of complete complementarity with the target nucleic acid would have 77.8% overall complementarity with the target nucleic acid and would thus fall within the scope of the present invention. Percent complementarity of an antisense compound with a region of a target nucleic acid can be determined routinely using BLAST programs (basic local alignment search tools) and PowerBLAST programs known in the art (Altschul et al., J. Mol. Biol., 1990, 215, 403 410; Zhang and Madden, Genome Res., 1997, 7, 649 656). Percent homology, sequence identity or complementarity, can be determined by, for example, the Gap program (Wisconsin Sequence Analysis Package, Version 8 for Unix, Genetics Computer Group, University Research Park, Madison Wis.), using default settings, which uses the algorithm of Smith and Waterman (Adv. Appl. Math., 1981, 2, 482 489).

[0198] In certain embodiments, the antisense compounds provided herein, or specified portions thereof, are fully complementary (i.e. 100% complementary) to a target nucleic acid, or specified portion thereof. For example, antisense compound can be fully complementary to a DMPK nucleic acid, or a target region, or a target segment or target sequence thereof. As used herein, "fully complementary" means each nucleobase of an antisense compound is capable of precise base pairing with the corresponding nucleobases of a target nucleic acid. For example, a 20 nucleobase antisense compound is fully complementary to a target sequence that is 400 nucleobases long, so long as there is a corresponding 20 nucleobase portion of the target nucleic acid that is fully complementary to the antisense compound. Fully complementary can also be used in reference to a specified portion of the first and/or the second nucleic acid. For example, a 20 nucleobase portion of a 30 nucleobase antisense compound can be "fully complementary" to a target sequence that is 400 nucleobases long. The 20 nucleobase portion of the 30 nucleobase oligonucleotide is fully complementary to the target sequence if the target sequence has a corresponding 20 nucleobase portion wherein each nucleobase is complementary to the 20 nucleobase portion of the antisense compound. At the same time, the entire 30 nucleobase antisense compound can be fully complementary to the target sequence, depending on whether the remaining 10 nucleobases of the antisense compound are also complementary to the target sequence.

[0199] The location of a non-complementary nucleobase can be at the 5' end or 3' end of the antisense compound. Alternatively, the non-complementary nucleobase or nucleobases can be at an internal position of the antisense compound. When two or more non-complementary nucleobases are present, they can be either contiguous (i.e. linked) or non-contiguous. In one embodiment, a non-complementary nucleobase is located in the wing segment of a gapmer antisense oligonucleotide.

[0200] In certain embodiments, antisense compounds that are, or are up to 10, 12, 13, 14, 15, 16, 17, 18, 19, or 20 nucleobases in length comprise no more than 4, no more than 3, no more than 2, or no more than 1 non-complementary nucleobase(s) relative to a target nucleic acid, such as a DMPK nucleic acid, or specified portion thereof.

[0201] In certain embodiments, antisense compounds that are, or are up to 10, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 nucleobases in length comprise no more than 6, no more than 5, no more than 4, no more than 3, no more than 2, or no more than 1 non-complementary nucleobase(s) relative to a target nucleic acid, such as a DMPK nucleic acid, or specified portion thereof.

[0202] The antisense compounds provided herein also include those which are complementary to a portion of a target nucleic acid. As used herein, "portion" refers to a defined number of contiguous (i.e. linked) nucleobases within a region or segment of a target nucleic acid. A "portion" can also refer to a defined number of contiguous nucleobases of an antisense compound. In certain embodiments, the antisense compounds, are complementary to at least an 8 nucleobase portion of a target segment. In certain embodiments, the antisense compounds are complementary to at least a 10 nucleobase portion of a target segment. In certain embodiments, the antisense compounds are complementary to at least a 15 nucleobase portion of a target segment. Also contemplated are antisense compounds that are complementary to at least an 8, at least a 9, at least a 10, at least an 11, at least a 12, at least a 13, at least a 14, at least a 15, at least a 16, at least a 17, at least an 18, at least a 19, at least a 20, or more nucleobase portion of a target segment, or a range defined by any two of these values.

Identity

[0203] The antisense compounds provided herein can also have a defined percent identity to a particular nucleotide sequence, SEQ ID NO, or compound represented by a specific Isis number, or portion thereof. As used herein, an antisense compound is identical to the sequence disclosed herein if it has the same nucleobase pairing ability. For example, a RNA which contains uracil in place of thymidine in a disclosed DNA sequence would be considered identical to the DNA sequence since both uracil and thymidine pair with adenine. Shortened and lengthened versions of the antisense compounds described herein as well as compounds having non-identical bases relative to the antisense compounds provided herein also are contemplated. The non-identical bases can be adjacent to each other or dispersed throughout the antisense compound. Percent identity of an antisense compound is calculated according to the number of bases that have identical base pairing relative to the sequence to which it is being compared.

[0204] In certain embodiments, the antisense compounds, or portions thereof, are at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to one or more of the exemplary antisense compounds or SEQ ID NOs, or a portion thereof, disclosed herein.

Modifications

[0205] A nucleoside is a base-sugar combination. The nucleobase (also known as base) portion of the nucleoside is normally a heterocyclic base moiety. Nucleotides are nucleosides that further include a phosphate group covalently linked to the sugar portion of the nucleoside. For those nucleosides that include a pentofuranosyl sugar, the phosphate group can be linked to the 2', 3' or 5' hydroxyl moiety of the sugar. Oligonucleotides are formed through the covalent linkage of adjacent nucleosides to one another, to form a linear polymeric oligonucleotide. Within the oligonucleotide structure, the phosphate groups are commonly referred to as forming the internucleoside linkages of the oligonucleotide.

[0206] Modifications to antisense compounds encompass substitutions or changes to internucleoside linkages, sugar moieties, or nucleobases. Modified antisense compounds are often preferred over native forms because of desirable properties such as, for example, enhanced cellular uptake, enhanced affinity for nucleic acid target, increased stability in the presence of nucleases, or increased inhibitory activity.

[0207] Chemically modified nucleosides can also be employed to increase the binding affinity of a shortened or truncated antisense oligonucleotide for its target nucleic acid. Consequently, comparable results can often be obtained with shorter antisense compounds that have such chemically modified nucleosides.

Modified Internucleoside Linkages

[0208] The naturally occurring internucleoside linkage of RNA and DNA is a 3' to 5' phosphodiester linkage. Antisense compounds having one or more modified, i.e. non-naturally occurring, internucleoside linkages are often selected over antisense compounds having naturally occurring internucleoside linkages because of desirable properties such as, for example, enhanced cellular uptake, enhanced affinity for target nucleic acids, and increased stability in the presence of nucleases.

[0209] Oligonucleotides having modified internucleoside linkages include internucleoside linkages that retain a phosphorus atom as well as internucleoside linkages that do not have a phosphorus atom. Representative phosphorus containing internucleoside linkages include, but are not limited to, phosphodiesters, phosphotriesters, methylphosphonates, phosphoramidate, and phosphorothioates. Methods of preparation of phosphorous-containing and non-phosphorous-containing linkages are well known.

[0210] In certain embodiments, antisense compounds targeted to a DMPK nucleic acid comprise one or more modified internucleoside linkages. In certain embodiments, the modified internucleoside linkages are phosphorothioate linkages. In certain embodiments, each internucleoside linkage of an antisense compound is a phosphorothioate internucleoside linkage.

Modified Sugar Moieties

[0211] Antisense compounds of the invention can optionally contain one or more nucleosides wherein the sugar group has been modified. Such sugar modified nucleosides may impart enhanced nuclease stability, increased binding affinity, or some other beneficial biological property to the antisense compounds. In certain embodiments, nucleosides comprise chemically modified ribofuranose ring moieties. Examples of chemically modified ribofuranose rings include without limitation, addition of substitutent groups (including 5' and 2' substituent groups, bridging of non-geminal ring atoms to form bicyclic nucleic acids (BNA), replacement of the ribosyl ring oxygen atom with S, N(R), or C(R.sub.1)(R.sub.2) (R, R.sub.1 and R.sub.2 are each independently H, C.sub.1-C.sub.12 alkyl or a protecting group) and combinations thereof. Examples of chemically modified sugars include 2'-F-5'-methyl substituted nucleoside (see PCT International Application WO 2008/101157 Published on Aug. 21, 2008 for other disclosed 5',2'-bis substituted nucleosides) or replacement of the ribosyl ring oxygen atom with S with 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 BNA (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).

[0212] Examples of nucleosides having modified sugar moieties include without limitation nucleosides comprising 5'-vinyl, 5'-methyl (R or S), 4'-S, 2'-F, 2'-OCH.sub.3, 2'-OCH.sub.2CH.sub.3, 2'-OCH.sub.2CH.sub.2F and 2'-O(CH.sub.2).sub.2OCH.sub.3 substituent groups. The substituent at the 2' position can also be selected from allyl, amino, azido, thio, O-allyl, O--C.sub.1-C.sub.10 alkyl, OCF.sub.3, OCH.sub.2F, 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--C(.dbd.O)--N(R.sub.m)(R.sub.n), and O--CH.sub.2--C(.dbd.O)--N(R.sub.1)--(CH.sub.2).sub.2--N(R.sub.m)(R.sub.n)- , where each R.sub.l, R.sub.m and R.sub.n is, independently, H or substituted or unsubstituted C.sub.1-C.sub.10 alkyl.

[0213] Examples of bicyclic nucleic acids (BNAs) include without limitation nucleosides comprising a bridge between the 4' and the 2' ribosyl ring atoms. In certain embodiments, antisense compounds provided herein include one or more BNA nucleosides wherein the bridge comprises one of the formulas: 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' and 4'-CH(CH.sub.2OCH.sub.3)--O-2' (and analogs thereof see 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 PCT/US2008/068922 published as WO/2009/006478, published Jan. 8, 2009); 4'-CH.sub.2--N(OCH.sub.3)-2' (and analogs thereof see PCT/US2008/064591 published as WO/2008/150729, published Dec. 11, 2008); 4'-CH.sub.2--O--N(CH.sub.3)-2' (see published U.S. Patent Application US2004-0171570, published Sep. 2, 2004); 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 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 PCT/US2008/066154 published as WO 2008/154401, published on Dec. 8, 2008).

[0214] Further bicyclic nucleosides have been reported in published literature (see for example: Srivastava et al., J. Am. Chem. Soc., 2007, 129(26) 8362-8379; Frieden et al., Nucleic Acids Research, 2003, 21, 6365-6372; 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; Wahlestedt et al., Proc. Natl. Acad. Sci. U.S.A, 2000, 97, 5633-5638; Singh et al., Chem. Commun., 1998, 4, 455-456; Koshkin et al., Tetrahedron, 1998, 54, 3607-3630; Kumar et al., Bioorg. Med. Chem. Lett., 1998, 8, 2219-2222; Singh et al., J. Org. Chem., 1998, 63, 10035-10039; U.S. Pat. Nos. 7,399,845; 7,053,207; 7,034,133; 6,794,499; 6,770,748; 6,670,461; 6,525,191; 6,268,490; U.S. Patent Publication Nos.: US2008-0039618; US2007-0287831; US2004-0171570; U.S. patent application Ser. No. 12/129,154; 61/099,844; 61/097,787; 61/086,231; 61/056,564; 61/026,998; 61/026,995; 60/989,574; International applications WO 2007/134181; WO 2005/021570; WO 2004/106356; WO 94/14226; and PCT International Applications Nos.: PCT/US2008/068922; PCT/US2008/066154; and PCT/US2008/064591). Each of the foregoing bicyclic nucleosides can be prepared having one or more stereochemical sugar configurations including for example .alpha.-L-ribofuranose and .beta.-D-ribofuranose (see PCT international application PCT/DK98/00393, published on Mar. 25, 1999 as WO 99/14226).

[0215] In certain embodiments, bicyclic nucleosides comprise a bridge between the 4' and the 2' carbon atoms of the pentofuranosyl sugar moiety including without limitation, bridges comprising 1 or 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)--; wherein: x is 0, 1, or 2; n is 1, 2, 3, or 4; 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

[0216] 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.

[0217] In certain embodiments, the bridge of a bicyclic sugar moiety is, --[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)--. In certain embodiments, the bridge is 4'-CH.sub.2-2', 4'-(CH.sub.2).sub.2-2', 4'-(CH.sub.2).sub.3-2', 4'-(CH.sub.2).sub.2--O-2', 4'-CH.sub.2--O--N(R)-2' and 4'-CH.sub.2--N(R)--O-2'- wherein each R is, independently, H, a protecting group or C.sub.1-C.sub.12 alkyl.

[0218] In certain embodiments, bicyclic nucleosides are further defined by isomeric configuration. For example, a nucleoside comprising a 4'-(CH.sub.2)--O-2' bridge, may be in the .alpha.-L configuration or in the .beta.-D configuration. Previously, .alpha.-L-methyleneoxy (4'-CH.sub.2--O-2') BNA's have been incorporated into antisense oligonucleotides that showed antisense activity (Frieden et al., Nucleic Acids Research, 2003, 21, 6365-6372).

[0219] In certain embodiments, bicyclic nucleosides include those having a 4' to 2' bridge wherein such bridges include without limitation, .alpha.-L-4'-(CH.sub.2)--O-2', .beta.-D-4'-(CH.sub.2).sub.2--O-2', 4'-(CH.sub.2).sub.2--O-2', 4'-CH.sub.2--O--N(R)-2', 4'-CH.sub.2--N(R)--O-2', 4'-CH(CH.sub.3)--O-2', 4'-CH.sub.2--S-2', 4'-CH.sub.2--N(R)-2', 4'-CH.sub.2--CH(CH.sub.3)-2', and 4'-(CH.sub.2).sub.3-2', wherein R is H, a protecting group or C.sub.1-C.sub.12 alkyl.

[0220] In certain embodiments, bicyclic nucleosides have the formula:

##STR00001##

wherein:

[0221] Bx is a heterocyclic base moiety;

[0222] -Q.sub.a-Q.sub.b-Q.sub.c- is --CH.sub.2--N(R.sub.c)--CH.sub.2--, --C(.dbd.O)--N(R.sub.c)--CH.sub.2--, --CH.sub.2--O--N(R.sub.c)--, --CH.sub.2--N(R.sub.c)--O-- or --N(R.sub.c)--O--CH.sub.2;

[0223] R.sub.c is C.sub.1-C.sub.12 alkyl or an amino protecting group; and

[0224] T.sub.a and T.sub.b are each, independently H, a hydroxyl protecting group, a conjugate group, a reactive phosphorus group, a phosphorus moiety or a covalent attachment to a support medium.

[0225] In certain embodiments, bicyclic nucleosides have the formula:

##STR00002##

wherein:

[0226] Bx is a heterocyclic base moiety;

[0227] T.sub.a and T.sub.b are each, independently H, a hydroxyl protecting group, a conjugate group, a reactive phosphorus group, a phosphorus moiety or a covalent attachment to a support medium;

[0228] Z.sub.a is C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.2-C.sub.6 alkynyl, substituted C.sub.1-C.sub.6 alkyl, substituted C.sub.2-C.sub.6 alkenyl, substituted C.sub.2-C.sub.6 alkynyl, acyl, substituted acyl, substituted amide, thiol or substituted thiol.

[0229] In one embodiment, each of the substituted groups, is, independently, mono or poly substituted with substituent groups independently selected from halogen, oxo, hydroxyl, OJ.sub.c, NJ.sub.cJ.sub.d, SJ.sub.c, N.sub.3, OC(.dbd.X)J.sub.c, and NJ.sub.eC(.dbd.X)NJ.sub.cJ.sub.d, wherein each J.sub.c, J.sub.d and J.sub.e is, independently, H, C.sub.1-C.sub.6 alkyl, or substituted C.sub.1-C.sub.6 alkyl and X is O or NJ.sub.c.

[0230] In certain embodiments, bicyclic nucleosides have the formula:

##STR00003##

wherein:

[0231] Bx is a heterocyclic base moiety;

[0232] T.sub.a and T.sub.b are each, independently H, a hydroxyl protecting group, a conjugate group, a reactive phosphorus group, a phosphorus moiety or a covalent attachment to a support medium;

[0233] Z.sub.b is C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.2-C.sub.6 alkynyl, substituted C.sub.1-C.sub.6 alkyl, substituted C.sub.2-C.sub.6 alkenyl, substituted C.sub.2-C.sub.6 alkynyl or substituted acyl (C(.dbd.O)--).

[0234] In certain embodiments, bicyclic nucleosides have the formula:

##STR00004##

wherein:

[0235] Bx is a heterocyclic base moiety;

[0236] T.sub.a and T.sub.b are each, independently H, a hydroxyl protecting group, a conjugate group, a reactive phosphorus group, a phosphorus moiety or a covalent attachment to a support medium;

[0237] R.sub.d is 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;

[0238] each q.sub.a, q.sub.b, q.sub.c and q.sub.d is, independently, H, halogen, 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, C.sub.1-C.sub.6 alkoxyl, substituted C.sub.1-C.sub.6 alkoxyl, acyl, substituted acyl, C.sub.1-C.sub.6 aminoalkyl or substituted C.sub.1-C.sub.6 aminoalkyl;

[0239] In certain embodiments, bicyclic nucleosides have the formula:

##STR00005##

wherein:

[0240] Bx is a heterocyclic base moiety;

[0241] T.sub.a and T.sub.b are each, independently H, a hydroxyl protecting group, a conjugate group, a reactive phosphorus group, a phosphorus moiety or a covalent attachment to a support medium;

[0242] q.sub.a, q.sub.b, q.sub.e and q.sub.f are each, independently, hydrogen, halogen, 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.1-C.sub.12 alkoxy, substituted C.sub.1-C.sub.12 alkoxy, OJ.sub.j, SJ.sub.j, SOJ.sub.j, SO.sub.2J.sub.j, NJ.sub.jJ.sub.k, N.sub.3, CN, C(.dbd.O)OJ.sub.j, C(.dbd.O)NJ.sub.jJ.sub.k, C(.dbd.O)J.sub.j, O--C(.dbd.O)NJ.sub.jJ.sub.k, N(H)C(.dbd.NH)NJ.sub.jJ.sub.k, N(H)C(.dbd.O)NJ.sub.jJ.sub.k or N(H)C(.dbd.S)NJ.sub.jJ.sub.k;

[0243] or q.sub.e and of together are .dbd.C(q.sub.g)(q.sub.h);

[0244] q.sub.g and q.sub.h are each, independently, H, halogen, C.sub.1-C.sub.12 alkyl or substituted C.sub.1-C.sub.12 alkyl.

[0245] The synthesis and preparation of adenine, cytosine, guanine, 5-methyl-cytosine, thymine and uracil bicyclic nucleosides having a 4'-CH.sub.2--O-2' bridge, along with their oligomerization, and nucleic acid recognition properties have been described (Koshkin et al., Tetrahedron, 1998, 54, 3607-3630). The synthesis of bicyclic nucleosides has also been described in WO 98/39352 and WO 99/14226.

[0246] Analogs of various bicyclic nucleosides that have 4' to 2' bridging groups such as 4'-CH.sub.2--O-2' and 4'-CH.sub.2--S-2', have also been prepared (Kumar et al., Bioorg. Med. Chem. Lett., 1998, 8, 2219-2222). Preparation of oligodeoxyribonucleotide duplexes comprising bicyclic nucleosides for use as substrates for nucleic acid polymerases has also been described (Wengel et al., WO 99/14226). Furthermore, synthesis of 2'-amino-BNA, a novel conformationally restricted high-affinity oligonucleotide analog has been described in the art (Singh et al., J. Org. Chem., 1998, 63, 10035-10039). In addition, 2'-amino- and 2'-methylamino-BNA's have been prepared and the thermal stability of their duplexes with complementary RNA and DNA strands has been previously reported.

[0247] In certain embodiments, bicyclic nucleosides have the formula:

##STR00006##

wherein:

[0248] Bx is a heterocyclic base moiety;

[0249] T.sub.a and T.sub.b are each, independently H, a hydroxyl protecting group, a conjugate group, a reactive phosphorus group, a phosphorus moiety or a covalent attachment to a support medium;

[0250] each q.sub.1, q.sub.j, q.sub.k and q.sub.l is, independently, H, halogen, 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.1-C.sub.12 alkoxyl, substituted C.sub.1-C.sub.12 alkoxyl, OJ.sub.j, SJ.sub.j, SOJ.sub.j, SO.sub.2J.sub.j, NJ.sub.jJ.sub.k, N.sub.3, CN, C(.dbd.O)OJ.sub.j, C(.dbd.O)NJ.sub.jJ.sub.k, C(.dbd.O)J.sub.j, O--C(.dbd.O)NJ.sub.jJ.sub.k, N(H)C(.dbd.NH)NJ.sub.jJ.sub.k, N(H)C(.dbd.O)NJ.sub.jJ.sub.k or N(H)C(.dbd.S)NJ.sub.jJ.sub.k; and

[0251] q.sub.1 and q.sub.j or q.sub.l and q.sub.k together are .dbd.C(q.sub.g)(q.sub.h), wherein q.sub.g and q.sub.h are each, independently, H, halogen, C.sub.1-C.sub.12 alkyl or substituted C.sub.1-C.sub.12 alkyl.

[0252] One carbocyclic bicyclic nucleoside having a 4'-(CH.sub.2).sub.3-2' bridge and the alkenyl analog bridge 4'-CH.dbd.CH--CH.sub.2-2' have been described (Frier et al., Nucleic Acids Research, 1997, 25(22), 4429-4443 and Albaek et al., J. Org. Chem., 2006, 71, 7731-7740). The synthesis and preparation of carbocyclic bicyclic nucleosides along with their oligomerization and biochemical studies have also been described (Srivastava et al., J. Am. Chem. Soc. 2007, 129(26), 8362-8379).

[0253] In certain embodiments, 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, (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, (J) propylene carbocyclic (4'-(CH.sub.2).sub.3-2') BNA, and (K) vinyl BNA as depicted below.

##STR00007## ##STR00008##

wherein Bx is the base moiety and R is, independently, H, a protecting group, C.sub.1-C.sub.6 alkyl or C.sub.1-C.sub.6 alkoxy.

[0254] In certain embodiments, nucleosides are modified by replacement of the ribosyl ring with a sugar surrogate. Such modification includes without limitation, replacement of the ribosyl ring with a surrogate ring system (sometimes referred to as DNA analogs) such as a morpholino ring, a cyclohexenyl ring, a cyclohexyl ring or a tetrahydropyranyl ring such as one having one of the formula:

##STR00009##

[0255] In certain embodiments, sugar surrogates are selected having the formula:

##STR00010##

wherein:

[0256] Bx is a heterocyclic base moiety;

[0257] T.sub.3 and T.sub.4 are each, independently, an internucleoside linking group linking the tetrahydropyran nucleoside analog to the oligomeric compound or one of T.sub.3 and T.sub.4 is an internucleoside linking group linking the tetrahydropyran nucleoside analog to an oligomeric compound or oligonucleotide 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

[0258] one of R.sub.1 and R.sub.2 is hydrogen and the other is selected from 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.

[0259] In certain embodiments, 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 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.

[0260] Such sugar surrogates include, but are not limited to, what is referred to in the art as hexitol nucleic acid (HNA), altritol nucleic acid (ANA), and mannitol nucleic acid (MNA) (see Leumann, C. J., Bioorg. & Med. Chem., 2002, 10, 841-854).

[0261] In certain embodiments, antisense compounds comprise one or more modified cyclohexenyl nucleosides, which is a nucleoside having a six-membered cyclohexenyl in place of the pentofuranosyl residue in naturally occurring nucleosides. Modified cyclohexenyl nucleosides include, but are not limited to those described in the art (see for example commonly owned, published PCT Application WO 2010/036696, published on Apr. 10, 2010, Robeyns et al., J. Am. Chem. Soc., 2008, 130(6), 1979-1984; Horvath et al., Tetrahedron Letters, 2007, 48, 3621-3623; Nauwelaerts et al., J. Am. Chem. Soc., 2007, 129(30), 9340-9348; Gu et al., Nucleosides, Nucleotides & Nucleic Acids, 2005, 24(5-7), 993-998; Nauwelaerts et al., Nucleic Acids Research, 2005, 33(8), 2452-2463; Robeyns et al., Acta Crystallographica, Section F: Structural Biology and Crystallization Communications, 2005, F61(6), 585-586; Gu et al., Tetrahedron, 2004, 60(9), 2111-2123; Gu et al., Oligonucleotides, 2003, 13(6), 479-489; Wang et al., J. Org. Chem., 2003, 68, 4499-4505; Verbeure et al., Nucleic Acids Research, 2001, 29(24), 4941-4947; Wang et al., J. Org. Chem., 2001, 66, 8478-82; Wang et al., Nucleosides, Nucleotides & Nucleic Acids, 2001, 20(4-7), 785-788; Wang et al., J. Am. Chem., 2000, 122, 8595-8602; Published PCT application, WO 06/047842; and Published PCT Application WO 01/049687; the text of each is incorporated by reference herein, in their entirety). Certain modified cyclohexenyl nucleosides have the formula:

##STR00011##

wherein:

[0262] Bx is a heterocyclic base moiety;

[0263] T.sub.3 and T.sub.4 are each, independently, an internucleoside linking group linking the cyclohexenyl nucleoside analog to an antisense compound or one of T.sub.3 and T.sub.4 is an internucleoside linking group linking the tetrahydropyran nucleoside analog to an 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; and q.sub.1, q.sub.2, q.sub.3, q.sub.4, q.sub.5, q.sub.6, q.sub.7, q.sub.8 and q.sub.9 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, substituted C.sub.2-C.sub.6 alkynyl or other sugar substituent group.

[0264] Many other bicyclic and tricyclic sugar surrogate ring systems are also known in the art that can be used to modify nucleosides for incorporation into antisense compounds (see for example review article: Leumann, Christian J., Bioorg. & Med. Chem., 2002, 10, 841-854). Such ring systems can undergo various additional substitutions to enhance activity.

[0265] Methods for the preparations of modified sugars are well known to those skilled in the art. Some representative U.S. patents that teach the preparation of such modified sugars include without limitation, U.S.: 4,981,957; 5,118,800; 5,319,080; 5,359,044; 5,393,878; 5,446,137; 5,466,786; 5,514,785; 5,519,134; 5,567,811; 5,576,427; 5,591,722; 5,597,909; 5,610,300; 5,627,053; 5,639,873; 5,646,265; 5,670,633; 5,700,920; 5,792,847 and 6,600,032 and International Application PCT/US2005/019219, filed Jun. 2, 2005 and published as WO 2005/121371 on Dec. 22, 2005, and each of which is herein incorporated by reference in its entirety.

[0266] In nucleotides having modified sugar moieties, the nucleobase moieties (natural, modified or a combination thereof) are maintained for hybridization with an appropriate nucleic acid target.

[0267] In certain embodiments, antisense compounds targeted to a DMPK nucleic acid comprise one or more nucleotides having modified sugar moieties. In certain embodiments, the modified sugar moiety is 2'-MOE. In certain embodiments, the 2'-MOE modified nucleotides are arranged in a gapmer motif.

Modified Nucleobases

[0268] Nucleobase (or base) modifications or substitutions are structurally distinguishable from, yet functionally interchangeable with, naturally occurring or synthetic unmodified nucleobases. Both natural and modified nucleobases are capable of participating in hydrogen bonding. Such nucleobase modifications can impart nuclease stability, binding affinity or some other beneficial biological property to antisense compounds. Modified nucleobases include synthetic and natural nucleobases such as, for example, 5-methylcytosine (5-me-C). Certain nucleobase substitutions, including 5-methylcytosine substitutions, are particularly useful for increasing the binding affinity of an antisense compound for a target nucleic acid. For example, 5-methylcytosine substitutions have been shown to increase nucleic acid duplex stability by 0.6-1.2.degree. C. (Sanghvi, Y. S., Crooke, S. T. and Lebleu, B., eds., Antisense Research and Applications, CRC Press, Boca Raton, 1993, pp. 276-278).

[0269] Additional unmodified nucleobases include 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--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 and 3-deazaguanine and 3-deazaadenine.

[0270] Heterocyclic base moieties can 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. Nucleobases that are particularly useful for increasing the binding affinity of antisense compounds include 5-substituted pyrimidines, 6-azapyrimidines and N-2, N-6 and O-6 substituted purines, including 2 aminopropyladenine, 5-propynyluracil and 5-propynylcytosine.

[0271] In certain embodiments, antisense compounds targeted to a DMPK nucleic acid comprise one or more modified nucleobases. In certain embodiments, gap-widened antisense oligonucleotides targeted to a DMPK nucleic acid comprise one or more modified nucleobases. In certain embodiments, the modified nucleobase is 5-methylcytosine. In certain embodiments, each cytosine is a 5-methylcytosine.

Compositions and Methods for Formulating Pharmaceutical Compositions

[0272] Antisense oligonucleotides can be admixed with pharmaceutically acceptable active or inert substance for the preparation of pharmaceutical compositions or formulations. Compositions and methods for the formulation of pharmaceutical compositions are dependent upon a number of criteria, including, but not limited to, route of administration, extent of disease, or dose to be administered.

[0273] Antisense compound targeted to a DMPK nucleic acid can be utilized in pharmaceutical compositions by combining the antisense compound with a suitable pharmaceutically acceptable diluent or carrier. A pharmaceutically acceptable diluent includes phosphate-buffered saline (PBS). PBS is a diluent suitable for use in compositions to be delivered parenterally. Accordingly, in one embodiment, employed in the methods described herein is a pharmaceutical composition comprising an antisense compound targeted to a DMPK nucleic acid and a pharmaceutically acceptable diluent. In certain embodiments, the pharmaceutically acceptable diluent is PBS. In certain embodiments, the antisense compound is an antisense oligonucleotide.

[0274] Pharmaceutical compositions comprising antisense compounds encompass any pharmaceutically acceptable salts, esters, or salts of such esters, or any other 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.

[0275] A prodrug can include the incorporation of additional nucleosides at one or both ends of an antisense compound which are cleaved by endogenous nucleases within the body, to form the active antisense compound.

Conjugated Antisense Compounds

[0276] Antisense compounds can be covalently linked to one or more moieties or conjugates which enhance the activity, cellular distribution or cellular uptake of the resulting antisense oligonucleotides. Typical conjugate groups include cholesterol moieties and lipid moieties. Additional conjugate groups include carbohydrates, phospholipids, biotin, phenazine, folate, phenanthridine, anthraquinone, acridine, fluoresceins, rhodamines, coumarins, and dyes.

[0277] Antisense compounds can also be modified to have one or more stabilizing groups that are generally attached to one or both termini of antisense compounds to enhance properties such as, for example, nuclease stability. Included in stabilizing groups are cap structures. These terminal modifications protect the antisense compound having terminal nucleic acid from exonuclease degradation, and can help in delivery and/or localization within a cell. The cap can be present at the 5'-terminus (5'-cap), or at the 3'-terminus (3'-cap), or can be present on both termini. Cap structures are well known in the art and include, for example, inverted deoxy abasic caps. Further 3' and 5'-stabilizing groups that can be used to cap one or both ends of an antisense compound to impart nuclease stability include those disclosed in WO 03/004602 published on Jan. 16, 2003.

Cell Culture and Antisense Compounds Treatment

[0278] The effects of antisense compounds on the level, activity or expression of DMPK nucleic acids can be tested in vitro in a variety of cell types. Cell types used for such analyses are available from commercial vendors (e.g. American Type Culture Collection, Manassas, Va.; Zen-Bio, Inc., Research Triangle Park, N.C.; Clonetics Corporation, Walkersville, Md.) and cells are cultured according to the vendor's instructions using commercially available reagents (e.g. Invitrogen Life Technologies, Carlsbad, Calif.). Illustrative cell types include, but are not limited to, HepG2 cells, Hep3B cells, primary hepatocytes, A549 cells, GM04281 fibroblasts and LLC-MK2 cells.

In Vitro Testing of Antisense Oligonucleotides

[0279] Described herein are methods for treatment of cells with antisense oligonucleotides, which can be modified appropriately for treatment with other antisense compounds.

[0280] In general, cells are treated with antisense oligonucleotides when the cells reach approximately 60-80% confluence in culture.

[0281] One reagent commonly used to introduce antisense oligonucleotides into cultured cells includes the cationic lipid transfection reagent LIPOFECTIN.RTM. (Invitrogen, Carlsbad, Calif.). Antisense oligonucleotides are mixed with LIPOFECTIN.RTM. in OPTI-MEM.RTM. 1 (Invitrogen, Carlsbad, Calif.) to achieve the desired final concentration of antisense oligonucleotide and a LIPOFECTIN.RTM. concentration that typically ranges 2 to 12 ug/mL per 100 nM antisense oligonucleotide.

[0282] Another reagent used to introduce antisense oligonucleotides into cultured cells includes LIPOFECTAMINE 2000.RTM. (Invitrogen, Carlsbad, Calif.). Antisense oligonucleotide is mixed with LIPOFECTAMINE 2000.RTM. in OPTI-MEM.RTM. 1 reduced serum medium (Invitrogen, Carlsbad, Calif.) to achieve the desired concentration of antisense oligonucleotide and a LIPOFECTAMINE.RTM. concentration that typically ranges 2 to 12 ug/mL per 100 nM antisense oligonucleotide.

[0283] Another reagent used to introduce antisense oligonucleotides into cultured cells includes Cytofectin.RTM. (Invitrogen, Carlsbad, Calif.). Antisense oligonucleotide is mixed with Cytofectin.RTM. in OPTI-MEM.RTM. 1 reduced serum medium (Invitrogen, Carlsbad, Calif.) to achieve the desired concentration of antisense oligonucleotide and a Cytofectin.RTM. concentration that typically ranges 2 to 12 ug/mL per 100 nM antisense oligonucleotide.

[0284] Another technique used to introduce antisense oligonucleotides into cultured cells includes electroporation.

[0285] Cells are treated with antisense oligonucleotides by routine methods. Cells are typically harvested 16-24 hours after antisense oligonucleotide treatment, at which time RNA or protein levels of target nucleic acids are measured by methods known in the art and described herein. In general, when treatments are performed in multiple replicates, the data are presented as the average of the replicate treatments.

[0286] The concentration of antisense oligonucleotide used varies from cell line to cell line. Methods to determine the optimal antisense oligonucleotide concentration for a particular cell line are well known in the art. Antisense oligonucleotides are typically used at concentrations ranging from 1 nM to 300 nM when transfected with LIPOFECTAMINE 2000.RTM., Lipofectin or Cytofectin. Antisense oligonucleotides are used at higher concentrations ranging from 625 to 20,000 nM when transfected using electroporation.

RNA Isolation

[0287] RNA analysis can be performed on total cellular RNA or poly(A)+ mRNA. Methods of RNA isolation are well known in the art. RNA is prepared using methods well known in the art, for example, using the TRIZOL.RTM. Reagent (Invitrogen, Carlsbad, Calif.) according to the manufacturer's recommended protocols.

Analysis of Inhibition of Target Levels or Expression

[0288] Inhibition of levels or expression of a DMPK nucleic acid can be assayed in a variety of ways known in the art. For example, target nucleic acid levels can be quantitated by, e.g., Northern blot analysis, competitive polymerase chain reaction (PCR), or quantitative real-time PCR. RNA analysis can be performed on total cellular RNA or poly(A)+ mRNA. Methods of RNA isolation are well known in the art. Northern blot analysis is also routine in the art. Quantitative real-time PCR can be conveniently accomplished using the commercially available ABI PRISM.RTM. 7600, 7700, or 7900 Sequence Detection System, available from PE-Applied Biosystems, Foster City, Calif. and used according to manufacturer's instructions.

Quantitative Real-Time PCR Analysis of Target RNA Levels

[0289] Quantitation of target RNA levels can be accomplished by quantitative real-time PCR using the ABI PRISM.RTM. 7600, 7700, or 7900 Sequence Detection System (PE-Applied Biosystems, Foster City, Calif.) according to manufacturer's instructions. Methods of quantitative real-time PCR are well known in the art.

[0290] Prior to real-time PCR, the isolated RNA is subjected to a reverse transcriptase (RT) reaction, which produces complementary DNA (cDNA) that is then used as the substrate for the real-time PCR amplification. The RT and real-time PCR reactions are performed sequentially in the same sample well. RT and real-time PCR reagents are obtained from Invitrogen (Carlsbad, Calif.). RT, real-time-PCR reactions are carried out by methods well known to those skilled in the art.

[0291] Gene (or RNA) target quantities obtained by real time PCR are normalized using either the expression level of a gene whose expression is constant, such as cyclophilin A, or by quantifying total RNA using RIBOGREEN.RTM. (Invitrogen, Inc. Carlsbad, Calif.). Cyclophilin A expression is quantified by real time PCR, by being run simultaneously with the target, multiplexing, or separately. Total RNA is quantified using RIBOGREEN.RTM. RNA quantification reagent (Invitrogen, Inc. Eugene, Oreg.). Methods of RNA quantification by RIBOGREEN.RTM. are taught in Jones, L. J., et al, (Analytical Biochemistry, 1998, 265, 368-374). A CYTOFLUOR.RTM. 4000 instrument (PE Applied Biosystems) is used to measure RIBOGREEN.RTM. fluorescence.

[0292] Probes and primers are designed to hybridize to a DMPK nucleic acid. Methods for designing real-time PCR probes and primers are well known in the art, and can include the use of software such as PRIMER EXPRESS.RTM. Software (Applied Biosystems, Foster City, Calif.).

Analysis of Protein Levels

[0293] Antisense inhibition of DMPK nucleic acids can be assessed by measuring DMPK protein levels. Protein levels of DMPK can be evaluated or quantitated in a variety of ways well known in the art, such as immunoprecipitation, Western blot analysis (immunoblotting), enzyme-linked immunosorbent assay (ELISA), quantitative protein assays, protein activity assays (for example, caspase activity assays), immunohistochemistry, immunocytochemistry or fluorescence-activated cell sorting (FACS). Antibodies directed to a target can be identified and obtained from a variety of sources, such as the MSRS catalog of antibodies (Aerie Corporation, Birmingham, Mich.), or can be prepared via conventional monoclonal or polyclonal antibody generation methods well known in the art.

In Vivo Testing of Antisense Compounds

[0294] Antisense compounds, for example, antisense oligonucleotides, are tested in animals to assess their ability to inhibit expression of DMPK and produce phenotypic changes. Testing can be performed in normal animals, or in experimental disease models, for example, the HSA.sup.LR mouse model of myotonic dystrophy (DM1).

[0295] The HSA.sup.LR mouse model is an established model for DM1 (Mankodi, A. et al. Science. 289: 1769, 2000). The mice carry a human skeletal actin (hACTA1) transgene with 220 CTG repeats inserted in the 3' UTR of the gene. The hACTA1-CUG.sup.exp transcript accumulates in nuclear foci in skeletal muscles and results in myotonia similar to that in human DM1 (Mankodi, A. et al. Mol. Cell 10: 35, 2002; Lin, X. et al. Hum. Mol. Genet. 15: 2087, 2006). Hence, it is expected that amelioration of DM1 symptoms in the HSA.sup.LR mouse by antisense inhibition of the hACTA1 transgene would predict amelioration of similar symptoms in human patients by antisense inhibition of the DMPK transcript.

[0296] Expression of CUG.sup.exp RNA in mice causes extensive remodeling of the muscle transcriptome, much of which is reproduced by ablation of MBNL1. Hence, it is expected that normalization of the transcriptome in HSA.sup.LR mice would predict normalization of the human transcriptome in DM1 patients by antisense inhibition of the DMPK transcript.

[0297] For administration to animals, antisense oligonucleotides are formulated in a pharmaceutically acceptable diluent, such as phosphate-buffered saline. Administration includes parenteral routes of administration. Following a period of treatment with antisense oligonucleotides, RNA is isolated from tissue and changes in DMPK nucleic acid expression are measured. Changes in DMPK protein levels are also measured.

Splicing

[0298] Myotonic dystrophy (DM1) is caused by CTG repeat expansions in the 3' untranslated region of the DMPK gene (Brook, J. D. et al. Cell. 68: 799, 1992). This mutation leads to RNA dominance, a process in which expression of RNA containing an expanded CUG repeat (CUGexp) induces cell dysfunction (Osborne R J and Thornton C A., Human Molecular Genetics., 2006, 15(2): R162-R169). Such CUGexp are retained in the nuclear foci of skeletal muscles (Davis, B. M. et al. Proc. Natl. Acad. Sci. U.S.A. 94:7388, 1997). The accumulation of CUGexp in the nuclear foci leads to the sequestration of poly(CUG)-binding proteins, such as, Muscleblind-like 1 (MBLN1) (Miller, J. W. et al. EMBO J. 19: 4439, 2000). MBLN1 is a splicing factor and regulates the splicing of genes such as Serca1, CIC-1, Titin, and Zasp. Therefore, sequestration of MBLN1 by CUGexp triggers misregulated alternative splicing of the exons of genes that MBLN1 normally controls (Lin, X. et al. Hum. Mol. Genet. 15: 2087, 2006). Correction of alternative splicing in an animal displaying such disregulation, such as, for example, in a DM1 patient and the HSALR mouse model, is a useful indicator for the efficacy of a treatment, including treatment with an antisense oligonucleotide.

Certain Biomarkers

[0299] DM1 severity in mouse models is determined, at least in part, by the level of CUG.sup.exp transcript accumulation in the nucleus or nuclear foci. A useful physiological marker for DM1 severity is the development of high-frequency runs of involuntary action potentials (myotonia).

Certain Indications

[0300] In certain embodiments, provided herein are methods of treating an individual comprising administering one or more pharmaceutical compositions as described herein. In certain embodiments, the individual has type 1 myotonic dystrophy (DM1).

[0301] Accordingly, provided herein are methods for ameliorating a symptom associated with type 1 myotonic dystrophy in a subject in need thereof. In certain embodiments, provided is a method for reducing the rate of onset of a symptom associated with type 1 myotonic dystrophy. In certain embodiments, provided is a method for reducing the severity of a symptom associated with type 1 myotonic dystrophy. In certain embodiments, symptoms associated with DM1 include muscle stiffness, myotonia, disabling distal weakness, weakness in face and jaw muscles, difficulty in swallowing, drooping of the eyelids (ptosis), weakness of neck muscles, weakness in arm and leg muscles, persistent muscle pain, hypersomnia, muscle wasting, dysphagia, respiratory insufficiency, irregular heartbeat, heart muscle damage, apathy, insulin resistance, and cataracts. In children, the symptoms may also be developmental delays, learning problems, language and speech issues, and personality development issues.

[0302] In certain embodiments, the methods comprise administering to an individual in need thereof a therapeutically effective amount of a compound targeted to a DMPK nucleic acid.

[0303] In certain embodiments, administration of an antisense compound targeted to a DMPK nucleic acid results in reduction of DMPK expression by at least about 15%, by at least about 20%, by at least about 25%, by at least about 30%, by at least about 35%, by at least about 40%, by at least about 45%, by at least about 50%, by at least about 55%, by at least about 60%, by least about 65%, by least about 70%, by least about 75%, by least about 80%, by at least about 85%, by at least about 90%, by at least about 95% or by at least about 99%, or a range defined by any two of these values.

[0304] In certain embodiments, pharmaceutical compositions comprising an antisense compound targeted to DMPK are used for the preparation of a medicament for treating a patient suffering or susceptible to type 1 myotonic dystrophy.

[0305] In certain embodiments, the methods described herein include administering a compound comprising a modified oligonucleotide having a contiguous nucleobases portion as described herein of a sequence recited in SEQ ID NO: 12-156, 160-770, and 774-792.

Administration

[0306] In certain embodiments, the compounds and compositions as described herein are administered parenterally.

[0307] In certain embodiments, parenteral administration is by infusion. Infusion can be chronic or continuous or short or intermittent. In certain embodiments, infused pharmaceutical agents are delivered with a pump. In certain embodiments, parenteral administration is by injection (e.g., bolus injection). The injection can be delivered with a syringe.

[0308] Parenteral administration includes subcutaneous administration, intravenous administration, intramuscular administration, intraarterial administration, intraperitoneal administration, or intracranial administration, e.g., intrathecal or intracerebroventricular administration. Administration can be continuous, or chronic, or short, or intermittent.

[0309] In certain embodiments, the administering is subcutaneous, intravenous, intracerebral, intracerebroventricular, intrathecal or another administration that results in a systemic effect of the oligonucleotide (systemic administration is characterized by a systemic effect, i.e., an effect in more than one tissue) or delivery to the CNS or to the CSF.

[0310] The duration of action as measured by inhibition of alpha 1 actin and reduction of myotonia in the HSA.sup.LR mouse model of DM1 is prolonged in muscle tissue including quadriceps, gastrocnemius, and the tibialis anterior (see Examples, below). Subcutaneous injections of antisense oligonucleotide for 4 weeks results in inhibition of alpha 1 actin by at least 70% in quadriceps, gastrocnemius, and the tibialis anterior in HSA.sup.LR mice for at least 11 weeks (77 days) after termination of dosing. Subcutaneous injections of antisense oligonucleotide for 4 weeks results in elimination of myotonia in quadriceps, gastrocnemius, and the tibialis anterior in HSA.sup.LR mice for at least 11 weeks (77 days) after termination of dosing.

[0311] In certain embodiments, delivery of a compound of composition, as described herein, results in at least 70% down-regulation of a target mRNA and/or target protein for at least 77 days. In certain embodiments, delivery of a compound or composition, as described herein, results in 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% down-regulation of a target mRNA and/or target protein for at least 30 days, at least 35 days, at least 40 days, at least 45 days, at least 50 days, at least 55 days, at least 60 days, at least 65 days, at least 70 days, at least 75 days, at least 76 days, at least 77 days, at least 78 days, at least 79 days, at least 80 days, at least 85 days, at least 90 days, at least 95 days, at least 100 days, at least 105 days, at least 110 days, at least 115 days, at least 120 days, at least 1 year.

[0312] In certain embodiments, an antisense oligonucleotide is delivered by injection or infusion once every 77 days. In certain embodiments, an antisense oligonucleotide is delivered by injection or infusion once every month, every two months, every three months, every 6 months, twice a year or once a year.

Certain Combination Therapies

[0313] In certain embodiments, a first agent comprising the modified oligonucleotide of the invention is co-administered with one or more secondary agents. In certain embodiments, such second agents are designed to treat the same type 1 myotonic dystrophy as the first agent described herein. In certain embodiments, such second agents are designed to treat a different disease, disorder, or condition as the first agent described herein. In certain embodiments, such second agents are designed to treat an undesired side effect of one or more pharmaceutical compositions as described herein. In certain embodiments, second agents are co-administered with the first agent to treat an undesired effect of the first agent. In certain embodiments, second agents are co-administered with the first agent to produce a combinational effect. In certain embodiments, second agents are co-administered with the first agent to produce a synergistic effect.

[0314] In certain embodiments, a first agent and one or more second agents are administered at the same time. In certain embodiments, the first agent and one or more second agents are administered at different times. In certain embodiments, the first agent and one or more second agents are prepared together in a single pharmaceutical formulation. In certain embodiments, the first agent and one or more second agents are prepared separately.

Examples

Non-Limiting Disclosure and Incorporation by Reference

[0315] 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 recited in the present application is incorporated herein by reference in its entirety.

Example 1: Antisense Inhibition of Human Dystrophia Myotonica Protein Kinase (DMPK) in Human Skeletal Muscle Cells (hSKMC)

[0316] Antisense oligonucleotides targeted to a human DMPK nucleic acid were tested for their effect on DMPK RNA transcript in vitro. Cultured hSKM cells at a density of 20,000 cells per well were transfected using electroporation with 100 nM antisense oligonucleotide. After approximately 24 hours, RNA was isolated from the cells and DMPK RNA transcript levels were measured by quantitative real-time PCR with human primer probe set RTS3164 (forward sequence AGCCTGAGCCGGGAGATG, designated herein as SEQ ID NO: 9; reverse sequence GCGTAGTTGACTGGCGAAGTT, designated herein as SEQ ID NO: 10; probe sequence AGGCCATCCGCACGGACAACCX, designated herein as SEQ ID NO: 11). DMPK RNA transcript levels were adjusted according to total RNA content, as measured by RIBOGREEN.RTM.. Results are presented as percent inhibition of hDMPK, relative to untreated control cells.

[0317] The antisense oligonucleotides in Tables 1 and 2 are 5-10-5 gapmers, where the gap segment comprises ten 2'-deoxynucleosides and each wing segment comprises five 2'-MOE nucleosides. The internucleoside linkages throughout each gapmer are phosphorothioate (P.dbd.S) linkages. All cytosine residues throughout each gapmer are 5-methylcytosines. `Target start site` indicates the 5'-most nucleoside to which the antisense oligonucleotide is targeted. `Target stop site` indicates the 3'-most nucleoside to which the antisense oligonucleotide is targeted. All the antisense oligonucleotides listed in Table 1 target SEQ ID NO: 1 (GENBANK Accession No. NM_001081560.1). All the antisense oligonucleotides listed in Table 2 target SEQ ID NO: 2 (the complement of GENBANK Accession No. NT_011109.15 truncated from nucleotides 18540696 to 18555106).

[0318] Several antisense oligonucleotides demonstrated significant inhibition of human DMPK mRNA levels under the conditions specified above.

TABLE-US-00001 TABLE 1 Inhibition of human DMPK RNA transcript in hSKMC by 5-10-5 gapmers targeting SEQ ID NO: 1 Target Target Start Stop % SEQ ID Site Site ISIS No Sequence inhibition NO. 93 112 299476 CTGGCTGCATGTCTGCCTGT 81 12 277 296 299479 CCAGGAGAAGGTCGAGCAGG 57 13 737 756 299493 TCTATGGCCATGACAATCTC 57 14 773 792 299494 ATGTCCCTGTGCACGTAGCC 77 15 1194 1213 299501 ATGTGTCCGGAAGTCGCCTG 50 16 1628 1647 299511 CTCAGGCTCTGCCGGGTGAG 70 17 1855 1874 299517 GGCACTGGCCCACAGCCACG 78 18 2379 2398 299526 CCTGGCCGAAAGAAAGAAAT 31 19 2367 2386 444380 AAAGAAATGGTCTGTGATCC 56 20 2370 2389 444381 AAGAAAGAAATGGTCTGTGA 77 21 2376 2395 444382 GGCCGAAAGAAAGAAATGGT 61 22 2385 2404 444383 CCTCAGCCTGGCCGAAAGAA 57 23 2388 2407 444384 GGGCCTCAGCCTGGCCGAAA 65 24 2391 2410 444385 TCAGGGCCTCAGCCTGGCCG 61 25 2411 2430 444386 CTGCAGTTTGCCCATCCACG 68 26 2414 2433 444387 GGCCTGCAGTTTGCCCATCC 77 27 2417 2436 444388 CCAGGCCTGCAGTTTGCCCA 54 28 2423 2442 444389 GCCTTCCCAGGCCTGCAGTT 77 29 2426 2445 444390 GCTGCCTTCCCAGGCCTGCA 83 30 2429 2448 444391 CTTGCTGCCTTCCCAGGCCT 69 31 2435 2454 444392 GCCCGGCTTGCTGCCTTCCC 82 32 2438 2457 444393 ACGGCCCGGCTTGCTGCCTT 78 33 2441 2460 444394 CGGACGGCCCGGCTTGCTGC 57 34 2444 2463 444395 ACACGGACGGCCCGGCTTGC 73 35 2450 2469 444396 GATGGAACACGGACGGCCCG 80 36 2453 2472 444397 GAGGATGGAACACGGACGGC 86 37 2456 2475 444398 GTGGAGGATGGAACACGGAC 84 38 2481 2500 444399 GCGAACCAACGATAGGTGGG 80 39 2484 2503 444400 TTTGCGAACCAACGATAGGT 86 40 2490 2509 444401 TTGCACTTTGCGAACCAACG 89 41 2493 2512 444402 GCTTTGCACTTTGCGAACCA 89 42 2496 2515 444403 AAAGCTTTGCACTTTGCGAA 83 43 2499 2518 444404 AAGAAAGCTTTGCACTTTGC 91 44 2502 2521 444405 CACAAGAAAGCTTTGCACTT 70 45 2508 2527 444406 GTCATGCACAAGAAAGCTTT 34 46 2527 2546 444407 ACGCTCCCCAGAGCAGGGCG 39 47 2543 2562 444408 GCAGAGATCGCGCCAGACGC 85 48 2546 2565 444409 CAGGCAGAGATCGCGCCAGA 65 49 2549 2568 444410 AAGCAGGCAGAGATCGCGCC 84 50 2555 2574 444411 CCGAGTAAGCAGGCAGAGAT 58 51 2558 2577 444412 TTCCCGAGTAAGCAGGCAGA 70 52 2564 2583 444413 GCAAATTTCCCGAGTAAGCA 62 53 2567 2586 444414 AAAGCAAATTTCCCGAGTAA 53 54 2573 2592 444415 TTGGCAAAAGCAAATTTCCC 64 55 2576 2595 444416 GGTTTGGCAAAAGCAAATTT 23 56 2579 2598 444417 GCGGGTTTGGCAAAAGCAAA 70 57 2582 2601 444418 AAAGCGGGTTTGGCAAAAGC 43 58 2588 2607 444419 CCCGAAAAAGCGGGTTTGGC 71 59 2591 2610 444420 ATCCCCGAAAAAGCGGGTTT 53 60 2595 2614 444421 CGGGATCCCCGAAAAAGCGG 45 61 2598 2617 444422 GCGCGGGATCCCCGAAAAAG 48 62 2623 2642 444423 GAGAGCAGCGCAAGTGAGGA 77 63 2626 2645 444424 TCCGAGAGCAGCGCAAGTGA 62 64 2629 2648 444425 GGCTCCGAGAGCAGCGCAAG 79 65 2649 2668 444426 AAGCGGGCGGAGCCGGCTGG 20 66 2652 2671 444427 CCGAAGCGGGCGGAGCCGGC 0 67 2658 2677 444428 AAACCGCCGAAGCGGGCGGA 0 68 2661 2680 444429 TCCAAACCGCCGAAGCGGGC 45 69 2664 2683 444430 ATATCCAAACCGCCGAAGCG 31 70 2667 2686 444431 TAAATATCCAAACCGCCGAA 42 71 2670 2689 444432 CAATAAATATCCAAACCGCC 53 72 2676 2695 444433 CGAGGTCAATAAATATCCAA 63 73 2679 2698 444434 GGACGAGGTCAATAAATATC 83 74 2682 2701 444435 GGAGGACGAGGTCAATAAAT 82 75 2685 2704 444436 GTCGGAGGACGAGGTCAATA 86 76 2688 2707 444437 CGAGTCGGAGGACGAGGTCA 73 77 2694 2713 444438 TGTCAGCGAGTCGGAGGACG 79 78 2697 2716 444439 GCCTGTCAGCGAGTCGGAGG 83 79 2700 2719 444440 GTAGCCTGTCAGCGAGTCGG 94 80 2703 2722 444441 CCTGTAGCCTGTCAGCGAGT 90 81 2706 2725 444442 GGTCCTGTAGCCTGTCAGCG 90 82 2764 2783 444443 AAATACCGAGGAATGTCGGG 82 83 2767 2786 444444 AATAAATACCGAGGAATGTC 66 84 2770 2789 444445 GACAATAAATACCGAGGAAT 67 85 2093 2112 445546 CGGGGCCCCGGAGTCGAAGA 0 86 2097 2116 445547 CCAACGGGGCCCCGGAGTCG 38 87 2099 2118 445548 TTCCAACGGGGCCCCGGAGT 22 88 2102 2121 445549 GTCTTCCAACGGGGCCCCGG 50 89 2104 2123 445550 CAGTCTTCCAACGGGGCCCC 27 90 2106 2125 445551 CTCAGTCTTCCAACGGGGCC 57 91 2109 2128 445552 GCACTCAGTCTTCCAACGGG 69 92 2115 2134 445553 CCCCGGGCACTCAGTCTTCC 76 93 2117 2136 445554 TGCCCCGGGCACTCAGTCTT 59 94 2119 2138 445555 CGTGCCCCGGGCACTCAGTC 61 95 2123 2142 445556 GTGCCGTGCCCCGGGCACTC 26 96 2126 2145 445557 TCTGTGCCGTGCCCCGGGCA 50 97 2129 2148 445558 GCTTCTGTGCCGTGCCCCGG 57 98 2132 2151 445559 GCGGCTTCTGTGCCGTGCCC 27 99 2134 2153 445560 GCGCGGCTTCTGTGCCGTGC 0 100 2136 2155 445561 GGGCGCGGCTTCTGTGCCGT 8 101 2142 2161 445562 GGCGGTGGGCGCGGCTTCTG 62 102 2146 2165 445563 GGCAGGCGGTGGGCGCGGCT 49 103 2148 2167 445564 CTGGCAGGCGGTGGGCGCGG 51 104 2150 2169 445565 AACTGGCAGGCGGTGGGCGC 38 105 2153 2172 445566 GTGAACTGGCAGGCGGTGGG 64 106 2157 2176 445567 GGTTGTGAACTGGCAGGCGG 66 107 2159 2178 445568 GCGGTTGTGAACTGGCAGGC 85 108 2163 2182 445569 CGGAGCGGTTGTGAACTGGC 92 109 2167 2186 445570 CGCTCGGAGCGGTTGTGAAC 51 110 2171 2190 445571 CCCACGCTCGGAGCGGTTGT 74 111 2174 2193 445572 AGACCCACGCTCGGAGCGGT 80 112 2177 2196 445573 CGGAGACCCACGCTCGGAGC 83 113 2180 2199 445574 GGGCGGAGACCCACGCTCGG 62 114 2183 2202 445575 GCTGGGCGGAGACCCACGCT 11 115 2186 2205 445576 GGAGCTGGGCGGAGACCCAC 42 116 2188 2207 445577 CTGGAGCTGGGCGGAGACCC 17 117 2191 2210 445578 GGACTGGAGCTGGGCGGAGA 53 118 2193 2212 445579 CAGGACTGGAGCTGGGCGGA 46 119 2197 2216 445580 ATCACAGGACTGGAGCTGGG 66 120 2209 2228 445581 GGGCGGGCCCGGATCACAGG 85 121 2211 2230 445582 GGGGGCGGGCCCGGATCACA 96 122 179 198 445583 AGGCAGCACCATGGCCCCTC 88 123 235 254 445584 GGTCCAACACCAGCTGCTGG 84 124 418 437 445585 CGATCACCTTCAGAATCTCG 11 125 498 517 445586 CTTGTTCATGATCTTCATGG 0 126 565 584 445587 CCCCATTCACCAACACGTCC 83 127 583 602 445588 GCGTGATCCACCGCCGGTCC 59 128 639 658 445589 GTAATACTCCATGACCAGGT 86 129 664 683 445590 GCAGTGTCAGCAGGTCCCCG 83 130 744 763 445591 CACCGAGTCTATGGCCATGA 60 131 761 780 445592 ACGTAGCCAAGCCGGTGCAC 68 132

812 831 445593 ATGTGGCCACAGCGGTCCAG 56 133 1099 1118 445594 CTTCGTCCACCAGCGGCAGA 32 134 1104 1123 445595 GACCCCTTCGTCCACCAGCG 83 135 1178 1197 445596 CCTGCTCCACCCCGGCCCAG 82 136 1187 1206 445597 CGGAAGTCGCCTGCTCCACC 81 137 1229 1248 445598 CGGAGACCATCCCAGTCGAG 67 138 1402 1421 445599 TGAGGGCCATGCAGGAGTAG 26 139 1443 1462 445600 CTCCAGTTCCATGGGTGTGG 80 140 1477 1496 445601 GCGCTTGCACGTGTGGCTCA 94 141 1526 1545 445602 GCCACTTCAGCTGTTTCATC 54 142 1562 1581 445603 GCCTCAGCCTCTGCCGCAGG 71 143 1576 1595 445604 GCAGCGTCACCTCGGCCTCA 31 144 1630 1649 445605 GGCTCAGGCTCTGCCGGGTG 86 145 1700 1719 445606 TTCCGAGCCTCTGCCTCGCG 73 146 1708 1727 445607 GGTCCCGGTTCCGAGCCTCT 76 147 1742 1761 445608 ATCCGCTCCTGCAACTGCCG 93 148 1750 1769 445609 GCAACTCCATCCGCTCCTGC 60 149 1812 1831 445610 AGGTGGATCCGTGGCCCGGG 48 150 2133 2152 445611 CGCGGCTTCTGTGCCGTGCC 24 151 2428 2447 445612 TTGCTGCCTTCCCAGGCCTG 80 152

TABLE-US-00002 TABLE 2 Inhibition of human DMPK RNA transcript in hSKMC by 5-10-5 gapmers targeting SEQ ID NO: 2 Target Target Start Stop % SEQ ID Site Site ISIS No Sequence inhibition NO. 812 831 299471 TGCTCCCGACAAGCTCCAGA 95 153 876 895 299473 AGAACCTGCCCATTGCTGAA 68 154 2381 2400 299535 CACTGAGGGCCAGACATATG 68 155 3289 3308 299544 CTCTAGATTCAGATGCAGGT 88 156

[0319] The antisense oligonucleotides from Tables 1 and 2 were also tested in an assay with similar conditions as described above, and mRNA levels measured with the human primer probe RTS3162 (forward sequence CGGGCCGTCCGTGTT, designated herein as SEQ ID NO: 157; reverse sequence CTTTGCACTTTGCGAACCAA, designated herein as SEQ ID NO: 158; probe sequence CATCCTCCACGCACCCCCACCX, designated herein as SEQ ID NO: 159). The results are presented in Table 3. DMPK mRNA expression was also assessed by RTS3162 which targets the DMPK gene near the 3'UTR. The use of a second primer probe was employed to confirm that the expression of the entire DMPK gene had been inhibited

TABLE-US-00003 TABLE 3 Inhibition of human DMPK RNA transcript in hSKMC by 5- 10-5 gapmers measured using primer probe set RTS3162 ISIS No % inhibition 299471 91 299473 65 299476 76 299479 53 299493 60 299494 66 299501 44 299511 39 299517 71 299526 39 299535 75 299544 84 444380 72 444381 82 444382 67 444383 63 444384 66 444385 66 444386 74 444387 85 444388 60 444389 81 444390 88 444391 79 444392 94 444393 88 444394 94 444395 96 444396 96 444397 95 444398 96 444399 95 444400 95 444401 95 444402 91 444403 84 444404 89 444405 71 444406 47 444407 42 444408 80 444409 56 444410 79 444411 66 444412 67 444413 55 444414 45 444415 57 444416 18 444417 64 444418 51 444419 66 444420 0 444421 46 444422 33 444423 74 444424 73 444425 78 444426 0 444427 0 444428 0 444429 75 444430 28 444431 58 444432 52 444433 60 444434 87 444435 76 444436 83 444437 71 444438 76 444439 73 444440 91 444441 87 444442 93 444443 77 444444 64 444445 67 445546 0 445547 59 445548 49 445549 77 445550 62 445551 74 445552 84 445553 70 445554 63 445555 75 445556 52 445557 78 445558 81 445559 58 445560 12 445561 42 445562 70 445563 76 445564 69 445565 60 445566 86 445567 84 445568 92 445569 93 445570 59 445571 84 445572 88 445573 84 445574 74 445575 26 445576 56 445577 38 445578 69 445579 70 445580 75 445581 85 445582 95 445583 88 445584 87 445585 34 445586 0 445587 82 445588 66 445589 87 445590 82 445591 68 445592 64 445593 54 445594 52 445595 77 445596 84 445597 78 445598 73 445599 29 445600 68 445601 92 445602 53 445603 70 445604 32 445605 61 445606 84 445607 80 445608 91 445609 68 445610 63 445611 44 445612 91

Example 2: Design of Antisense Oligonucleotides Targeting CUG Repeats

[0320] Antisense oligonucleotides were designed targeting mRNA transcripts that contain multiple CUG repeats. The chemistry of these oligonucleotides as well as their sequence is shown in Table 4. The symbols designated to the sugar type are shown after the base in subscript and are as follows: b=2'-O--N-[2-(dimethylamino)ethyl]acetamido ribose; d=2'-deoxyribose; e=2'-O-methoxyethyl ribose; f=2'-alpha-fluoro-2'-deoxyribose; g=2'-O-2[2-(2-methoxyethoxy)ethoxy]ethyl ribose; h=3'-fluoro-HNA; k=(S)-cEt; 1=LNA (Locked Nucleic Acids); n=2'-O--(N-methylacetamide) ribose; o=2'-O-dimethylaminooxyethyl (DMAOE) ribose; p=PNA; r=propylribose; and x=amino acid core. The heterocycle names are defined with standard symbols for adenine, cytosine, thymine and guanine, `mC` for 5-methylcytosine, and `K` for Lysine Side Chain. Linkers are shown after the sugar type in subscript and designated with the following symbols: g=PNA-glycine full; a=amino acid; and s=thioate ester.

TABLE-US-00004 TABLE 4 Design of antisense oligonucleotides targeting CUG repeats ISIS SEQ No Sequence Chemistry Backbone ID NO 431896 G.sub.dsC.sub.dsA.sub.lsG.sub.dsC.sub.dsA.sub.lsG.sub.dsC.sub.dsA.s- ub.ls Deoxy and LNA units Phosphorothioate 802 G.sub.dsC.sub.dsA.sub.lsG.sub.dsC.sub.dsA.sub.lsG.sub.dsC.sub.dsA.sub.lsG- .sub.d 433804 K.sub.xaG.sub.pgC.sub.pgA.sub.pgG.sub.pgC.sub.pgA.sub.pgG.sub.pgC.s- ub.pgA.sub.pgG.sub.pgC.sub.pgA.sub.pgG.sub.pg PNA and Amino Acid mixed 803 C.sub.pgA.sub.pgG.sub.pgC.sub.pgA.sub.pgG.sub.pgK.sub.xaK.sub.xaK.sub.xaK- .sub.xaK.sub.xaK.sub.xaK.sub.xaK.sub.xa Core units with a Carboxy-amide endcap 444745 A.sub.esG.sub.esmC.sub.esA.sub.esG.sub.esmC.sub.esA.sub.esG.sub.esm- C.sub.esA.sub.esG.sub.esmC.sub.es Uniform MOE Phosphorothioate 789 A.sub.esG.sub.esmC.sub.esA.sub.esG.sub.esmC.sub.esA.sub.esG.sub.esmC.sub.- esA.sub.esG.sub.esmC.sub.esA.sub.e 444746 A.sub.esG.sub.esmC.sub.esA.sub.esG.sub.esmC.sub.esA.sub.esG.sub.esm- C.sub.esA.sub.es Uniform MOE Phosphorothioate 804 G.sub.esmC.sub.esA.sub.esG.sub.esmC.sub.esA.sub.esG.sub.esmC.sub.esA.sub.- esG.sub.e 444747 G.sub.esmC.sub.esA.sub.esG.sub.esmC.sub.esA.sub.esG.sub.esmC.sub.es- A.sub.es Uniform MOE Phosphorothioate 802 G.sub.esmC.sub.esA.sub.esG.sub.esmC.sub.esA.sub.esG.sub.esmC.sub.esA.sub.- esG.sub.es 444748 G.sub.esmC.sub.esA.sub.esG.sub.esmC.sub.esA.sub.esG.sub.esmC.sub.es- A.sub.es Uniform MOE Phosphorothioate 805 G.sub.esmC.sub.esA.sub.esG.sub.esmC.sub.esA.sub.esG.sub.esmC.sub.esA.sub.- e 444750 G.sub.ksC.sub.ksA.sub.dsG.sub.dsC.sub.ksA.sub.dsG.sub.dsC.sub.ksA.s- ub.ds Deoxy and (S)-cEt units Phosphorothioate 805 G.sub.dsC.sub.ksA.sub.dsG.sub.dsC.sub.ksA.sub.dsG.sub.dsC.sub.ksA.sub.k 444752 G.sub.ksC.sub.ksA.sub.esG.sub.esC.sub.ksA.sub.esG.sub.esC.sub.ksA.s- ub.es MOE and (S)-cEt units Phosphorothioate 805 G.sub.esC.sub.ksA.sub.esG.sub.esC.sub.ksA.sub.esG.sub.esC.sub.ksA.sub.k 444754 G.sub.esmC.sub.esA.sub.fsG.sub.fsC.sub.fsA.sub.fsG.sub.fsC.sub.fsA.- sub.fs MOE and Phosphorothioate 805 G.sub.fsC.sub.fsA.sub.fsG.sub.fsC.sub.fsA.sub.fsG.sub.fsmC.sub.esA.sub.es 2'-alpha-flouro units 444759 G.sub.hsmC.sub.hsA.sub.hsG.sub.hsmC.sub.hsA.sub.hsG.sub.hsmC.sub.hs- A.sub.hs Uniform 3'-fluoro-HNA Phosphorothioate 805 G.sub.hsmC.sub.hsA.sub.hsG.sub.hsmC.sub.hsA.sub.hsG.sub.hsmC.sub.hsA.sub.- h 444761 G.sub.rsmC.sub.rsA.sub.rsG.sub.rsmC.sub.rsA.sub.rsG.sub.rsmC.sub.rs- A.sub.rs Uniform 2'-O- Phosphorothioate 805 G.sub.rsmC.sub.rsA.sub.rsG.sub.rsmC.sub.rsA.sub.rsG.sub.rsmC.sub.rsA.sub.- r propylribose 444762 G.sub.nsmC.sub.nsA.sub.nsG.sub.nsmC.sub.nsA.sub.nsG.sub.nsmC.sub.ns- A.sub.ns Uniform 2'-O--(N- Phosphorothioate 805 G.sub.nsmC.sub.nsA.sub.nsG.sub.nsmC.sub.nsA.sub.nsG.sub.nsmC.sub.nsA.sub.- n methylacetamide) ribose 444763 G.sub.osmC.sub.esA.sub.osG.sub.osmC.sub.esA.sub.osG.sub.osmC.sub.es- A.sub.os MOE and 2'-O- Phosphorothioate 805 G.sub.osmC.sub.esA.sub.osG.sub.osmC.sub.esA.sub.osG.sub.osmC.sub.esA.sub.- o dimethylaminooxyethyl (DMAOE) ribose units 444764 G.sub.gsmC.sub.esA.sub.esG.sub.gsmC.sub.esA.sub.esG.sub.gsmC.sub.es- A.sub.es MOE and 2'-O-2[2-(2- Phosphorothioate 802 G.sub.gsmC.sub.esA.sub.esG.sub.gsmC.sub.esA.sub.esG.sub.gsmC.sub.esA.sub.- esG.sub.g methoxyethoxy)ethoxy] ethyl ribose units 444765 G.sub.bsmC.sub.esA.sub.esG.sub.bsmC.sub.esA.sub.esG.sub.bsmC.sub.es- A.sub.es MOE and 2'-O--N-[2- Phosphorothioate 802 G.sub.bsmC.sub.esA.sub.esG.sub.bsmC.sub.esA.sub.esG.sub.bsmC.sub.esA.sub.- esG.sub.b (dimethylamino)ethyl]acetamido ribose units 473810 A.sub.ksG.sub.dsmC.sub.dsA.sub.ksG.sub.dsmC.sub.dsA.sub.ksG.sub.asm- C.sub.ds Deoxy and (S)-cEt units Phosphorothioate 806 A.sub.ksG.sub.dsmC.sub.dsA.sub.ksG.sub.dsmC.sub.dsA.sub.ksG.sub.dsmC.sub.- dsA.sub.k 473811 A.sub.ksG.sub.dsmC.sub.dsA.sub.ksG.sub.dsmC.sub.dsA.sub.ksG.sub.ds Deoxy and (S)-cEt units Phosphorothioate 807 mC.sub.dsA.sub.ksG.sub.dsmC.sub.dsA.sub.ksG.sub.dsmC.sub.dsA.sub.k

Example 3: Dose-Dependent Antisense Inhibition of Human DMPK in Human Skeletal Muscle Cells

[0321] Several of the antisense oligonucleotides exhibiting in vitro inhibition of DMPK in hSKMC (see Example 1) were tested at various doses. Cells were plated at a density of 20,000 cells per well and transfected using electroporation with 1,250 nM, 2,500 nM, 5,000 nM, 10,000 nM and 20,000 nM concentrations of each antisense oligonucleotide. After approximately 16 hours, RNA was isolated from the cells and DMPK mRNA transcript levels were measured by quantitative real-time PCR using primer probe set RTS3164, described hereinabove. DMPK mRNA transcript levels were normalized to total RNA content, as measured by RIBOGREEN.RTM.. Results are presented in Table 5 as percent inhibition of DMPK, relative to untreated control cells.

[0322] The tested antisense oligonucleotides demonstrated dose-dependent inhibition of DMPK mRNA levels under the conditions specified above.

TABLE-US-00005 TABLE 5 Dose-dependent antisense inhibition of human DMPK in hSKMC tested with primer probe set RTS3164 ISIS 1,250 2,500 IC.sub.50 No. nM nM 5,000 nM 10,000 nM 20,000 nM (.mu.M) 299471 34 65 87 91 94 1.60 299473 2 33 60 89 92 4.31 299476 15 17 49 81 91 4.89 299535 0 12 34 62 59 9.95 299535 20 33 47 67 80 5.11 299544 32 63 81 85 87 1.82 444397 10 30 58 85 82 4.51 444398 33 57 74 85 87 2.07 444400 52 46 63 82 88 1.76 444401 51 71 84 89 91 0.71 444402 53 79 83 87 84 <1.25 444404 48 68 77 86 90 0.95 444408 26 47 70 87 87 2.80 444410 22 47 67 83 87 3.12 444436 28 67 76 89 92 1.94 444440 70 77 83 89 85 <1.25 444441 33 55 81 87 86 1.99 444442 54 73 84 89 88 <1.25 445568 65 83 85 84 76 <1.25 445569 60 77 87 93 91 <1.25 445581 16 44 78 86 94 3.13 445582 0 7 26 96 99 5.60 445583 39 53 73 89 94 2.00 445584 20 26 61 81 93 4.02 445589 42 61 81 91 87 1.36 445601 49 79 87 93 94 0.66 445608 26 59 71 85 97 2.41 445612 46 59 72 88 93 1.51

[0323] The antisense oligonucleotides from Table 5 were also tested with primer probe set RTS3162, described hereinabove. The results are presented in Table 6. DMPK mRNA expression was also assessed by RTS3162 which targets the DMPK gene near the 3'UTR. The use of a second primer probe was employed to confirm that the expression of the entire DMPK gene had been inhibited.

TABLE-US-00006 TABLE 6 Dose-dependent antisense inhibition of human DMPK in hSKMC tested with primer probe set RTS3164 ISIS 1,250 2,500 IC.sub.50 No. nM nM 5,000 nM 10,000 nM 20,000 nM (.mu.M) 299471 40 72 86 91 93 1.17 299473 6 43 63 87 89 3.86 299476 3 21 48 74 86 5.58 299535 9 22 36 62 77 7.05 299535 6 19 49 68 70 6.70 299544 35 66 81 84 87 1.52 444397 88 90 95 97 96 <1.25 444398 91 97 97 97 98 <1.25 444400 72 87 93 96 96 <1.25 444401 86 92 97 98 97 <1.25 444402 83 91 94 95 95 <1.25 444404 49 69 81 90 93 0.92 444408 21 46 70 84 86 3.10 444410 35 55 77 89 91 2.02 444436 37 66 81 89 92 1.50 444440 66 79 89 92 89 <1.25 444441 40 62 85 89 89 1.40 444442 55 75 86 90 91 <1.25 445568 74 92 91 92 91 <1.25 445569 68 83 90 94 93 <1.25 445581 8 48 77 85 92 3.33 445582 15 22 44 97 99 4.29 445583 36 58 71 87 92 1.96 445584 25 43 66 86 94 3.05 445589 38 56 77 85 81 1.74 445601 55 76 84 93 93 <1.25 445608 22 56 72 86 94 2.66 445612 61 75 85 91 94 <1.25

Example 4: Dose-Dependent Antisense Inhibition of Human DMPK in Human Skeletal Muscle Cells

[0324] Several of the antisense oligonucleotides exhibiting in vitro inhibition of DMPK in hSKMC (see Example 3) were tested at various doses. Cells were plated at a density of 20,000 cells per well and transfected using electroporation with 1,250 nM, 2,500 nM, 5,000 nM, 10,000 nM and 20,000 nM concentrations of each antisense oligonucleotide. After approximately 16 hours, RNA was isolated from the cells and DMPK mRNA transcript levels were measured by quantitative real-time PCR using primer probe set RTS3164, described hereinabove. DMPK mRNA transcript levels were normalized to total RNA content, as measured by RIBOGREEN.RTM.. Results are presented in Table 7 as percent inhibition of DMPK, relative to untreated control cells.

[0325] The majority of the tested antisense oligonucleotides demonstrated dose-dependent inhibition of DMPK mRNA levels under the conditions specified above.

TABLE-US-00007 TABLE 7 Dose-dependent antisense inhibition of human DMPK in hSKMC tested with primer probe set RTS3164 ISIS 1,250 2,500 IC.sub.50 No. nM nM 5,000 nM 10,000 nM 20,000 nM (.mu.M) 299471 34 65 87 91 94 1.59 299473 2 33 60 89 92 4.31 299476 15 17 49 81 91 4.89 299535 0 12 34 62 59 9.95 299535 20 33 47 67 80 5.11 299544 32 63 81 85 87 1.82 444397 10 30 58 85 82 4.51 444398 33 57 74 85 87 2.07 444400 52 46 63 82 88 1.76 444401 51 71 84 89 91 <1.25 444402 53 79 83 87 84 <1.25 444404 48 68 77 86 90 0.95 444408 26 47 70 87 87 2.80 444410 22 47 67 83 87 3.12 444436 28 67 76 89 92 1.94 444440 66 77 83 89 85 <1.25 444441 33 55 81 87 86 1.99 444442 54 73 84 89 88 <1.25 445568 65 83 85 84 76 <1.25 445569 60 77 87 93 91 <1.25 445581 16 44 78 86 94 3.13 445582 0 7 26 96 99 5.62 445583 39 53 73 89 94 1.97 445584 20 26 61 81 93 4.20 445589 42 61 81 91 87 1.36 445601 49 79 87 93 94 0.66 445608 26 59 71 85 97 2.41 445612 46 59 72 88 93 1.51

Example 5: Dose-Dependent Antisense Inhibition of Human DMPK in Human Skeletal Muscle Cells

[0326] Several antisense oligonucleotides were designed to target human DMPK mRNA and were tested in hSKMC at various doses. Several other antisense oligonucleotides were designed to target human actin mRNA and were also tested in hSKMC at various doses. The newly designed gapmers are 2-10-2 MOE or 3-10-3 MOE gapmers. The 2-10-2 MOE gapmers are 14 nucleosides in length and where the gap segment comprises ten 2'-deoxynucleosides and each wing segment comprises two 2'-MOE nucleosides. The 3-10-3 MOE gapmers are 16 nucleosides in length and where the gap segment comprises ten 2'-deoxynucleosides and each wing segment comprises three 2'-MOE nucleosides. The internucleoside linkages throughout each gapmer are phosphorothioate (P.dbd.S) linkages. All cytosine residues throughout each gapmer are 5-methylcytosines. `Target start site` indicates the 5'-most nucleoside to which the antisense oligonucleotide is targeted. `Target stop site` indicates the 3'-most nucleoside to which the antisense oligonucleotide is targeted. The antisense oligonucleotides listed in Table 8 target either the human DMPK genomic sequence, designated herein as SEQ ID NO: 2 (the complement of GENBANK Accession No. NT_011109.15 truncated from nucleotides 18540696 to 18555106) or the human actin sequence, designated herein as SEQ ID NO: 801 (GENBANK Accession No. NM_001100.3).

[0327] Cells were plated at a density of 20,000 cells per well and transfected using electroporation with 1,250 nM, 2,500 nM, 5,000 nM, 10,000 nM and 20,000 nM concentrations of each antisense oligonucleotide. After approximately 16 hours, RNA was isolated from the cells and DMPK mRNA transcript levels were measured by quantitative real-time PCR using primer probe set RTS3162, described hereinabove. DMPK mRNA transcript levels were normalized to total RNA content, as measured by RIBOGREEN.RTM.. Results are presented in Table 8 as percent inhibition of DMPK, relative to untreated control cells. The antisense oligonucleotides were also tested under similar conditions with RTS3164. The results are presented in Table 9.

[0328] Many of the tested antisense oligonucleotides demonstrated dose-dependent inhibition of DMPK mRNA levels under the conditions specified above.

TABLE-US-00008 TABLE 8 Dose-dependent antisense inhibition of human DMPK and human actin in hSKMC tested with primer probe set RTS3162 Target SEQ SEQ ID Start 1,250 2,500 5,000 10,000 20,000 IC.sub.50 ID ISIS No Sequence Motif NO Site nM nM nM nM nM (nM) NO 468787 CTCCCGACAAGCTCCA 3-10-3 2 814 28 47 51 84 88 3.27 808 468772 TCCCGACAAGCTCC 2-10-2 2 815 17 39 67 72 80 4.04 809 468795 GCTTGCACGTGTGGCT 3-10-3 2 10935 32 58 77 85 75 1.94 810 468780 CTTGCACGTGTGGC 2-10-2 2 10936 22 17 43 66 77 6.23 811 468793 GGTTGTGAACTGGCAG 3-10-3 2 13224 69 77 93 96 96 <1.25 812 468778 GTTGTGAACTGGCA 2-10-2 2 13225 60 69 89 95 97 <1.25 813 468794 GAGCGGTTGTGAACTG 3-10-3 2 13228 21 32 61 70 86 4.27 814 468779 AGCGGTTGTGAACT 2-10-2 2 13229 40 45 72 91 97 2.20 815 468796 GCTGCCTTCCCAGGCC 3-10-3 2 13493 73 79 91 96 95 <1.25 816 468781 CTGCCTTCCCAGGC 2-10-2 2 13494 36 53 66 86 90 2.28 817 468788 GCACTTTGCGAACCAA 3-10-3 2 13555 55 80 84 94 96 <1.25 818 468773 CACTTTGCGAACCA 2-10-2 2 13556 31 52 82 91 93 2.16 819 468789 GAAAGCTTTGCACTTT 3-10-3 2 13564 42 66 83 91 98 1.31 820 468774 AAAGCTTTGCACTT 2-10-2 2 13565 21 0 31 41 55 1.87 821 468790 CGGAGGACGAGGTCAA 3-10-3 2 13750 43 57 79 87 89 1.51 822 468775 GGAGGACGAGGTCA 2-10-2 2 13751 27 51 58 78 81 3.18 823 468791 AGCCTGTCAGCGAGTC 3-10-3 2 13765 49 63 85 62 95 1.04 824 468776 GCCTGTCAGCGAGT 2-10-2 2 13766 65 47 81 88 93 <1.25 825 468792 TCCTGTAGCCTGTCAG 3-10-3 2 13771 38 57 73 85 93 1.91 826 468777 CCTGTAGCCTGTCA 2-10-2 2 13772 15 58 66 85 92 2.99 827 468783 GAAGCGAGGCTTCACT 3-10-3 801 22 0 20 5 0 0 >20.00 828 468768 AAGCGAGGCTTCAC 2-10-2 801 23 25 22 5 17 0 >20.00 829 468784 ACCTGCCCGTCTGGCA 3-10-3 801 836 15 25 32 18 25 >20.00 830 468769 CCTGCCCGTCTGGC 2-10-2 801 837 32 11 11 20 32 >20.00 831 468782 GGTCAGCGATCCCAGG 3-10-3 801 1030 0 0 0 0 0 >20.00 832 468767 GTCAGCGATCCCAG 2-10-2 801 1031 15 0 11 0 0 >20.00 833 468785 ATTTTCTTCCACAGGG 3-10-3 801 1432 12 0 0 0 0 >20.00 834 468770 TTTTCTTCCACAGG 2-10-2 801 1433 36 2 0 0 28 >20.00 835 468786 GAATGACTTTAATGCT 3-10-3 801 1462 0 0 0 4 0 >20.00 836 468771 AATGACTTTAATGC 2-10-2 801 1463 8 16 0 5 0 >20.00 837

TABLE-US-00009 TABLE 9 Dose-dependent antisense inhibition of human DMPK in hSKMC tested with primer probe set RTS3164 1,250 2,500 IC.sub.50 ISIS No nM nM 5,000 nM 10,000 nM 20,000 nM (.mu.M) 468777 20 66 72 87 96 2.41 468776 68 48 86 90 96 <1.25 468794 18 23 58 65 86 4.97 468787 36 50 51 88 92 2.69 468772 12 47 69 80 86 3.57 468773 33 48 82 91 96 2.21 468774 21 0 30 42 59 1.60 468790 50 57 77 91 91 1.26 468780 23 22 55 73 85 4.69 468775 29 52 55 79 84 3.03 468782 9 0 0 0 0 >20.00 468786 2 0 0 0 0 >20.00 468785 15 0 1 0 5 >20.00 468788 57 74 76 94 96 <1.25 468791 45 66 88 61 97 1.10 468789 26 65 82 90 97 2.02 468781 28 46 59 82 84 3.08 468779 26 31 66 90 97 3.29 468784 7 23 26 7 18 >20.00 468783 0 16 8 0 0 >20.00 468792 26 49 73 84 92 2.72 468795 30 53 83 86 85 2.14 468793 49 66 90 96 95 0.93 468768 23 3 5 9 0 >20.00 468767 0 0 14 0 0 >20.00 468769 31 0 0 16 25 >20.00 468771 4 0 0 0 0 >20.00 468770 33 0 0 0 32 >20.00 468796 62 72 84 96 95 <1.25 468778 44 58 86 96 98 1.44

Example 6: Dose Response Studies with Antisense Oligonucleotides Targeting Human Dystrophia Myotonica-Protein Kinase (DMPK) in DM1 Fibroblast Cells

[0329] The mutant form of the DMPK mRNA, harboring large CUG repeats, are fully transcribed and polyadenylated, but remain trapped in the nucleus (Davis et al, 1997, Proc. Natl. Acad. Sci. U.S.A 94, 7388-7393). These mutant nuclear-retained mRNAs are one of the most important pathological features of myotonic dystrophy 1 (DM1). Antisense inhibition of mutant DMPK mRNA in DM1 fibroblast cells was studied.

[0330] The DMPK gene normally has 5-37 CTG repeats in the 3' untranslated region. In myotonic dystrophy type I, this number is significantly expanded and may be in the range of 50 to greater than 3,500 (Harper, Myotonic Dystrophy (Saunders, London, ed. 3, 2001); Annu. Rev. Neurosci. 29: 259, 2006; EMBO J. 19: 4439, 2000; Curr Opin Neurol. 20: 572, 2007). DM1 fibroblast cells were plated at a density of 4,500 cells per well and transfected using Cytofectin reagent with 9.4 nM, 18.8 nM, 37.5 nM, 75.0 nM, 150.0 nM, and 300.0 nM concentrations of each antisense oligonucleotide. After approximately 16 hours, RNA was isolated from the cells and DMPK RNA transcript levels were measured by quantitative real-time PCR using primer probe set RTS3164, described hereinabove. DMPK RNA transcript levels were normalized to total RNA content, as measured by RIBOGREEN.RTM.. Results are presented in Table 10 as percent inhibition of DMPK, relative to untreated control cells.

[0331] An assay with similar conditions was also performed with primer probe set RTS3162, described hereinabove, which targets the 3'-end of the DMPK transcript. Results are presented in Table 11 as percent inhibition of DMPK, relative to untreated control cells.

[0332] The tested antisense oligonucleotides demonstrated dose-dependent inhibition of DMPK mRNA levels under the conditions specified above.

TABLE-US-00010 TABLE 10 Dose-dependent antisense inhibition of DMPK mRNA in DM1 fibroblast cells with RTS3164 ISIS 9.4 150.0 300.0 IC.sub.50 No. nM 18.8 nM 37.5 nM 75.0 nM nM nM (nM) 299471 10 25 31 47 61 73 86.3 444401 8 27 41 60 67 74 64.3 444404 10 21 31 43 55 73 100.0 444436 7 17 36 64 68 70 72.3 445569 19 31 41 59 46 77 72.2

TABLE-US-00011 TABLE 11 Dose-dependent antisense inhibition of DMPK mRNA in DM1 fibroblast cells with RTS3162 9.4 150.0 300.0 IC.sub.50 ISIS No nM 18.8 nM 37.5 nM 75.0 nM nM nM (nM) 299471 7 25 29 46 48 69 115.3 444401 20 34 52 72 83 89 35.8 444404 5 20 28 42 54 77 98.8 444436 12 15 27 61 68 75 74.3 445569 5 25 33 53 50 76 89.6

Example 7: Antisense Inhibition of Human DMPK in Human Skeletal Muscle Cells (hSKMc)

[0333] Antisense oligonucleotides targeted to a human DMPK nucleic acid were tested for their effect on DMPK RNA transcript in vitro. Cultured hSKMc at a density of 20,000 cells per well were transfected using electroporation with 10,000 nM antisense oligonucleotide. After approximately 24 hours, RNA was isolated from the cells and DMPK transcript levels were measured by quantitative real-time PCR. DMPK RNA transcript levels were adjusted according to total RNA content, as measured by RIBOGREEN.RTM.. Results are presented as percent inhibition of DMPK, relative to untreated control cells.

[0334] The antisense oligonucleotides in Tables 12 and 13 are 5-10-5 gapmers, where the gap segment comprises ten 2'-deoxynucleosides and each wing segment comprises five 2'-MOE nucleosides. The internucleoside linkages throughout each gapmer are phosphorothioate (P.dbd.S) linkages. All cytsoine residues throughout each gapmer are 5-methylcytosines. `Target start site` indicates the 5'-most nucleoside to which the antisense oligonucleotide is targeted in the human genomic gene sequence. `Target stop site` indicates the 3'-most nucleoside to which the antisense oligonucleotide is targeted in the human genomic sequence. All the antisense oligonucleotides listed in Table 12 target SEQ ID NO: 1 (GENBANK Accession No. NM_001081560.1). All the antisense oligonucleotides listed in Table 13 target SEQ ID NO: 2 (the complement of GENBANK Accession No. NT 011109.15 truncated from nucleotides 18540696 to 18555106).

[0335] Several of the antisense oligonucleotides demonstrated significant inhibition of DMPK mRNA levels under the conditions specified above.

TABLE-US-00012 TABLE 12 Inhibition of human DMPK RNA transcript in hSKMc by 5-10-5 gapmers targeting SEQ ID NO: 1 Target Target Start Stop % SEQ Site Site ISIS No Sequence inhibition ID NO. 124 143 502369 GCCTGGCAGCCCCTGTCCAG 16 160 125 144 502370 GGCCTGGCAGCCCCTGTCCA 58 161 126 145 502371 GGGCCTGGCAGCCCCTGTCC 62 162 169 188 502372 ATGGCCCCTCCCCGGGCCGG 41 163 170 189 502373 CATGGCCCCTCCCCGGGCCG 29 164 171 190 502374 CCATGGCCCCTCCCCGGGCC 34 165 172 191 502375 ACCATGGCCCCTCCCCGGGC 60 166 173 192 502376 CACCATGGCCCCTCCCCGGG 68 167 174 193 502377 GCACCATGGCCCCTCCCCGG 75 168 175 194 502378 AGCACCATGGCCCCTCCCCG 65 169 176 195 502379 CAGCACCATGGCCCCTCCCC 63 170 177 196 502380 GCAGCACCATGGCCCCTCCC 73 171 178 197 502381 GGCAGCACCATGGCCCCTCC 80 172 180 199 502382 CAGGCAGCACCATGGCCCCT 82 173 181 200 502383 ACAGGCAGCACCATGGCCCC 72 174 183 202 502384 GGACAGGCAGCACCATGGCC 70 175 184 203 502385 TGGACAGGCAGCACCATGGC 71 176 185 204 502386 TTGGACAGGCAGCACCATGG 73 177 186 205 502387 GTTGGACAGGCAGCACCATG 73 178 187 206 502388 TGTTGGACAGGCAGCACCAT 60 179 188 207 502389 ATGTTGGACAGGCAGCACCA 75 180 189 208 502390 CATGTTGGACAGGCAGCACC 81 181 190 209 502391 ACATGTTGGACAGGCAGCAC 67 182 191 210 502392 GACATGTTGGACAGGCAGCA 71 183 192 211 502393 TGACATGTTGGACAGGCAGC 81 184 193 212 502394 CTGACATGTTGGACAGGCAG 76 185 194 213 502395 GCTGACATGTTGGACAGGCA 70 186 195 214 502396 GGCTGACATGTTGGACAGGC 77 187 196 215 502397 CGGCTGACATGTTGGACAGG 74 188 197 216 502398 TCGGCTGACATGTTGGACAG 63 189 198 217 502399 CTCGGCTGACATGTTGGACA 80 190 199 218 502400 CCTCGGCTGACATGTTGGAC 71 191 200 219 502401 ACCTCGGCTGACATGTTGGA 64 192 201 220 502402 CACCTCGGCTGACATGTTGG 71 193 202 221 502403 GCACCTCGGCTGACATGTTG 77 194 203 222 502404 CGCACCTCGGCTGACATGTT 80 195 204 223 502405 CCGCACCTCGGCTGACATGT 80 196 205 224 502406 GCCGCACCTCGGCTGACATG 79 197 206 225 502407 AGCCGCACCTCGGCTGACAT 74 198 207 226 502408 CAGCCGCACCTCGGCTGACA 66 199 208 227 502409 TCAGCCGCACCTCGGCTGAC 15 200 209 228 502410 CTCAGCCGCACCTCGGCTGA 32 201 210 229 502411 CCTCAGCCGCACCTCGGCTG 65 202 211 230 502412 GCCTCAGCCGCACCTCGGCT 81 203 232 251 502413 CCAACACCAGCTGCTGGAGC 90 204 233 252 502414 TCCAACACCAGCTGCTGGAG 78 205 234 253 502415 GTCCAACACCAGCTGCTGGA 84 206 236 255 502416 GGGTCCAACACCAGCTGCTG 69 207 257 276 502417 GGCTCCAGCCCCAGGAAGCC 46 208 258 277 502418 GGGCTCCAGCCCCAGGAAGC 28 209 276 295 502419 CAGGAGAAGGTCGAGCAGGG 41 210 278 297 502420 CCCAGGAGAAGGTCGAGCAG 71 211 279 298 502421 GCCCAGGAGAAGGTCGAGCA 85 212 280 299 451363 CGCCCAGGAGAAGGTCGAGC 84 213 281 300 502422 ACGCCCAGGAGAAGGTCGAG 67 214 317 336 502423 TCCTGGGCCAGTTCGGAGGC 58 215 318 337 502424 GTCCTGGGCCAGTTCGGAGG 71 216 319 338 502425 TGTCCTGGGCCAGTTCGGAG 69 217 320 339 502426 TTGTCCTGGGCCAGTTCGGA 71 218 321 340 502427 CTTGTCCTGGGCCAGTTCGG 66 219 322 341 502428 ACTTGTCCTGGGCCAGTTCG 59 220 323 342 502429 TACTTGTCCTGGGCCAGTTC 75 221 324 343 502430 GTACTTGTCCTGGGCCAGTT 78 222 325 344 502431 CGTACTTGTCCTGGGCCAGT 74 223 343 362 502432 ACTGCAAGAAGTCGGCCACG 73 224 345 364 502433 CCACTGCAAGAAGTCGGCCA 65 225 346 365 451364 CCCACTGCAAGAAGTCGGCC 32 226 347 366 502434 GCCCACTGCAAGAAGTCGGC 70 227 348 367 502435 CGCCCACTGCAAGAAGTCGG 61 228 349 368 502436 CCGCCCACTGCAAGAAGTCG 54 229 350 369 502437 TCCGCCCACTGCAAGAAGTC 40 230 351 370 502438 CTCCGCCCACTGCAAGAAGT 33 231 352 371 502439 GCTCCGCCCACTGCAAGAAG 23 232 353 372 502440 GGCTCCGCCCACTGCAAGAA 23 233 354 373 502441 GGGCTCCGCCCACTGCAAGA 17 234 355 374 502442 TGGGCTCCGCCCACTGCAAG 22 235 356 375 502443 ATGGGCTCCGCCCACTGCAA 14 236 357 376 502444 GATGGGCTCCGCCCACTGCA 43 237 358 377 502445 CGATGGGCTCCGCCCACTGC 37 238 359 378 502446 ACGATGGGCTCCGCCCACTG 0 239 360 379 502447 CACGATGGGCTCCGCCCACT 59 240 361 380 502448 CCACGATGGGCTCCGCCCAC 69 241 362 381 502449 ACCACGATGGGCTCCGCCCA 63 242 363 382 502450 CACCACGATGGGCTCCGCCC 73 243 364 383 502451 TCACCACGATGGGCTCCGCC 77 244 365 384 502452 CTCACCACGATGGGCTCCGC 66 245 366 385 502453 CCTCACCACGATGGGCTCCG 81 246 367 386 502454 GCCTCACCACGATGGGCTCC 77 247 368 387 502455 AGCCTCACCACGATGGGCTC 63 248 369 388 502456 AAGCCTCACCACGATGGGCT 70 249 370 389 502457 TAAGCCTCACCACGATGGGC 78 250 371 390 502458 TTAAGCCTCACCACGATGGG 76 251 372 391 502459 CTTAAGCCTCACCACGATGG 78 252 373 392 502460 CCTTAAGCCTCACCACGATG 68 253 374 393 502461 TCCTTAAGCCTCACCACGAT 67 254 375 394 502462 CTCCTTAAGCCTCACCACGA 84 255 376 395 502463 CCTCCTTAAGCCTCACCACG 76 256 377 396 502464 ACCTCCTTAAGCCTCACCAC 64 257 378 397 502465 GACCTCCTTAAGCCTCACCA 72 258 379 398 502466 GGACCTCCTTAAGCCTCACC 69 259 380 399 502467 CGGACCTCCTTAAGCCTCAC 81 260 381 400 502468 TCGGACCTCCTTAAGCCTCA 78 261 382 401 502469 GTCGGACCTCCTTAAGCCTC 57 262 384 403 502470 CAGTCGGACCTCCTTAAGCC 62 263 385 404 502471 GCAGTCGGACCTCCTTAAGC 45 264 386 405 502472 TGCAGTCGGACCTCCTTAAG 60 265 412 431 502473 CCTTCAGAATCTCGAAGTCG 67 266 413 432 502474 ACCTTCAGAATCTCGAAGTC 50 267 415 434 502475 TCACCTTCAGAATCTCGAAG 54 268 416 435 502476 ATCACCTTCAGAATCTCGAA 38 269 417 436 502477 GATCACCTTCAGAATCTCGA 35 270 419 438 502478 CCGATCACCTTCAGAATCTC 52 271 420 439 502479 TCCGATCACCTTCAGAATCT 50 272 421 440 502480 GTCCGATCACCTTCAGAATC 44 273 422 441 502481 CGTCCGATCACCTTCAGAAT 41 274 467 486 502482 CCCGTCTGCTTCATCTTCAC 67 275 468 487 502483 GCCCGTCTGCTTCATCTTCA 76 276 469 488 502484 GGCCCGTCTGCTTCATCTTC 57 277 470 489 502485 TGGCCCGTCTGCTTCATCTT 64 278 471 490 502486 CTGGCCCGTCTGCTTCATCT 64 279 472 491 502487 CCTGGCCCGTCTGCTTCATC 73 280

473 492 502488 ACCTGGCCCGTCTGCTTCAT 64 281 474 493 502489 CACCTGGCCCGTCTGCTTCA 80 282 475 494 502490 ACACCTGGCCCGTCTGCTTC 71 283 476 495 502491 TACACCTGGCCCGTCTGCTT 74 284 497 516 502492 TTGTTCATGATCTTCATGGC 56 285 499 518 502493 ACTTGTTCATGATCTTCATG 23 286 500 519 502494 CACTTGTTCATGATCTTCAT 43 287 501 520 502495 CCACTTGTTCATGATCTTCA 43 288 502 521 502496 CCCACTTGTTCATGATCTTC 47 289 503 522 502497 TCCCACTTGTTCATGATCTT 34 290 504 523 502498 GTCCCACTTGTTCATGATCT 34 291 505 524 502499 TGTCCCACTTGTTCATGATC 27 292 506 525 502500 ATGTCCCACTTGTTCATGAT 23 293 507 526 502501 CATGTCCCACTTGTTCATGA 51 294 508 527 502502 GCATGTCCCACTTGTTCATG 20 295 509 528 502503 AGCATGTCCCACTTGTTCAT 52 296 510 529 502504 CAGCATGTCCCACTTGTTCA 72 297 511 530 502505 TCAGCATGTCCCACTTGTTC 70 298 512 531 502506 TTCAGCATGTCCCACTTGTT 53 299 513 532 502507 CTTCAGCATGTCCCACTTGT 52 300 514 533 502508 TCTTCAGCATGTCCCACTTG 45 301 516 535 502509 CCTCTTCAGCATGTCCCACT 68 302 517 536 502510 CCCTCTTCAGCATGTCCCAC 68 303 518 537 502511 CCCCTCTTCAGCATGTCCCA 79 304 519 538 502512 GCCCCTCTTCAGCATGTCCC 85 305 520 539 502513 CGCCCCTCTTCAGCATGTCC 84 306 521 540 502514 TCGCCCCTCTTCAGCATGTC 80 307 522 541 502515 CTCGCCCCTCTTCAGCATGT 82 308 523 542 502516 CCTCGCCCCTCTTCAGCATG 78 309 524 543 502517 ACCTCGCCCCTCTTCAGCAT 73 310 525 544 502518 CACCTCGCCCCTCTTCAGCA 76 311 526 545 502519 ACACCTCGCCCCTCTTCAGC 79 312 527 546 502520 GACACCTCGCCCCTCTTCAG 73 313 821 840 502521 GCCAGGCGGATGTGGCCACA 57 314 868 887 502522 ACCGCACCGTTCCATCTGCC 62 315 869 888 502523 GACCGCACCGTTCCATCTGC 29 316 923 942 502524 ACAGCCTGCAGGATCTCGGG 86 317 924 943 502525 CACAGCCTGCAGGATCTCGG 81 318 925 944 502526 CCACAGCCTGCAGGATCTCG 83 319 926 945 502527 CCCACAGCCTGCAGGATCTC 84 320 927 946 502528 GCCCACAGCCTGCAGGATCT 91 321 928 947 502529 CGCCCACAGCCTGCAGGATC 90 322 929 948 502530 CCGCCCACAGCCTGCAGGAT 82 323 930 949 502531 ACCGCCCACAGCCTGCAGGA 83 324 931 950 502532 CACCGCCCACAGCCTGCAGG 85 325 932 951 502533 CCACCGCCCACAGCCTGCAG 84 326 933 952 502534 CCCACCGCCCACAGCCTGCA 80 327 934 953 502535 GCCCACCGCCCACAGCCTGC 90 328 935 954 502536 GGCCCACCGCCCACAGCCTG 94 329 936 955 502537 AGGCCCACCGCCCACAGCCT 88 330 937 956 502538 CAGGCCCACCGCCCACAGCC 91 331 938 957 502539 CCAGGCCCACCGCCCACAGC 73 332 939 958 502540 CCCAGGCCCACCGCCCACAG 86 333 940 959 502541 TCCCAGGCCCACCGCCCACA 88 334 941 960 502542 GTCCCAGGCCCACCGCCCAC 84 335 942 961 502543 TGTCCCAGGCCCACCGCCCA 85 336 943 962 502544 CTGTCCCAGGCCCACCGCCC 65 337 944 963 502545 CCTGTCCCAGGCCCACCGCC 81 338 945 964 502546 GCCTGTCCCAGGCCCACCGC 90 339 946 965 502547 TGCCTGTCCCAGGCCCACCG 85 340 947 966 502548 CTGCCTGTCCCAGGCCCACC 89 341 948 967 502549 GCTGCCTGTCCCAGGCCCAC 91 342 949 968 502550 AGCTGCCTGTCCCAGGCCCA 94 343 950 969 502551 TAGCTGCCTGTCCCAGGCCC 92 344 951 970 502552 GTAGCTGCCTGTCCCAGGCC 88 345 952 971 502553 CGTAGCTGCCTGTCCCAGGC 85 346 953 972 502554 CCGTAGCTGCCTGTCCCAGG 83 347 954 973 502555 CCCGTAGCTGCCTGTCCCAG 64 348 955 974 502556 GCCCGTAGCTGCCTGTCCCA 83 349 956 975 502557 GGCCCGTAGCTGCCTGTCCC 89 350 1004 1023 502558 TAGAACATTTCATAGGCGAA 68 351 1042 1061 502559 TCTCCGCCGTGGAATCCGCG 75 352 1043 1062 502560 GTCTCCGCCGTGGAATCCGC 79 353 1044 1063 502561 GGTCTCCGCCGTGGAATCCG 66 354 1045 1064 502562 AGGTCTCCGCCGTGGAATCC 50 355 1046 1065 502563 TAGGTCTCCGCCGTGGAATC 71 356 1067 1086 502564 TTGTAGTGGACGATCTTGCC 68 357 1068 1087 502565 CTTGTAGTGGACGATCTTGC 70 358 1069 1088 502566 CCTTGTAGTGGACGATCTTG 61 359 1070 1089 502567 TCCTTGTAGTGGACGATCTT 72 360 1071 1090 502568 CTCCTTGTAGTGGACGATCT 75 361 1072 1091 502569 GCTCCTTGTAGTGGACGATC 75 362 1073 1092 502570 TGCTCCTTGTAGTGGACGAT 83 363 1074 1093 502571 GTGCTCCTTGTAGTGGACGA 72 364 1075 1094 502572 GGTGCTCCTTGTAGTGGACG 66 365 1076 1095 502573 AGGTGCTCCTTGTAGTGGAC 51 366 1077 1096 502574 GAGGTGCTCCTTGTAGTGGA 46 367 1078 1097 502575 AGAGGTGCTCCTTGTAGTGG 70 368 1079 1098 502576 GAGAGGTGCTCCTTGTAGTG 47 369 1080 1099 502577 AGAGAGGTGCTCCTTGTAGT 65 370 1081 1100 502578 GAGAGAGGTGCTCCTTGTAG 45 371 1082 1101 502579 AGAGAGAGGTGCTCCTTGTA 63 372 1083 1102 502580 CAGAGAGAGGTGCTCCTTGT 77 373 1085 1104 502581 GGCAGAGAGAGGTGCTCCTT 70 374 1086 1105 502582 CGGCAGAGAGAGGTGCTCCT 80 375 1087 1106 502583 GCGGCAGAGAGAGGTGCTCC 62 376 1088 1107 502584 AGCGGCAGAGAGAGGTGCTC 44 377 1089 1108 502585 CAGCGGCAGAGAGAGGTGCT 78 378 1090 1109 502586 CCAGCGGCAGAGAGAGGTGC 71 379 1165 1184 502587 GGCCCAGCCGTGTCTCCGGG 77 380 1166 1185 502588 CGGCCCAGCCGTGTCTCCGG 69 381 1167 1186 502589 CCGGCCCAGCCGTGTCTCCG 70 382 1168 1187 502590 CCCGGCCCAGCCGTGTCTCC 75 383 1169 1188 502591 CCCCGGCCCAGCCGTGTCTC 77 384 1170 1189 502592 ACCCCGGCCCAGCCGTGTCT 73 385 1171 1190 502593 CACCCCGGCCCAGCCGTGTC 84 386 1172 1191 502594 CCACCCCGGCCCAGCCGTGT 78 387 1173 1192 502595 TCCACCCCGGCCCAGCCGTG 71 388 1174 1193 502596 CTCCACCCCGGCCCAGCCGT 81 389 1175 1194 502597 GCTCCACCCCGGCCCAGCCG 86 390 1176 1195 502598 TGCTCCACCCCGGCCCAGCC 83 391 1177 1196 502599 CTGCTCCACCCCGGCCCAGC 88 392 1199 1218 502600 AAGGGATGTGTCCGGAAGTC 60 393 1200 1219 502601 GAAGGGATGTGTCCGGAAGT 58 394 1201 1220 502602 AGAAGGGATGTGTCCGGAAG 63 395 1202 1221 502603 AAGAAGGGATGTGTCCGGAA 62 396 1203 1222 502604 GAAGAAGGGATGTGTCCGGA 61 397 1204 1223 502605 AGAAGAAGGGATGTGTCCGG 62 398 1205 1224 502606 AAGAAGAAGGGATGTGTCCG 56 399 1206 1225 502607 AAAGAAGAAGGGATGTGTCC 58 400 1207 1226 502608 CAAAGAAGAAGGGATGTGTC 50 401 1208 1227 502609 CCAAAGAAGAAGGGATGTGT 61 402 1210 1229 502610 GGCCAAAGAAGAAGGGATGT 73 403 1211 1230 502611 AGGCCAAAGAAGAAGGGATG 56 404 1212 1231 502612 GAGGCCAAAGAAGAAGGGAT 73 405 1213 1232 502613 CGAGGCCAAAGAAGAAGGGA 75 406

1214 1233 502614 TCGAGGCCAAAGAAGAAGGG 75 407 1215 1234 502615 GTCGAGGCCAAAGAAGAAGG 83 408 1216 1235 502616 AGTCGAGGCCAAAGAAGAAG 58 409 1217 1236 502617 CAGTCGAGGCCAAAGAAGAA 52 410 1218 1237 502618 CCAGTCGAGGCCAAAGAAGA 68 411 1219 1238 502619 CCCAGTCGAGGCCAAAGAAG 78 412 1220 1239 502620 TCCCAGTCGAGGCCAAAGAA 66 413 1221 1240 502621 ATCCCAGTCGAGGCCAAAGA 75 414 1222 1241 502622 CATCCCAGTCGAGGCCAAAG 70 415 1223 1242 502623 CCATCCCAGTCGAGGCCAAA 81 416 1224 1243 502624 ACCATCCCAGTCGAGGCCAA 82 417 1225 1244 502625 GACCATCCCAGTCGAGGCCA 88 418 1226 1245 502626 AGACCATCCCAGTCGAGGCC 79 419 1227 1246 502627 GAGACCATCCCAGTCGAGGC 82 420 1228 1247 502628 GGAGACCATCCCAGTCGAGG 60 421 1263 1282 502629 TTCGAAATCCGGTGTAAAGG 84 422 1264 1283 502630 CTTCGAAATCCGGTGTAAAG 57 423 1265 1284 502631 CCTTCGAAATCCGGTGTAAA 64 424 1266 1285 502632 ACCTTCGAAATCCGGTGTAA 73 425 1267 1286 502633 CACCTTCGAAATCCGGTGTA 77 426 1268 1287 502634 GCACCTTCGAAATCCGGTGT 59 427 1269 1288 502635 GGCACCTTCGAAATCCGGTG 85 428 1270 1289 502636 TGGCACCTTCGAAATCCGGT 86 429 1271 1290 502637 GTGGCACCTTCGAAATCCGG 74 430 1272 1291 502638 GGTGGCACCTTCGAAATCCG 79 431 1273 1292 502639 CGGTGGCACCTTCGAAATCC 85 432 1274 1293 502640 TCGGTGGCACCTTCGAAATC 71 433 1275 1294 502641 GTCGGTGGCACCTTCGAAAT 88 434 1276 1295 502642 TGTCGGTGGCACCTTCGAAA 89 435 1277 1296 502643 GTGTCGGTGGCACCTTCGAA 88 436 1278 1297 502644 TGTGTCGGTGGCACCTTCGA 87 437 1279 1298 502645 ATGTGTCGGTGGCACCTTCG 88 438 1280 1299 502646 CATGTGTCGGTGGCACCTTC 88 439 1281 1300 502647 GCATGTGTCGGTGGCACCTT 91 440 1282 1301 502648 TGCATGTGTCGGTGGCACCT 87 441 1283 1302 502649 TTGCATGTGTCGGTGGCACC 86 442 1284 1303 502650 GTTGCATGTGTCGGTGGCAC 83 443 1285 1304 502651 AGTTGCATGTGTCGGTGGCA 81 444 1286 1305 502652 AAGTTGCATGTGTCGGTGGC 79 445 1287 1306 502653 GAAGTTGCATGTGTCGGTGG 58 446 1288 1307 502654 CGAAGTTGCATGTGTCGGTG 85 447 1290 1309 502655 GTCGAAGTTGCATGTGTCGG 77 448 1291 1310 502656 AGTCGAAGTTGCATGTGTCG 79 449 1292 1311 502657 AAGTCGAAGTTGCATGTGTC 74 450 1293 1312 502658 CAAGTCGAAGTTGCATGTGT 82 451 1294 1313 502659 CCAAGTCGAAGTTGCATGTG 82 452 1295 1314 502660 ACCAAGTCGAAGTTGCATGT 70 453 1296 1315 502661 CACCAAGTCGAAGTTGCATG 76 454 1297 1316 502662 CCACCAAGTCGAAGTTGCAT 79 455 1298 1317 502663 TCCACCAAGTCGAAGTTGCA 68 456 1299 1318 502664 CTCCACCAAGTCGAAGTTGC 71 457 1300 1319 502665 CCTCCACCAAGTCGAAGTTG 67 458 1301 1320 502666 TCCTCCACCAAGTCGAAGTT 70 459 1302 1321 502667 GTCCTCCACCAAGTCGAAGT 80 460 1303 1322 502668 CGTCCTCCACCAAGTCGAAG 76 461 1304 1323 502669 CCGTCCTCCACCAAGTCGAA 78 462 1305 1324 502670 CCCGTCCTCCACCAAGTCGA 83 463 1306 1325 502671 GCCCGTCCTCCACCAAGTCG 76 464 1307 1326 502672 AGCCCGTCCTCCACCAAGTC 72 465 1308 1327 502673 GAGCCCGTCCTCCACCAAGT 71 466 1309 1328 502674 TGAGCCCGTCCTCCACCAAG 60 467 1702 1721 502675 GGTTCCGAGCCTCTGCCTCG 44 468 1703 1722 502676 CGGTTCCGAGCCTCTGCCTC 74 469 1704 1723 502677 CCGGTTCCGAGCCTCTGCCT 72 470 1705 1724 502678 CCCGGTTCCGAGCCTCTGCC 73 471 1706 1725 502679 TCCCGGTTCCGAGCCTCTGC 84 472 1707 1726 502680 GTCCCGGTTCCGAGCCTCTG 66 473 1709 1728 502681 AGGTCCCGGTTCCGAGCCTC 82 474 1710 1729 502682 TAGGTCCCGGTTCCGAGCCT 83 475 1711 1730 502683 CTAGGTCCCGGTTCCGAGCC 81 476 1712 1731 502684 TCTAGGTCCCGGTTCCGAGC 74 477 1713 1732 502685 CTCTAGGTCCCGGTTCCGAG 78 478 1714 1733 502686 CCTCTAGGTCCCGGTTCCGA 75 479 1715 1734 502687 GCCTCTAGGTCCCGGTTCCG 80 480 1743 1762 502688 CATCCGCTCCTGCAACTGCC 89 481 1744 1763 502689 CCATCCGCTCCTGCAACTGC 81 482 1745 1764 502690 TCCATCCGCTCCTGCAACTG 71 483 1746 1765 502691 CTCCATCCGCTCCTGCAACT 75 484 1747 1766 502692 ACTCCATCCGCTCCTGCAAC 64 485 1748 1767 502693 AACTCCATCCGCTCCTGCAA 52 486 1749 1768 502694 CAACTCCATCCGCTCCTGCA 45 487 1751 1770 502695 AGCAACTCCATCCGCTCCTG 78 488 1752 1771 502696 CAGCAACTCCATCCGCTCCT 64 489 1753 1772 502697 GCAGCAACTCCATCCGCTCC 56 490 1774 1793 502698 CAGCTGTGGCTCCCTCTGCC 60 491 1775 1794 502699 ACAGCTGTGGCTCCCTCTGC 45 492 1776 1795 502700 GACAGCTGTGGCTCCCTCTG 49 493 1777 1796 502701 TGACAGCTGTGGCTCCCTCT 26 494 1778 1797 502702 GTGACAGCTGTGGCTCCCTC 32 495 1779 1798 502703 CGTGACAGCTGTGGCTCCCT 28 496 1780 1799 502704 CCGTGACAGCTGTGGCTCCC 35 497 1781 1800 502705 CCCGTGACAGCTGTGGCTCC 33 498 1782 1801 502706 CCCCGTGACAGCTGTGGCTC 53 499 1783 1802 502707 CCCCCGTGACAGCTGTGGCT 39 500 1784 1803 502708 ACCCCCGTGACAGCTGTGGC 53 501 1785 1804 502709 GACCCCCGTGACAGCTGTGG 51 502 1786 1805 502710 GGACCCCCGTGACAGCTGTG 58 503 1787 1806 502711 GGGACCCCCGTGACAGCTGT 71 504 1814 1833 502712 GAAGGTGGATCCGTGGCCCG 73 505 1815 1834 502713 GGAAGGTGGATCCGTGGCCC 70 506 1816 1835 502714 GGGAAGGTGGATCCGTGGCC 72 507 1817 1836 502715 TGGGAAGGTGGATCCGTGGC 50 508 1818 1837 502716 ATGGGAAGGTGGATCCGTGG 62 509 1819 1838 502717 GATGGGAAGGTGGATCCGTG 75 510 1821 1840 502718 TAGATGGGAAGGTGGATCCG 52 511 1822 1841 502719 CTAGATGGGAAGGTGGATCC 56 512 1823 1842 502720 TCTAGATGGGAAGGTGGATC 21 513 1824 1843 502721 ATCTAGATGGGAAGGTGGAT 34 514 1826 1845 502722 CCATCTAGATGGGAAGGTGG 43 515 1827 1846 502723 GCCATCTAGATGGGAAGGTG 17 516 1828 1847 451383 GGCCATCTAGATGGGAAGGT 0 517 1863 1882 502724 CACCAGCGGGCACTGGCCCA 51 518 1864 1883 502725 CCACCAGCGGGCACTGGCCC 55 519 1865 1884 502726 CCCACCAGCGGGCACTGGCC 61 520 1866 1885 502727 CCCCACCAGCGGGCACTGGC 43 521 1868 1887 502728 GGCCCCACCAGCGGGCACTG 16 522 1869 1888 502729 TGGCCCCACCAGCGGGCACT 43 523 1870 1889 502730 CTGGCCCCACCAGCGGGCAC 43 524 1871 1890 502731 CCTGGCCCCACCAGCGGGCA 41 525 1872 1891 502732 GCCTGGCCCCACCAGCGGGC 30 526 1874 1893 502733 GGGCCTGGCCCCACCAGCGG 66 527 1892 1911 502734 AGGTGGCGGCGGTGCATGGG 31 528 1893 1912 502735 CAGGTGGCGGCGGTGCATGG 23 529 1894 1913 502736 GCAGGTGGCGGCGGTGCATG 57 530 1895 1914 502737 AGCAGGTGGCGGCGGTGCAT 54 531

1896 1915 502738 CAGCAGGTGGCGGCGGTGCA 61 532 1897 1916 502739 GCAGCAGGTGGCGGCGGTGC 57 533 1898 1917 502740 AGCAGCAGGTGGCGGCGGTG 36 534 1899 1918 502741 GAGCAGCAGGTGGCGGCGGT 53 535 1900 1919 502742 GGAGCAGCAGGTGGCGGCGG 39 536 1901 1920 502743 GGGAGCAGCAGGTGGCGGCG 36 537 1902 1921 502744 AGGGAGCAGCAGGTGGCGGC 62 538 1903 1922 502745 CAGGGAGCAGCAGGTGGCGG 56 539 1904 1923 502746 GCAGGGAGCAGCAGGTGGCG 58 540 1905 1924 502747 GGCAGGGAGCAGCAGGTGGC 65 541 1906 1925 502748 TGGCAGGGAGCAGCAGGTGG 47 542 1907 1926 502749 CTGGCAGGGAGCAGCAGGTG 41 543 1909 1928 451432 CCCTGGCAGGGAGCAGCAGG 53 544 1910 1929 502750 ACCCTGGCAGGGAGCAGCAG 52 545 1911 1930 502751 GACCCTGGCAGGGAGCAGCA 77 546 1912 1931 502752 GGACCCTGGCAGGGAGCAGC 0 547 1919 1938 502753 GGCCTAGGGACCCTGGCAGG 39 548 1920 1939 502754 AGGCCTAGGGACCCTGGCAG 35 549 1922 1941 502755 CCAGGCCTAGGGACCCTGGC 44 550 1923 1942 502756 GCCAGGCCTAGGGACCCTGG 60 551 1924 1943 502757 GGCCAGGCCTAGGGACCCTG 58 552 1925 1944 502758 AGGCCAGGCCTAGGGACCCT 57 553 1926 1945 502759 TAGGCCAGGCCTAGGGACCC 52 554 1927 1946 502760 ATAGGCCAGGCCTAGGGACC 51 555 1928 1947 502761 GATAGGCCAGGCCTAGGGAC 41 556 1929 1948 502762 CGATAGGCCAGGCCTAGGGA 69 557 1930 1949 502763 CCGATAGGCCAGGCCTAGGG 80 558 1931 1950 502764 TCCGATAGGCCAGGCCTAGG 78 559 1932 1951 502765 CTCCGATAGGCCAGGCCTAG 89 560 1933 1952 502766 CCTCCGATAGGCCAGGCCTA 79 561 1934 1953 502767 GCCTCCGATAGGCCAGGCCT 73 562 1936 1955 502768 GCGCCTCCGATAGGCCAGGC 83 563 1952 1971 502769 AACAGGAGCAGGGAAAGCGC 83 564 1953 1972 502770 GAACAGGAGCAGGGAAAGCG 70 565 1954 1973 502771 CGAACAGGAGCAGGGAAAGC 43 566 1955 1974 502772 GCGAACAGGAGCAGGGAAAG 47 567 1956 1975 502773 GGCGAACAGGAGCAGGGAAA 61 568 1957 1976 502774 CGGCGAACAGGAGCAGGGAA 74 569 1958 1977 502775 ACGGCGAACAGGAGCAGGGA 60 570 1959 1978 502776 AACGGCGAACAGGAGCAGGG 86 571 1960 1979 502777 CAACGGCGAACAGGAGCAGG 84 572 1981 2000 502778 GGGCGGCGGCACGAGACAGA 80 573 1982 2001 502779 AGGGCGGCGGCACGAGACAG 76 574 1983 2002 502780 CAGGGCGGCGGCACGAGACA 58 575 1984 2003 502781 CCAGGGCGGCGGCACGAGAC 80 576 1985 2004 502782 CCCAGGGCGGCGGCACGAGA 59 577 1986 2005 502783 GCCCAGGGCGGCGGCACGAG 68 578 1987 2006 502784 AGCCCAGGGCGGCGGCACGA 75 579 1988 2007 502785 CAGCCCAGGGCGGCGGCACG 76 580 1989 2008 502786 GCAGCCCAGGGCGGCGGCAC 70 581 2026 2045 502787 CTGCGGTGAGTTGGCCGGCG 68 582 2027 2046 502788 ACTGCGGTGAGTTGGCCGGC 67 583 2028 2047 502789 GACTGCGGTGAGTTGGCCGG 58 584 2029 2048 502790 AGACTGCGGTGAGTTGGCCG 71 585 2030 2049 502791 CAGACTGCGGTGAGTTGGCC 70 586 2031 2050 502792 CCAGACTGCGGTGAGTTGGC 79 587 2032 2051 502793 GCCAGACTGCGGTGAGTTGG 76 588 2033 2052 502794 CGCCAGACTGCGGTGAGTTG 66 589 2077 2096 502795 AAGACAGTTCTAGGGTTCAG 87 590 2078 2097 502796 GAAGACAGTTCTAGGGTTCA 78 591 2079 2098 502797 CGAAGACAGTTCTAGGGTTC 85 592 2080 2099 502798 TCGAAGACAGTTCTAGGGTT 78 593 2081 2100 502799 GTCGAAGACAGTTCTAGGGT 92 594 2082 2101 502800 AGTCGAAGACAGTTCTAGGG 85 595 2083 2102 502801 GAGTCGAAGACAGTTCTAGG 83 596 2084 2103 502802 GGAGTCGAAGACAGTTCTAG 86 597 2085 2104 502803 CGGAGTCGAAGACAGTTCTA 91 598 2086 2105 502804 CCGGAGTCGAAGACAGTTCT 76 599 2087 2106 502805 CCCGGAGTCGAAGACAGTTC 90 600 2088 2107 502806 CCCCGGAGTCGAAGACAGTT 83 601 2089 2108 502807 GCCCCGGAGTCGAAGACAGT 82 602 2090 2109 502808 GGCCCCGGAGTCGAAGACAG 73 603 2091 2110 502809 GGGCCCCGGAGTCGAAGACA 67 604 2143 2162 502810 AGGCGGTGGGCGCGGCTTCT 73 605 2144 2163 502811 CAGGCGGTGGGCGCGGCTTC 57 606 2145 2164 502812 GCAGGCGGTGGGCGCGGCTT 69 607 2147 2166 502813 TGGCAGGCGGTGGGCGCGGC 73 608 2149 2168 502814 ACTGGCAGGCGGTGGGCGCG 56 609 2151 2170 502815 GAACTGGCAGGCGGTGGGCG 71 610 2152 2171 502816 TGAACTGGCAGGCGGTGGGC 80 611 2154 2173 502817 TGTGAACTGGCAGGCGGTGG 85 612 2187 2206 502818 TGGAGCTGGGCGGAGACCCA 55 613 2189 2208 502819 ACTGGAGCTGGGCGGAGACC 53 614 2190 2209 502820 GACTGGAGCTGGGCGGAGAC 55 615 2192 2211 502821 AGGACTGGAGCTGGGCGGAG 76 616 2194 2213 502822 ACAGGACTGGAGCTGGGCGG 77 617 2195 2214 502823 CACAGGACTGGAGCTGGGCG 74 618 2196 2215 502824 TCACAGGACTGGAGCTGGGC 90 619 2386 2405 502825 GCCTCAGCCTGGCCGAAAGA 80 620 2387 2406 502826 GGCCTCAGCCTGGCCGAAAG 72 621 2490 2509 444401 TTGCACTTTGCGAACCAACG 97 41

TABLE-US-00013 TABLE 13 Inhibition of human DMPK RNA transcript in hSKMc by 5-10-5 gapmers targeting SEQ ID NO: 2 Target Target Start Stop ISIS SEQ ID Site Site No Sequence % inhibition NO. 503 522 502983 TGGTGGAGCCAAGCCCTCCC 83 622 561 580 502984 GGGCACCCTCAGAGCCTGAA 82 623 1197 1216 502369 GCCTGGCAGCCCCTGTCCAG 16 160 1198 1217 502370 GGCCTGGCAGCCCCTGTCCA 58 161 1199 1218 502371 GGGCCTGGCAGCCCCTGTCC 62 162 1242 1261 502372 ATGGCCCCTCCCCGGGCCGG 41 163 1243 1262 502373 CATGGCCCCTCCCCGGGCCG 29 164 1244 1263 502374 CCATGGCCCCTCCCCGGGCC 34 165 1245 1264 502375 ACCATGGCCCCTCCCCGGGC 60 166 1246 1265 502376 CACCATGGCCCCTCCCCGGG 68 167 1247 1266 502377 GCACCATGGCCCCTCCCCGG 75 168 1248 1267 502378 AGCACCATGGCCCCTCCCCG 65 169 1249 1268 502379 CAGCACCATGGCCCCTCCCC 63 170 1250 1269 502380 GCAGCACCATGGCCCCTCCC 73 171 1251 1270 502381 GGCAGCACCATGGCCCCTCC 80 172 1253 1272 502382 CAGGCAGCACCATGGCCCCT 82 173 1254 1273 502383 ACAGGCAGCACCATGGCCCC 72 174 1256 1275 502384 GGACAGGCAGCACCATGGCC 70 175 1257 1276 502385 TGGACAGGCAGCACCATGGC 71 176 1258 1277 502386 TTGGACAGGCAGCACCATGG 73 177 1259 1278 502387 GTTGGACAGGCAGCACCATG 73 178 1260 1279 502388 TGTTGGACAGGCAGCACCAT 60 179 1261 1280 502389 ATGTTGGACAGGCAGCACCA 75 180 1262 1281 502390 CATGTTGGACAGGCAGCACC 81 181 1263 1282 502391 ACATGTTGGACAGGCAGCAC 67 182 1264 1283 502392 GACATGTTGGACAGGCAGCA 71 183 1265 1284 502393 TGACATGTTGGACAGGCAGC 81 184 1266 1285 502394 CTGACATGTTGGACAGGCAG 76 185 1267 1286 502395 GCTGACATGTTGGACAGGCA 70 186 1268 1287 502396 GGCTGACATGTTGGACAGGC 77 187 1269 1288 502397 CGGCTGACATGTTGGACAGG 74 188 1270 1289 502398 TCGGCTGACATGTTGGACAG 63 189 1271 1290 502399 CTCGGCTGACATGTTGGACA 80 190 1272 1291 502400 CCTCGGCTGACATGTTGGAC 71 191 1273 1292 502401 ACCTCGGCTGACATGTTGGA 64 192 1274 1293 502402 CACCTCGGCTGACATGTTGG 71 193 1275 1294 502403 GCACCTCGGCTGACATGTTG 77 194 1276 1295 502404 CGCACCTCGGCTGACATGTT 80 195 1277 1296 502405 CCGCACCTCGGCTGACATGT 80 196 1278 1297 502406 GCCGCACCTCGGCTGACATG 79 197 1279 1298 502407 AGCCGCACCTCGGCTGACAT 74 198 1280 1299 502408 CAGCCGCACCTCGGCTGACA 66 199 1281 1300 502409 TCAGCCGCACCTCGGCTGAC 15 200 1282 1301 502410 CTCAGCCGCACCTCGGCTGA 32 201 1283 1302 502411 CCTCAGCCGCACCTCGGCTG 65 202 1284 1303 502412 GCCTCAGCCGCACCTCGGCT 81 203 1305 1324 502413 CCAACACCAGCTGCTGGAGC 90 204 1306 1325 502414 TCCAACACCAGCTGCTGGAG 78 205 1307 1326 502415 GTCCAACACCAGCTGCTGGA 84 206 1309 1328 502416 GGGTCCAACACCAGCTGCTG 69 207 1330 1349 502417 GGCTCCAGCCCCAGGAAGCC 46 208 1331 1350 502418 GGGCTCCAGCCCCAGGAAGC 28 209 1349 1368 502419 CAGGAGAAGGTCGAGCAGGG 41 210 1351 1370 502420 CCCAGGAGAAGGTCGAGCAG 71 211 1352 1371 502421 GCCCAGGAGAAGGTCGAGCA 85 212 1353 1372 451363 CGCCCAGGAGAAGGTCGAGC 84 213 1354 1373 502422 ACGCCCAGGAGAAGGTCGAG 67 214 1390 1409 502423 TCCTGGGCCAGTTCGGAGGC 58 215 1391 1410 502424 GTCCTGGGCCAGTTCGGAGG 71 216 1392 1411 502425 TGTCCTGGGCCAGTTCGGAG 69 217 1393 1412 502426 TTGTCCTGGGCCAGTTCGGA 71 218 1394 1413 502427 CTTGTCCTGGGCCAGTTCGG 66 219 1395 1414 502428 ACTTGTCCTGGGCCAGTTCG 59 220 1396 1415 502429 TACTTGTCCTGGGCCAGTTC 75 221 1397 1416 502430 GTACTTGTCCTGGGCCAGTT 78 222 1398 1417 502431 CGTACTTGTCCTGGGCCAGT 74 223 1416 1435 502432 ACTGCAAGAAGTCGGCCACG 73 224 1418 1437 502433 CCACTGCAAGAAGTCGGCCA 65 225 1419 1438 451364 CCCACTGCAAGAAGTCGGCC 32 226 1421 1440 502985 ACCCCACTGCAAGAAGTCGG 60 624 1551 1570 502986 GCCCCAGGATGGGAGGATCT 58 625 1597 1616 502987 CATAGGACAGAGAAATGTTG 70 626 1630 1649 502988 TGCTGACCTTACTCTGCCCC 86 627 1666 1685 502989 TAAGCCATGGCTCTGAGTCA 51 628 1712 1731 502990 AGAGAGGCCATGGGAGGCTG 42 629 1841 1860 502991 CTGGCCCTCCTGGCTTGCCC 72 630 1853 1872 502992 AGCTGCCCCATGCTGGCCCT 76 631 1862 1881 502993 GCCCCTGGCAGCTGCCCCAT 70 632 1873 1892 502994 CTGTCGGCTGCGCCCCTGGC 78 633 1887 1906 502995 CGCCGAACACCTGCCTGTCG 68 634 1931 1950 502996 CCTCCCAGTGCCTGGGCACC 52 635 1981 2000 502998 GCGCCTGTCTGCAAAGCTGG 84 636 2025 2044 502999 CCCAAAGTTGTCCCTCCTGG 83 637 2038 2057 503000 ACACCCAGAAGAACCCAAAG 75 638 2117 2136 503001 CTGACCCACACGGCTCATAG 65 639 2235 2254 503002 TGGCCCCAGGCCCTGGAAAG 67 640 2278 2297 503003 GACAAGGCAGCTGGCAGAAG 79 641 2331 2350 503004 AAGAAACCAGTGACCAGTGA 85 642 2523 2542 503005 CTGTGAAATGGGAGGAGGAG 0 643 2578 2597 503006 GAAGGTTTTTCCAGAGGCTG 88 644 2615 2634 503007 GGCCAGGAGAGTCATTAGGG 84 645 2710 2729 503008 CCACAAAAGGAGTGCTCCTC 79 646 2789 2808 503009 CCTTTTAAGGCAGCAGGAAC 78 647 3629 3648 503010 CTAGGACTGTCTGCTTCCCA 88 648 3761 3780 502452 CTCACCACGATGGGCTCCGC 66 245 3762 3781 502453 CCTCACCACGATGGGCTCCG 81 246 3763 3782 502454 GCCTCACCACGATGGGCTCC 77 247 3764 3783 502455 AGCCTCACCACGATGGGCTC 63 248 3765 3784 502456 AAGCCTCACCACGATGGGCT 70 249 3766 3785 502457 TAAGCCTCACCACGATGGGC 78 250 3767 3786 502458 TTAAGCCTCACCACGATGGG 76 251 3768 3787 502459 CTTAAGCCTCACCACGATGG 78 252 3769 3788 502460 CCTTAAGCCTCACCACGATG 68 253 3770 3789 502461 TCCTTAAGCCTCACCACGAT 67 254 3771 3790 502462 CTCCTTAAGCCTCACCACGA 84 255 3772 3791 502463 CCTCCTTAAGCCTCACCACG 76 256 3773 3792 502464 ACCTCCTTAAGCCTCACCAC 64 257 3774 3793 502465 GACCTCCTTAAGCCTCACCA 72 258 3775 3794 502466 GGACCTCCTTAAGCCTCACC 69 259 3776 3795 502467 CGGACCTCCTTAAGCCTCAC 81 260 3777 3796 502468 TCGGACCTCCTTAAGCCTCA 78 261 3778 3797 502469 GTCGGACCTCCTTAAGCCTC 57 262 3780 3799 502470 CAGTCGGACCTCCTTAAGCC 62 263 3781 3800 502471 GCAGTCGGACCTCCTTAAGC 45 264 3782 3801 502472 TGCAGTCGGACCTCCTTAAG 60 265 3808 3827 502473 CCTTCAGAATCTCGAAGTCG 67 266 3809 3828 502474 ACCTTCAGAATCTCGAAGTC 50 267 3811 3830 502475 TCACCTTCAGAATCTCGAAG 54 268 3812 3831 502476 ATCACCTTCAGAATCTCGAA 38 269 3813 3832 502477 GATCACCTTCAGAATCTCGA 35 270 3815 3834 502478 CCGATCACCTTCAGAATCTC 52 271

3816 3835 502479 TCCGATCACCTTCAGAATCT 50 272 3817 3836 502480 GTCCGATCACCTTCAGAATC 44 273 3818 3837 502481 CGTCCGATCACCTTCAGAAT 41 274 3921 3940 503011 GTCATTCATCAATTTCTAAG 44 649 4118 4137 502482 CCCGTCTGCTTCATCTTCAC 67 275 4119 4138 502483 GCCCGTCTGCTTCATCTTCA 76 276 4120 4139 502484 GGCCCGTCTGCTTCATCTTC 57 277 4121 4140 502485 TGGCCCGTCTGCTTCATCTT 64 278 4122 4141 502486 CTGGCCCGTCTGCTTCATCT 64 279 4123 4142 502487 CCTGGCCCGTCTGCTTCATC 73 280 4124 4143 502488 ACCTGGCCCGTCTGCTTCAT 64 281 4125 4144 502489 CACCTGGCCCGTCTGCTTCA 80 282 4126 4145 502490 ACACCTGGCCCGTCTGCTTC 71 283 4127 4146 502491 TACACCTGGCCCGTCTGCTT 74 284 4148 4167 502492 TTGTTCATGATCTTCATGGC 56 285 4150 4169 502493 ACTTGTTCATGATCTTCATG 23 286 4151 4170 502494 CACTTGTTCATGATCTTCAT 43 287 4152 4171 502495 CCACTTGTTCATGATCTTCA 43 288 4153 4172 502496 CCCACTTGTTCATGATCTTC 47 289 4154 4173 502497 TCCCACTTGTTCATGATCTT 34 290 4155 4174 502498 GTCCCACTTGTTCATGATCT 34 291 4156 4175 502499 TGTCCCACTTGTTCATGATC 27 292 4157 4176 502500 ATGTCCCACTTGTTCATGAT 23 293 4158 4177 502501 CATGTCCCACTTGTTCATGA 51 294 4159 4178 502502 GCATGTCCCACTTGTTCATG 20 295 4160 4179 502503 AGCATGTCCCACTTGTTCAT 52 296 4161 4180 502504 CAGCATGTCCCACTTGTTCA 72 297 4162 4181 502505 TCAGCATGTCCCACTTGTTC 70 298 4163 4182 502506 TTCAGCATGTCCCACTTGTT 53 299 4164 4183 502507 CTTCAGCATGTCCCACTTGT 52 300 4165 4184 502508 TCTTCAGCATGTCCCACTTG 45 301 4167 4186 502509 CCTCTTCAGCATGTCCCACT 68 302 4168 4187 502510 CCCTCTTCAGCATGTCCCAC 68 303 4169 4188 502511 CCCCTCTTCAGCATGTCCCA 79 304 4170 4189 502512 GCCCCTCTTCAGCATGTCCC 85 305 4171 4190 502513 CGCCCCTCTTCAGCATGTCC 84 306 4172 4191 502514 TCGCCCCTCTTCAGCATGTC 80 307 4173 4192 502515 CTCGCCCCTCTTCAGCATGT 82 308 4174 4193 502516 CCTCGCCCCTCTTCAGCATG 78 309 4175 4194 502517 ACCTCGCCCCTCTTCAGCAT 73 310 4176 4195 502518 CACCTCGCCCCTCTTCAGCA 76 311 4239 4258 503012 GGAGGAGCTGCAGCCGGAGA 7 650 4245 4264 503013 GCACCCGGAGGAGCTGCAGC 0 651 4261 4280 503014 GCACGACACCTGCAGGGCAC 23 652 4355 4374 503015 AGCTCACCAGGTAGTTCTCA 49 653 4427 4446 503016 GCTTCCTCTCCCCACCTCCT 65 654 4447 4466 503017 GCAGCACCCCCAATCCTAGA 67 655 4508 4527 503018 GCCCCTCATCCACCTGACAC 62 656 4613 4632 503019 TTCCAGGTAAGAGACCCCCC 87 657 4679 4698 503020 AGAATAGGTCCCAGACACTC 81 658 4731 4750 503021 CTCCCCCTGAGATGTTCTGG 53 659 4858 4877 503022 CCCCAGCCCAGAGATAACCA 74 660 4927 4946 503023 CCTGATCCATCACGGATGGC 69 661 4987 5006 503024 TACTCCATGACCAGGTACTG 81 662 5185 5204 503025 GCTCTGACCTTCCAAGAACC 56 663 5354 5373 503026 CTCCCTTCTGTGGTCCCACC 0 664 5407 5426 503027 GTCGGGTTTGATGTCCCTGC 75 665 5445 5464 502521 GCCAGGCGGATGTGGCCACA 57 314 5500 5519 503028 AGGGCACTGGCTCACCGTTC 45 666 5681 5700 503029 GGGCCCTCCTTCCAACCACT 28 667 5708 5727 503030 GCCCACCCCTCTGGGCCCAC 45 668 5728 5747 503031 AGGAGCAGAGCGAGGCTTGG 38 669 5800 5819 502524 ACAGCCTGCAGGATCTCGGG 86 317 5801 5820 502525 CACAGCCTGCAGGATCTCGG 81 318 5802 5821 502526 CCACAGCCTGCAGGATCTCG 83 319 5803 5822 502527 CCCACAGCCTGCAGGATCTC 84 320 5804 5823 502528 GCCCACAGCCTGCAGGATCT 91 321 5805 5824 502529 CGCCCACAGCCTGCAGGATC 90 322 5806 5825 502530 CCGCCCACAGCCTGCAGGAT 82 323 5807 5826 502531 ACCGCCCACAGCCTGCAGGA 83 324 5808 5827 502532 CACCGCCCACAGCCTGCAGG 85 325 5809 5828 502533 CCACCGCCCACAGCCTGCAG 84 326 5810 5829 502534 CCCACCGCCCACAGCCTGCA 80 327 5811 5830 502535 GCCCACCGCCCACAGCCTGC 90 328 5812 5831 502536 GGCCCACCGCCCACAGCCTG 94 329 5813 5832 502537 AGGCCCACCGCCCACAGCCT 88 330 5814 5833 502538 CAGGCCCACCGCCCACAGCC 91 331 5815 5834 502539 CCAGGCCCACCGCCCACAGC 73 332 5816 5835 502540 CCCAGGCCCACCGCCCACAG 86 333 5817 5836 502541 TCCCAGGCCCACCGCCCACA 88 334 5818 5837 502542 GTCCCAGGCCCACCGCCCAC 84 335 5819 5838 502543 TGTCCCAGGCCCACCGCCCA 85 336 5820 5839 502544 CTGTCCCAGGCCCACCGCCC 65 337 5821 5840 502545 CCTGTCCCAGGCCCACCGCC 81 338 5822 5841 502546 GCCTGTCCCAGGCCCACCGC 90 339 5823 5842 502547 TGCCTGTCCCAGGCCCACCG 85 340 5824 5843 502548 CTGCCTGTCCCAGGCCCACC 89 341 5825 5844 502549 GCTGCCTGTCCCAGGCCCAC 91 342 5826 5845 502550 AGCTGCCTGTCCCAGGCCCA 94 343 5827 5846 502551 TAGCTGCCTGTCCCAGGCCC 92 344 5828 5847 502552 GTAGCTGCCTGTCCCAGGCC 88 345 5829 5848 502553 CGTAGCTGCCTGTCCCAGGC 85 346 5830 5849 502554 CCGTAGCTGCCTGTCCCAGG 83 347 5831 5850 502555 CCCGTAGCTGCCTGTCCCAG 64 348 5832 5851 502556 GCCCGTAGCTGCCTGTCCCA 83 349 5833 5852 502557 GGCCCGTAGCTGCCTGTCCC 89 350 5881 5900 502558 TAGAACATTTCATAGGCGAA 68 351 5919 5938 502559 TCTCCGCCGTGGAATCCGCG 75 352 5920 5939 502560 GTCTCCGCCGTGGAATCCGC 79 353 5921 5940 502561 GGTCTCCGCCGTGGAATCCG 66 354 5922 5941 502562 AGGTCTCCGCCGTGGAATCC 50 355 5923 5942 502563 TAGGTCTCCGCCGTGGAATC 71 356 5944 5963 502564 TTGTAGTGGACGATCTTGCC 68 357 5945 5964 502565 CTTGTAGTGGACGATCTTGC 70 358 5946 5965 502566 CCTTGTAGTGGACGATCTTG 61 359 5948 5967 503032 CACCTTGTAGTGGACGATCT 62 670 6039 6058 502582 CGGCAGAGAGAGGTGCTCCT 80 375 6040 6059 502583 GCGGCAGAGAGAGGTGCTCC 62 376 6041 6060 502584 AGCGGCAGAGAGAGGTGCTC 44 377 6042 6061 502585 CAGCGGCAGAGAGAGGTGCT 78 378 6043 6062 502586 CCAGCGGCAGAGAGAGGTGC 71 379 6118 6137 502587 GGCCCAGCCGTGTCTCCGGG 77 380 6119 6138 502588 CGGCCCAGCCGTGTCTCCGG 69 381 6120 6139 502589 CCGGCCCAGCCGTGTCTCCG 70 382 6121 6140 502590 CCCGGCCCAGCCGTGTCTCC 75 383 6122 6141 502591 CCCCGGCCCAGCCGTGTCTC 77 384 6123 6142 502592 ACCCCGGCCCAGCCGTGTCT 73 385 6124 6143 502593 CACCCCGGCCCAGCCGTGTC 84 386 6125 6144 502594 CCACCCCGGCCCAGCCGTGT 78 387 6126 6145 502595 TCCACCCCGGCCCAGCCGTG 71 388 6127 6146 502596 CTCCACCCCGGCCCAGCCGT 81 389 6128 6147 502597 GCTCCACCCCGGCCCAGCCG 86 390 6129 6148 502598 TGCTCCACCCCGGCCCAGCC 83 391 6130 6149 502599 CTGCTCCACCCCGGCCCAGC 88 392 6152 6171 502600 AAGGGATGTGTCCGGAAGTC 60 393 6153 6172 502601 GAAGGGATGTGTCCGGAAGT 58 394

6154 6173 502602 AGAAGGGATGTGTCCGGAAG 63 395 6155 6174 502603 AAGAAGGGATGTGTCCGGAA 62 396 6156 6175 502604 GAAGAAGGGATGTGTCCGGA 61 397 6157 6176 502605 AGAAGAAGGGATGTGTCCGG 62 398 6158 6177 502606 AAGAAGAAGGGATGTGTCCG 56 399 6159 6178 502607 AAAGAAGAAGGGATGTGTCC 58 400 6160 6179 502608 CAAAGAAGAAGGGATGTGTC 50 401 6161 6180 502609 CCAAAGAAGAAGGGATGTGT 61 402 6163 6182 502610 GGCCAAAGAAGAAGGGATGT 73 403 6164 6183 502611 AGGCCAAAGAAGAAGGGATG 56 404 6165 6184 502612 GAGGCCAAAGAAGAAGGGAT 73 405 6166 6185 502613 CGAGGCCAAAGAAGAAGGGA 75 406 6167 6186 502614 TCGAGGCCAAAGAAGAAGGG 75 407 6168 6187 502615 GTCGAGGCCAAAGAAGAAGG 83 408 6169 6188 502616 AGTCGAGGCCAAAGAAGAAG 58 409 6170 6189 502617 CAGTCGAGGCCAAAGAAGAA 52 410 6171 6190 502618 CCAGTCGAGGCCAAAGAAGA 68 411 6172 6191 502619 CCCAGTCGAGGCCAAAGAAG 78 412 6173 6192 502620 TCCCAGTCGAGGCCAAAGAA 66 413 6174 6193 502621 ATCCCAGTCGAGGCCAAAGA 75 414 6175 6194 502622 CATCCCAGTCGAGGCCAAAG 70 415 6176 6195 502623 CCATCCCAGTCGAGGCCAAA 81 416 6177 6196 502624 ACCATCCCAGTCGAGGCCAA 82 417 6178 6197 502625 GACCATCCCAGTCGAGGCCA 88 418 6179 6198 502626 AGACCATCCCAGTCGAGGCC 79 419 6180 6199 502627 GAGACCATCCCAGTCGAGGC 82 420 6181 6200 502628 GGAGACCATCCCAGTCGAGG 60 421 6216 6235 502629 TTCGAAATCCGGTGTAAAGG 84 422 6217 6236 502630 CTTCGAAATCCGGTGTAAAG 57 423 6218 6237 502631 CCTTCGAAATCCGGTGTAAA 64 424 6219 6238 502632 ACCTTCGAAATCCGGTGTAA 73 425 6220 6239 502633 CACCTTCGAAATCCGGTGTA 77 426 6221 6240 502634 GCACCTTCGAAATCCGGTGT 59 427 6222 6241 502635 GGCACCTTCGAAATCCGGTG 85 428 6223 6242 502636 TGGCACCTTCGAAATCCGGT 86 429 6224 6243 502637 GTGGCACCTTCGAAATCCGG 74 430 6225 6244 502638 GGTGGCACCTTCGAAATCCG 79 431 6226 6245 502639 CGGTGGCACCTTCGAAATCC 85 432 6227 6246 502640 TCGGTGGCACCTTCGAAATC 71 433 6228 6247 502641 GTCGGTGGCACCTTCGAAAT 88 434 6229 6248 502642 TGTCGGTGGCACCTTCGAAA 89 435 6230 6249 502643 GTGTCGGTGGCACCTTCGAA 88 436 6231 6250 502644 TGTGTCGGTGGCACCTTCGA 87 437 6232 6251 502645 ATGTGTCGGTGGCACCTTCG 88 438 6233 6252 502646 CATGTGTCGGTGGCACCTTC 88 439 6234 6253 502647 GCATGTGTCGGTGGCACCTT 91 440 6235 6254 502648 TGCATGTGTCGGTGGCACCT 87 441 6236 6255 502649 TTGCATGTGTCGGTGGCACC 86 442 6237 6256 502650 GTTGCATGTGTCGGTGGCAC 83 443 6238 6257 502651 AGTTGCATGTGTCGGTGGCA 81 444 6239 6258 502652 AAGTTGCATGTGTCGGTGGC 79 445 6240 6259 502653 GAAGTTGCATGTGTCGGTGG 58 446 6241 6260 502654 CGAAGTTGCATGTGTCGGTG 85 447 6243 6262 502655 GTCGAAGTTGCATGTGTCGG 77 448 6244 6263 502656 AGTCGAAGTTGCATGTGTCG 79 449 6245 6264 502657 AAGTCGAAGTTGCATGTGTC 74 450 6246 6265 502658 CAAGTCGAAGTTGCATGTGT 82 451 6247 6266 502659 CCAAGTCGAAGTTGCATGTG 82 452 6248 6267 502660 ACCAAGTCGAAGTTGCATGT 70 453 6249 6268 502661 CACCAAGTCGAAGTTGCATG 76 454 6250 6269 502662 CCACCAAGTCGAAGTTGCAT 79 455 6251 6270 502663 TCCACCAAGTCGAAGTTGCA 68 456 6252 6271 502664 CTCCACCAAGTCGAAGTTGC 71 457 6253 6272 502665 CCTCCACCAAGTCGAAGTTG 67 458 6254 6273 502666 TCCTCCACCAAGTCGAAGTT 70 459 6255 6274 502667 GTCCTCCACCAAGTCGAAGT 80 460 6256 6275 502668 CGTCCTCCACCAAGTCGAAG 76 461 6257 6276 502669 CCGTCCTCCACCAAGTCGAA 78 462 6258 6277 502670 CCCGTCCTCCACCAAGTCGA 83 463 6259 6278 502671 GCCCGTCCTCCACCAAGTCG 76 464 6260 6279 502672 AGCCCGTCCTCCACCAAGTC 72 465 6261 6280 502673 GAGCCCGTCCTCCACCAAGT 71 466 6262 6281 502674 TGAGCCCGTCCTCCACCAAG 60 467 6289 6308 503033 CTACCCCGCCCCCGCTCACC 60 671 6445 6464 503034 CTAGGTCACTGCTGGGTCCT 86 672 6596 6615 503035 CTCAGATAGCTCCCCACTCC 55 673 6794 6813 503036 AATTCTCTAATTCTCTAGAC 19 674 8666 8685 503037 TACCTGAGGGCCATGCAGGA 51 675 8765 8784 503038 GTTCCAAGACTGATCCTGCA 69 676 11975 11994 502675 GGTTCCGAGCCTCTGCCTCG 44 468 11976 11995 502676 CGGTTCCGAGCCTCTGCCTC 74 469 11977 11996 502677 CCGGTTCCGAGCCTCTGCCT 72 470 11978 11997 502678 CCCGGTTCCGAGCCTCTGCC 73 471 11979 11998 502679 TCCCGGTTCCGAGCCTCTGC 84 472 11980 11999 502680 GTCCCGGTTCCGAGCCTCTG 66 473 11982 12001 502681 AGGTCCCGGTTCCGAGCCTC 82 474 11983 12002 502682 TAGGTCCCGGTTCCGAGCCT 83 475 11984 12003 502683 CTAGGTCCCGGTTCCGAGCC 81 476 11985 12004 502684 TCTAGGTCCCGGTTCCGAGC 74 477 11986 12005 502685 CTCTAGGTCCCGGTTCCGAG 78 478 11987 12006 502686 CCTCTAGGTCCCGGTTCCGA 75 479 11988 12007 502687 GCCTCTAGGTCCCGGTTCCG 80 480 12016 12035 502688 CATCCGCTCCTGCAACTGCC 89 481 12017 12036 502689 CCATCCGCTCCTGCAACTGC 81 482 12018 12037 502690 TCCATCCGCTCCTGCAACTG 71 483 12019 12038 502691 CTCCATCCGCTCCTGCAACT 75 484 12020 12039 502692 ACTCCATCCGCTCCTGCAAC 64 485 12021 12040 502693 AACTCCATCCGCTCCTGCAA 52 486 12022 12041 502694 CAACTCCATCCGCTCCTGCA 45 487 12024 12043 502695 AGCAACTCCATCCGCTCCTG 78 488 12025 12044 502696 CAGCAACTCCATCCGCTCCT 64 489 12026 12045 502697 GCAGCAACTCCATCCGCTCC 56 490 12173 12192 503039 AGGAGGGCGGTGGCGCGGCG 0 677 12221 12240 503040 TGACAGCTGGAAGGAGAAGA 41 678 12258 12277 502712 GAAGGTGGATCCGTGGCCCG 73 505 12259 12278 502713 GGAAGGTGGATCCGTGGCCC 70 506 12260 12279 502714 GGGAAGGTGGATCCGTGGCC 72 507 12261 12280 502715 TGGGAAGGTGGATCCGTGGC 50 508 12262 12281 502716 ATGGGAAGGTGGATCCGTGG 62 509 12263 12282 451417 CATGGGAAGGTGGATCCGTG 77 679 12463 12482 503041 GGAGGTTATCTAGGGAGATC 42 680 12542 12561 503042 GAAGGGACAGGTGACCCGAT 69 681 12596 12615 502724 CACCAGCGGGCACTGGCCCA 51 518 12597 12616 502725 CCACCAGCGGGCACTGGCCC 55 519 12598 12617 502726 CCCACCAGCGGGCACTGGCC 61 520 12599 12618 502727 CCCCACCAGCGGGCACTGGC 43 521 12601 12620 502728 GGCCCCACCAGCGGGCACTG 16 522 12602 12621 502729 TGGCCCCACCAGCGGGCACT 43 523 12603 12622 502730 CTGGCCCCACCAGCGGGCAC 43 524 12604 12623 502731 CCTGGCCCCACCAGCGGGCA 41 525 12605 12624 502732 GCCTGGCCCCACCAGCGGGC 30 526 12607 12626 502733 GGGCCTGGCCCCACCAGCGG 66 527 12625 12644 502734 AGGTGGCGGCGGTGCATGGG 31 528 12626 12645 502735 CAGGTGGCGGCGGTGCATGG 23 529 12627 12646 502736 GCAGGTGGCGGCGGTGCATG 57 530

12628 12647 502737 AGCAGGTGGCGGCGGTGCAT 54 531 12629 12648 502738 CAGCAGGTGGCGGCGGTGCA 61 532 12630 12649 502739 GCAGCAGGTGGCGGCGGTGC 57 533 12631 12650 502740 AGCAGCAGGTGGCGGCGGTG 36 534 12632 12651 502741 GAGCAGCAGGTGGCGGCGGT 53 535 12633 12652 502742 GGAGCAGCAGGTGGCGGCGG 39 536 12634 12653 502743 GGGAGCAGCAGGTGGCGGCG 36 537 12635 12654 502744 AGGGAGCAGCAGGTGGCGGC 62 538 12636 12655 502745 CAGGGAGCAGCAGGTGGCGG 56 539 12637 12656 502746 GCAGGGAGCAGCAGGTGGCG 58 540 12638 12657 502747 GGCAGGGAGCAGCAGGTGGC 65 541 12639 12658 502748 TGGCAGGGAGCAGCAGGTGG 47 542 12640 12659 502749 CTGGCAGGGAGCAGCAGGTG 41 543 12642 12661 451432 CCCTGGCAGGGAGCAGCAGG 53 544 12643 12662 502750 ACCCTGGCAGGGAGCAGCAG 52 545 12646 12665 503043 CGTACCCTGGCAGGGAGCAG 59 682 12918 12937 502977 GGACTCGCCCCGCCTACGCC 71 683 12924 12943 502978 CTCCTGGGACTCGCCCCGCC 67 684 12925 12944 503044 GCTCCTGGGACTCGCCCCGC 66 685 12929 12948 503045 ATTGGCTCCTGGGACTCGCC 77 686 12930 12949 502979 GATTGGCTCCTGGGACTCGC 70 687 12936 12955 502980 GCCTCTGATTGGCTCCTGGG 56 688 12942 12961 502981 GCATGGGCCTCTGATTGGCT 20 689 12948 12967 502982 CACCCGGCATGGGCCTCTGA 20 690 12986 13005 503046 GCCAGGCCTAGGGACCTGCG 58 691 12990 13009 502760 ATAGGCCAGGCCTAGGGACC 51 555 12991 13010 502761 GATAGGCCAGGCCTAGGGAC 41 556 12992 13011 502762 CGATAGGCCAGGCCTAGGGA 69 557 12993 13012 502763 CCGATAGGCCAGGCCTAGGG 80 558 12994 13013 502764 TCCGATAGGCCAGGCCTAGG 78 559 12995 13014 502765 CTCCGATAGGCCAGGCCTAG 89 560 12996 13015 502766 CCTCCGATAGGCCAGGCCTA 79 561 12997 13016 502767 GCCTCCGATAGGCCAGGCCT 73 562 12999 13018 502768 GCGCCTCCGATAGGCCAGGC 83 563 13015 13034 502769 AACAGGAGCAGGGAAAGCGC 83 564 13016 13035 502770 GAACAGGAGCAGGGAAAGCG 70 565 13017 13036 502771 CGAACAGGAGCAGGGAAAGC 43 566 13018 13037 502772 GCGAACAGGAGCAGGGAAAG 47 567 13019 13038 502773 GGCGAACAGGAGCAGGGAAA 61 568 13020 13039 502774 CGGCGAACAGGAGCAGGGAA 74 569 13021 13040 502775 ACGGCGAACAGGAGCAGGGA 60 570 13022 13041 502776 AACGGCGAACAGGAGCAGGG 86 571 13023 13042 502777 CAACGGCGAACAGGAGCAGG 84 572 13044 13063 502778 GGGCGGCGGCACGAGACAGA 80 573 13045 13064 502779 AGGGCGGCGGCACGAGACAG 76 574 13046 13065 502780 CAGGGCGGCGGCACGAGACA 58 575 13047 13066 502781 CCAGGGCGGCGGCACGAGAC 80 576 13048 13067 502782 CCCAGGGCGGCGGCACGAGA 59 577 13049 13068 502783 GCCCAGGGCGGCGGCACGAG 68 578 13050 13069 502784 AGCCCAGGGCGGCGGCACGA 75 579 13051 13070 502785 CAGCCCAGGGCGGCGGCACG 76 580 13052 13071 502786 GCAGCCCAGGGCGGCGGCAC 70 581 13089 13108 502787 CTGCGGTGAGTTGGCCGGCG 68 582 13090 13109 502788 ACTGCGGTGAGTTGGCCGGC 67 583 13091 13110 502789 GACTGCGGTGAGTTGGCCGG 58 584 13092 13111 502790 AGACTGCGGTGAGTTGGCCG 71 585 13093 13112 502791 CAGACTGCGGTGAGTTGGCC 70 586 13094 13113 502792 CCAGACTGCGGTGAGTTGGC 79 587 13095 13114 502793 GCCAGACTGCGGTGAGTTGG 76 588 13096 13115 502794 CGCCAGACTGCGGTGAGTTG 66 589 13140 13159 502795 AAGACAGTTCTAGGGTTCAG 87 590 13141 13160 502796 GAAGACAGTTCTAGGGTTCA 78 591 13142 13161 502797 CGAAGACAGTTCTAGGGTTC 85 592 13143 13162 502798 TCGAAGACAGTTCTAGGGTT 78 593 13144 13163 502799 GTCGAAGACAGTTCTAGGGT 92 594 13145 13164 502800 AGTCGAAGACAGTTCTAGGG 85 595 13146 13165 502801 GAGTCGAAGACAGTTCTAGG 83 596 13147 13166 502802 GGAGTCGAAGACAGTTCTAG 86 597 13148 13167 502803 CGGAGTCGAAGACAGTTCTA 91 598 13149 13168 502804 CCGGAGTCGAAGACAGTTCT 76 599 13150 13169 502805 CCCGGAGTCGAAGACAGTTC 90 600 13151 13170 502806 CCCCGGAGTCGAAGACAGTT 83 601 13152 13171 502807 GCCCCGGAGTCGAAGACAGT 82 602 13153 13172 502808 GGCCCCGGAGTCGAAGACAG 73 603 13154 13173 502809 GGGCCCCGGAGTCGAAGACA 67 604 13206 13225 502810 AGGCGGTGGGCGCGGCTTCT 73 605 13207 13226 502811 CAGGCGGTGGGCGCGGCTTC 57 606 13208 13227 502812 GCAGGCGGTGGGCGCGGCTT 69 607 13210 13229 502813 TGGCAGGCGGTGGGCGCGGC 73 608 13212 13231 502814 ACTGGCAGGCGGTGGGCGCG 56 609 13214 13233 502815 GAACTGGCAGGCGGTGGGCG 71 610 13215 13234 502816 TGAACTGGCAGGCGGTGGGC 80 611 13217 13236 502817 TGTGAACTGGCAGGCGGTGG 85 612 13250 13269 502818 TGGAGCTGGGCGGAGACCCA 55 613 13252 13271 502819 ACTGGAGCTGGGCGGAGACC 53 614 13253 13272 502820 GACTGGAGCTGGGCGGAGAC 55 615 13255 13274 502821 AGGACTGGAGCTGGGCGGAG 76 616 13257 13276 502822 ACAGGACTGGAGCTGGGCGG 77 617 13258 13277 502823 CACAGGACTGGAGCTGGGCG 74 618 13259 13278 502824 TCACAGGACTGGAGCTGGGC 90 619 13449 13468 502825 GCCTCAGCCTGGCCGAAAGA 80 620 13450 13469 502826 GGCCTCAGCCTGGCCGAAAG 72 621 13553 13572 444401 TTGCACTTTGCGAACCAACG 97 41 14037 14056 503047 TTCCTCCCCCAACCCTGATT 34 692 14255 14274 503048 AAGTTTGCAGCAACTTTTCT 0 693 14325 14344 503049 GCCCCTCGGAATTCCCGGCT 0 694 14343 14362 503050 CATCTCGGCCTGCGCTCCGC 39 695 14361 14380 503051 GCAGGCCCCCACATTCCCCA 0 696 14392 14411 503052 CTTCTGCACGCCTCCGTCTC 30 697

Example 8: Antisense Inhibition of Murine DMPK in Mouse Primary Hepatocytes

[0336] Antisense oligonucleotides targeted to a murine DMPK nucleic acid were tested for their effect on DMPK RNA transcript in vitro. Cultured mouse primary hepatocytes at a density of 35,000 cells per well were transfected using electroporation with 8,000 nM antisense oligonucleotide. After approximately 24 hours, RNA was isolated from the cells and DMPK transcript levels were measured by quantitative real-time PCR. DMPK RNA transcript levels were adjusted according to total RNA content, as measured by RIBOGREEN.RTM.. Results are presented as percent inhibition of DMPK, relative to untreated control cells.

[0337] The antisense oligonucleotides in Tables 14, 15, and 16 are 5-10-5 gapmers, where the gap segment comprises ten 2'-deoxynucleosides and each wing segment comprises five 2'-MOE nucleosides. The internucleoside linkages throughout each gapmer are phosphorothioate (P.dbd.S) linkages. All cytosine residues throughout each gapmer are 5-methylcytosines. `Murine Target start site` indicates the 5'-most nucleoside to which the antisense oligonucleotide is targeted in the murine gene sequence. `Murine Target stop site` indicates the 3'-most nucleoside to which the antisense oligonucleotide is targeted in the murine gene sequence. All the antisense oligonucleotides listed in Table 12 target SEQ ID NO: 3 (GENBANK Accession No. NT 039413.7 truncated from nucleotides 16666001 to 16681000). All the antisense oligonucleotides listed in Table 13 target SEQ ID NO: 4 (GENBANK Accession No. NM_032418.1). The antisense oligonucleotides of Table 14 target SEQ ID NO: 5 (GENBANK Accession No. AI007148.1), SEQ ID NO: 6 (GENBANK Accession No. AI304033.1), SEQ ID NO: 7 (GENBANK Accession No. BC024150.1), SEQ ID NO: 8 (GENBANK Accession No. BC056615.1), SEQ ID NO: 793 (GENBANK Accession No. BC075715.1), SEQ ID NO: 794 (GENBANK Accession No. BU519245.1), SEQ ID NO: 795 (GENBANK Accession No. CB247909.1), SEQ ID NO: 796 (GENBANK Accession No. CX208906.1), SEQ ID NO: 797 (GENBANK Accession No. CX732022.1), SEQ ID NO: 798 (GENBANK Accession No. S60315.1), or SEQ ID NO: 799 (GENBANK Accession No. S60316.1). In addition, the human antisense oligonucleotide ISIS 451421 targeting SEQ ID NO: 800 (GENBANK Accession No. NM_001081562.1) was also included in this assay and is listed in Table 14.

[0338] The murine oligonucleotides of Tables 14, 15, and 16 may also be cross-reactive with human gene sequences. `Mismatches` indicate the number of nucleobases by which the murine oligonucleotide is mismatched with a human gene sequence. The greater the complementarity between the murine oligonucleotide and the human sequence, the more likely the murine oligonucleotide can cross-react with the human sequence. The murine oligonucleotides in Tables 14, 15, and 16 were compared to SEQ ID NO: 800 (GENBANK Accession No. NM_001081562.1). "Human Target start site" indicates the 5'-most nucleoside to which the gapmer is targeted in the human gene sequence. "Human Target stop site" indicates the 3'-most nucleoside to which the gapmer is targeted human gene sequence.

[0339] Several of the tested antisense oligonucleotides demonstrated significant inhibition of DMPK mRNA levels under the conditions specified above. Certain of the tested antisense oligonucleotides are cross-reactive with human gene sequences.

TABLE-US-00014 TABLE 14 Inhibition of murine DMPK RNA transcript in mouse primary hepatocytes by 5-10-5 gapmers targeting SEQ ID NO: 800 Murine Murine Human Human Target Target SEQ Target Target Start Stop % ID Start Stop Site Site ISIS No Sequence inhibition NO. Site Site Mismatches 11904 11923 299516 TGGCCCACAGCCACGGCCGG 47 698 1850 1869 0 11927 11946 299520 GGCCTGGCCCCACCAGCGGG 58 699 1873 1892 0 11962 11981 299521 CCTGGCAGGGAGCAGCAGGT 44 700 1908 1927 0 3345 3364 451360 CAGCCGCACTTCGGCTGACA 29 701 207 226 1 3378 3397 451361 GCCTGGGTCCAGCACCAGCT 67 702 240 259 2 3388 3407 451362 GTCCCAGGAAGCCTGGGTCC 62 703 250 269 2 3418 3437 451363 CGCCCAGGAGAAGGTCGAGC 69 213 280 299 0 3484 3503 451364 CCCACTGCAAGAAGTCGGCC 69 226 346 365 0 6264 6283 451366 CGTTAGCAGGTCCCCGCCCA 73 704 660 679 2 6342 6361 451367 GTCTATGGCCATGACAATCT 61 705 738 757 0 6363 6382 451368 GTAGCCCAGCCGGTGCACGG 54 706 759 778 2 6851 6870 451370 GGGTGCCCACAGCCACCAGC 72 707 889 908 0 6919 6938 451371 TGGCCCGTAGCTGCCTGCCC 80 708 957 976 2 7448 7467 451373 GGAAATCACCTGCCCCACCT 80 709 n/a n/a n/a 7458 7477 451374 GGATGTTTCTGGAAATCACC 84 710 n/a n/a n/a 7533 7552 451375 GTGGCACCCTCGAAGTCTGG 77 711 1271 1290 3 7589 7608 451376 CCCCGCTCACCATGGCAGTG 31 712 n/a n/a n/a 10278 10297 451378 GGTCCGGGACCTGATTGTCT 85 713 n/a n/a n/a 3229 3248 451385 GCTGCATGTCTGCCCGTCCC 74 714 90 109 1 3244 3263 451386 GGCCCCAGAACCCTAGCTGC 73 715 n/a n/a n/a 3270 3289 451387 TCACAGGGCCTGGCTGCCCC 62 716 131 150 1 3333 3352 451388 GGCTGACATGTTGGGCAGGC 60 717 195 214 1 3250 3269 451389 TGTCCAGGCCCCAGAACCCT 68 718 111 130 3 12295 12314 451391 GGCCAGGCCTAGGGATCTGC 51 719 n/a n/a n/a 12306 12325 451392 CGCCTCGGATAGGCCAGGCC 52 720 1935 1954 1 12450 12469 451393 GGCTTGGAGTCTTAGGGTTC 85 721 n/a n/a n/a 12623 12642 451394 TCCCCGGCCGCCAGGTGGCA 43 722 2224 2243 3 12651 12670 451395 GGTGCTGGGCACGAGCCCTG 62 723 n/a n/a n/a 12698 12717 451396 GCCCAGCTGCTGCAGCAGCG 66 724 n/a n/a n/a 12876 12895 451397 CCGTGTGTGCTGGCAGAGGT 76 725 n/a n/a n/a 13084 13103 451398 ATAAATACCGAGGAATGTCG 77 726 2766 2785 0 13094 13113 451399 GGGACAGACAATAAATACCG 80 727 2776 2795 0 12362 12381 451405 GTGCAGCCCAGTGTGGCGGC 69 728 1991 2010 3 11175 11194 451415 CCTGGAGAAGTTCTGGTTGG 48 729 1674 1693 3 11585 11604 451417 CATGGGAAGGTGGATCCGTG 65 679 1819 1838 1 11854 11873 451419 GGTGACCCGATCGGAGCCCA 11 730 n/a n/a n/a 11874 11893 451420 AGCTGGAGAGAGAAGGGACA 37 731 n/a n/a n/a 11379 11398 451422 GTGAGGGACTCGCCTGCGGC 36 732 n/a n/a n/a 11479 11498 451423 GCGGCTGCGGTGCCCCAGCC 50 733 n/a n/a n/a 11883 11902 451424 GGGCCATCTAGCTGGAGAGA 45 734 n/a n/a n/a 3485 3504 451427 CCCCACTGCAAGAAGTCGGC 57 735 347 366 1 4621 4640 451428 TTGAGCCCTTTTAAGGCAGC 43 736 n/a n/a n/a 6232 6251 451429 TGACCAGGTACTGGGAGCGG 47 737 n/a n/a n/a 10985 11004 451430 CCTGGAGCTGGATCAGTCCC 6 738 n/a n/a n/a 11586 11605 451431 ACATGGGAAGGTGGATCCGT 70 739 1820 1839 1 11963 11982 451432 CCCTGGCAGGGAGCAGCAGG 42 544 1909 1928 0 11973 11992 451433 GTGGGACATACCCTGGCAGG 34 740 n/a n/a n/a 12294 12313 451434 GCCAGGCCTAGGGATCTGCA 35 741 n/a n/a n/a

TABLE-US-00015 TABLE 15 Inhibition of murine DMPK RNA transcript in mouse primary hepatocytes by 5-10-5 gapmers targeting SEQ ID NO: 800 Murine Murine Human Human Target Target SEQ Target Target Start Stop ISIS % ID Start Stop Site Site No Sequence inhibition NO. Site Site Mismatches 330 349 451365 GGAAGCACGACACCTCGCCT 67 742 535 554 1 662 681 451369 CCTCACCATTCCATCAGGCT 81 743 n/a n/a n/a 881 900 451372 CGGCAGCGACAAGTGTTCCC 90 744 n/a n/a n/a 1217 1236 451377 GTCTCTGAAGGCCATGCAGC 69 745 1407 1426 3 1329 1348 451379 CAGCCACTTGATCCGGTGGG 62 746 n/a n/a n/a 1342 1361 451380 AGGTCGGCCTCTTCAGCCAC 74 747 n/a n/a n/a 1494 1513 451381 GTTGGCTGGAGAAGTTCTGG 39 748 1678 1697 2 1598 1617 451382 CCCCGTGATGGCTGCGGCTC 54 749 1782 1801 3 1644 1663 451383 GGCCATCTAGATGGGAAGGT 21 517 1828 1847 0 1741 1760 451384 AGGCCAGGCCTAGGGATCCT 39 750 1925 1944 1

TABLE-US-00016 TABLE 16 Inhibition of murine DMPK RNA transcript in mouse primary hepatocytes by 5-10-5 gapmers targeting SEQ ID NOs: 5-8 and 793-799 Murine Murine Murine Human Human Target Target Target SEQ Target Target Start Stop SEQ ISIS % ID Start Stop Site Site ID NO No Sequence inhibition NO. Site Site Mismatches 324 343 5 451410 GGCGCGGTGCCCCAGCCTGG 67 751 n/a n/a n/a 485 504 5 451411 GTCCTGGCCCCACCAGCGGG 66 752 1873 1892 1 534 553 5 451412 CCAGGCCTAGGAATCCTGGC 17 753 1922 1941 2 547 566 5 451413 GCGCCTCGGATAGCCAGGCC 51 754 n/a n/a n/a 594 613 5 451414 CCCAGTGTGGCGCAGCAGCC 65 755 n/a n/a n/a 393 412 6 451402 GTGTTTCATCTTCACCACCG 80 756 462 481 3 1475 1494 7 451390 AGGTCAGCCTCTTCAGCCAC 60 757 n/a n/a n/a n/a n/a n/a 451425 GGCCATATGGGAAGGTGGAT 48 758 1824 1843 0 1763 1782 8 451418 GGAGGATTTGGCGAGAAGCA 48 759 n/a n/a n/a 1032 1051 793 451403 CGAAGTCTGCCCCACCTCGA 58 760 n/a n/a n/a 1042 1061 793 451404 GTGGCACCCTCGAAGTCTGC 72 761 n/a n/a n/a 217 236 794 451400 GGGTCCATTGTAAGGAAGCT 4 762 n/a n/a n/a 754 773 794 451401 GGTGCCCACAGCCACCAGGG 82 763 888 907 1 322 341 795 451406 TCCATGGCAGTGAGCCGGTC 55 764 1319 1338 1 523 542 795 451407 GGGACCACTTGATCCGGTGG 63 765 n/a n/a n/a 534 553 795 451408 GGATCAGAGTTGGGACCACT 0 766 n/a n/a n/a 492 511 796 451416 CCCCGTGATGGCTGCGGTTC 49 767 n/a n/a n/a 469 488 797 451409 GTGTGTCCTCATACCCCGCC 60 768 n/a n/a n/a 629 648 798 451421 GCACCCTCGAAGTCTCGACC 72 769 n/a n/a n/a 854 873 799 451426 GCTCTGAAGGCCATGCAGCA 52 770 n/a n/a n/a

Example 9: Dose-Dependent Antisense Inhibition of Murine DMPK in Mouse Primary Hepatocytes

[0340] Several of the antisense oligonucleotides exhibiting in vitro inhibition of DMPK in mouse primary hepatocytes (see Example 8) were tested at various doses. Cells were plated at a density of 35,000 cells per well and transfected using electroporation with 1,000 nM, 2,000 nM, 4,000 nM, 8,000 nM, and 16,000 nM concentrations of each antisense oligonucleotide. After approximately 16 hours, RNA was isolated from the cells and DMPK transcript levels were measured by quantitative real-time PCR using primer probe set RTS3181 (forward sequence GACATATGCCAAGATTGTGCACTAC, designated herein as SEQ ID NO: 771; reverse sequence CACGAATGAGGTCCTGAGCTT, designated herein as SEQ ID NO: 772; probe sequence AACACTTGTCGCTGCCGCTGGCX, designated herein as SEQ ID NO: 773). DMPK transcript levels were normalized to total RNA content, as measured by RIBOGREEN.RTM.. Results are presented in Table 17 as percent inhibition of DMPK, relative to untreated control cells.

[0341] The majority of the tested antisense oligonucleotides demonstrated dose-dependent inhibition of DMPK mRNA levels under the conditions specified above.

TABLE-US-00017 TABLE 17 Dose-dependent antisense inhibition of murine DMPK in mouse primary hepatocytes 16,000 IC.sub.50 ISIS No 1,000 nM 2,000 nM 4,000 nM 8,000 nM nM (.mu.M) 451369 33 59 78 87 94 1.57 451371 60 77 84 90 91 0.24 451373 53 62 82 89 92 0.74 451374 33 42 76 88 94 2.00 451375 43 62 81 89 88 1.05 451378 39 79 80 87 94 0.87 451385 22 57 80 78 93 2.01 451393 49 63 86 80 80 0.59 451397 63 75 74 81 92 0.22 451398 29 72 84 83 90 1.29 451399 27 53 81 68 80 2.07 451401 34 71 87 86 92 1.12 451402 34 69 75 86 74 1.14

Example 10: Antisense Inhibition of Human Alpha1 Skeletal Actin in HepG2 Cells

[0342] Antisense oligonucleotides targeted to a human alpha1 skeletal actin nucleic acid, a gene which may carry an expanded CTG repeat capable of causing symptoms of DM1 when inserted into mouse models, were tested for their effect on alpha1 actin RNA transcript in vitro. Cultured HepG2 cells at a density of 20,000 cells per well were transfected using electroporation with 10,000 nM antisense oligonucleotide. After approximately 24 hours, RNA was isolated from the cells and alpha1 actin RNA transcript levels were measured by quantitative real-time PCR. Alpha1 actin RNA transcript levels were adjusted according to total RNA content, as measured by RIBOGREEN.RTM.. Results are presented as percent inhibition of alpha1 actin, relative to untreated control cells.

[0343] The antisense oligonucleotides in Table 18 are 5-10-5 gapmers, where the gap segment comprises ten 2'-deoxynucleosides and each wing segment comprises five 2'-MOE nucleosides. The internucleoside linkages throughout each gapmer are phosphorothioate (P.dbd.S) linkages. All cytosine residues throughout each gapmer are 5-methylcytosines. `Target start site` indicates the 5'-most nucleoside to which the antisense oligonucleotide is targeted. `Target stop site` indicates the 3'-most nucleoside to which the antisense oligonucleotide is targeted. All the antisense oligonucleotides listed in Table 18 target SEQ ID NO: 801 (GENBANK Accession No. NM_001100.3).

[0344] The tested antisense oligonucleotide sequences demonstrated dose-dependent inhibition of alpha 1 actin mRNA levels under the conditions specified above.

TABLE-US-00018 TABLE 18 Inhibition of human alpha1 actin RNA transcript in HepG2 cells by 5-10-5 gapmers targeting SEQ ID NO: 801 Target Target Start Stop % SEQ ID Site Site ISIS No Sequence inhibition NO. 16 35 445205 AGCGAGGCTTCACTTGGCGC 74 774 20 39 190403 GGGAAGCGAGGCTTCACTTG 75 775 1028 1047 190401 GCGGTCAGCGATCCCAGGGT 78 776 1058 1077 445225 GGGTGCCAGCGCGGTGATCT 73 777 1320 1339 445231 TGTTACAAAGAAAGTGACTG 74 778 1339 1358 445232 CGATGGCAGCAACGGAAGTT 96 779 1348 1367 445233 GTCAGTTTACGATGGCAGCA 100 780 1417 1436 445235 CAGGGCTTTGTTTCGAAAAA 91 781 1430 1449 445236 CCATTTTCTTCCACAGGGCT 99 782 1447 1466 445237 ATGCTTCTTCAAGTTTTCCA 97 783 1460 1479 445238 CAGAATGACTTTAATGCTTC 95 784

Example 11: Dose-Dependent Antisense Inhibition of Human Alpha1 Actin in HepG2 Cells

[0345] Several of the antisense oligonucleotides exhibiting in vitro inhibition of alpha1 actin in HepG2 cells (see Example 8) were tested at various doses. Cells were plated at a density of 20,000 cells per well and transfected using electroporation with 625 nM, 1,250 nM, 2,500 nM, 5,000 nM, 10,000 nM and 20,000 nM concentrations of each antisense oligonucleotide. After approximately 16 hours, RNA was isolated from the cells and alpha1 actin RNA transcript levels were measured by quantitative real-time PCR using primer probe set RTS3154 (forward sequence CCACCGCAAATGCTTCTAGAC, designated herein as SEQ ID NO: 785; reverse sequence CCCCCCCATTGAGAAGATTC, designated herein as SEQ ID NO: 786; probe sequence CTCCACCTCCAGCACGCGACTTCTX, designated herein as SEQ ID NO: 787). Alpha1 actin RNA transcript levels were normalized to total RNA content, as measured by RIBOGREEN.RTM.. Results are presented in Table 19 as percent inhibition of alpha1 actin, relative to untreated control cells.

[0346] Several of the antisense oligonucleotides demonstrated dose-dependent inhibition of alpha 1 actin mRNA levels under the conditions specified above.

TABLE-US-00019 TABLE 19 Dose-dependent antisense inhibition of human alpha1 actin in HepG2 cells ISIS 625 5,000 10,000 20,000 IC.sub.50 No. nM 1,250 nM 2,500 nM nM nM nM (.mu.M) 445233 21 72 63 82 96 83 1.1 445236 26 68 82 91 90 91 0.8 445237 36 59 76 84 83 90 0.8 445232 14 42 54 59 80 91 2.6 445238 27 43 54 73 76 90 2.0 445235 26 52 29 58 59 24 0.7 190403 25 29 36 25 61 54 11.9 190401 17 14 40 68 76 72 3.9 445225 25 23 49 28 52 50 15.8 445205 26 31 34 28 55 36 7.6 445231 30 25 39 26 42 36 >20.0

Example 12: In Vivo Antisense Inhibition of Human Alpha1 Actin by Intramuscular Administration in Transgenic Mice

[0347] To test the effect of antisense inhibition for the treatment of myotonic dystrophy, an appropriate mouse model was required. The HSA.sup.LR mouse model is an established model for DM1 (Mankodi, A. et al. Science. 289: 1769, 2000). The mice carry a human skeletal actin (hACTA1) transgene with 220 CTG repeats inserted in the 3' UTR of the gene. The hACTA1-CUGexp transcript accumulates in nuclear foci in skeletal muscles and results in myotonia similar to that in human DM1 (Mankodi, A. et al. Mol. Cell 10: 35, 2002; Lin, X. et al. Hum. Mol. Genet. 15: 2087, 2006). Hence, it was expected that amelioration of DM1 symptoms in the HSA.sup.LR mouse by antisense inhibition of the hACTA1 transgene would predict amelioration of similar symptoms in human patients by antisense inhibition of the DMPK transcript.

[0348] HSA (human skeletal actin).sup.LR (long repeat) DM1 mice were generated by insertion in FVB/N mice of a transgene with 250 CUG repeats in the 3' UTR of human skeletal actin. The transgene is expressed in the mice as a CUG repeat RNA, which is retained in the nucleus, forming nuclear inclusions or foci, similar to that seen in human tissue samples of patients with myotonic dystrophy (DM1).

[0349] ISIS 190403 and ISIS 445238, which demonstrated statistically significant dose-dependent inhibition in vitro (see Example 11), were evaluated for their ability to reduce human alpha1 actin RNA transcript in vivo.

Treatment

[0350] HSA.sup.LR mice were maintained on a 12-hour light/dark cycle and fed ad libitum normal Purina mouse chow. Animals were acclimated for at least 7 days in the research facility before initiation of the experiment. Antisense oligonucleotides (ASOs) were prepared in PBS and sterilized by filtering through a 0.2 micron filter. Oligonucleotides were dissolved in 0.9% PBS for injection.

[0351] The mice were divided into two treatment groups. The two groups received direct intramuscular injections of ISIS 190403 or ISIS 445238 at a dose of 0.8 nM into the tibialis anterior muscle on one side. The contralateral tibialis anterior muscle in each mouse received a single dose intramuscular injection of PBS. The PBS-injected muscle acted as the control.

Inhibition of Alpha1 Actin RNA

[0352] Twenty four hours after the final dose, the animals were sacrificed and tissue from the tibialis anterior muscles of both sides was isolated. RNA was isolated for real-time PCR analysis of alpha1 actin and normalized to 18s RNA. As presented in Table 20, treatment with antisense oligonucleotides reduced human alpha1 actin RNA transcript expression. The results are expressed as percent inhibition of alpha1 actin transcript, relative to the PBS control.

[0353] The results indicate that treatment with ISIS 190403 and ISIS 445238 resulted in inhibition of alpha 1 actin RNA levels in the mice.

TABLE-US-00020 TABLE 20 Percent inhibition of human alpha1 actin RNA transcript in HSA.sup.LR mice ISIS No. % inhibition 190403 38 445238 40

Example 13: Dose Dependent Antisense Inhibition of Human Alpha1 Actin by Intramuscular Administration in Transgenic Mice

[0354] ISIS 445236, which demonstrated statistically significant dose-dependent inhibition in vitro (see Example 11), was evaluated for its ability to reduce human alpha1 actin RNA transcript in vivo.

Treatment

[0355] HSA.sup.LR mice were maintained on a 12-hour light/dark cycle and fed ad libitum normal Purina mouse chow. Animals were acclimated for at least 7 days in the research facility before initiation of the experiment. Antisense oligonucleotides (ASOs) were prepared in PBS and sterilized by filtering through a 0.2 micron filter. Oligonucleotides were dissolved in 0.9% PBS for injection.

[0356] The mice were divided into three treatment groups. The groups received direct intramuscular injections of ISIS 445236 at doses of 0.2 nM, 0.4 nM or 0.8 nM into the tibialis anterior muscle of one side. The contralateral tibialis anterior muscle in each mouse received a single dose intramuscular injection of PBS. The PBS-injected muscle acted as the control.

Inhibition of Alpha1 Actin RNA

[0357] Twenty four hours after the final dose, the animals were sacrificed and tissue from the tibialis anterior muscles of both sides was isolated. RNA was isolated for real-time PCR analysis of alpha1 actin and normalized to 18s RNA. As presented in Table 21, treatment with ISIS 445236 reduced human alpha1 actin RNA transcript expression at all dosages. The results are expressed as percent inhibition of alpha1 actin transcript, relative to the control.

[0358] The results indicate that treatment with ISIS 445236 resulted in significant inhibition of alpha 1 actin mRNA levels under the conditions specified above.

TABLE-US-00021 TABLE 21 Inhibition of human alpha1 actin RNA transcript by ISIS 445236 in HSA.sup.LR mice Dose (nM) % inhibition 0.2 70 0.4 54 0.8 78

Assessment of Myotonia by Electromyography

[0359] Myotonia refers to repetitive action potential that is due to delayed relaxation of muscle fibers. This phenomenon is observed in patients of myotonic dystrophy as well as in the HSA.sup.LR mice. When the EMG needle is inserted into a myotonic muscle, the electrical activity is prolonged for up to several seconds past when the insertional activity should normally cease. The frequency of myotonic discharges ranges from 50 to 100 impulses per second.

[0360] Myotonia was measured via electromyography and graded in the following manner: grade 0 refers to no myotonia elicited by any needle insertion (0%); grade 1 refers to myotonia elicited by less than 50% needle insertions; grade 2 refers to myotonia elicited by more than 50% needle insertions; and grade 3 refers to mytonia elicited by 100% needle insertions.

[0361] Before electromyography, mice were anesthetized by using i.p. a cocktail of 100 mg/kg ketamine, 10 mg/kg xylazine, and 3 mg/kg acepromazine. Electromyography on left and right quadriceps, left and right gastrocnemius muscles, left and right tibialis anterior muscles and lumbar paraspinals muscles was performed as previously described (Kanadia et al, 2003, Science, 302: 1978-1980) by using 30 gauge concentric needle electrodes and a minimum of 10 needle insertions for each muscle. The data is presented in Table 22 as the average myotonia grade observed in four mice of each group and demonstrates significant reduction of myotonia in mice treated with ISIS 445236.

TABLE-US-00022 TABLE 22 Average reduction of myotonia in various muscles of antisense oligonucleotide-treated HSA.sup.LR mice Treatment Dose (nM) Myotonia grade PBS 2.7 ISIS 0.2 1.3 455236 0.4 1.0 0.8 1.0

Correction of Alternative Splicing

[0362] In DM1/HSA.sup.LR mouse model, the accumulation of expanded CUG RNA in the nucleus leads to the sequestration of poly(CUG)-binding proteins, such as Muscleblind-like 1 (MBLN1) (Miller, J. W. et al. EMBO J. 19: 4439, 2000). The splicing factor MBNL1, which controls alternative splicing of the Serca1 gene is sequestered in expanded CUG foci. This triggers dysregulation of the alternative splicing of this gene. To evaluate the effect of antisense inhibition of human alpha 1 actin on such alternative splicing, total RNA was purified from the tibialis anterior, gastrocnemius, and quadriceps muscle using RNeasy Lipid Tissue Mini Kit (Qiagen), according to the manufacturer's instructions. RT-PCR was performed with the SuperScript III One-Step RT-PCR System and Platinum Taq Polymerase (Invitrogen), using gene-specific primers for cDNA synthesis and PCR amplification. The forward and reverse primers for Serca-1 have been described in Bennett and Swayze (Annu. Rev. Pharmacol. 2010; 50: 259-93). PCR products were separated on agarose gels, stained with SybrGreen I Nucleic Acid Gel Stain (Invitrogen), and imaged using a Fujifilm LAS-3000 Intelligent Dark Box.

[0363] The PCR products of Serca1 splicing in the PBS control demonstrated exon 22 exclusion as a result of dysregulation of MBLN1. Treatment with ISIS 445236 resulted in exon 22 inclusion and normalization of alternative splicing of the Serca1 gene in the tibialis anterior, gastrocnemius, and quadriceps muscles.

[0364] Therefore, antisense inhibition of alpha1 actin corrected Serca1 splicing dysregulation, which indicates that treatment with antisense oligonucleotide reduced accumulation of CUGexp in the nuclear foci. Reduced accumulation of CUGexp in the nuclear foci corrects MBLN1 sequestration thereby allowing normal splicing to occur.

Example 14: In Vivo Antisense Inhibition of Human Alpha1 Actin by Subcutaneous Administration in Transgenic Mice

[0365] ISIS 190403, ISIS 445236 and ISIS 445238 were evaluated for their ability to reduce human alpha1 actin RNA transcript in vivo.

Treatment

[0366] HSA.sup.LR mice were maintained on a 12-hour light/dark cycle and fed ad libitum normal Purina mouse chow. Animals were acclimated for at least 7 days in the research facility before initiation of the experiment. Antisense oligonucleotides (ASOs) were prepared in PBS and sterilized by filtering through a 0.2 micron filter. Oligonucleotides were dissolved in 0.9% PBS for injection.

[0367] The mice were divided into four treatment groups. The first three groups received subcutaneous injections of ISIS 190403, ISIS 445236 or ISIS 445238 at a dose of 25 mg/kg twice per week for 4 weeks. The fourth group received subcutaneous injections of PBS twice weekly for 4 weeks. The PBS-injected group served as the control group to which the oligonucleotide-treated group was compared.

Inhibition of Alpha1 Actin RNA

[0368] Twenty four hours after the final dose, the animals were sacrificed and tissue from the quadriceps muscles (left and right), gastrocnemius muscles (left and right), and tibialis anterior muscles (left and right) was isolated. RNA was isolated for real-time PCR analysis of alpha1 actin and normalized to 18s RNA. As presented in Table 23, treatment with antisense oligonucleotides reduced human alpha1 actin RNA transcript expression. The results are expressed as percent inhibition of alpha1 actin transcript, relative to the control.

[0369] Both ISIS 445236 and ISIS 445238 demonstrated significant inhibition of alpha1 actin mRNA levels under the conditions specified above.

TABLE-US-00023 TABLE 23 Percent inhibition of human alpha1 actin RNA transcript in HSA.sup.LR mice Muscle Type ISIS 190403 ISIS 445236 ISIS 445238 Quadriceps 16 83 72 Gastrocnemius 0 85 73 Tibialis anterior 2 81 71

Fluorescence In Situ Hybridization of Alpha1 Actin in Muscles

[0370] Frozen muscle tissue sections were fixed in fresh 3% paraformaldehyde in PBS solution for 15-20 minutes, after which they were rinsed twice with PBS for 5 minutes. The nuclei were permeabilized with 0.5% Triton X-100 for 5 minutes after which the tissue was blocked with normal goat serum for 30 minutes. The sections were incubated a 2'-O-methyl RNA targeted to alpha1 actin that is 5'-labeled with Texas Red (Integrated DNA Technologies). The sections were counter-stained with DAPI to label the nuclei. The sections were mounted and viewed with a standard fluorescence microscope. Image acquisition was by Metavue software and deconvolution was achieved by Autoquant software.

[0371] All muscle tissue sections from mice treated with ISIS 445236 and ISIS 445238 displayed reduced fluorescent intensity of alpha1 actin signal at the ribonuclear foci, indicating antisense inhibition of human alpha1 actin mRNA and reduction of the RNA in the nuclear foci.

Assessment of Myotonia by Electromyography

[0372] Myotonia refers to repetitive action potential that is due to delayed relaxation of muscle fibers. This phenomenon is observed in patients of myotonic dystrophy as well as in the HSA.sup.LR mice. When the EMG needle is inserted into a myotonic muscle, the electrical activity is prolonged for up to several seconds past when the insertional activity should normally cease. The frequency of myotonic discharges ranges from 50 to 100 impulses per second.

[0373] Myotonia may be measured via electromyography and is graded in the following manner: grade 0 refers to no myotonia elicited by any needle insertion (0%); grade 1 refers to myotonia elicited by less than 50% needle insertions; grade 2 refers to myotonia elicited by more than 50% needle insertions; and grade 3 refers to mytonia elicited by 100% needle insertions.

[0374] Before electromyography, mice were anesthetized by using i.p. 100 mg/kg ketamine, 10 mg/kg xylazine, and 3 mg/kg acepromazine or 250 mg/kg 2,2,2-tribromoethanol. Electromyography on left and right quadriceps, left and right gastrocnemius muscles, left and right tibialis anterior muscles and lumbar paraspinals muscles was performed as previously described (Kanadia et al, 2003, Science, 302: 1978-1980) by using 30 gauge concentric needle electrodes and a minimum of 10 needle insertions for each muscle. The data is presented in Table 24 as the average myotonia grade observed in four mice of each group and demonstrates significant reduction of myotonia in mice treated with ISIS 445236 and ISIS 445238.

TABLE-US-00024 TABLE 24 Average reduction of myotonia in various muscles of antisense oligonucleotide-treated HSA.sup.LR mice PBS ISIS 190403 ISIS 445236 ISIS 445238 Left quadriceps 3.00 3.00 0.00 0.25 Right quadriceps 3.00 3.00 0.00 0.00 Left gastrocnemius 3.00 3.00 0.00 0.25 Right gastrocnemius 3.00 3.00 0.00 0.25 Left Tibialis anterior 2.75 2.50 0.00 0.00 Right Tibialis anterior 2.75 2.50 0.00 0.00 Lumbar paraspinals 3.00 3.00 0.00 0.75

Correction of Alternative Splicing

[0375] The splicing factor MBNL1, which controls Serca1 splicing, m-Titin splicing, CIC-1 chloride channel gene (Clcn1) splicing, and Zasp splicing, is sequestered in expanded CUG foci. MBNL1 sequestration triggers dysregulated splicing in each of these genes. To evaluate the effect of antisense inhibition of human alpha 1 actin on splicing, total RNA was purified from the tibialis anterior, gastrocnemius, and quadriceps muscle and RT-PCR was performed, as described in Example 13. The forward and reverse primers for Serca-1, m-Titin, Clcn1, and ZASP have been described in Bennett and Swayze, Annu. Rev. Pharmacol. 2010; 50: 259-93.

[0376] In PBS treated HSA.sup.LR mice, Serca1 splicing is dysregulated as demonstrated by exon 22 exclusion. Treatment with each of ISIS 445236 and ISIS 445238 resulted in exon 22 inclusion and normalization of alternative splicing of the Serca1 gene in the tibialis anterior, gastrocnemius, and quadriceps muscles.

[0377] In PBS treated HSA.sup.LR mice, m-Titin splicing is dysregulated as demonstrated by exon 5 inclusion. Treatment with each of ISIS 445236 and ISIS 445238 resulted in skipping of exon 5 and normalization of alternative splicing of the m-Titin gene in the tibialis anterior, gastrocnemius, and quadriceps muscles.

[0378] In PBS treated HSA.sup.LR mice, Clcn1 splicing is dysregulated as demonstrated by exon 7a inclusion. Treatment with each of ISIS 445236 and ISIS 445238 resulted in skipping of exon 7a and normalization of alternative splicing of the Clcn1 gene in the tibialis anterior, gastrocnemius, and quadriceps muscles.

[0379] In PBS treated HSA.sup.LR mice, Zasp splicing is dysregulated as demonstrated by exon 11 inclusion. Treatment with each of ISIS 445236 and ISIS 445238 resulted in skipping of exon 11 and normalization of alternative splicing of the Zasp gene in the tibialis anterior, gastrocnemius, and quadriceps muscles.

[0380] Therefore, antisense inhibition of alpha1 actin corrected Serca1, m-Titin, Clcn1, and Zasp splicing dysregulation, which indicates that treatment with antisense oligonucleotide reduced accumulation of CUGexp in the nuclear foci. Reduced accumulation of CUGexp in the nuclear foci correct MBLN1 sequestration thereby allowing normal splicing to occur.

Example 15: In Vivo Antisense Inhibition of Human Alpha1 Actin in Transgenic Mice

[0381] Antisense inhibition of human alpha1 actin RNA transcript by ISIS 445236 and ISIS 445238 on myotonia in HSA.sup.LR mice was further evaluated.

Treatment

[0382] HSA.sup.LR mice were divided into three treatment groups. The first two groups received subcutaneous injections of ISIS 445236 or ISIS 445238 at a dose of 25 mg/kg twice per week for 2 weeks. The third group received subcutaneous injections of PBS twice per week for 2 weeks. The PBS-injected group served as the control group to which the oligonucleotide-treated group was compared.

Inhibition of Alpha1 Actin RNA

[0383] Twenty four hours after the final dose, the animals were sacrificed and tissue from the quadriceps muscles, gastrocnemius muscles, and tibialis anterior muscles was isolated. RNA was isolated for real-time PCR analysis of alpha1 actin and normalized to 18s RNA. As presented in Table 25, treatment with antisense oligonucleotides reduced human alpha1 actin RNA transcript expression. The results are expressed as percent inhibition of alpha1 actin transcript, relative to the PBS control.

[0384] Both ISIS 445236 and ISIS 445238 demonstrated significant inhibition of alpha1 actin mRNA levels under the conditions specified above.

TABLE-US-00025 TABLE 25 Percent inhibition of human alpha1 actin RNA transcript in HSA.sup.LR mice Muscle Type ISIS 445236 ISIS 445238 Quadriceps 61 64 Gastrocnemius 68 37 Tibialis anterior 68 41

Assessment of Myotonia by Electromyography

[0385] Electromyography on left and right quadriceps, left and right gastrocnemius muscles, left and right tibialis anterior muscles and lumbar paraspinals muscles was performed as previously described (Kanadia et al, 2003, Science, 302: 1978-1980) by using 30 gauge concentric needle electrodes and a minimum of 10 needle insertions for each muscle. The data is presented in Table 26 as the average myotonia grade observed in four mice of each group and demonstrates significant reduction of myotonia in mice treated with ISIS 445236 and ISIS 445238.

TABLE-US-00026 TABLE 26 Average reduction of myotonia in various muscles of antisense oligonucleotide-treated HSA.sup.LR mice PBS ISIS 445236 ISIS 445238 Left quadriceps 3.00 0.00 1.75 Right quadriceps 3.00 0.00 1.75 Left gastrocnemius 3.00 0.25 1.5 Right gastrocnemius 3.00 0.25 1.00 Left Tibialis anterior 2.75 0.00 0.00 Right Tibialis anterior 2.75 0.00 0.00 Lumbar paraspinals 3.00 0.50 2.00

Correction of Alternative Splicing

[0386] To evaluate the effect of ISIS 190401 on alternative splicing of Serca1, total RNA purified from the tibialis anterior gastrocnemius, and quadriceps muscle was analyzed in a procedure similar to that described in Example 13.

[0387] In PBS treated HSA.sup.LR mice, Serca1 splicing is dysregulated as demonstrated by exon 22 exclusion, as a result of MBLN1 dysregulation. Treatment with each of ISIS 445236 and ISIS 445238 resulted in near-complete inclusion and normalization of alternative splicing of exon 22 of the Serca1 gene in the tibialis anterior and quadriceps muscles.

[0388] Therefore, antisense inhibition of alpha1 actin corrected Serca1 splicing dysregulation, which indicates that treatment with antisense oligonucleotide reduced accumulation of CUGexp in the nuclear foci. Reduced accumulation of CUGexp in the nuclear foci correct MBLN1 sequestration thereby allowing normal splicing to occur.

Example 16: Dose-Dependent Antisense Inhibition of Human Alpha1 Actin in Transgenic Mice

[0389] Dose-dependent inhibition of human alpha1 actin RNA transcript by ISIS 445236 and ISIS 445238 on myotonia in HSA.sup.LR mice was evaluated.

Treatment

[0390] HSA.sup.LR mice were subcutaneously injected with ISIS 445236 or ISIS 445238 at doses of 2.5 mg/kg, 8.5 mg/kg or 25.0 mg/kg twice per week for 4 weeks. The control group received subcutaneous injections of PBS twice per week for 4 weeks. The PBS-injected group served as the control group to which the oligonucleotide-treated group was compared.

Inhibition of Alpha1 Actin RNA

[0391] Twenty four hours after the final dose, the animals were sacrificed and tissue from the quadriceps muscles (Quad), gastrocnemius muscles (Gastroc), and tibialis anterior muscles (TA) was isolated. RNA was isolated for real-time PCR analysis of alpha1 actin and normalized to 18s RNA. As presented in Table 27, treatment with antisense oligonucleotides reduced human alpha1 actin RNA transcript expression. The results are expressed as percent inhibition of alpha1 actin transcript, relative to the PBS control.

[0392] Both the antisense oligonucleotides demonstrated dose-dependent inhibition of alpha1 actin mRNA levels in quadriceps muscles, gastrocnemius muscles, and tibialis anterior muscles under the conditions specified above.

TABLE-US-00027 TABLE 27 Dose-dependent inhibition of human alpha1 actin RNA transcript in HSA.sup.LR mice mg/kg/wk Quad Gastroc TA ISIS 445236 5 24 36 46 17 53 57 59 50 86 86 90 ISIS 445238 5 21 37 3 17 30 39 60 50 59 81 70

Assessment of Myotonia by Electromyography

[0393] Electromyography on left and right quadriceps (Quad), left and right gastrocnemius muscles (Gastroc), left and right tibialis anterior (TA) muscles and lumbar paraspinals muscles was performed as previously described (Kanadia et al, 2003, Science, 302: 1978-1980) by using 30 gauge concentric needle electrodes and a minimum of 10 needle insertions for each muscle. The data is presented in Table 28 as the average myotonia grade observed in four mice of each group and demonstrates significant dose-dependent reduction of myotonia in mice treated with ISIS 445236 and ISIS 445238.

TABLE-US-00028 TABLE 28 Average reduction of myotonia in various muscles of antisense oligonucleotide-treated HSA.sup.LR mice Right Left Right Left Right Lumbar mg/kg/wk Left Quad Quad Gastroc Gastroc TA TA paraspinals PBS -- 3.00 3.00 3.00 3.00 2.75 2.75 3.00 ISIS 5 3.00 3.00 3.00 3.00 2.25 2.25 3.00 445236 17 0.75 0.75 0.75 1.00 0.00 0.00 1.75 50 0.00 0.00 0.00 0.00 0.00 0.00 0.00 ISIS 5 2.75 2.75 2.50 2.50 2.00 1.75 2.75 445238 17 3.00 3.00 2.00 2.25 0.00 0.00 2.75 50 0.75 0.75 0.25 0.25 0.00 0.00 1.00

Correction of Alternative Splicing

[0394] To evaluate the effect of ISIS 190401 on alternative splicing of Serca1, total RNA purified from the tibialis anterior gastrocnemius, and quadriceps muscle was analyzed in a procedure similar to that described in Example 13.

[0395] In PBS treated HSA.sup.LR mice, Serca1 splicing is dysregulated as demonstrated by exon 22 exclusion, as a result of MBLN1 dysregulation. Treatment with either ISIS 445236 or ISIS 445238 at doses of 8.5 mg/kg or 25.0 mg/kg twice a week (or 17.0 mg/kg/week and 50.0 mg/kg/week) resulted in complete inclusion and normalization of alternative splicing of exon 22 of the Serca1 gene in all three muscle types.

[0396] Therefore, antisense inhibition of alpha1 actin corrected Serca1 splicing dysregulation, which indicates that treatment with antisense oligonucleotide reduced accumulation of CUGexp in the nuclear foci. Reduced accumulation of CUGexp in the nuclear foci correct MBLN1 sequestration thereby allowing normal splicing to occur.

Example 17: In Vivo Antisense Inhibition by an Oligonucleotide Targeting the HSA Coding Region of Human Alpha1 Actin in Transgenic Mice

[0397] Antisense inhibition of human alpha1 actin RNA transcript by ISIS 190401 (5'-GCGGTCAGCGATCCCAGGGT-3' (SEQ ID NO: 788), target start site 1028 of SEQ ID NO: 1) on myotonia in HSA.sup.LR mice was evaluated.

Treatment

[0398] HSA.sup.LR mice received subcutaneous injections of ISIS 190401 at a dose of 25 mg/kg twice per week for 4 weeks. A control group received subcutaneous injections of PBS twice per week for 2 weeks. The PBS-injected group served as the control group to which the oligonucleotide-treated group was compared.

Inhibition of Alpha1 Actin RNA

[0399] Twenty four hours after the final dose, the animals were sacrificed and tissue from the quadriceps muscles, gastrocnemius muscles, and tibialis anterior muscles was isolated. RNA was isolated for real-time PCR analysis of alpha1 actin and normalized to 18s RNA. As presented in Table 29, treatment with antisense oligonucleotides reduced human alpha1 actin RNA transcript expression. The results are expressed as percent inhibition of alpha1 actin transcript, relative to the PBS control.

[0400] Treatment with ISIS 190401 resulted in significant inhibition of alpha1 actin mRNA levels in quadriceps muscle, gastrocnemius muscle, and tibialis anterior muscle under the conditions specified above.

TABLE-US-00029 TABLE 29 Antisense inhibition of human alpha1 actin RNA transcript in HSA.sup.LR mice Muscle Type % inhibition Quadriceps 85 Gastrocnemius 86 Tibialis anterior 89

Assessment of Myotonia by Electromyography

[0401] Electromyography on left and right quadriceps, left and right gastrocnemius muscles, left and right tibialis anterior muscles and lumbar paraspinals muscles was performed as previously described (Kanadia et al, 2003, Science, 302: 1978-1980) by using 30 gauge concentric needle electrodes and a minimum of 10 needle insertions for each muscle. The data is presented in Table 30 as the average myotonia grade observed in four mice of each group and demonstrates significant reduction of myotonia in mice treated with ISIS 190401.

TABLE-US-00030 TABLE 30 Average reduction of myotonia in various muscles of antisense oligonucleotide-treated HSA.sup.LR mice PBS ISIS 190401 Left quadriceps 3.00 0.00 Right quadriceps 3.00 0.00 Left gastrocnemius 3.00 0.00 Right gastrocnemius 3.00 0.00 Left Tibialis anterior 2.50 0.00 Right Tibialis anterior 2.50 0.00 Lumbar paraspinals 3.00 0.50

Correction of Alternative Splicing

[0402] To evaluate the effect of ISIS 190401 on alternative splicing of Serca1, total RNA purified from the tibialis anterior gastrocnemius, and quadriceps muscle was analyzed in a procedure similar to that described in Example 13.

[0403] In PBS treated HSA.sup.LR mice, Serca1 splicing is dysregulated as demonstrated by exon 22 exclusion, as a result of MBLN1 dysregulation. Treatment with ISIS 190401 resulted in complete inclusion and normalization of alternative splicing of exon 22 of the Serca1 gene in all three muscle types.

[0404] Therefore, antisense inhibition of alpha1 actin corrected Serca1 splicing dysregulation, which indicates that treatment with antisense oligonucleotide reduced accumulation of CUGexp in the nuclear foci. Reduced accumulation of CUGexp in the nuclear foci corrects MBLN1 sequestration thereby allowing normal splicing to occur.

Example 18: Duration of Action of Antisense Inhibition by an Oligonucleotide Targeting Human Alpha1 Actin in Transgenic Mice

[0405] The duration of action of antisense inhibition of human alpha1 actin RNA transcript by ISIS 445236 in HSA.sup.LR mice was evaluated.

Treatment

[0406] HSA.sup.LR mice received subcutaneous injections of ISIS 445236 at a dose of 25 mg/kg twice per week for 4 weeks. A control group received subcutaneous injections of PBS twice per week for 2 weeks. The PBS-injected group served as the control group to which the oligonucleotide-treated group was compared. The mice were analyzed 6 weeks after administration of the last dose.

Inhibition of Alpha1 Actin RNA

[0407] Six weeks after the final dose, the animals were sacrificed and tissue from the quadriceps muscles, gastrocnemius muscles, and tibialis anterior muscles was isolated. RNA was isolated for real-time PCR analysis of alpha1 actin and normalized to 18s RNA. As presented in Table 31, treatment with ISIS 445236 reduced human alpha1 actin RNA transcript expression, and this effect was sustained at least for 6 weeks. The results are expressed as percent inhibition of alpha1 actin transcript, relative to the PBS control.

[0408] Treatment with ISIS 445236 resulted in significant inhibition of alpha1 actin mRNA levels in quadriceps muscle, gastrocnemius muscle, and tibialis anterior muscle under the conditions specified above.

TABLE-US-00031 TABLE 31 Antisense inhibition of human alpha1 actin RNA transcript in HSA.sup.LR mice Muscle Type % inhibition Quadriceps 88 Gastrocnemius 76 Tibialis anterior 67

Assessment of Myotonia by Electromyography

[0409] Electromyography on left and right quadriceps, left and right gastrocnemius muscles, left and right tibialis anterior muscles and lumbar paraspinals muscles was performed as previously described (Kanadia et al, 2003, Science, 302: 1978-1980) by using 30 gauge concentric needle electrodes and a minimum of 10 needle insertions for each muscle. The data is presented in Table 32 as the average myotonia grade observed in four mice of each group and demonstrates significant reduction of myotonia in mice treated with ISIS 445236. Therefore, the effect of antisense inhibition of alpha actin by ISIS 445236 was sustained at least for 6 weeks.

TABLE-US-00032 TABLE 32 Average reduction of myotonia in various muscles of antisense oligonucleotide-treated HSA.sup.LR mice PBS ISIS 445236 Left quadriceps 3.00 0.00 Right quadriceps 3.00 0.00 Left gastrocnemius 3.00 0.00 Right gastrocnemius 3.00 0.00 Left Tibialis anterior 2.50 0.00 Right Tibialis anterior 2.50 0.00 Lumbar paraspinals 3.00 0.00

Example 19: In Vivo Effect of Antisense Inhibition of mRNA with CUG Repeats by Intramuscular Administration in Transgenic Mice

[0410] The effect of antisense inhibition of mRNA transcripts containing multiple CUG repeats on myotonia in HSA.sup.LR mice was evaluated. Three antisense oligonucleotides targeting the CUG repeats and with varying lengths were assayed for their effectiveness in inhibiting myotonia in the mice. ISIS 444745 (AGCAGCAGCAGCAGCAGCAGCAGCA (SEQ ID NO: 789) is a uniform 2'-O-methoxyethyl oligonucleotide, 25 nucleotides in length and with a phosphorothioate backbone. ISIS 444746 (AGCAGCAGCAGCAGCAGCAG (SEQ ID NO: 790) is a uniform 2'-O-methoxyethyl oligonucleotide, 20 nucleotides in length and with a phosphorothioate backbone. ISIS 444749 (GCAGCAGCAGCAGCA (SEQ ID NO: 791) is a uniform 2'-O-methoxyethyl oligonucleotide, 15 nucleotides in length and with a phosphorothioate backbone. ISIS 445236 was included in the assay as a positive control.

Treatment

[0411] HSA.sup.LR mice were divided into three treatment groups. The groups received direct intramuscular injections of ISIS 444745, ISIS 444746 or ISIS 444749 at a dose of 0.4 nM into the tibialis anterior muscle. The contralateral tibialis anterior muscle in each mouse received a single dose intramuscular injection of PBS. The PBS-injected muscle acted as the control.

Inhibition of Alpha1 Actin RNA

[0412] Twenty four hours after the final dose, the animals were sacrificed and tissue from the tibialis anterior (left and right) was isolated. RNA was isolated for real-time PCR analysis of alpha1 actin and normalized to 18s RNA. As presented in Table 33, only treatment with ISIS 444745 reduced human alpha1 actin RNA transcript expression. The results are expressed as percent inhibition of alpha1 actin transcript, relative to the PBS control.

TABLE-US-00033 TABLE 33 Percent inhibition of human alpha1 actin RNA transcript in HSA.sup.LR mice ISIS No. % inhibition 444745 51 444746 0 444749 12

Example 20: In Vivo Dose Dependent Inhibition of mRNA with CUG Repeats by Intramuscular Administration in Transgenic Mice

[0413] ISIS 444745 and ISIS 444746 were further evaluated for their ability to reduce human alpha 1 actin mRNA in vivo.

Treatment

[0414] HSA.sup.LR mice were maintained on a 12-hour light/dark cycle and fed ad libitum normal Purina mouse chow. Animals were acclimated for at least 7 days in the research facility before initiation of the experiment. Antisense oligonucleotides (ASOs) were prepared in PBS and sterilized by filtering through a 0.2 micron filter. Oligonucleotides were dissolved in 0.9% PBS for injection.

[0415] The mice were divided into 6 treatment groups. Three of the groups received direct intramuscular injections of ISIS 444745 at doses of 0.2 nM, 0.5 nM, or 1.0 nM into the tibialis anterior muscle on one side. Another three groups direct intramuscular injections of ISIS 444746 at doses of 0.2 nM, 0.5 nM, or 1.0 nM into the tibialis anterior muscle on one side. The contralateral tibialis anterior muscle in each mouse received a single dose intramuscular injection of PBS. The PBS-injected muscle acted as the control for the corresponding muscle treated with ISIS oligonucleotide.

Assessment of Myotonia by Electromyography

[0416] Electromyography on left and right quadriceps, left and right gastrocnemius muscles, left and right tibialis anterior muscles and lumbar paraspinals muscles was performed as previously described (Kanadia et al, 2003, Science, 302: 1978-1980) by using 30 gauge concentric needle electrodes and a minimum of 10 needle insertions for each muscle. The data is presented in Table 34 as the average myotonia grade observed in four mice of each group and demonstrates significant reduction of myotonia in mice treated with either ISIS 444745 or ISIS 444746. The effect of antisense inhibition of alpha actin by ISIS 444745 and 444746 was sustained at least for 6 weeks.

TABLE-US-00034 TABLE 34 Dose-dependent reduction of myotonia in muscles of antisense oligonucleotide-treated HSA.sup.LR mice 0.2 nM 0.5 nM 1.0 nM PBS 3.00 3.00 2.33 ISIS 444745 1.67 1.00 0.33 PBS 2.50 2.00 3.00 ISIS444746 2.00 0.00 1.00

Example 21: In Vivo Effect of Antisense Inhibition of mRNA with CUG Repeats by Subcutaneous Administration in Transgenic Mice

[0417] The effect of antisense inhibition of mRNA transcripts containing multiple CUG repeats on myotonia in HSA.sup.LR mice was evaluated. ISIS 445236 was included in the assay as a positive control.

Treatment

[0418] HSA.sup.LR mice were divided into five treatment groups. The first three groups received subcutaneous injections of ISIS 444745, ISIS 444746 or ISIS 444749 at a dose of 25 mg/kg twice per week for 4 weeks. The fourth group received subcutaneous injections of PBS twice per week for 4 weeks. The fifth group received subcutaneous injections of ISIS 445236 at a dose of 25 mg/kg twice per week for 4 weeks. The PBS-injected group served as the control group to which the oligonucleotide-treated group was compared.

Assessment of Myotonia by Electromyography

[0419] Electromyography on left and right quadriceps, left and right gastrocnemius muscles, left and right tibialis anterior muscles and lumbar paraspinals muscles was performed as previously described (Kanadia et al, 2003, Science, 302: 1978-1980) by using 30 gauge concentric needle electrodes and a minimum of 10 needle insertions for each muscle. The data is presented in Table 35 as the average myotonia grade observed in four mice of each group.

[0420] Treatment with ISIS 445236 led to significant reduction in myotonia. Treatment with ISIS 444745 and ISIS 444746 also resulted in reduced myotonia in some of the tissues tested.

TABLE-US-00035 TABLE 35 Average reduction of myotonia in various muscles of antisense oligonucleotide-treated HSA.sup.LR mice ISIS ISIS ISIS ISIS PBS 444745 444746 444749 445236 Left quadriceps 3.00 3.00 3.00 3.00 0.00 Right quadriceps 3.00 3.00 3.00 3.00 0.00 Left gastrocnemius 3.00 2.75 3.00 3.00 0.00 Right gastrocnemius 3.00 2.75 2.75 3.00 0.00 Left Tibialis anterior 3.00 2.25 2.75 2.75 0.00 Right Tibialis anterior 3.00 2.25 2.50 2.75 0.00 Lumbar paraspinals 3.00 3.00 3.00 3.00 0.00

Example 22: Dose-Dependent Inhibition of Long CUG Repeat mRNA (HSA.sup.LR Mice) and a Short CUG Repeat (HSA.sup.SR Mice) by Subcutaneous Administration in Transgenic Mice

[0421] Dose-dependent inhibition of mRNA transcripts containing a long CUG repeat (HSA.sup.LR mice) and a short CUG repeat (HSA.sup.SR mice), was evaluated. HSA-short repeat (HSA.sup.SR) mice express the identical transgene as the HSA.sup.LR mice, except that 5 instead of 250 CUG repeats are inserted in the 3' UTR. HSA.sup.SR mice do not have myotonia, splicing changes, or any other observable myotonia phenotype. ISIS 445236 was used in this assay.

Treatment

[0422] HSA.sup.LR mice were divided into four treatment groups. The first three groups received subcutaneous injections of ISIS 445236 at doses of 2.5 mg/kg, 8.5 mg/kg or 25.0 mg/kg twice per week for 4 weeks. The fourth group received subcutaneous injections of PBS twice per week for 4 weeks. The PBS-injected group served as the control group to which the oligonucleotide-treated group was compared. HSA.sup.SR mice were also divided into four groups and similarly treated.

Inhibition of Alpha1 Actin RNA

[0423] Twenty four hours after the final dose, the animals were sacrificed and tissue from the quadriceps muscles (left and right), gastrocnemius muscles (left and right), and tibialis anterior muscles (left and right) was isolated. RNA was isolated for real-time PCR analysis of alpha1 actin and normalized to 18s RNA. The results are presented in Tables 36 and 37 and are expressed as percent inhibition of alpha1 actin transcript, relative to the control. Greater inhibition of the nuclear-retained long repeat in the muscle of HSA.sup.LR mice was achieved compared with the non-nuclear-retained short repeat in the muscle of HSA.sup.LR mice.

TABLE-US-00036 TABLE 36 Percent inhibition of human alpha1 actin RNA transcript in HSA.sup.LR mice Dose (mg/kg) Quadriceps Gastrocnemius Tibialis anterior 2.5 24 36 46 8.5 53 66 59 25 86 86 90

TABLE-US-00037 TABLE 37 Percent inhibition of human alpha1 actin RNA transcript in HSA.sup.SR mice Dose (mg/kg) Quadriceps Gastrocnemius Tibialis anterior 2.5 15 14 0 8.5 30 11 0 25 59 48 54

Example 23: In Vivo Antisense Inhibition of Human DMPK in Transgenic Mice

[0424] LC15 mice, Line A, are transgenic mice containing the entire human DMPK 3'UTR (developed by Wheeler et al, University of Rochester). The mice are the second generation of mice backcrossed to an FVB background. The transgene is expressed in the mice as a CUG repeat RNA, which is retained in the nucleus, forming nuclear inclusions or foci, similar to that seen in human tissue samples of patients with myotonic dystrophy (DM1). There are 350-400 CUG repeats in the DMPK transgene. These mice display early signs of DM1 and do not display any myotonia in their muscle tissues.

[0425] ISIS 445569, ISIS 444404, ISIS 444436 and ISIS 473810, which demonstrated statistically significant dose-dependent inhibition in vitro (see Example 5), were evaluated for their ability to reduce human DMPK RNA transcript in vivo.

Treatment

[0426] LC15, Line A mice were maintained on a 12-hour light/dark cycle and fed ad libitum normal Purina mouse chow. Animals were acclimated for at least 7 days in the research facility before initiation of the experiment. Antisense oligonucleotides (ASOs) were prepared in PBS and sterilized by filtering through a 0.2 micron filter. Oligonucleotides were dissolved in 0.9% PBS for injection.

[0427] The mice were divided into five treatment groups. The first three groups received subcutaneous injections of ISIS 445569, ISIS 444404 or ISIS 444436 at a dose of 25 mg/kg twice per week for 4 weeks. The fourth group received subcutaneous injections of ISIS 473810 at a dose of 12.5 mg/kg twice per week for 4 weeks. The fifth group received subcutaneous injections of PBS twice weekly for 4 weeks. The PBS-injected group served as the control group to which the oligonucleotide-treated group was compared.

Inhibition of DMPK RNA

[0428] Twenty four hours after the final dose, the animals were sacrificed and tissue from the quadriceps muscles was isolated. RNA was isolated for real-time PCR analysis of DMPK and normalized to 18s RNA. As presented in Table 38, treatment with antisense oligonucleotides reduced human DMPK RNA transcript expression. The results are expressed as percent inhibition of DMPK transcript, relative to the PBS control.

TABLE-US-00038 TABLE 38 Antisense inhibition of human DMPK RNA transcript in LC15 mice ISIS No mg/kg/wk % inhibition 444404 50 20 444404 50 55 444436 50 41 473810 25 56

Assessment of Myotonia by Electromyography

[0429] Electromyography on left and right quadriceps, left and right gastrocnemius muscles, left and right tibialis anterior muscles and lumbar paraspinals muscles was performed as previously described (Kanadia et al, 2003, Science, 302: 1978-1980) by using 30 gauge concentric needle electrodes and a minimum of 10 needle insertions for each muscle. Since LC15 mice do not have myotonia, neither the control group nor the treatment groups displayed any myotonia in any muscle tested.

Example 24: In Vivo Antisense Inhibition of Human DMPK in Transgenic Mice

[0430] LC15 mice, Line D, are transgenic mice containing the entire human DMPK 3'UTR (developed by Wheeler et al, University of Rochester). The mice are the third generation of mice backcrossed to an FVB background. The transgene is expressed in the mice as a CUG repeat RNA, which is retained in the nucleus, forming nuclear inclusions or foci, similar to that seen in human tissue samples of patients with myotonic dystrophy (DM1). There are 350-400 CUG repeats in the DMPK transgene. These mice display early signs of DM1 and do not display any myotonia in their muscle tissues.

[0431] ISIS 445569, ISIS 444404, ISIS 444436 and ISIS 473810 were further evaluated for their ability to reduce human DMPK RNA transcript in vivo.

Treatment

[0432] LC15, Line D mice were maintained on a 12-hour light/dark cycle and fed ad libitum normal Purina mouse chow. Animals were acclimated for at least 7 days in the research facility before initiation of the experiment. Antisense oligonucleotides (ASOs) were prepared in PBS and sterilized by filtering through a 0.2 micron filter. Oligonucleotides were dissolved in 0.9% PBS for injection.

[0433] The mice were divided into six treatment groups. The first three groups received subcutaneous injections of ISIS 445569, ISIS 444404 or ISIS 444436 at a dose of 25.00 mg/kg twice per week for 4 weeks. The fourth group received subcutaneous injections of ISIS 473810 at a dose of 12.50 mg/kg twice per week for 4 weeks. The fifth group received subcutaneous injections of ISIS 473810 at a dose of 6.25 mg/kg twice per week for 4 weeks. The sixth group received subcutaneous injections of PBS twice weekly for 4 weeks. The PBS-injected group served as the control group to which the oligonucleotide-treated group was compared.

Inhibition of DMPK RNA

[0434] Twenty four hours after the final dose, the animals were sacrificed and tissue from the quadriceps muscles was isolated. RNA was isolated for real-time PCR analysis of DMPK and normalized to 18s RNA. As presented in Table 39, treatment with antisense oligonucleotides reduced human DMPK RNA transcript expression. The results are expressed as percent inhibition of DMPK transcript, relative to the PBS control.

[0435] The results indicate that treatment with the antisense oligonucleotides resulted in inhibition of DMPK mRNA in the mice.

TABLE-US-00039 TABLE 39 Antisense inhibition of human DMPK RNA transcript in LC15 mice ISIS No mg/kg/wk % inhibition 444404 50.00 24 444404 50.00 30 444436 50.00 17 473810 25.00 7 473810 12.50 18

Assessment of Myotonia by Electromyography

[0436] Electromyography on left and right quadriceps, left and right gastrocnemius muscles, left and right tibialis anterior muscles and lumbar paraspinals muscles was performed as previously described (Kanadia et al, 2003, Science, 302: 1978-1980) by using 30 gauge concentric needle electrodes and a minimum of 10 needle insertions for each muscle. Since LC15 mice do not have myotonia, neither the control group nor the treatment groups displayed any myotonia in any muscle tested.

Example 25: In Vivo Antisense Inhibition of Human DMPK in SXL Transgenic Mouse Model

[0437] Using hDMPK-targeting ASOs 444401 and 299471 target knockdown in soleus muscle was measured in SXL mice. The SXL mouse is transgenic for the entire DMPK gene and promoter and contains a 1000 CUG repeat sequence in the 3'UTR of DMPK gene. Mice were dosed 50 mg/kg twice weekly for 4 weeks (n=3 mice per group, except n=2 for saline-injected controls). Results of Taqman assays demonstrated that treatment with either ISISI 444401 or ISIS 299471 significantly reduced mut-hDMPK mRNA levels but had negligible effect on endogenous mouse Dmpk mRNA levels.

[0438] Therefore, ISIS 444401 and ISIS 299471 selectively target human DMPK mRNA transcript.

Example 26: Duration of Action of Antisense Inhibition by an Oligonucleotide Targeting Human Alpha1 Actin in Transgenic Mice

[0439] The duration of action of antisense inhibition of human alpha1 actin RNA transcript by ISIS 190401 in HSA.sup.LR mice was evaluated.

Treatment

[0440] HSA.sup.LR mice received subcutaneous injections of ISIS 190401 at a dose of 25 mg/kg twice per week for 4 weeks. A control group received subcutaneous injections of PBS twice per week for 4 weeks. The PBS-injected group served as the control group to which the oligonucleotide-treated group was compared. The mice were analyzed 15 weeks after administration of the last dose.

Inhibition of Alpha1 Actin RNA

[0441] Fifteen weeks after the final dose, the animals were sacrificed and tissue from the quadriceps muscles, gastrocnemius muscles, and tibialis anterior muscles was isolated. RNA was isolated for real-time PCR analysis of alpha1 actin and normalized to 18s RNA. As presented in Table 40, treatment with ISIS 190401 reduced human alpha1 actin RNA transcript expression, and this effect was sustained at least for 15 weeks. The results are expressed as percent inhibition of alpha1 actin transcript, relative to the PBS control.

[0442] Treatment with ISIS 190401 resulted in significant inhibition of alpha1 actin mRNA levels under the conditions specified above.

TABLE-US-00040 TABLE 40 Antisense inhibition of human alpha1 actin RNA transcript in HSA.sup.LR mice Muscle Type % inhibition Quadriceps 74 Gastrocnemius 81 Tibialis anterior 75

Assessment of Myotonia by Electromyography

[0443] Electromyography on left and right quadriceps, left and right gastrocnemius muscles, left and right tibialis anterior muscles and lumbar paraspinals muscles was performed as previously described (Kanadia et al, 2003, Science, 302: 1978-1980) by using 30 gauge concentric needle electrodes and a minimum of 10 needle insertions for each muscle. The data is presented in Table 41 as the average myotonia grade observed in four mice of each group and demonstrates significant reduction of myotonia in mice treated with ISIS 190401. Therefore, the effect of antisense inhibition of alpha actin by ISIS 190401 was sustained at least for 15 weeks.

TABLE-US-00041 TABLE 41 Average reduction of myotonia in various muscles of antisense oligonucleotide-treated HSA.sup.LR mice PBS ISIS 190401 Left quadriceps 3.0 0.0 Right quadriceps 3.0 0.0 Left gastrocnemius 2.5 0.0 Right gastrocnemius 2.5 0.0 Left Tibialis anterior 2.5 0.0 Right Tibialis anterior 2.5 0.0 Lumbar paraspinals 2.5 0.0

Correction of Alternative Splicing

[0444] To evaluate the effect of ISIS 190401 on alternative splicing of Serca1, total RNA purified from the tibialis anterior gastrocnemius, and quadriceps muscle was analyzed in a procedure similar to that described in Example 13.

[0445] In PBS treated HSA.sup.LR mice, Serca1 splicing is dysregulated as demonstrated by exon 22 exclusion. Treatment with ISIS 190401 resulted in complete inclusion and normalization of alternative splicing of exon 22 of the Serca1 gene in all three muscle types, which was sustained even after 15 weeks.

[0446] Therefore, antisense inhibition of alpha1 actin corrected Serca1 splicing dysregulation, which indicates that treatment with antisense oligonucleotide reduced accumulation of CUGexp in the nuclear foci. Reduced accumulation of CUGexp in the nuclear foci corrects MBLN1 sequestration thereby allowing normal splicing to occur.

Example 27: Microarray Analysis of Transcriptomic Effect of Antisense Inhibition of Human Actin

[0447] Expression of actin mRNA with expanded CUG repeats causes extensive remodeling of the muscle transcriptome. To evaluate the overall transcriptomic effects of ISIS 190401 and ISIS 445236, microarray analyses was utilized in HSA.sup.LR mice.

Treatment

[0448] HSA.sup.LR mice received subcutaneous injections of ISIS 190401 or ISIS 445236 at a dose of 25 mg/kg twice per week for 4 weeks. A control group received subcutaneous injections of PBS twice per week for 4 weeks. The PBS-injected group served as the control group to which the oligonucleotide-treated group was compared.

Transcriptome Analysis by Microarray

[0449] RNA was isolated from the quadriceps muscle of wild-type or HSA.sup.LR mice. RNA integrity was verified using an Agilent Bioanalyzer (RNA integrity number >7.5). RNA was processed to complementary RNA (cRNA) and hybridized on microbeads using MouseRef-8 v2.0 Expression BeadChip Kits (Illumina, San Diego), according to the manufacturer's recommendations. Image data were quantified using BeadStudio software (Illumina). Signal intensities were quantile normalized. Row-specific offsets were used to avoid any values of less than 2 prior to normalization. Data from all probe sets with 6 or more nucleotides of CUG, UGC, or GCU repeats was suppressed to eliminate the possibility that expanded repeats in the hybridization mixture (CAG repeats in cRNA originating from CUG repeats in the mRNA) could cross-hybridize with repeat sequences in the probes. To eliminate genes whose expression was not readily quantified on the arrays, probes showing a P value for detection probability of <0.1 were suppressed in all samples. Comparisons between groups were summarized and rank-ordered by fold-changes of mean expression level and t tests. The software package R (Butler et al. Diabetes. 2002; 51: 1028-34) was used to perform principal components analysis (Levin et al. In Antisense Drug Technology: Principles, Strategies, and Applications, S. T. Crooke, Ed. (CRC Press, Boca Raton, 2008), pp 183-215; Geary et al. Drug Metab. Dispos. 2003; 31: 1419-28) on wild-type, ISIS oligonucleotide-treated, and PBS-treated microarray samples. The principle components allowed the capture of the majority of the expression variation in each sample within 3 dimensions. The first three principal components of each sample were plotted.

[0450] The principle component analysis of untreated wild-type and HSA.sup.LR mice demonstrated segregation of HSA.sup.LR away from wild-type mice, in widely separated clusters. In contrast, antisense oligonucleotide-treated HSA.sup.LR mice clustered more closely to wild-type mice, suggesting an overall trend for transcriptome normalization. Comparisons of HSA.sup.LR transgenic mice with wild-type mice identified 93 transcripts whose expression levels were altered more than two-fold (P<0.0001), as presented in Table 42, below. The extent of dysregulation for these transcripts was reduced or normalized for antisense oligonucleotides (88% dysregulated transcripts responded to ISIS 445236, P<0.05 for ISIS 445236 vs. PBS control, whereas 90% responded to ISIS 190401).

[0451] In order to consider transcripts that have off-target knockdown, all transcripts whose expression was reduced in antisense oligonucleotide-treated HSA.sup.LR mice were identified (>two-fold reduction by either oligonucleotide, P<0.0001, n=41 transcripts). All transcripts that were down-regulated by these criteria demonstrated upregulation in HSA.sup.LR mice. The only exception, collagen 6 alpha2, is unlikely to result from off-target cleavage because it was down-regulated by the two antisense oligonucleotides with non-overlapping sequences.

[0452] These results indicate that treatment with antisense oligonucleotides for 4 weeks resulted in a general improvement of the muscle transcriptome without any evidence for off-target effects.

TABLE-US-00042 TABLE 42 Comparisons of HSA.sup.LR transgenic mice with wild-type mice identified 93 transcripts Fold- Fold- Fold- change t test Fold- change t test Fold- change t test HSALR- HASLR change t test HSALR- HSALR- change t test HSALR- HSALR- 190104 vs. 190401 vs. HSALR- HSALR- 445236 vs. 445236 vs. HSALR- HSALR- saline vs. Saline vs. HSALR- HSALR- 190401 vs. 190401 HSALR- HSALR- 445236 445236 Transcript WT WT saline saline WT vs. WT saline saline vs. WT vs. WT OSBPL10 15.11 0.0000 0.46 0.0023 6.95 0.0008 0.39 0.0007 5.92 0.0002 FBXL13 12.12 0.0000 0.49 0.0159 5.91 0.0385 0.65 0.0255 7.93 0.0026 NGFR 11.57 0.0000 0.23 0.0001 2.66 0.0314 0.16 0.0000 1.84 0.0133 SLC1A1 9.39 0.0000 0.39 0.0001 3.66 0.0001 0.30 0.0001 2.85 0.0116 CXADR 9.13 0.0000 0.14 0.0000 1.30 0.6119 0.21 0.0001 1.94 0.2244 NFATC2 8.48 0.0000 0.32 0.0002 2.67 0.0043 0.22 0.0001 1.84 0.0394 ATP1B4 7.02 0.0000 0.24 0.0000 1.68 0.0021 0.24 0.0000 1.70 0.0091 UCHL1 6.80 0.0000 0.71 0.0168 4.86 0.0005 0.72 0.1187 4.91 0.0090 TEAD4 6.76 0.0000 0.50 0.0030 3.39 0.0085 0.30 0.0004 2.06 0.1213 TAS1R1 6.72 0.0000 0.28 0.0003 1.91 0.1857 0.43 0.0002 2.88 0.0047 MUSTN1 6.52 0.0000 0.31 0.0000 2.01 0.0006 0.33 0.0000 2.15 0.0115 IRF5 6.01 0.0000 0.21 0.0000 1.28 0.0556 0.33 0.0001 1.96 0.0035 CRIP3 5.82 0.0000 0.33 0.0000 1.92 0.0151 0.29 0.0001 1.67 0.1470 TAL2 5.75 0.0000 0.20 0.0001 1.13 0.7717 0.36 0.0002 2.08 0.0274 ORF63 5.39 0.0000 0.27 0.0001 1.45 0.0206 0.47 0.0018 2.51 0.0066 COPG 5.05 0.0000 0.30 0.0000 1.53 0.0218 0.25 0.0001 1.25 0.3617 CAMK1D 4.92 0.0000 0.23 0.0002 1.12 0.8157 0.27 0.0000 1.32 0.2449 HSPA2 4.76 0.0000 0.43 0.0000 2.02 0.0079 0.42 0.0000 2.02 0.0197 CAMK2D 4.70 0.0000 0.36 0.0001 1.70 0.0493 0.45 0.0004 2.12 0.0095 CNTNAP2 4.49 0.0000 0.58 0.0001 2.59 0.0000 0.67 0.0007 3.02 0.0000 TTC7 4.33 0.0000 0.38 0.0000 1.63 0.0085 0.68 0.0468 2.96 0.0126 CD276 4.08 0.0001 0.36 0.0001 1.47 0.1613 0.59 0.0029 2.39 0.0072 USH1C 4.07 0.0000 0.50 0.0011 2.04 0.0077 0.38 0.0029 1.55 0.2881 LRP11 4.03 0.0000 0.55 0.0017 2.24 0.0011 0.55 0.0006 2.23 0.0000 PHLDA3 3.96 0.0000 0.40 0.0001 1.60 0.0019 0.36 0.0001 1.42 0.0609 HSPB7 3.80 0.0000 0.30 0.0000 1.14 0.5358 0.30 0.0000 1.15 0.4474 TRIT1 3.74 0.0000 0.43 0.0000 1.62 0.0003 0.31 0.0000 1.16 0.1043 PCNX 3.66 0.0000 0.37 0.0002 1.34 0.1628 0.42 0.0001 1.53 0.0105 3632451O06RIK 3.51 0.0000 0.81 0.1094 2.83 0.0025 0.71 0.0015 2.51 0.0002 AMHR2 3.46 0.0000 0.45 0.0001 1.56 0.0037 0.52 0.0003 1.79 0.0016 SNX13 3.27 0.0000 0.47 0.0000 1.55 0.0007 0.44 0.0000 1.42 0.0003 ATP9A 3.26 0.0000 0.60 0.0001 1.96 0.0024 0.42 0.0002 1.38 0.2009 D030028O16RIK 3.22 0.0000 0.53 0.0011 1.70 0.0104 0.48 0.0001 1.56 0.0007 RPS6KA3 3.09 0.0000 0.38 0.0000 1.17 0.1845 0.44 0.0001 1.37 0.0321 GCA 3.00 0.0000 0.70 0.0031 2.09 0.0005 0.74 0.0103 2.22 0.0006 PACRG 2.89 0.0001 0.51 0.0002 1.46 0.0063 0.46 0.0001 1.34 0.0229 SPSB2 2.88 0.0001 0.33 0.0000 0.95 0.6599 0.37 0.0000 1.07 0.6216 POU4F1 2.83 0.0000 0.42 0.0000 1.19 0.2046 0.60 0.0007 1.68 0.0074 STRN4 2.72 0.0000 0.38 0.0000 1.03 0.8900 0.46 0.0000 1.25 0.2128 NCAM1 2.67 0.0001 0.70 0.0259 1.87 0.0135 0.54 0.0006 1.43 0.0343 A930018M24Rik 2.65 0.0001 0.58 0.0058 1.53 0.0727 0.43 0.0002 1.13 0.3919 TUBA4A 2.60 0.0000 0.42 0.0000 1.09 0.1806 0.50 0.0000 1.31 0.0041 lAP 2.57 0.0000 0.57 0.0002 1.46 0.0108 0.59 0.0016 1.52 0.0333 ANKRD40 2.56 0.0000 0.63 0.0155 1.60 0.0683 0.57 0.0002 1.46 0.0047 UVRAG 2.48 0.0000 0.59 0.0000 1.48 0.0005 0.52 0.0000 1.28 0.0165 HIST1H4H 2.46 0.0001 0.55 0.0001 1.34 0.0474 0.65 0.0014 1.60 0.0125 EPS15 2.44 0.0000 0.61 0.0001 1.50 0.0057 0.77 0.0043 1.87 0.0007 PANX1 2.41 0.0001 0.46 0.0004 1.11 0.4311 0.36 0.0000 0.87 0.0561 CALML4 2.41 0.0001 0.45 0.0008 1.10 0.6994 0.67 0.0154 1.62 0.0538 ASPH 2.40 0.0000 0.40 0.0000 0.95 0.6969 0.44 0.0000 1.05 0.7267 CREB3L2 2.37 0.0001 0.71 0.0287 1.67 0.0416 0.65 0.0051 1.54 0.0410 TRAF3 2.32 0.0001 0.50 0.0001 1.16 0.2851 0.57 0.0001 1.32 0.0481 CMYA1 2.30 0.0000 0.44 0.0007 1.02 0.9450 0.44 0.0000 1.01 0.9265 ADAMTSL5 2.30 0.0001 0.48 0.0000 1.11 0.3365 0.53 0.0004 1.22 0.1827 HS2ST1 2.27 0.0001 0.64 0.0002 1.44 0.0223 0.74 0.0041 1.68 0.0062 HIST1H4J 2.21 0.0000 0.59 0.0000 1.31 0.0283 0.72 0.0002 1.60 0.0023 SPSB1 2.20 0.0000 0.53 0.0005 1.16 0.2409 0.48 0.0000 1.05 0.3088 LANCL1 2.20 0.0000 0.63 0.0002 1.39 0.0002 0.66 0.0006 1.46 0.0005 KCNC4 2.16 0.0000 0.91 0.3892 1.96 0.0036 0.98 0.8712 2.12 0.0029 PRRC1 2.16 0.0000 0.57 0.0001 1.23 0.0324 0.59 0.0000 1.26 0.0070 MID1IP1 2.13 0.0001 1.27 0.0161 2.70 0.0001 1.09 0.4336 2.32 0.0014 DICER1 2.13 0.0000 0.65 0.0006 1.39 0.0051 0.69 0.0018 1.47 0.0035 IKBKB 2.10 0.0001 0.74 0.0240 1.56 0.0262 0.78 0.0039 1.64 0.0015 D5WSU178E 2.10 0.0000 0.86 0.1447 1.80 0.0049 0.88 0.0352 1.84 0.0002 ZFP106 2.08 0.0000 0.53 0.0000 1.11 0.1324 0.58 0.0002 1.20 0.0706 B930041F14RIK 2.06 0.0000 0.71 0.0002 1.47 0.0000 0.72 0.0030 1.49 0.0025 FHL1 2.04 0.0000 0.58 0.0000 1.17 0.1332 0.40 0.0000 0.81 0.0815 UHRF1BP1L 2.04 0.0001 0.78 0.0315 1.59 0.0071 0.68 0.0024 1.38 0.0151 PHCA 2.02 0.0000 0.64 0.0001 1.29 0.0354 0.74 0.0070 1.50 0.0145 B230312A22RIK 2.02 0.0000 0.79 0.0022 1.59 0.0004 0.77 0.0019 1.56 0.0007 PPP2R5C 2.01 0.0000 0.59 0.0001 1.16 0.0161 0.66 0.0017 1.32 0.0177 UCK2 2.01 0.0001 0.70 0.0004 1.41 0.0129 0.64 0.0001 1.28 0.0510 LEPROTL1 0.50 0.0000 1.45 0.0013 0.72 0.0004 1.47 0.0011 0.73 0.0005 COPS7A 0.49 0.0000 1.35 0.0645 0.66 0.0039 1.49 0.0026 0.73 0.0016 PRM17 0.48 0.0001 1.51 0.2023 0.73 0.1585 1.34 0.0445 0.65 0.0002 LDB3 0.47 0.0000 1.55 0.0550 0.73 0.0607 1.57 0.0010 0.74 0.0055 LOC100046120 0.47 0.0000 1.31 0.0077 0.61 0.0000 1.27 0.0381 0.60 0.0002 LOC677317 0.45 0.0001 1.49 0.0004 0.68 0.0012 1.93 0.0011 0.88 0.2082 LDB2 0.45 0.0000 1.73 0.0424 0.78 0.1234 1.23 0.0817 0.56 0.0000 SUM03 0.44 0.0000 1.70 0.0123 0.74 0.0223 1.37 0.0960 0.60 0.0023 LRRC24 0.43 0.0001 1.89 0.0009 0.82 0.0212 1.42 0.0898 0.61 0.0041 HNRPH1 0.42 0.0000 1.64 0.0077 0.69 0.0094 1.70 0.0057 0.71 0.0144 ARMETL1 0.38 0.0000 2.58 0.0000 0.98 0.7666 2.70 0.0000 1.02 0.7109 LOC100041504 0.37 0.0000 2.02 0.0001 0.75 0.0061 1.84 0.0040 0.68 0.0094 MMP9 0.32 0.0000 2.40 0.0006 0.77 0.0340 1.37 0.1834 0.44 0.0009 CBFB 0.28 0.0000 2.66 0.0304 0.75 0.1852 1.94 0.0056 0.55 0.0004 MDH2 0.24 0.0000 1.20 0.0473 0.29 0.0000 1.12 0.1037 0.27 0.0000 APCDD1 0.20 0.0000 1.98 0.2157 0.39 0.0059 4.55 0.0001 0.90 0.2873 LOC654842 0.19 0.0000 1.28 0.1712 0.24 0.0000 1.07 0.8807 0.20 0.0001 F2RL3 0.15 0.0000 5.78 0.0001 0.86 0.1901 4.92 0.0004 0.73 0.0310 EIF3H 0.13 0.0000 1.99 0.2185 0.26 0.0001 1.86 0.1997 0.24 0.0000 AVIL 0.12 0.0000 4.22 0.0156 0.52 0.0081 1.88 0.2270 0.23 0.0001 ACTC1 0.08 0.0000 1.42 0.0346 0.11 0.0000 6.07 0.0098 0.48 0.0087

Sequence CWU 1 SEQUENCE LISTING <160> NUMBER OF SEQ ID NOS: 837 <210> SEQ ID NO 1 <211> LENGTH: 2877 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <400> SEQUENCE: 1 aggggggctg gaccaagggg tggggagaag gggaggaggc ctcggccggc cgcagagaga 60 agtggccaga gaggcccagg ggacagccag ggacaggcag acatgcagcc agggctccag 120 ggcctggaca ggggctgcca ggccctgtga caggaggacc ccgagccccc ggcccgggga 180 ggggccatgg tgctgcctgt ccaacatgtc agccgaggtg cggctgaggc ggctccagca 240 gctggtgttg gacccgggct tcctggggct ggagcccctg ctcgaccttc tcctgggcgt 300 ccaccaggag ctgggcgcct ccgaactggc ccaggacaag tacgtggccg acttcttgca 360 gtgggcggag cccatcgtgg tgaggcttaa ggaggtccga ctgcagaggg acgacttcga 420 gattctgaag gtgatcggac gcggggcgtt cagcgaggta gcggtagtga agatgaagca 480 gacgggccag gtgtatgcca tgaagatcat gaacaagtgg gacatgctga agaggggcga 540 ggtgtcgtgc ttccgtgagg agagggacgt gttggtgaat ggggaccggc ggtggatcac 600 gcagctgcac ttcgccttcc aggatgagaa ctacctgtac ctggtcatgg agtattacgt 660 gggcggggac ctgctgacac tgctgagcaa gtttggggag cggattccgg ccgagatggc 720 gcgcttctac ctggcggaga ttgtcatggc catagactcg gtgcaccggc ttggctacgt 780 gcacagggac atcaaacccg acaacatcct gctggaccgc tgtggccaca tccgcctggc 840 cgacttcggc tcttgcctca agctgcgggc agatggaacg gtgcggtcgc tggtggctgt 900 gggcacccca gactacctgt cccccgagat cctgcaggct gtgggcggtg ggcctgggac 960 aggcagctac gggcccgagt gtgactggtg ggcgctgggt gtattcgcct atgaaatgtt 1020 ctatgggcag acgcccttct acgcggattc cacggcggag acctatggca agatcgtcca 1080 ctacaaggag cacctctctc tgccgctggt ggacgaaggg gtccctgagg aggctcgaga 1140 cttcattcag cggttgctgt gtcccccgga gacacggctg ggccggggtg gagcaggcga 1200 cttccggaca catcccttct tctttggcct cgactgggat ggtctccggg acagcgtgcc 1260 cccctttaca ccggatttcg aaggtgccac cgacacatgc aacttcgact tggtggagga 1320 cgggctcact gccatggaga cactgtcgga cattcgggaa ggtgcgccgc taggggtcca 1380 cctgcctttt gtgggctact cctactcctg catggccctc agggacagtg aggtcccagg 1440 ccccacaccc atggaactgg aggccgagca gctgcttgag ccacacgtgc aagcgcccag 1500 cctggagccc tcggtgtccc cacaggatga aacagctgaa gtggcagttc cagcggctgt 1560 ccctgcggca gaggctgagg ccgaggtgac gctgcgggag ctccaggaag ccctggagga 1620 ggaggtgctc acccggcaga gcctgagccg ggagatggag gccatccgca cggacaacca 1680 gaacttcgcc agtcaactac gcgaggcaga ggctcggaac cgggacctag aggcacacgt 1740 ccggcagttg caggagcgga tggagttgct gcaggcagag ggagccacag ctgtcacggg 1800 ggtccccagt ccccgggcca cggatccacc ttcccatcta gatggccccc cggccgtggc 1860 tgtgggccag tgcccgctgg tggggccagg ccccatgcac cgccgccacc tgctgctccc 1920 tgccagggtc cctaggcctg gcctatcgga ggcgctttcc ctgctcctgt tcgccgttgt 1980 tctgtctcgt gccgccgccc tgggctgcat tgggttggtg gcccacgccg gccaactcac 2040 cgcagtctgg cgccgcccag gagccgcccg cgctccctga accctagaac tgtcttcgac 2100 tccggggccc cgttggaaga ctgagtgccc ggggcacggc acagaagccg cgcccaccgc 2160 ctgccagttc acaaccgctc cgagcgtggg tctccgccca gctccagtcc tgtgatccgg 2220 gcccgccccc tagcggccgg ggagggaggg gccgggtccg cggccggcga acggggctcg 2280 aagggtcctt gtagccggga atgctgctgc tgctgctgct gctgctgctg ctgctgctgc 2340 tgctgctgct gctgctgctg ctggggggat cacagaccat ttctttcttt cggccaggct 2400 gaggccctga cgtggatggg caaactgcag gcctgggaag gcagcaagcc gggccgtccg 2460 tgttccatcc tccacgcacc cccacctatc gttggttcgc aaagtgcaaa gctttcttgt 2520 gcatgacgcc ctgctctggg gagcgtctgg cgcgatctct gcctgcttac tcgggaaatt 2580 tgcttttgcc aaacccgctt tttcggggat cccgcgcccc cctcctcact tgcgctgctc 2640 tcggagcccc agccggctcc gcccgcttcg gcggtttgga tatttattga cctcgtcctc 2700 cgactcgctg acaggctaca ggacccccaa caaccccaat ccacgttttg gatgcactga 2760 gaccccgaca ttcctcggta tttattgtct gtccccacct aggaccccca cccccgaccc 2820 tcgcgaataa aaggccctcc atctgcccaa aaaaaaaaaa aaaaaaaaaa aaaaaaa 2877 <210> SEQ ID NO 2 <211> LENGTH: 14411 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <400> SEQUENCE: 2 ctcccagccc agcgcctccc accccttttc atagcaggaa aagccggagc ccagggaggg 60 aacggacctg cgagtcacac aactggtgac ccacaccagc ggctggagca ggaccctctt 120 ggggagaaga gcatcctgcc cgcagccagg gcccctcatc aaagtcctcg gtgtttttta 180 aattatcaga actgcccagg accacgtttc ccaggccctg cccagctggg actcctcggt 240 ccttgcctcc tagtttctca ggcctggccc tctcaaggcc caggcacccc aggccggttg 300 gaggccccga cttccactct ggagaaccgt ccaccctgga aagaagagct cagattcctc 360 ttggctctcg gagccgcagg gagtgtgtct tcccgcgcca ccctccaccc cccgaaatgt 420 ttctgtttct aatcccagcc tgggcaggaa tgtggctccc cggccagggg ccaaggagct 480 attttggggt ctcgtttgcc cagggagggc ttggctccac cactttcctc ccccagcctt 540 tgggcagcag gtcacccctg ttcaggctct gagggtgccc cctcctggtc ctgtcctcac 600 caccccttcc ccacctcctg ggaaaaaaaa aaaaaaaaaa aaaaaaagct ggtataaagc 660 agagagcctg agggctaaat ttaactgtcc gagtcggaat ccatctctga gtcacccaag 720 aagctgccct ggcctcccgt ccccttccca ggcctcaacc cctttctccc acccagcccc 780 aacccccagc cctcaccccc tagcccccag ttctggagct tgtcgggagc aagggggtgg 840 ttgctactgg gtcactcagc ctcaattggc cctgtttcag caatgggcag gttcttcttg 900 aaattcatca cacctgtggc ttcctctgtg ctctaccttt ttattggggt gacagtgtga 960 cagctgagat tctccatgca ttccccctac tctagcactg aagggttctg aagggccctg 1020 gaaggaggga gcttgggggg ctggcttgtg aggggttaag gctgggaggc gggagggggg 1080 ctggaccaag gggtggggag aaggggagga ggcctcggcc ggccgcagag agaagtggcc 1140 agagaggccc aggggacagc cagggacagg cagacatgca gccagggctc cagggcctgg 1200 acaggggctg ccaggccctg tgacaggagg accccgagcc cccggcccgg ggaggggcca 1260 tggtgctgcc tgtccaacat gtcagccgag gtgcggctga ggcggctcca gcagctggtg 1320 ttggacccgg gcttcctggg gctggagccc ctgctcgacc ttctcctggg cgtccaccag 1380 gagctgggcg cctccgaact ggcccaggac aagtacgtgg ccgacttctt gcagtggggt 1440 gagtgcctac cctcggggct cctgcagatg gggtgggggt ggggcaggag acaggtctgg 1500 gcacagaggc ctggctgttg ggggggcagg atggcaggat gggcatgggg agatcctccc 1560 atcctggggc tcagagtgtg gacctgggcc ctggggcaac atttctctgt cctatgccac 1620 cactctggag gggcagagta aggtcagcag aggctagggt ggctgtgact cagagccatg 1680 gcttaggagt cacagcaggc taggctgcca acagcctccc atggcctctc tgcaccccgc 1740 ctcagggtca gggtcagggt catgctggga gctccctctc ctaggaccct ccccccaaaa 1800 gtgggctcta tggccctctc ccctggtttc ctgtggcctg gggcaagcca ggagggccag 1860 catggggcag ctgccagggg cgcagccgac aggcaggtgt tcggcgccag cctctccagc 1920 tgccccaaca ggtgcccagg cactgggagg gcggtgactc acgcgggccc tgtgggagaa 1980 ccagctttgc agacaggcgc caccagtgcc ccctcctctg cgatccagga gggacaactt 2040 tgggttcttc tgggtgtgtc tccttctttt gtaggttctg cacccacccc cacccccagc 2100 cccaaagtct cggttcctat gagccgtgtg ggtcagccac cattcccgcc accccgggtc 2160 cctgcgtcct ttagttctcc tggcccaggg cctccaacct tccagctgtc ccacaaaacc 2220 ccttcttgca agggctttcc agggcctggg gccagggctg gaaggaggat gcttccgctt 2280 ctgccagctg ccttgtctgc ccacctcctc cccaagccca ggactcgggc tcactggtca 2340 ctggtttctt tcattcccag caccctgccc ctctggccct catatgtctg gccctcagtg 2400 actggtgttt ggtttttggc ctgtgtgtaa caaactgtgt gtgacacttg tttcctgttt 2460 ctccgccttc ccctgcttcc tcttgtgtcc atctctttct gacccaggcc tggttccttt 2520 ccctcctcct cccatttcac agatgggaag gtggaggcca agaagggcca ggccattcag 2580 cctctggaaa aaccttctcc caacctccca cagcccctaa tgactctcct ggcctccctt 2640 tagtagagga tgaagttggg ttggcagggt aaactgagac cgggtggggt aggggtctgg 2700 cgctcccggg aggagcactc cttttgtggc ccgagctgca tctcgcggcc cctcccctgc 2760 caggcctggg gcgggggagg gggccagggt tcctgctgcc ttaaaagggc tcaatgtctt 2820 ggctctctcc tccctccccc gtcctcagcc ctggctggtt cgtccctgct ggcccactct 2880 cccggaaccc cccggaaccc ctctctttcc tccagaaccc actgtctcct ctccttccct 2940 cccctcccat acccatccct ctctccatcc tgcctccact tcttccaccc ccgggagtcc 3000 aggcctccct gtccccacag tccctgagcc acaagcctcc accccagctg gtcccccacc 3060 caggctgccc agtttaacat tcctagtcat aggaccttga cttctgagag gcctgattgt 3120 catctgtaaa taaggggtag gactaaagca ctcctcctgg aggactgaga gatgggctgg 3180 accggagcac ttgagtctgg gatatgtgac catgctacct ttgtctccct gtcctgttcc 3240 ttcccccagc cccaaatcca gggttttcca aagtgtggtt caagaaccac ctgcatctga 3300 atctagaggt actggataca accccacgtc tgggccgtta cccaggacat tctacatgag 3360 aacgtggggg tggggccctg gctgcacctg aactgtcacc tggagtcagg gtggaaggtg 3420 gaagaactgg gtcttatttc cttctcccct tgttctttag ggtctgtcct tctgcagact 3480 ccgttacccc accctaacca tcctgcacac ccttggagcc ctctgggcca atgccctgtc 3540 ccgcaaaggg cttctcaggc atctcacctc tatgggaggg catttttggc ccccagaacc 3600 ttacacggtg tttatgtggg gaagcccctg ggaagcagac agtcctaggg tgaagctgag 3660 aggcagagag aaggggagac agacagaggg tggggctttc ccccttgtct ccagtgccct 3720 ttctggtgac cctcggttct tttcccccac caccccccca gcggagccca tcgtggtgag 3780 gcttaaggag gtccgactgc agagggacga cttcgagatt ctgaaggtga tcggacgcgg 3840 ggcgttcagc gaggtaagcc gaaccgggcg ggagcctgac ttgactcgtg gtgggcgggg 3900 cataggggtt ggggcggggc cttagaaatt gatgaatgac cgagccttag aacctagggc 3960 tgggctggag gcggggcttg ggaccaatgg gcgtggtgtg gcaggtgggg cggggccacg 4020 gctgggtgca gaagcgggtg gagttgggtc tgggcgagcc cttttgtttt cccgccgtct 4080 ccactctgtc tcactatctc gacctcaggt agcggtagtg aagatgaagc agacgggcca 4140 ggtgtatgcc atgaagatca tgaacaagtg ggacatgctg aagaggggcg aggtgagggg 4200 ctgggcggac gtggggggct ttgaggatcc gcgccccgtc tccggctgca gctcctccgg 4260 gtgccctgca ggtgtcgtgc ttccgtgagg agagggacgt gttggtgaat ggggaccggc 4320 ggtggatcac gcagctgcac ttcgccttcc aggatgagaa ctacctggtg agctccgggc 4380 cggggtgact aggaagaggg acaagagccc gtgctgtcac tggacgagga ggtggggaga 4440 ggaagctcta ggattggggg tgctgcccgg aaacgtctgt gggaaagtct gtgtgcggta 4500 agagggtgtg tcaggtggat gaggggcctt ccctatctga gacggggatg gtgtccttca 4560 ctgcccgttt ctggggtgat ctgggggact cttataaaga tgtctctgtt gcggggggtc 4620 tcttacctgg aatgggatag gtcttcagga attctaacgg ggccactgcc tagggaagga 4680 gtgtctggga cctattctct gggtgttggg tggcctctgg gttctctttc ccagaacatc 4740 tcagggggag tgaatctgcc cagtgacatc ccaggaaagt ttttttgttt gtgttttttt 4800 ttgaggggcg ggggcggggg ccgcaggtgg tctctgattt ggcccggcag atctctatgg 4860 ttatctctgg gctggggctg caggtctctg cccaaggatg gggtgtctct gggaggggtt 4920 gtcccagcca tccgtgatgg atcagggcct caggggacta ccaaccaccc atgacgaacc 4980 ccttctcagt acctggtcat ggagtattac gtgggcgggg acctgctgac actgctgagc 5040 aagtttgggg agcggattcc ggccgagatg gcgcgcttct acctggcgga gattgtcatg 5100 gccatagact cggtgcaccg gcttggctac gtgcacaggt gggtgcagca tggccgaggg 5160 gatagcaagc ttgttccctg gccgggttct tggaaggtca gagcccagag aggccagggc 5220 ctggagaggg accttcttgg ttggggccca ccggggggtg cctgggagta ggggtcagaa 5280 ctgtagaagc cctacagggg cggaacccga ggaagtgggg tcccaggtgg cactgcccgg 5340 aggggcggag cctggtggga ccacagaagg gaggttcatt tatcccaccc ttctcttttc 5400 ctccgtgcag ggacatcaaa cccgacaaca tcctgctgga ccgctgtggc cacatccgcc 5460 tggccgactt cggctcttgc ctcaagctgc gggcagatgg aacggtgagc cagtgccctg 5520 gccacagagc aactggggct gctgatgagg gatggaaggc acagagtgtg ggagcgggac 5580 tggatttgga ggggaaaaga ggtggtgtga cccaggctta agtgtgcatc tgtgtggcgg 5640 agtattagac caggcagagg gaggggctaa gcatttgggg agtggttgga aggagggccc 5700 agagctggtg ggcccagagg ggtgggccca agcctcgctc tgctcctttt ggtccaggtg 5760 cggtcgctgg tggctgtggg caccccagac tacctgtccc ccgagatcct gcaggctgtg 5820 ggcggtgggc ctgggacagg cagctacggg cccgagtgtg actggtgggc gctgggtgta 5880 ttcgcctatg aaatgttcta tgggcagacg cccttctacg cggattccac ggcggagacc 5940 tatggcaaga tcgtccacta caaggtgagc acggccgcag ggagacctgg cctctcccgg 6000 taggcgctcc caggctatcg cctcctctcc ctctgagcag gagcacctct ctctgccgct 6060 ggtggacgaa ggggtccctg aggaggctcg agacttcatt cagcggttgc tgtgtccccc 6120 ggagacacgg ctgggccggg gtggagcagg cgacttccgg acacatccct tcttctttgg 6180 cctcgactgg gatggtctcc gggacagcgt gccccccttt acaccggatt tcgaaggtgc 6240 caccgacaca tgcaacttcg acttggtgga ggacgggctc actgccatgg tgagcggggg 6300 cggggtaggt acctgtggcc cctgctcggc tgcgggaacc tccccatgct ccctccataa 6360 agttggagta aggacagtgc ctaccttctg gggtcctgaa tcactcattc cccagagcac 6420 ctgctctgtg cccatctact actgaggacc cagcagtgac ctagacttac agtccagtgg 6480 gggaacacag agcagtcttc agacagtaag gccccagagt gatcagggct gagacaatgg 6540 agtgcagggg gtgggggact cctgactcag caaggaaggt cctggagggc tttctggagt 6600 ggggagctat ctgagctgag acttggaggg atgagaagca ggagaggact cctcctccct 6660 taggccgtct ctcttcaccg tgtaacaagc tgtcatggca tgcttgctcg gctctgggtg 6720 cccttttgct gaacaatact ggggatccag cacggaccag atgagctctg gtccctgccc 6780 tcatccagtt gcagtctaga gaattagaga attatggaga gtgtggcagg tgccctgaag 6840 ggaagcaaca ggatacaaga aaaaatgatg gggccaggca cggtggctca cgcctgtaac 6900 cccagcaatt tggcaggccg aagtgggtgg attgcttgag cccaggagtt cgagaccagc 6960 ctgggcaatg tggtgagacc cccgtctcta caaaaatgtt ttaaaaattg gttgggcgtg 7020 gtggcgcatg cctgtatact cagctactag ggtggccgac gtgggcttga gcccaggagg 7080 tcaaggctgc agtgagctgt gattgtgcca ctgcactcca gcctgggcaa cggagagaga 7140 ctctgtctca aaaataagat aaactgaaat taaaaaatag gctgggctgg ccgggcgtgg 7200 tggctcacgc ctgtaatctc agcactttgg gaggccgagg cgggtggatc acgaggtcag 7260 gagatcgaga ccatcttggc taacacggtg aaaccccatc tctcctaaaa atacaaaaaa 7320 ttagccaggc gtggtggcgg gcgcctgtag tcccagctac tcaggaggct gaggcaggag 7380 aatggcgtga acccgggagg cagagtttgc agtgagccga gatcgtgcca ctgcactcca 7440 gcctgggcga cagagcgaga ctctgtctca gaaaaaaaaa aaaaaaaaaa aaaaaatagg 7500 ctggaccgcg gccgggcgct gtggctcatg cctgtaatcc cagcactttg ggagtccaag 7560 gccggtgggt catgagatca ggagttttga gactaggctg gccaacacgg tgaaaccccg 7620 tctctactaa aaatacaaga aaattagctg ggtgtggtct cgggtgcctg taattccagt 7680 tactggggaa gctgaggcag gagaattgct tgaacctggg aggcagagtt tgcagtgagc 7740 caagatcatg ccactacact ccagtctggg tgacagagtg agactctgtc tcaaaaaaaa 7800 aaaaaaaaaa aagggttggg caaggtggtt cacgcctgta atcccagaac tttgggaggc 7860 tgaggcaggc agatcactgg aagtcaggag ttcaagacca gcctggccaa catggtgaaa 7920 ccctgtgtct actaaaaata caaaatttag ccaggcttgg tggcgtatgc ctgtaatgcc 7980 agctactcag gaggctgagg caggagaatc gcttgattga acctgggagg cagagtttgc 8040 agtgggctgg ggttgtgcca ctgcactcta ggctgggaga cagcaagact ccatctaaaa 8100 aaaaaaaaca gaactgggct gggcacagtg gcttatattt gtaatcccag cactttggga 8160 ggctgaggtt ggaggactgc ttgagcccag agtttgggac tacaacagct gaggtaggcg 8220 gatcacttga ggtcagaaga tggagaccag cctggccagc gtggcgaaac cccgtctcta 8280 ccaaaaatat aaaaaattag ccaggcgtgg tagagggcgc ctgtaatctc agctactcag 8340 gacgctgagg caggagaatc gcctgaacct gggaggcgga ggttgcagtg agctgagatt 8400 gcaccactgc actccagcct gggtaacaga gcgagactcc gtatcaaaga aaaagaaaaa 8460 agaaaaaatg ctggaggggc cactttagat aagccctgag ttggggctgg tttgggggga 8520 acatgtaagc caagatcaaa aagcagtgag gggcccgccc tgacgactgc tgctcacatc 8580 tgtgtgtctt gcgcaggaga cactgtcgga cattcgggaa ggtgcgccgc taggggtcca 8640 cctgcctttt gtgggctact cctactcctg catggccctc aggtaagcac tgccctggac 8700 ggcctccagg ggccacgagg ctgcttgagc ttcctgggtc ctgctccttg gcagccaatg 8760 gagttgcagg atcagtcttg gaaccttact gttttgggcc caaagactcc taagaggcca 8820 gagttggagg accttaaatt ttcagatcta tgtacttcaa aatgttagat tgaattttaa 8880 aacctcagag tcacagactg ggcttcccag aatcttgtaa ccattaactt ttacgtctgt 8940 agtacacaga gccacaggac ttcagaactt ggaaaatatg aagtttagac ttttacaatc 9000 agttgtaaaa gaatgcaaat tctttgaatc agccatataa caataaggcc atttaaaagt 9060 attaatttag gcgggccgcg gtggctcacg cctgtaatcc tagcactttg ggaggccaag 9120 gcaggtggat catgaggtca ggagatcgag accatcctgg ctaacacggt gaaaccccgt 9180 ctctactaaa aatacaaaaa aattagccgg gcatggtggc gggcgcttgc ggtcccagct 9240 acttgggagg cgaggcagga gaatggcatg aacccgggag gcggagcttg cagtgagccg 9300 agatcatgcc actgcactcc agcctgggcg acagagcaag actccgtctc aaaaaaaaaa 9360 aaaaaaaagt atttatttag gccgggtgtg gtggctcacg cctgtaattc cagtgctttg 9420 ggaggatgag gtgggtggat cacctgaggt caggagttcg agaccagcct gaccaacgtg 9480 gagaaacctc atctctacta aaaaacaaaa ttagccaggc gtggtggcat atacctgtaa 9540 tcccagctac tcaggaggct gaggcaggag aatcagaacc caggaggggg aggttgtggt 9600 gagctgagat cgtgccattg cattccagcc tgggcaacaa gagtgaaact tcatctcaaa 9660 aaaaaaaaaa aaaaagtact aatttacagg ctgggcatgg tggctcacgc ttggaatccc 9720 agcactttgg gaggctgaag tggacggatt gcttcagccc aggagttcaa gaccagcctg 9780 agcaacataa tgagaccctg tctctacaaa aaattgaaaa aatcgtgcca ggcatggtgg 9840 tctgtgcctg cagtcctagc tactcaggag tctgaagtag gagaatcact tgagcctgga 9900 gtttgaggct tcagtgagcc atgatagatt ccagcctagg caacaaagtg agacctggtc 9960 tcaacaaaag tattaattac acaaataatg cattgcttat cacaagtaaa ttagaaaata 10020 cagataagga aaaggaagtt gatatctcgt gagctcacca gatggcagtg gtccctggct 10080 cacacgtgta ctgacacatg tttaaatagt ggagaacagg tgtttttttg gtttgttttt 10140 ttccccttcc tcatgctact ttgtctaaga gaacagttgg ttttctagtc agcttttatt 10200 actggacaac attacacata ctatacctta tcattaatga actccagctt gattctgaac 10260 cgctgcgggg cctgaacggt gggtcaggat tgaacccatc ctctattaga acccaggcgc 10320 atgtccagga tagctaggtc ctgagccgtg ttcccacagg agggactgct gggttggagg 10380 ggacagccac ttcatacccc agggaggagc tgtccccttc ccacagctga gtggggtgtg 10440 ctgacctcaa gttgccatct tggggtccca tgcccagtct taggaccaca tctgtggagg 10500 tggccagagc caagcagtct ccccatcagg tcggcctccc tgtcctgagg ccctgagaag 10560 aggggtctgc agcggtcaca tgtcaaggga ggagatgagc tgaccctaga acatgggggt 10620 ctggacccca agtccctgca gaaggtttag aaagagcagc tcccaggggc ccaaggccag 10680 gagaggggca gggcttttcc taagcagagg aggggctatt ggcctacctg ggactctgtt 10740 ctcttcgctc tgctgctccc cttcctcaaa tcaggaggtc ttggaagcag ctgcccctac 10800 ccacaggcca gaagttctgg ttctccacca gagaatcagc attctgtctc cctccccact 10860 ccctcctcct ctccccaggg acagtgaggt cccaggcccc acacccatgg aactggaggc 10920 cgagcagctg cttgagccac acgtgcaagc gcccagcctg gagccctcgg tgtccccaca 10980 ggatgaaaca gtaagttggt ggaggggagg gggtccgtca gggacaattg ggagagaaaa 11040 ggtgagggct tcccgggtgg cgtgcactgt agagccctct agggacttcc tgaacagaag 11100 cagacagaaa ccacggagag acgaggttac ttcagacatg ggacggtctc tgtagttaca 11160 gtggggcatt aagtaagggt gtgtgtgttg ctggggatct gagaagtcga tctttgagct 11220 gagcgctggt gaaggagaaa caagccatgg aaggaaaggt gccaagtggt caggcgagag 11280 cctccagggc aaaggccttg ggcaggtggg aatcctgatt tgttcctgaa aggtagtttg 11340 gctgaatcat tcctgagaag gctggagagg ccagcaggaa acaaaaccca gcaaggcctt 11400 ttgtcgtgag ggcattaggg agctggaggg attttgagca gcagagggac ataggttgtg 11460 ttagtgtttg agcaccagcc ctctggtccc tgtgtagatt tagaggacca gactcaggga 11520 tggggctgag ggaggtaggg aagggagggg gcttggatca ttgcaggagc tatggggatt 11580 ccagaaatgt tgaggggacg gaggagtagg ggataaacaa ggattcctag cctggaacca 11640 gtgcccaagt cctgagtctt ccaggagcca caggcagcct taagcctggt ccccatacac 11700 aggctgaagt ggcagttcca gcggctgtcc ctgcggcaga ggctgaggcc gaggtgacgc 11760 tgcgggagct ccaggaagcc ctggaggagg aggtgctcac ccggcagagc ctgagccggg 11820 agatggaggc catccgcacg gacaaccaga acttcgccag gtcgggatcg gggccggggc 11880 cggggccggg atgcgggccg gtggcaaccc ttggcatccc ctctcgtccg gcccggacgg 11940 actcaccgtc cttacctccc cacagtcaac tacgcgaggc agaggctcgg aaccgggacc 12000 tagaggcaca cgtccggcag ttgcaggagc ggatggagtt gctgcaggca gagggagcca 12060 caggtgagtc cctcatgtgt ccccttcccc ggaggaccgg gaggaggtgg gccgtctgct 12120 ccgcggggcg tgtatagaca cctggaggag ggaagggacc cacgctgggg cacgccgcgc 12180 caccgccctc cttcgcccct ccacgcgccc tatgcctctt tcttctcctt ccagctgtca 12240 cgggggtccc cagtccccgg gccacggatc caccttccca tgtaagaccc ctctctttcc 12300 cctgcctcag acctgctgcc cattctgcag atcccctccc tggctcctgg tctccccgtc 12360 cagatatagg gctcacccta cgtctttgcg actttagagg gcagaagccc tttattcagc 12420 cccagatctc cctccgttca ggcctcacca gattccctcc gggatctccc tagataacct 12480 ccccaacctc gattcccctc gctgtctctc gccccaccgc tgagggctgg gctgggctcc 12540 gatcgggtca cctgtccctt ctctctccag ctagatggcc ccccggccgt ggctgtgggc 12600 cagtgcccgc tggtggggcc aggccccatg caccgccgcc acctgctgct ccctgccagg 12660 gtacgtccgg ctgcccacgc ccccctccgc cgtcgcgccc cgcgctccac ccgccccttg 12720 ccacccgctt agctgcgcat ttgcggggct gggcccacgg caggagggcg gatcttcggg 12780 cagccaatca acacaggccg ctaggaagca gccaatgacg agttcggacg ggattcgagg 12840 cgtgcgagtg gactaacaac agctgtaggc tgttggggcg ggggcggggc gcagggaaga 12900 gtgcgggccc acctatgggc gtaggcgggg cgagtcccag gagccaatca gaggcccatg 12960 ccgggtgttg acctcgccct ctccccgcag gtccctaggc ctggcctatc ggaggcgctt 13020 tccctgctcc tgttcgccgt tgttctgtct cgtgccgccg ccctgggctg cattgggttg 13080 gtggcccacg ccggccaact caccgcagtc tggcgccgcc caggagccgc ccgcgctccc 13140 tgaaccctag aactgtcttc gactccgggg ccccgttgga agactgagtg cccggggcac 13200 ggcacagaag ccgcgcccac cgcctgccag ttcacaaccg ctccgagcgt gggtctccgc 13260 ccagctccag tcctgtgatc cgggcccgcc ccctagcggc cggggaggga ggggccgggt 13320 ccgcggccgg cgaacggggc tcgaagggtc cttgtagccg ggaatgctgc tgctgctgct 13380 gctgctgctg ctgctgctgc tgctgctgct gctgctgctg ctgctggggg gatcacagac 13440 catttctttc tttcggccag gctgaggccc tgacgtggat gggcaaactg caggcctggg 13500 aaggcagcaa gccgggccgt ccgtgttcca tcctccacgc acccccacct atcgttggtt 13560 cgcaaagtgc aaagctttct tgtgcatgac gccctgctct ggggagcgtc tggcgcgatc 13620 tctgcctgct tactcgggaa atttgctttt gccaaacccg ctttttcggg gatcccgcgc 13680 ccccctcctc acttgcgctg ctctcggagc cccagccggc tccgcccgct tcggcggttt 13740 ggatatttat tgacctcgtc ctccgactcg ctgacaggct acaggacccc caacaacccc 13800 aatccacgtt ttggatgcac tgagaccccg acattcctcg gtatttattg tctgtcccca 13860 cctaggaccc ccacccccga ccctcgcgaa taaaaggccc tccatctgcc caaagctctg 13920 gactccacag tgtccgcggt ttgcgttgtg ggccggaggc tccgcagcgg gccaatccgg 13980 aggcgtgtgg aggcggccga aggtctggga ggagctagcg ggatgcgaag cggccgaatc 14040 agggttgggg gaggaaaagc cacggggcgg ggctttggcg tccggccaat aggagggcga 14100 gcgggccacc cggaggcacc gcccccgccc agctgtggcc cagctgtgcc accgagcgtc 14160 gagaagaggg ggctgggctg gcagcgcgcg cggccatcct ccttccactg cgcctgcgca 14220 cgccacgcgc atccgctcct gggacgcaag ctcgagaaaa gttgctgcaa actttctagc 14280 ccgttccccg cccctcctcc cggccagacc cgccccccct gcggagccgg gaattccgag 14340 gggcggagcg caggccgaga tggggaatgt gggggcctgc agaggaccct ggagacggag 14400 gcgtgcagaa g 14411 <210> SEQ ID NO 3 <211> LENGTH: 15000 <212> TYPE: DNA <213> ORGANISM: Mus musculus <400> SEQUENCE: 3 cagtgtcccc actgcccaag gctggctcca tcacgtaccg ctttggctca gctggccagg 60 acacacagtt ctgcctgtgg gacctcacag aagatgtgct ctcccctcat ccgtctctgg 120 cccgtacccg cacccttccg ggcacacctg gtgccacccc accagcttct ggtagttctc 180 gggccggaga gacaggtgca ggccccctgc cccgctccct gtctcgttcc aacagtctcc 240 cacacccagc tggtggtggc aaggctggtg ggcctagtgc atcgatggag cctggcatac 300 cattcagcat tggccgcttt gccacactga ccctgcagga gcggcgggac cggggagctg 360 agaaggaaca caaacgctac catagcctgg gaaacatcag ccgcggtggc agtgggggca 420 atagcagcaa tgacaagctc agtggtcctg ccccccgaag ccgattggac ccagctaagg 480 tgctgggcac ggcactgtgc cctcggatcc atgaggtgcc actgctggag cctctcgtgt 540 gcaagaagat tgctcaggaa cgcctgaccg tgctactgtt cctggaggat tgtatcatca 600 ctgcctgcca agagggcctc atctgcacct gggcccggcc aggcaaggcg gtgagtccgc 660 acctgcccaa gcgctgaggg gcaccagttc tgtccctacc ggatgccagt tatccgtcag 720 cagaaaggtc aggtatagga gacagaatgg ggggaaccac agctaacgtc tttagagcct 780 ctgctggccc atatggctca tccttagtac ttcacactca aggcagaacc tgtgtttata 840 ggaaatctga agtgtagatg gtgaaacttt attcaggtct agggatgtga ttgagctggg 900 ggcccacttc tggcctgcct cttagacact gtttctgagc cagctgctga aggcctggat 960 gggaattagc cagggtccag gcctgcactt cctcttgctg ctgtgtggtc ctggtcattg 1020 ggtctcacag atgggctgtg cagtggctgt gctcttagtt ggtgaggtgc aggcctgtca 1080 cctggtcagg cttgagcatg tggtctcagt gtctaggacc ctactctgcc ctcagtcctt 1140 cagtcccttg ctttggaagg ctagagtcca gaagccttag aacgtcaggc agttgcagag 1200 ccactgccag gctagtaggg ctgcgggagt tgactgagtt ctcacagaca cccctctgtc 1260 tccctagttc acagacgagg agaccgaggc ccaggcaggg caagcaagtt ggcccaggtc 1320 acccagcaag tcagttgtag aggtaggaca acccctgaag ctgcaagtgg accccagttt 1380 cttttctctc cactgtcgtc ccctgtatgc ccaggacacc tggggccaca ttactgtgga 1440 agtgctactc tgggtcagtg gagacggccg agctgtttgt tcctagctag gacagcagct 1500 ttaggcctgg ggggcagatc ccagctgggg cagcagctcc aaggcctttg ggtggctcct 1560 tctccgggtt ctggcagaag cccaggtgct gtctaatcca cctttctcct cttgttctcc 1620 ccagggcatc tcctcccaac caggcagctc ccccagtggc actgtggtgt gaaatgtgga 1680 tgtcccatgt tcccggcctc ctagccataa ccctccccgc tgacctcaag aatcactgta 1740 ttaacaagac taatcatgat ggaaggactg ctccaagccc cacgctgcac acatactggg 1800 ggtcccctag gttggcccag ccatggggat gtagtgtcct gtgtggcctt ggccctgtcc 1860 tccacccact gccaagtaca atgacctgtt ctctgaaaca tcagtgttaa ccatatccct 1920 gtcccagcat gtgactgttc actcctggga gagacttagc ccacagtacc cctgggtgag 1980 agggcagggc aggggccatc cccactcctg cccaaactcc accccttgct atggtctgtg 2040 attttgaaag tgttaaatta tggaagccct gagggccctc cttgttcccc tggacctctt 2100 atttatacta aagtccttgt ttgcacagtg tttctgttcc ctggggcagg gtagggtggg 2160 ggttgcagta cttggcctcc aagctgtgct ctgaccaaag gaagcccaat cttagctgtt 2220 tccccatccc tagccccgag cagagagccc tctgaaagat gagtctcgac ccccaaagtc 2280 aagaggctga gatggccttc ctactaggtc cttggagatg tttgaaactt gttttaaaca 2340 ccaggactat ccaagcatgc tctccttggg gagaggagga tgctggaatt gactgcactc 2400 cctgcctcct ctgaacatgc ctttgcagtc tgctgcccct ggcccattta tgactggcca 2460 tctagtgcca gctggaggtc atgatttcct ccccagagaa ctggccaccc tagaaagaag 2520 ctaacttgtc gcctggcttg ctgtccaggc agctccgccc tcaaccccta aaatgtttct 2580 gtctctaatc ctagcccagg caggaatgtg gctgccccgg cctgtggcca aggagctatt 2640 ttggggttct cttttgctta aggagggcct ggatccacca cttgcctccc ccaggctggg 2700 gccagcaggt cacccctggc cctggcggct gagcaaactc tctcctgatc ttccttctac 2760 ctcctgccaa aaaatggggg ggcgggtaat acagcaggca caggggctaa atttaactgt 2820 cccaaagtcg gaatccattg ctgagtcacg aagaagctgc ccctggcctt tgcccccccc 2880 actaccccct caccccctgt tgcccaggca tcagcccttt cccccaaccc ctcccagctc 2940 tgagtctata gactggctct cctgggcact gacacctccc acctgtaact ccctgtgctc 3000 tctttatggg tgggtagagt caatgggggg gggcaaccct ggagtattac tctgtcccct 3060 gacattgggc tctgaagagt tttgaggggc cctggaagaa gggagttggg gtgttggctc 3120 aggaggggtt aaaaactggg aggcgggagg ggggctgggc caaggggtgg agaaaagagg 3180 aggaggcctt aagcatagaa ctggccagag agacccaagg gatagtcagg gacgggcaga 3240 catgcagcta gggttctggg gcctggacag gggcagccag gccctgtgac gggaagaccc 3300 cgagctccgg cccggggagg ggccatggtg ttgcctgccc aacatgtcag ccgaagtgcg 3360 gctgaggcag ctccagcagc tggtgctgga cccaggcttc ctgggactgg agcccctgct 3420 cgaccttctc ctgggcgtcc accaggagct gggtgcctct cacctagccc aggacaagta 3480 tgtggccgac ttcttgcagt ggggtgagta tggataggaa gcctggggtt gggtgcaagg 3540 cagaggtggg tctacagggc aagaatgggc tatggagggg caggagggcc tggaaagggc 3600 tttttgtaag ggagccaagc agagctcatg acctgacccc aagctcccct ggtgaggcac 3660 cagggtcagt gaggccacct atgactcagc cagtgcaggc tggggtgggc atagcctcct 3720 gctatctcag cacccacact aggacctggc agctttctct tttaggaccc ttggctcctc 3780 aaactggctt catagccctc cccagtttcc cagagtgtgg ggagggacag cgtggggcag 3840 ctgccagggt gtggcccata ggcaggtgtt tggcgtctgc ctccccagct gccctgacag 3900 gtgtccagga gctatgaggg cactgtgact cacagaggcc ctgggggaga accagcccgg 3960 cagacaggcg ccaccgagca ccctttctgt tccccaaatt aagaggaagg aacaacttca 4020 gcttctgagt gtgcccatcc ctagcactct gatcccgccc agcctttgtg ggccagattg 4080 gtcatccctc ctggcttctc atctgctttt gtggttctag ctcaagacct ctaattcctc 4140 tgctgactta aatgcccttc cccagaggtc ttctcaggcc tagtggacaa gcttggagcc 4200 ttatctgctc ctgcccaaca ttgagccaaa gctccagctt accccagctt ccttacaagt 4260 aacgacctgt tttgttgctc tgtgcctatt attaagggtc caggtcttga ttcttggctg 4320 tctgcccatg tgtgtgaccc tagtgcattc tcccctcctc ccccgtttca cagatggaaa 4380 ggttgaggcc atcggttaga ctgctaagcc tgtgaaagac tttttctcct ctccagtctt 4440 tagtgtctcc ctcaaccttt cttttgaagg atggggtttg ggctggcagg gtaaactgag 4500 aactggggtg ggggcagggg gtctgaccct ctgggaagga gcagtccttt tgtggcctga 4560 gcagcatcct gtgggcccct cccctgccag gcctgggcgg gggagggggc ctgggttccc 4620 gctgccttaa aagggctcaa cgccttggct ctctcctcct ccccaccccc cagccttggc 4680 cctagctgta tcttccccgg ctgcccactt tcccaaaccc ctttcttctc tgtgacccca 4740 tctccccgct tccccacacg tccctcctcc atccttactc cccggcctta gaacttccct 4800 aagggagatc tgacctccct ctgcccaccc cgcaccccca gtcgccagcc tcagacctag 4860 ctgctctccc ctctggctga accaccctag cacaggacct tataccctgg agctttggtt 4920 ataagaagac tctccttcac cctttggaaa ccaagaaagc ccttccaaca gtgtccagga 4980 tgctggaggg cagtgaccct cccccacttc ttcttcgtgc tggctgtgct gacacagctc 5040 cagttcgagg ttgtggcccg agacattaag tgagagcccc gggtgacctg acttagcacc 5100 ctgatcatca catgggagtg aaaggcctga tgcgccagct tctcccactg cctccctttc 5160 tgccctgcaa ccctgtggaa acaggcagtt ctgggtccca caaacatcac agaggttttg 5220 aaagcagaat cctaaagccg atttaagggg cagaaggaag gaggctataa agtcactacc 5280 cttaccgcta gtgttctgat gacccttggt tcttcttccc ccacccccgc ccagtggagc 5340 ccattgcagc aaggcttaag gaggtccgac tgcagaggga tgattttgag attttgaagg 5400 tgatcgggcg tggggcgttc agcgaggtga gtcttcagtg gcctgggaat ggaactttac 5460 ttgatgtggg tggggcataa cagctggggc agagccttaa aaattgatga atgagcttga 5520 atttaaggct ggaggggtgg gggcggagct tgtggtcagt gggcggtgtg cacgtgaggg 5580 cggggctaag gttgggtgga gataagggtg gagtcctgtc tgggtgagcc ttgctggttt 5640 tccctgccac ctcttgctgt catctcggtt ccgtatttag gtagcggtgg tgaagatgaa 5700 acagacgggc caagtgtatg ccatgaagat tatgaataag tgggacatgc tgaagagagg 5760 cgaggtgagg gccagggatt agggcagcgc cctcatctct ccaactcacc tcctgtagct 5820 tctctcctac ctcacaggtg tcgtgcttcc gggaagaaag ggatgtatta gtgaaagggg 5880 accggcgctg gatcacacag ctgcactttg ccttccagga tgagaactac ctggtaagct 5940 ccgggttcag gtgactagga aagagtgaca gttacatcgc cccaagtcaa gaaggctgga 6000 gaagggagaa gctgctgtag atcggggggg tgggggtggg ggggacacac acaggggatg 6060 ggggacgggg gtaggattgt gtctcaagta taggagagac cttccttgag acaggagtga 6120 tatctggttt ggcctttgga tggggcgctc tctcactgtg cgggggtcct ctgtgcttgg 6180 gaacggggtg tctttgggag tcttgggggc taccaaaccc ctgtgacaca cccgctccca 6240 gtacctggtc atggaatact acgtgggcgg ggacctgcta acgctgctga gcaagtttgg 6300 ggagcggatc cccgccgaga tggctcgctt ctacctggcc gagattgtca tggccataga 6360 ctccgtgcac cggctgggct acgtgcacag gtgggcgtgg cggggccctt ggagggttag 6420 cagaatttgt gtgggaagga agggtacctg aaggtcagat cccattgggg acagaatcgg 6480 ggtctagaat tgtagaatcc tgggtggggt ggaagtggat cgagctgacg ggccctaaga 6540 gggaaggttt tcaagaaagc acactttccc tcttctctct atgcacaggg acatcaaacc 6600 agataacatt ctgctggacc gatgtgggca cattcgcctg gcagacttcg gctcctgcct 6660 caaactgcag cctgatggaa tggtaagaag agcctggcga aactctcctc attggtgaag 6720 gaccggatta gggggcgggg ctgggttgag gagcaggagg ggagcttggt ctgggatgtc 6780 ctgcgcacca tatttggaca gtcaagggaa aggttttaag cattcaggtc tgattggcac 6840 aggtgaggtc gctggtggct gtgggcaccc cggactacct gtctcctgag attctgcagg 6900 ccgttggtgg agggcctggg gcaggcagct acgggccaga gtgtgactgg tgggcactgg 6960 gcgtgttcgc ctatgagatg ttctatgggc agaccccctt ctacgcggac tccacagccg 7020 agacatatgc caagattgtg cactacaggg tgagcacaag caccatgcag gggggctgac 7080 ttagtggctt gtgctcccag actgtctttt ttaaaagata tttatttata tgtgtgtgtt 7140 ttctgtgtat gtatatctgt gcactgagta ggtgtgcgaa ggtcagaggg catgggatcc 7200 cctggaactg gagtcacaga ctattgtgtg ctgccatgct gagtgctggg aaacagaacc 7260 ttgatcactc tgcaagagca gccagtgcac tgaaacgaca gagccagctc tgcagcccag 7320 ggctaactgt tgcttttctt tctaaatagg aacacttgtc gctgccgctg gcagacacag 7380 ttgtccccga ggaagctcag gacctcattc gtgggctgct gtgtcctgct gagataaggc 7440 taggtcgagg tggggcaggt gatttccaga aacatccttt cttctttggc cttgattggg 7500 agggtctccg agacagtgta ccccccttta caccagactt cgagggtgcc acggacacat 7560 gcaatttcga tgtggtggag gaccggctca ctgccatggt gagcgggggc ggggtacgta 7620 cctgcagttc ctgatccgtt gaggggactt ccctagcctc ttccataaaa ttggggtgat 7680 tggccaggtg tggtggtgca tacctttaat cgtagaactt cataggcaga ggcaggtggc 7740 tctctggtaa atcaaggcca tcttggtcta catagtgact tctaggccag tcaggagtga 7800 gatcctccct tgaaaaataa aaaagggggt gttgaccttc ctgggtccca aattattatc 7860 ctagagcact gctatgtatc cactcaggta tgaggacaca caggtgacca gtcccaaaga 7920 cagtgagtga ggcctcactc ttggcagtac taaaattgat tgtagggggc tgggctcttg 7980 acccagcctg gaaagtgctg gagggcttcc tggaggagga gactagctga gcccagaagg 8040 atgcaggaga tcctttctcg ggtgagtgct ctcagcattt taacaagctc taggccctgc 8100 agagagaagt ctggtgtggg cagagcccca atagaaagca acaagataga agagaaaatg 8160 gtggagtttg ttagtggggg cagttatgcc gtgaacatag aggggcgaag ggccatctcg 8220 gataactgct agccacaaga gccctgtctg tcttcctagg agacgctgtc agacatgcag 8280 gaagacatgc cccttggggt gcgcctgccc ttcgtgggct actcctactg ctgcatggcc 8340 ttcaggtgag cacgactgcc ccctgctggg gcctgtgtgc aggcccacca cagccactca 8400 attgaaggct cagtcttcaa accaagtatt cctaggagct gtctaagtta ggctttctgc 8460 tgctgcgatg aaccctgact aaaagcaagc tggggaggaa aaggcttatc gggcttacgt 8520 ttccacatgg gagcccatca ctgaaggaag ccaggacagg aactcacagc ggggcaggaa 8580 cgtggagctg atgcagaggc aatggagggg agctgcttac tgacttgatc cttatgtctt 8640 cctcagcctg tttccttgta gagcccagga ccaccaggcc agtgagggct ccactcacaa 8700 tgggctgagc tctcatctat gatcactagt tatgaaaatg cccgataggc ttgcctgcag 8760 cttcagtttt tgaggcactt tccttccttc cttccttcct tccttccttc cttccttcct 8820 ttctttcttt ctttctttct ttctttcttt ctttctttct ttctttcttt ctttctttct 8880 tagtctttta gagacagggt ctttctatgt agctctggct gtcttggaat tcattctgta 8940 gaccaggctg gtcttattta tttattttat gtatgtgagt ccactatcac tgtcctcaga 9000 cacaccagaa gagggcatca gatcccatta cagatggctg tgagccacca tgtggttgct 9060 gggaattgaa ctcaggacct ctggaagagc agccagtgct cctgccctgt agaggcattt 9120 tcttcatgaa ggctgtctcc tctctgatga cttgatgact ctagcttgtt gtgtcaagtg 9180 gacataagac taggaaagca gctacacatg cactttgttt atttttgttt tgctttttga 9240 gactgggtct ctccatctca tagctctggc catcctgcct ggtgacattc cagtccagtt 9300 gtataaccta agaatctgag actcagcctt gcagaatcct gctattaacg ggtctaggac 9360 actccataga atccaggatc ttagaaaaac aaacctgaag tgtgacagtt tattttaaga 9420 acacaattgg agcacataac aataatacaa cttttcagtt ttaaaaagtt ttctgtcttg 9480 ttttttgagg caggagctcc ttaatatagt ctaagccgcc ctgcgagtgc tgtgattgat 9540 gggcatgtac caccatgcct agtcaataaa gcctttaaaa agcatccgtt atgctggctg 9600 tggtgccaca aacctgtaat cccagcactt agaaggtaga ggcaagatta tcagaaattc 9660 aaggccatcc tgggctatac agtaatctaa ggctagcctg gtctacaaga gactctgtct 9720 aaagaaacaa aagataaata gcacccacta ttgctaggca atataaccct ataaccccac 9780 cattgaggag gctgaggctg gagcatcact gcaaatttga ggccaggatg gtcaacaaat 9840 aagtcccaga gctggcatag aggaactctg tctcaacaat aaagagaact tatctagcat 9900 ttatgagggt aaataaaaat ttaccattgc cacaaaaaat gtaaatgaag agactgcttt 9960 taggagtgaa ctgggaagca gggaacactt agaggatgct cactcacaca ggtatccacc 10020 atcaggcatg cctcaggcct gcacagggaa ggacaacttg tttcatgatt tgcaagcagc 10080 atcccatgct ccttagagcg ggttgggccc agcccaccct ctgtggagtt atcgctcagc 10140 caggcagcaa ggcagccaag gtgctgaggc cctggcagtc tgctctcttc tctgctctga 10200 acctccttta gctttagcct aggagcctgg cctggtgccc acaggctagg gagtccctag 10260 cctcttcctc ttctcagaga caatcaggtc ccggacccca cccctatgga actagaggcc 10320 ctgcagttgc ctgtgtcaga cttgcaaggg cttgacttgc agcccccagt gtccccaccg 10380 gatcaagtgg tgagtagact gagaggtggg caaagcttcc tgggtgggtg tacctgcagt 10440 gccaactgcc aggctgttaa ttcagtagga cactgtcccc aactggccca actgcacatc 10500 ctgtagtcag gaggcacagg cagaaaaatc ccaaattcaa ggcttgctcc cgttatgtaa 10560 tgagatcctg tcttggagta aaaaacaaag aagagaacta gggatagctc agaggtagat 10620 gctctcctgg catgggggtg gggtcagaaa gcaacaccaa ccggggcctg ggagggaggg 10680 actgccaacc acctggagga gtctggggta gacttggtga acaaagttca gaggccatca 10740 ggtgggatgc tggtttctta aaagccacag ataggtgggt agcattggaa agaggagtgg 10800 ggggttgcag aaagtgacaa gacacaaact ggggaggcct aagggtaaag ccagggttgt 10860 ctgaagcact gtggagctgg gaggaacacg ctaaacttct gacttcagcc cttcagttcc 10920 cctgttgact acactgtccc cagggaccca gggatgggga gaggtggacg ggggagggaa 10980 gtacgggact gatccagctc caggtcccaa ctctgatccc caccgacagg ctgaagaggc 11040 tgacctagtg gctgtccctg cccctgtggc tgaggcagag accacggtaa cgctgcagca 11100 gctccaggaa gccctggaag aagaggttct cacccggcag agcctgagcc gcgagctgga 11160 ggccatccgg accgccaacc agaacttctc caggtcaggg tcacagtgct ggggtgaggg 11220 gagaggagag cagcaaccct cgcagtctcc tcaccgatag gtcggctcac tcccctatct 11280 ttcccagcca actacaggag gccgaggtcc gaaaccgaga cctggaggcg catgttcggc 11340 agctacagga acggatggag atgctgcagg ccccaggagc cgcaggcgag tccctcacct 11400 gcttccagcc aagggggcac tgggtggaga tggggggcat gttgggtgtg tgaaccctcg 11460 gggcagggga ggagtccagg ctggggcacc gcagccgcgc cactgccttt ctcctccatc 11520 ctccacactc catacacctc tctcttctcc ttccagccat cacgggggtc cccagtcccc 11580 gggccacgga tccaccttcc catgtaagac ccctctctcc cctccccgat ccccatctta 11640 gatatgctac ccacagccct tctcccgtcc acgtttaggg tccattctcc ttgggggttc 11700 cagaagaaag ctgcccttca ctcatccatt cagcatgcac tatctaccag ctctccctcg 11760 tttcaggctt ctcgccaaat cctccccaag ggaactccct atactcccgt tctggcctcg 11820 actagattcc cgcactgcct ctcgccctgc tgctgggctc cgatcgggtc acctgtccct 11880 tctctctcca gctagatggc cccccggccg tggctgtggg ccagtgcccg ctggtggggc 11940 caggccccat gcaccgccgt cacctgctgc tccctgccag ggtatgtccc acgtccgccc 12000 accacgggcc tctgcctagc tctgcccact gagtgtcacc actgcttgct gtgcctctgt 12060 ggagctcggc ccaccgcagg gagggggggt attcgggcgg ccaatcaaca caggctgctg 12120 ctaagtagcc aatgacgagt tccaacagga gctctttctt gcgagcagac caactttagc 12180 tgcgggctgt ggggaccaga gatgcgctca gaggcccatc tatgggtata ggctgggcgg 12240 ctcccaggag ccagtgggcc cctgtagcct agtgctaatc caaccttctc tcctgcagat 12300 ccctaggcct ggcctatccg aggcgcgttg cctgctcctg ttcgccgctg ctctggctgc 12360 tgccgccaca ctgggctgca ctgggttggt ggcctatacc ggcggtctca ccccagtctg 12420 gtgtttcccg ggagccacct tcgccccctg aaccctaaga ctccaagcca tctttcattt 12480 aggcctccta ggaaggtcga gcgaccaggg agcgacccaa agcgtctctg tgcccatcgc 12540 gccccccccc cccccccacc gctccgctcc acacttctgt gagcctgggt ccccacccag 12600 ctccgctcct gtgatccagg cctgccacct ggcggccggg gagggaggaa cagggctcgt 12660 gcccagcacc cctggttcct gcagagctgg tagccaccgc tgctgcagca gctgggcatt 12720 cgccgacctt gctttactca gccccgacgt ggatgggcaa actgctcagc tcatccgatt 12780 tcactttttc actctcccag ccatcagtta caagccataa gcatgagccc cctatttcca 12840 gggacatccc attcccatag tgatggatca gcaagacctc tgccagcaca cacggagtct 12900 ttggcttcgg acagcctcac tcctgggggt tgctgcaact ccttccccgt gtacacgtct 12960 gcactctaac aacggagcca cagctgcact cccccctccc ccaaagcagt gtgggtattt 13020 attgatcttg ttatctgact cactgacaga ctccgggacc cacgttttag atgcattgag 13080 actcgacatt cctcggtatt tattgtctgt ccccacctac gacctccact cccgaccctt 13140 gcgaataaaa tacttctggt ctgccctaaa tcccgcgcaa tatctctgtt gtggaaagga 13200 aaccgccccg caggccaatg gagagtccaa tagagacaac caatggcttg agtgggagct 13260 agaggggagg caaagcgcac gaatcaggtt gaagggtggg gcttaggcat ccagccagta 13320 ggagagaagc aacaagccac cagagacacc accgcccccc accctccccc ccagctgtga 13380 cccagctgtg ccactcaagt ttggaaaaaa gtagggggtt gggccagcag cgggcacacc 13440 atcttcccac tgcgcctgcg caagccacgc gcatccgctt tttggaccga cactccagaa 13500 aagttgctgc aaactttcta gcgcgattcc ccgcccctcc tcccagctag atccaccgcc 13560 tacccgcggg gccgggaatt ccgaggggcg gagcacggcg cggagatggg aagggagggg 13620 gcccttcaag ggacccggga gatgggagcg gcttcgcgcc cttaaccctc cggacggccc 13680 attaccttct ccgttgctct gatagggaaa ctgaggccct gagtcagagg cacacaaggg 13740 gggaaggcca aaagcgcggc cagagacgga gggaaaacaa agaatcctga cagcccggga 13800 ggggggcgga cacacaggga caaggacaga cccgagtgca gagctgggtc tagtctttgg 13860 gagggggcca gaagactgca aggggaccgg gggggggggc ggcgaggagg actgggcgga 13920 ggagggggct ggggaagccc gcgggaggcg gcaaaggagg gaggaacttt ccaaagttgc 13980 caaacatggc tacctcgcct gcggagccga gcgcggggcc cgcggctcgg ggggaggcgg 14040 cggcggcgac cgaggagcag gaggaggaag cgcgccagct tctgcagact ctgcaggcag 14100 ccgaggggga ggcggcggcg gccggggcgg gagatgcggc ggcggcggcg gactctgggt 14160 ccccgagtgg cccggggtct ccccgggaga ccgtgaccga ggtgcccact ggccttcgct 14220 tctcgcccga acaggtggca tgcgtgtgcg aggcgctgct gcaggcgggc cacgccggcc 14280 gcttgagccg cttcctgggc gcgctgcccc cggccgagcg cctacgtggc agcgatccgg 14340 tgctgcgcgc gcgggcccta gtggccttcc agcggggtga atacgccgag ctctaccaac 14400 ttctcgagag ccgccctttc cccgccgccc accacgcctt cctgcaggac ctctacctgc 14460 gcgcgcgcta ccacgaggcc gagcgggccc gtggccgtgc gctgggcgct gtggacaaat 14520 accggctgcg caagaagttc cctctgccca agaccatctg ggatggcgag gagaccgtct 14580 attgcttcaa ggagcgctcg cgagcggcgc tcaaggcctg ctaccgcggc aaccgctatc 14640 ccacgcctga cgagaagcgc cgcctggcca cgctcaccgg cctctcgctt acacaggtca 14700 gcaactggtt caagaaccgg cgacagcgcg accgcactgg gaccggcggt ggagcgcctt 14760 gcaaaaggtg aggggggaac cgaccctcct tcctcggtgg ccgctggagt ctgcgcaagt 14820 gacccttcac atccctcttc ggtggcgtcg gcgagtgcat aggctgagcg tggagagacc 14880 aggcacaccc tgggttctct gggcatcact gcctcagggg cagaggttgt tccagctact 14940 tctaagctgg gaacgcagtg ccaggaatgg gggggggggc gggggcggga cgggcagtga 15000 <210> SEQ ID NO 4 <211> LENGTH: 1896 <212> TYPE: DNA <213> ORGANISM: Mus musculus <400> SEQUENCE: 4 atgtcagccg aagtgcggct gaggcagctc cagcagctgg tgctggaccc aggcttcctg 60 ggactggagc ccctgctcga ccttctcctg ggcgtccacc aggagctggg tgcctctcac 120 ctagcccagg acaagtatgt ggccgacttc ttgcagtggg tggagcccat tgcagcaagg 180 cttaaggagg tccgactgca gagggatgat tttgagattt tgaaggtgat cgggcgtggg 240 gcgttcagcg aggtagcggt ggtgaagatg aaacagacgg gccaagtgta tgccatgaag 300 attatgaata agtgggacat gctgaagaga ggcgaggtgt cgtgcttccg ggaagaaagg 360 gatgtattag tgaaagggga ccggcgctgg atcacacagc tgcactttgc cttccaggat 420 gagaactacc tgtacctggt catggaatac tacgtgggcg gggacctgct aacgctgctg 480 agcaagtttg gggagcggat ccccgccgag atggctcgct tctacctggc cgagattgtc 540 atggccatag actccgtgca ccggctgggc tacgtgcaca gggacatcaa accagataac 600 attctgctgg accgatgtgg gcacattcgc ctggcagact tcggctcctg cctcaaactg 660 cagcctgatg gaatggtgag gtcgctggtg gctgtgggca ccccggacta cctgtctcct 720 gagattctgc aggccgttgg tggagggcct ggggcaggca gctacgggcc agagtgtgac 780 tggtgggcac tgggcgtgtt cgcctatgag atgttctatg ggcagacccc cttctacgcg 840 gactccacag ccgagacata tgccaagatt gtgcactaca gggaacactt gtcgctgccg 900 ctggcagaca cagttgtccc cgaggaagct caggacctca ttcgtgggct gctgtgtcct 960 gctgagataa ggctaggtcg aggtggggca ggtgatttcc agaaacatcc tttcttcttt 1020 ggccttgatt gggagggtct ccgagacagt gtacccccct ttacaccaga cttcgagggt 1080 gccacggaca catgcaattt cgatgtggtg gaggaccggc tcactgccat ggtgagcggg 1140 ggcggggaga cgctgtcaga catgcaggaa gacatgcccc ttggggtgcg cctgcccttc 1200 gtgggctact cctactgctg catggccttc agagacaatc aggtcccgga ccccacccct 1260 atggaactag aggccctgca gttgcctgtg tcagacttgc aagggcttga cttgcagccc 1320 ccagtgtccc caccggatca agtggctgaa gaggccgacc tagtggctgt ccctgcccct 1380 gtggctgagg cagagaccac ggtaacgctg cagcagctcc aggaagccct ggaagaagag 1440 gttctcaccc ggcagagcct gagccgcgag ctggaggcca tccggaccgc caaccagaac 1500 ttctccagcc aactacagga ggccgaggtc cgaaaccgag acctggaggc gcatgttcgg 1560 cagctacagg aacggatgga gatgctgcag gccccaggag ccgcagccat cacgggggtc 1620 cccagtcccc gggccacgga tccaccttcc catctagatg gccccccggc cgtggctgtg 1680 ggccagtgcc cgctggtggg gccaggcccc atgcaccgcc gtcacctgct gctccctgcc 1740 aggatcccta ggcctggcct atccgaggcg cgttgcctgc tcctgttcgc cgctgctctg 1800 gctgctgccg ccacactggg ctgcactggg ttggtggcct ataccggcgg tctcacccca 1860 gtctggtgtt tcccgggagc caccttcgcc ccctga 1896 <210> SEQ ID NO 5 <211> LENGTH: 771 <212> TYPE: DNA <213> ORGANISM: Mus musculus <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (89)..(89) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (238)..(238) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (506)..(506) <223> OTHER INFORMATION: n is a, c, g, or t <400> SEQUENCE: 5 cctgcccctg tggctgaggc agagaccacg gtaacgctgc agcagctcca ggaagccctg 60 gaagaagagg ttctcacccg gcagagctng agccgcgagc tggaggccat ccggaccgcc 120 aaccagaact tctccagcca actacaggag gccgaggtcc gaaaccgaga cctggaggcg 180 catgttcggc agctacagga acggatggag atgctgcagg ccccaggagc cgccggantc 240 cctcacctgc ttccagccaa gggggcactg ggtggagatg gggggcatgt tgggtgtgtg 300 aaccctcggg gcaggggagg agtccaggct ggggcaccgc gccgcgccac tgcctttctc 360 ctccatcctc cacactccat acacctctct cttctccttc cagccatcac gggggtccca 420 gtccccgggc cacggatcca ccttcccatc tagatggccc cccggcggtg gctgtgggcc 480 agtgcccgct ggtggggcca ggacantgtc accgccgtca cctgctgctc cctgccagga 540 ttcctaggcc tggctatccg aggcgcgttg ctgctcctgt tcgccgctgc tctggctgct 600 gcgccacact gggctgcact gggttggttg gctataccgg cggtcttcac ccagtctggt 660 gtttcccgtg agcacccttc gcccctgaaa cctaagactt caagccatct ttcatttagg 720 ccttctagga aggtcgagcg acaggggagc gacccaaagc gtctctgtgc c 771 <210> SEQ ID NO 6 <211> LENGTH: 434 <212> TYPE: DNA <213> ORGANISM: Mus musculus <400> SEQUENCE: 6 gagagaccca aggggtagtc agggacgggc agacatgcag ctagggttct ggggcctgga 60 caggggcagc caggccctgt gacgggaaga ccccgagctc cggcccgggg aggggccatg 120 gtgttgcctg cccaacatgt cagccgaagt gcggctgagg cagctccagc agctggtgct 180 ggacccaggc ttcctgggac tggagcccct gctcgacctt ctcctgggcg tccaccagga 240 gctgggtgcc tctcacctag cccaggacaa gtatgtggcc gacttcttgc agtgggtgga 300 gcccattgca gcaaggctta aggaggtccg actgcagagg gatgattttg agattttgaa 360 ggtgatcggg cgtggggcgt tcagcgaggt agcggtggtg aagatgaaac acacggagtc 420 tttggcttcg gaca 434 <210> SEQ ID NO 7 <211> LENGTH: 2688 <212> TYPE: DNA <213> ORGANISM: Mus musculus <400> SEQUENCE: 7 ccacgcgtcc gcccacgcgt ccggggcaga catgcagcta gggttctggg gcctggacag 60 gggcagccag gccctgtgac gggaagaccc cgagctccgg cccggggagg ggccatggtg 120 ttgcctgccc aacatgtcag ccgaagtgcg gctgaggcag ctccagcagc tggtgctgga 180 cccaggcttc ctgggactgg agcccctgct cgaccttctc ctgggcgtcc accaggagct 240 gggtgcctct cacctagccc aggacaagta tgtggccgac ttcttgcagt gggtggagcc 300 cattgcagca aggcttaagg aggtccgact gcagagggat gattttgaga ttttgaaggt 360 gatcgggcgt ggggcgttca gcgaggtagc ggtggtgaag atgaaacaga cgggccaagt 420 gtatgccatg aagattatga ataagtggga catgctgaag agaggcgagg tgtcgtgctt 480 ccgggaagaa agggatgtat tagtgaaagg ggaccggcgc tggatcacac agctgcactt 540 tgccttccag gatgagaact acctgtacct ggtcatggaa tactacgtgg gcggggacct 600 gctaacgctg ctgagcaagt ttggggagcg gatccccgcc gagatggctc gcttctacct 660 ggccgagatt gtcatggcca tagactccgt gcaccggctg ggctacgtgc acagggacat 720 caaaccagat aacattctgc tggaccgatg tgggcacatt cgcctggcag acttcggctc 780 ctgcctcaaa ctgcagcctg atggaatggt gaggtcgctg gtggctgtgg gcaccccgga 840 ctacctgtct cctgagattc tgcaggccgt tggtggaggg cctggggcag gcagctacgg 900 gccagagtgt gactggtggg cactgggcgt gttcacctat gagatgttct atgggcagac 960 ccccttctac gcggactcca cagccgagac atatgccaag attgtgcact acagggaaca 1020 cttgtcgctg ccgctggcag acacagttgt ccccgaggaa gctcaggacc tcattcgtgg 1080 gctgctgtgt cctgctgaga taaggctagg tcgaggtggg gcaggtgatt tccagaaaca 1140 tcctttcttc tttggccttg attgggaggg tctccgagac agtgtacccc cctttacacc 1200 agacttcgag ggtgccacgg acacatgcaa tttcgatgtg gtggaggacc ggctcactgc 1260 catggtgagc gggggcgggg agacgctgtc agacatgcag gaagacatgc cccttggggt 1320 gcgcctgccc ttcgtgggct actcctactg ctgcatggcc ttcagagaca atcaggtccc 1380 ggaccccacc cctatggaac tagaggccct gcagttgcct gtgtcagact tgcaagggct 1440 tgacttgcag cccccagtgt ccccaccgga tcaagtggct gaagaggctg acctagtggc 1500 tgtccctgcc cctgtggctg aggcagagac cacggtaacg ctgcagcagc tccaggaagc 1560 cctggaagaa gaggttctca cccggcagag cctgagccgc gagctggagg ccatccggac 1620 cgccaaccag aacttctcca gccaactaca ggaggccgag gtccgaaacc gagacctgga 1680 ggcgcatgtt cggcagctac aggaacggat ggagatgctg caggccccag gagccgcaga 1740 tccctaggcc tggcctatcc gaggcgcgtt gcctgctcct gttcgccgct gctctggctg 1800 ctgccgccac actgggctgc actgggttgg tggcctatac cggcggtctc accccagtct 1860 ggtgtttccc gggagccacc ttcgccccct gaaccctaag actccaagcc atctttcatt 1920 taggcctcct aggaaggtcg agcgaccagg gagcgaccca aagcgtctct gtgcccatcg 1980 cccccccccc cccccccacc gctccgctcc acacttctgt gagcctgggt ccccacccag 2040 ctccgctcct gtgatccagg cctgccacct ggcggccggg gagggaggaa cagggctcgt 2100 gcccagcacc cctggttcct gcagagctgg tagccaccgc tgctgcagca gctgggcatt 2160 cgccgacctt gctttactca gccccgacgt ggatgggcaa actgctcagc tcatccgatt 2220 tcactttttc actctcccag ccatcagtta caagccataa gcatgagccc cctatttcca 2280 gggacatccc attcccatag tgatggatca gcaagacctc tgccagcaca cacggagtct 2340 ttggcttcgg acagcctcac tcctgggggt tgctgcaact ccttccccgt gtacacgtct 2400 gcactctaac aacggagcca cagctgcact cccccctccc ccaaagcagt gtgggtattt 2460 attgatcttg ttatctgact cactgacaga ctccgggacc cacgttttag atgcattgag 2520 actcgacatt cctcggtatt tattgtctgt ccccacctac gacctccact cccgaccctt 2580 gcgaataaaa tacttctggt ctgccctaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 2640 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaa 2688 <210> SEQ ID NO 8 <211> LENGTH: 2862 <212> TYPE: DNA <213> ORGANISM: Mus musculus <400> SEQUENCE: 8 gggatagtca gggacgggca gacatgcagc tagggttctg gggcctggac aggggcagcc 60 aggccctgtg acgggaagac cccgagctcc ggcccgggga ggggccatgg tgttgcctgc 120 ccaacatgtc agccgaagtg cggctgaggc agctccagca gctggtgctg gacccaggct 180 tcctgggact ggagcccctg ctcgaccttc tcctgggcgt ccaccaggag ctgggtgcct 240 ctcacctagc ccaggacaag tatgtggccg acttcttgca gtgggtggag cccattgcag 300 caaggcttaa ggaggtccga ctgcagaggg atgattttga gattttgaag gtgatcgggc 360 gtggggcgtt cagcgaggta gcggtggtga agatgaaaca gacgggccaa gtgtatgcca 420 tgaagattac gaataagtgg gacatgctga agagaggcga ggtgtcgtgc ttccgggaag 480 aaagggatgt attagtgaaa ggggaccggc gctggatcac acagctgcac tttgccttcc 540 aggatgagaa ctacctgtac ctggtcatgg aatactacgt gggcggggac ctgctaacgc 600 tgctgagcaa gtttggggag cggatccccg ccgagatggc tcgcttctac ctggccgaga 660 ttgtcatggc catagactcc gtgcaccggc tgggctacgt gcacagggac atcaaaccag 720 ataacattct gctggaccga tgtgggcaca ttcgcctggc agacttcggc tcctgcctca 780 aactgcagcc tgatggaatg gtgaggtcgc tggtggctgt gggcaccccg gactacctgt 840 ctcctgagat tctgcaggcc gttggtggag ggcctggggc aggcagctac gggccagagt 900 gtgactggtg ggcactgggc gtgttcacct atgagatgtt ctatgggcag acccccttct 960 acgcggactc cacagccgag acatatgcca agattgtgca ctacagggaa cacttgtcgc 1020 tgccgctggc agacacagtt gtccccgagg aagctcagga cctcattcgt gggctgctgt 1080 gtcctgctga gataaggcta ggtcgaggtg gggcaggtga tttccagaaa catcctttct 1140 tctttggcct tgattgggag ggtctccgag acagtgtacc cccctttaca ccagacttcg 1200 agggtgccac ggacacatgc aatttcgatg tggtggagga ccggctcact gccatggaga 1260 cgctgtcaga catgcaggaa gacatgcccc ttggggtgcg cctgcccttc gtgggctact 1320 cctactgctg catggccttc agagacaatc aggtcccgga ccccacccct atggaactag 1380 aggccctgca gttgcctgtg tcagacttgc aagggcttga cttgcagccc ccagtgtccc 1440 caccggatca agtggctgaa gaggctgacc tagtggctgt ccctgcccct gtggctgagg 1500 cagagaccac ggtaacgctg cagcagctcc aggaagccct ggaagaagag gttctcaccc 1560 ggcagagcct gagccgcgag ctggaggcca tccggaccgc caaccagaac ttctccagcc 1620 aactacagga ggccgaggtc cgaaaccgag acctggaggc gcatgttcgg cagctacagg 1680 aacggatgga gatgctgcag gccccaggag ccgcagccat cacgggggtc cccagtcccc 1740 gggccacgga tccaccttcc catgcttctc gccaaatcct ccccaaggga actccctaga 1800 ctcccgttct ggcctcgact agattcccgc actgcctctc gccctgctgc tgggctccga 1860 tcgggtcacc tgtcccttct ctctccagct agatggcccc ccggccgtgg ctgtgggcca 1920 gtgcccgctg gtggggccag gccccatgca ccgccgtcac ctgctgctcc ctgccaggat 1980 ccctaggcct ggcctatccg aggcgcgttg cctgctcctg ttcgccgctg ctctggctgc 2040 tgccgccaca ctgggctgca ctgggttggt ggcctatacc ggcggtctca ccccagtctg 2100 gtgtttcccg ggagccacct tcgccccctg aaccctaaga ctccaagcca tctttcattt 2160 aggcctccta ggaaggtcga gcgaccaggg agcgacccaa agcgtctctg tgcccatcgc 2220 cccccccccc ccccccaccg ctccgctcca cacttctgtg agcctgggtc cccacccagc 2280 tccgctcctg tgatccaggc ctgccacctg gcggccgggg agggaggaac agggctcgtg 2340 cccagcaccc ctggttcctg cagagctggt agccaccgct gctgcagcag ctgggcattc 2400 gccgaccttg ctttactcag ccccgacgtg gatgggcaaa ctgctcagct catccgattt 2460 cactttttca ctctcccagc catcagttac aagccataag catgagcccc ctatttccag 2520 ggacatccca ttcccatagt gatggatcag caagacctct gccagcacac acggagtctt 2580 tggcttcgga cagcctcact cctgggggtt gctgcaactc cttccccgtg tacacgtctg 2640 cactctaaca acggagccac agctgcactc ccccctcccc caaagcagtg tgggtattta 2700 ttgatcttgt tatctgactc actgacagac tccgggaccc acgttttaga tgcattgaga 2760 ctcgacattc ctcggtattt attgtctgtc cccacctacg acctccactc ccgacccttg 2820 cgaataaaat acttctggtc tgccctaaaa aaaaaaaaaa aa 2862 <210> SEQ ID NO 9 <211> LENGTH: 18 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Primer <400> SEQUENCE: 9 agcctgagcc gggagatg 18 <210> SEQ ID NO 10 <211> LENGTH: 21 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Primer <400> SEQUENCE: 10 gcgtagttga ctggcgaagt t 21 <210> SEQ ID NO 11 <211> LENGTH: 21 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Probe <400> SEQUENCE: 11 aggccatccg cacggacaac c 21 <210> SEQ ID NO 12 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 12 ctggctgcat gtctgcctgt 20 <210> SEQ ID NO 13 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 13 ccaggagaag gtcgagcagg 20 <210> SEQ ID NO 14 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 14 tctatggcca tgacaatctc 20 <210> SEQ ID NO 15 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 15 atgtccctgt gcacgtagcc 20 <210> SEQ ID NO 16 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 16 atgtgtccgg aagtcgcctg 20 <210> SEQ ID NO 17 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 17 ctcaggctct gccgggtgag 20 <210> SEQ ID NO 18 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 18 ggcactggcc cacagccacg 20 <210> SEQ ID NO 19 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 19 cctggccgaa agaaagaaat 20 <210> SEQ ID NO 20 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 20 aaagaaatgg tctgtgatcc 20 <210> SEQ ID NO 21 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 21 aagaaagaaa tggtctgtga 20 <210> SEQ ID NO 22 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 22 ggccgaaaga aagaaatggt 20 <210> SEQ ID NO 23 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 23 cctcagcctg gccgaaagaa 20 <210> SEQ ID NO 24 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 24 gggcctcagc ctggccgaaa 20 <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 tcagggcctc agcctggccg 20 <210> SEQ ID NO 26 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 26 ctgcagtttg cccatccacg 20 <210> SEQ ID NO 27 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 27 ggcctgcagt ttgcccatcc 20 <210> SEQ ID NO 28 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 28 ccaggcctgc agtttgccca 20 <210> SEQ ID NO 29 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 29 gccttcccag gcctgcagtt 20 <210> SEQ ID NO 30 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 30 gctgccttcc caggcctgca 20 <210> SEQ ID NO 31 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 31 cttgctgcct tcccaggcct 20 <210> SEQ ID NO 32 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 32 gcccggcttg ctgccttccc 20 <210> SEQ ID NO 33 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 33 acggcccggc ttgctgcctt 20 <210> SEQ ID NO 34 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 34 cggacggccc ggcttgctgc 20 <210> SEQ ID NO 35 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 35 acacggacgg cccggcttgc 20 <210> SEQ ID NO 36 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 36 gatggaacac ggacggcccg 20 <210> SEQ ID NO 37 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 37 gaggatggaa cacggacggc 20 <210> SEQ ID NO 38 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 38 gtggaggatg gaacacggac 20 <210> SEQ ID NO 39 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 39 gcgaaccaac gataggtggg 20 <210> SEQ ID NO 40 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 40 tttgcgaacc aacgataggt 20 <210> SEQ ID NO 41 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 41 ttgcactttg cgaaccaacg 20 <210> SEQ ID NO 42 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 42 gctttgcact ttgcgaacca 20 <210> SEQ ID NO 43 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 43 aaagctttgc actttgcgaa 20 <210> SEQ ID NO 44 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 44 aagaaagctt tgcactttgc 20 <210> SEQ ID NO 45 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 45 cacaagaaag ctttgcactt 20 <210> SEQ ID NO 46 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 46 gtcatgcaca agaaagcttt 20 <210> SEQ ID NO 47 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 47 acgctcccca gagcagggcg 20 <210> SEQ ID NO 48 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 48 gcagagatcg cgccagacgc 20 <210> SEQ ID NO 49 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 49 caggcagaga tcgcgccaga 20 <210> SEQ ID NO 50 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 50 aagcaggcag agatcgcgcc 20 <210> SEQ ID NO 51 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 51 ccgagtaagc aggcagagat 20 <210> SEQ ID NO 52 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 52 ttcccgagta agcaggcaga 20 <210> SEQ ID NO 53 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 53 gcaaatttcc cgagtaagca 20 <210> SEQ ID NO 54 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 54 aaagcaaatt tcccgagtaa 20 <210> SEQ ID NO 55 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 55 ttggcaaaag caaatttccc 20 <210> SEQ ID NO 56 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 56 ggtttggcaa aagcaaattt 20 <210> SEQ ID NO 57 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 57 gcgggtttgg caaaagcaaa 20 <210> SEQ ID NO 58 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 58 aaagcgggtt tggcaaaagc 20 <210> SEQ ID NO 59 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 59 cccgaaaaag cgggtttggc 20 <210> SEQ ID NO 60 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 60 atccccgaaa aagcgggttt 20 <210> SEQ ID NO 61 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 61 cgggatcccc gaaaaagcgg 20 <210> SEQ ID NO 62 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 62 gcgcgggatc cccgaaaaag 20 <210> SEQ ID NO 63 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 63 gagagcagcg caagtgagga 20 <210> SEQ ID NO 64 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 64 tccgagagca gcgcaagtga 20 <210> SEQ ID NO 65 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 65 ggctccgaga gcagcgcaag 20 <210> SEQ ID NO 66 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 66 aagcgggcgg agccggctgg 20 <210> SEQ ID NO 67 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 67 ccgaagcggg cggagccggc 20 <210> SEQ ID NO 68 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 68 aaaccgccga agcgggcgga 20 <210> SEQ ID NO 69 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 69 tccaaaccgc cgaagcgggc 20 <210> SEQ ID NO 70 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 70 atatccaaac cgccgaagcg 20 <210> SEQ ID NO 71 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 71 taaatatcca aaccgccgaa 20 <210> SEQ ID NO 72 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 72 caataaatat ccaaaccgcc 20 <210> SEQ ID NO 73 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 73 cgaggtcaat aaatatccaa 20 <210> SEQ ID NO 74 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 74 ggacgaggtc aataaatatc 20 <210> SEQ ID NO 75 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 75 ggaggacgag gtcaataaat 20 <210> SEQ ID NO 76 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 76 gtcggaggac gaggtcaata 20 <210> SEQ ID NO 77 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 77 cgagtcggag gacgaggtca 20 <210> SEQ ID NO 78 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 78 tgtcagcgag tcggaggacg 20 <210> SEQ ID NO 79 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 79 gcctgtcagc gagtcggagg 20 <210> SEQ ID NO 80 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 80 gtagcctgtc agcgagtcgg 20 <210> SEQ ID NO 81 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 81 cctgtagcct gtcagcgagt 20 <210> SEQ ID NO 82 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 82 ggtcctgtag cctgtcagcg 20 <210> SEQ ID NO 83 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 83 aaataccgag gaatgtcggg 20 <210> SEQ ID NO 84 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 84 aataaatacc gaggaatgtc 20 <210> SEQ ID NO 85 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 85 gacaataaat accgaggaat 20 <210> SEQ ID NO 86 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 86 cggggccccg gagtcgaaga 20 <210> SEQ ID NO 87 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 87 ccaacggggc cccggagtcg 20 <210> SEQ ID NO 88 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 88 ttccaacggg gccccggagt 20 <210> SEQ ID NO 89 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 89 gtcttccaac ggggccccgg 20 <210> SEQ ID NO 90 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 90 cagtcttcca acggggcccc 20 <210> SEQ ID NO 91 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 91 ctcagtcttc caacggggcc 20 <210> SEQ ID NO 92 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 92 gcactcagtc ttccaacggg 20 <210> SEQ ID NO 93 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 93 ccccgggcac tcagtcttcc 20 <210> SEQ ID NO 94 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 94 tgccccgggc actcagtctt 20 <210> SEQ ID NO 95 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 95 cgtgccccgg gcactcagtc 20 <210> SEQ ID NO 96 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 96 gtgccgtgcc ccgggcactc 20 <210> SEQ ID NO 97 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 97 tctgtgccgt gccccgggca 20 <210> SEQ ID NO 98 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 98 gcttctgtgc cgtgccccgg 20 <210> SEQ ID NO 99 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 99 gcggcttctg tgccgtgccc 20 <210> SEQ ID NO 100 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 100 gcgcggcttc tgtgccgtgc 20 <210> SEQ ID NO 101 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 101 gggcgcggct tctgtgccgt 20 <210> SEQ ID NO 102 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 102 ggcggtgggc gcggcttctg 20 <210> SEQ ID NO 103 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 103 ggcaggcggt gggcgcggct 20 <210> SEQ ID NO 104 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 104 ctggcaggcg gtgggcgcgg 20 <210> SEQ ID NO 105 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 105 aactggcagg cggtgggcgc 20 <210> SEQ ID NO 106 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 106 gtgaactggc aggcggtggg 20 <210> SEQ ID NO 107 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 107 ggttgtgaac tggcaggcgg 20 <210> SEQ ID NO 108 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 108 gcggttgtga actggcaggc 20 <210> SEQ ID NO 109 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 109 cggagcggtt gtgaactggc 20 <210> SEQ ID NO 110 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 110 cgctcggagc ggttgtgaac 20 <210> SEQ ID NO 111 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 111 cccacgctcg gagcggttgt 20 <210> SEQ ID NO 112 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 112 agacccacgc tcggagcggt 20 <210> SEQ ID NO 113 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 113 cggagaccca cgctcggagc 20 <210> SEQ ID NO 114 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 114 gggcggagac ccacgctcgg 20 <210> SEQ ID NO 115 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 115 gctgggcgga gacccacgct 20 <210> SEQ ID NO 116 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 116 ggagctgggc ggagacccac 20 <210> SEQ ID NO 117 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 117 ctggagctgg gcggagaccc 20 <210> SEQ ID NO 118 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 118 ggactggagc tgggcggaga 20 <210> SEQ ID NO 119 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 119 caggactgga gctgggcgga 20 <210> SEQ ID NO 120 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 120 atcacaggac tggagctggg 20 <210> SEQ ID NO 121 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 121 gggcgggccc ggatcacagg 20 <210> SEQ ID NO 122 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 122 gggggcgggc ccggatcaca 20 <210> SEQ ID NO 123 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 123 aggcagcacc atggcccctc 20 <210> SEQ ID NO 124 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 124 ggtccaacac cagctgctgg 20 <210> SEQ ID NO 125 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 125 cgatcacctt cagaatctcg 20 <210> SEQ ID NO 126 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 126 cttgttcatg atcttcatgg 20 <210> SEQ ID NO 127 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 127 ccccattcac caacacgtcc 20 <210> SEQ ID NO 128 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 128 gcgtgatcca ccgccggtcc 20 <210> SEQ ID NO 129 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 129 gtaatactcc atgaccaggt 20 <210> SEQ ID NO 130 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 130 gcagtgtcag caggtccccg 20 <210> SEQ ID NO 131 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 131 caccgagtct atggccatga 20 <210> SEQ ID NO 132 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 132 acgtagccaa gccggtgcac 20 <210> SEQ ID NO 133 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 133 atgtggccac agcggtccag 20 <210> SEQ ID NO 134 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 134 cttcgtccac cagcggcaga 20 <210> SEQ ID NO 135 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 135 gaccccttcg tccaccagcg 20 <210> SEQ ID NO 136 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 136 cctgctccac cccggcccag 20 <210> SEQ ID NO 137 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 137 cggaagtcgc ctgctccacc 20 <210> SEQ ID NO 138 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 138 cggagaccat cccagtcgag 20 <210> SEQ ID NO 139 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 139 tgagggccat gcaggagtag 20 <210> SEQ ID NO 140 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 140 ctccagttcc atgggtgtgg 20 <210> SEQ ID NO 141 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 141 gcgcttgcac gtgtggctca 20 <210> SEQ ID NO 142 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 142 gccacttcag ctgtttcatc 20 <210> SEQ ID NO 143 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 143 gcctcagcct ctgccgcagg 20 <210> SEQ ID NO 144 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 144 gcagcgtcac ctcggcctca 20 <210> SEQ ID NO 145 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 145 ggctcaggct ctgccgggtg 20 <210> SEQ ID NO 146 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 146 ttccgagcct ctgcctcgcg 20 <210> SEQ ID NO 147 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 147 ggtcccggtt ccgagcctct 20 <210> SEQ ID NO 148 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 148 atccgctcct gcaactgccg 20 <210> SEQ ID NO 149 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 149 gcaactccat ccgctcctgc 20 <210> SEQ ID NO 150 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 150 aggtggatcc gtggcccggg 20 <210> SEQ ID NO 151 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 151 cgcggcttct gtgccgtgcc 20 <210> SEQ ID NO 152 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 152 ttgctgcctt cccaggcctg 20 <210> SEQ ID NO 153 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 153 tgctcccgac aagctccaga 20 <210> SEQ ID NO 154 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 154 agaacctgcc cattgctgaa 20 <210> SEQ ID NO 155 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 155 cactgagggc cagacatatg 20 <210> SEQ ID NO 156 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 156 ctctagattc agatgcaggt 20 <210> SEQ ID NO 157 <211> LENGTH: 15 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Primer <400> SEQUENCE: 157 cgggccgtcc gtgtt 15 <210> SEQ ID NO 158 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Primer <400> SEQUENCE: 158 ctttgcactt tgcgaaccaa 20 <210> SEQ ID NO 159 <211> LENGTH: 21 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Probe <400> SEQUENCE: 159 catcctccac gcacccccac c 21 <210> SEQ ID NO 160 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 160 gcctggcagc ccctgtccag 20 <210> SEQ ID NO 161 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 161 ggcctggcag cccctgtcca 20 <210> SEQ ID NO 162 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 162 gggcctggca gcccctgtcc 20 <210> SEQ ID NO 163 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 163 atggcccctc cccgggccgg 20 <210> SEQ ID NO 164 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 164 catggcccct ccccgggccg 20 <210> SEQ ID NO 165 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 165 ccatggcccc tccccgggcc 20 <210> SEQ ID NO 166 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 166 accatggccc ctccccgggc 20 <210> SEQ ID NO 167 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 167 caccatggcc cctccccggg 20 <210> SEQ ID NO 168 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 168 gcaccatggc ccctccccgg 20 <210> SEQ ID NO 169 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 169 agcaccatgg cccctccccg 20 <210> SEQ ID NO 170 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 170 cagcaccatg gcccctcccc 20 <210> SEQ ID NO 171 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 171 gcagcaccat ggcccctccc 20 <210> SEQ ID NO 172 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 172 ggcagcacca tggcccctcc 20 <210> SEQ ID NO 173 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 173 caggcagcac catggcccct 20 <210> SEQ ID NO 174 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 174 acaggcagca ccatggcccc 20 <210> SEQ ID NO 175 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 175 ggacaggcag caccatggcc 20 <210> SEQ ID NO 176 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 176 tggacaggca gcaccatggc 20 <210> SEQ ID NO 177 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 177 ttggacaggc agcaccatgg 20 <210> SEQ ID NO 178 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 178 gttggacagg cagcaccatg 20 <210> SEQ ID NO 179 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 179 tgttggacag gcagcaccat 20 <210> SEQ ID NO 180 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 180 atgttggaca ggcagcacca 20 <210> SEQ ID NO 181 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 181 catgttggac aggcagcacc 20 <210> SEQ ID NO 182 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 182 acatgttgga caggcagcac 20 <210> SEQ ID NO 183 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 183 gacatgttgg acaggcagca 20 <210> SEQ ID NO 184 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 184 tgacatgttg gacaggcagc 20 <210> SEQ ID NO 185 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 185 ctgacatgtt ggacaggcag 20 <210> SEQ ID NO 186 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 186 gctgacatgt tggacaggca 20 <210> SEQ ID NO 187 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 187 ggctgacatg ttggacaggc 20 <210> SEQ ID NO 188 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 188 cggctgacat gttggacagg 20 <210> SEQ ID NO 189 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 189 tcggctgaca tgttggacag 20 <210> SEQ ID NO 190 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 190 ctcggctgac atgttggaca 20 <210> SEQ ID NO 191 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 191 cctcggctga catgttggac 20 <210> SEQ ID NO 192 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 192 acctcggctg acatgttgga 20 <210> SEQ ID NO 193 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 193 cacctcggct gacatgttgg 20 <210> SEQ ID NO 194 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 194 gcacctcggc tgacatgttg 20 <210> SEQ ID NO 195 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 195 cgcacctcgg ctgacatgtt 20 <210> SEQ ID NO 196 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 196 ccgcacctcg gctgacatgt 20 <210> SEQ ID NO 197 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 197 gccgcacctc ggctgacatg 20 <210> SEQ ID NO 198 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 198 agccgcacct cggctgacat 20 <210> SEQ ID NO 199 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 199 cagccgcacc tcggctgaca 20 <210> SEQ ID NO 200 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 200 tcagccgcac ctcggctgac 20 <210> SEQ ID NO 201 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 201 ctcagccgca cctcggctga 20 <210> SEQ ID NO 202 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 202 cctcagccgc acctcggctg 20 <210> SEQ ID NO 203 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 203 gcctcagccg cacctcggct 20 <210> SEQ ID NO 204 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 204 ccaacaccag ctgctggagc 20 <210> SEQ ID NO 205 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 205 tccaacacca gctgctggag 20 <210> SEQ ID NO 206 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 206 gtccaacacc agctgctgga 20 <210> SEQ ID NO 207 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 207 gggtccaaca ccagctgctg 20 <210> SEQ ID NO 208 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 208 ggctccagcc ccaggaagcc 20 <210> SEQ ID NO 209 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 209 gggctccagc cccaggaagc 20 <210> SEQ ID NO 210 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 210 caggagaagg tcgagcaggg 20 <210> SEQ ID NO 211 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 211 cccaggagaa ggtcgagcag 20 <210> SEQ ID NO 212 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 212 gcccaggaga aggtcgagca 20 <210> SEQ ID NO 213 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 213 cgcccaggag aaggtcgagc 20 <210> SEQ ID NO 214 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 214 acgcccagga gaaggtcgag 20 <210> SEQ ID NO 215 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 215 tcctgggcca gttcggaggc 20 <210> SEQ ID NO 216 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 216 gtcctgggcc agttcggagg 20 <210> SEQ ID NO 217 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 217 tgtcctgggc cagttcggag 20 <210> SEQ ID NO 218 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 218 ttgtcctggg ccagttcgga 20 <210> SEQ ID NO 219 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 219 cttgtcctgg gccagttcgg 20 <210> SEQ ID NO 220 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 220 acttgtcctg ggccagttcg 20 <210> SEQ ID NO 221 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 221 tacttgtcct gggccagttc 20 <210> SEQ ID NO 222 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 222 gtacttgtcc tgggccagtt 20 <210> SEQ ID NO 223 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 223 cgtacttgtc ctgggccagt 20 <210> SEQ ID NO 224 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 224 actgcaagaa gtcggccacg 20 <210> SEQ ID NO 225 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 225 ccactgcaag aagtcggcca 20 <210> SEQ ID NO 226 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 226 cccactgcaa gaagtcggcc 20 <210> SEQ ID NO 227 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 227 gcccactgca agaagtcggc 20 <210> SEQ ID NO 228 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 228 cgcccactgc aagaagtcgg 20 <210> SEQ ID NO 229 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 229 ccgcccactg caagaagtcg 20 <210> SEQ ID NO 230 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 230 tccgcccact gcaagaagtc 20 <210> SEQ ID NO 231 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 231 ctccgcccac tgcaagaagt 20 <210> SEQ ID NO 232 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 232 gctccgccca ctgcaagaag 20 <210> SEQ ID NO 233 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 233 ggctccgccc actgcaagaa 20 <210> SEQ ID NO 234 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 234 gggctccgcc cactgcaaga 20 <210> SEQ ID NO 235 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 235 tgggctccgc ccactgcaag 20 <210> SEQ ID NO 236 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 236 atgggctccg cccactgcaa 20 <210> SEQ ID NO 237 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 237 gatgggctcc gcccactgca 20 <210> SEQ ID NO 238 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 238 cgatgggctc cgcccactgc 20 <210> SEQ ID NO 239 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 239 acgatgggct ccgcccactg 20 <210> SEQ ID NO 240 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 240 cacgatgggc tccgcccact 20 <210> SEQ ID NO 241 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 241 ccacgatggg ctccgcccac 20 <210> SEQ ID NO 242 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 242 accacgatgg gctccgccca 20 <210> SEQ ID NO 243 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 243 caccacgatg ggctccgccc 20 <210> SEQ ID NO 244 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 244 tcaccacgat gggctccgcc 20 <210> SEQ ID NO 245 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 245 ctcaccacga tgggctccgc 20 <210> SEQ ID NO 246 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 246 cctcaccacg atgggctccg 20 <210> SEQ ID NO 247 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 247 gcctcaccac gatgggctcc 20 <210> SEQ ID NO 248 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 248 agcctcacca cgatgggctc 20 <210> SEQ ID NO 249 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 249 aagcctcacc acgatgggct 20 <210> SEQ ID NO 250 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 250 taagcctcac cacgatgggc 20 <210> SEQ ID NO 251 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 251 ttaagcctca ccacgatggg 20 <210> SEQ ID NO 252 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 252 cttaagcctc accacgatgg 20 <210> SEQ ID NO 253 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 253 ccttaagcct caccacgatg 20 <210> SEQ ID NO 254 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 254 tccttaagcc tcaccacgat 20 <210> SEQ ID NO 255 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 255 ctccttaagc ctcaccacga 20 <210> SEQ ID NO 256 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 256 cctccttaag cctcaccacg 20 <210> SEQ ID NO 257 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 257 acctccttaa gcctcaccac 20 <210> SEQ ID NO 258 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 258 gacctcctta agcctcacca 20 <210> SEQ ID NO 259 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 259 ggacctcctt aagcctcacc 20 <210> SEQ ID NO 260 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 260 cggacctcct taagcctcac 20 <210> SEQ ID NO 261 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 261 tcggacctcc ttaagcctca 20 <210> SEQ ID NO 262 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 262 gtcggacctc cttaagcctc 20 <210> SEQ ID NO 263 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 263 cagtcggacc tccttaagcc 20 <210> SEQ ID NO 264 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 264 gcagtcggac ctccttaagc 20 <210> SEQ ID NO 265 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 265 tgcagtcgga cctccttaag 20 <210> SEQ ID NO 266 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 266 ccttcagaat ctcgaagtcg 20 <210> SEQ ID NO 267 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 267 accttcagaa tctcgaagtc 20 <210> SEQ ID NO 268 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 268 tcaccttcag aatctcgaag 20 <210> SEQ ID NO 269 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 269 atcaccttca gaatctcgaa 20 <210> SEQ ID NO 270 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 270 gatcaccttc agaatctcga 20 <210> SEQ ID NO 271 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 271 ccgatcacct tcagaatctc 20 <210> SEQ ID NO 272 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 272 tccgatcacc ttcagaatct 20 <210> SEQ ID NO 273 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 273 gtccgatcac cttcagaatc 20 <210> SEQ ID NO 274 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 274 cgtccgatca ccttcagaat 20 <210> SEQ ID NO 275 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 275 cccgtctgct tcatcttcac 20 <210> SEQ ID NO 276 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 276 gcccgtctgc ttcatcttca 20 <210> SEQ ID NO 277 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 277 ggcccgtctg cttcatcttc 20 <210> SEQ ID NO 278 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 278 tggcccgtct gcttcatctt 20 <210> SEQ ID NO 279 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 279 ctggcccgtc tgcttcatct 20 <210> SEQ ID NO 280 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 280 cctggcccgt ctgcttcatc 20 <210> SEQ ID NO 281 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 281 acctggcccg tctgcttcat 20 <210> SEQ ID NO 282 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 282 cacctggccc gtctgcttca 20 <210> SEQ ID NO 283 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 283 acacctggcc cgtctgcttc 20 <210> SEQ ID NO 284 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 284 tacacctggc ccgtctgctt 20 <210> SEQ ID NO 285 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 285 ttgttcatga tcttcatggc 20 <210> SEQ ID NO 286 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 286 acttgttcat gatcttcatg 20 <210> SEQ ID NO 287 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 287 cacttgttca tgatcttcat 20 <210> SEQ ID NO 288 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 288 ccacttgttc atgatcttca 20 <210> SEQ ID NO 289 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 289 cccacttgtt catgatcttc 20 <210> SEQ ID NO 290 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 290 tcccacttgt tcatgatctt 20 <210> SEQ ID NO 291 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 291 gtcccacttg ttcatgatct 20 <210> SEQ ID NO 292 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 292 tgtcccactt gttcatgatc 20 <210> SEQ ID NO 293 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 293 atgtcccact tgttcatgat 20 <210> SEQ ID NO 294 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 294 catgtcccac ttgttcatga 20 <210> SEQ ID NO 295 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 295 gcatgtccca cttgttcatg 20 <210> SEQ ID NO 296 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 296 agcatgtccc acttgttcat 20 <210> SEQ ID NO 297 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 297 cagcatgtcc cacttgttca 20 <210> SEQ ID NO 298 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 298 tcagcatgtc ccacttgttc 20 <210> SEQ ID NO 299 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 299 ttcagcatgt cccacttgtt 20 <210> SEQ ID NO 300 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 300 cttcagcatg tcccacttgt 20 <210> SEQ ID NO 301 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 301 tcttcagcat gtcccacttg 20 <210> SEQ ID NO 302 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 302 cctcttcagc atgtcccact 20 <210> SEQ ID NO 303 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 303 ccctcttcag catgtcccac 20 <210> SEQ ID NO 304 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 304 cccctcttca gcatgtccca 20 <210> SEQ ID NO 305 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 305 gcccctcttc agcatgtccc 20 <210> SEQ ID NO 306 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 306 cgcccctctt cagcatgtcc 20 <210> SEQ ID NO 307 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 307 tcgcccctct tcagcatgtc 20 <210> SEQ ID NO 308 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 308 ctcgcccctc ttcagcatgt 20 <210> SEQ ID NO 309 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 309 cctcgcccct cttcagcatg 20 <210> SEQ ID NO 310 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 310 acctcgcccc tcttcagcat 20 <210> SEQ ID NO 311 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 311 cacctcgccc ctcttcagca 20 <210> SEQ ID NO 312 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 312 acacctcgcc cctcttcagc 20 <210> SEQ ID NO 313 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 313 gacacctcgc ccctcttcag 20 <210> SEQ ID NO 314 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 314 gccaggcgga tgtggccaca 20 <210> SEQ ID NO 315 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 315 accgcaccgt tccatctgcc 20 <210> SEQ ID NO 316 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 316 gaccgcaccg ttccatctgc 20 <210> SEQ ID NO 317 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 317 acagcctgca ggatctcggg 20 <210> SEQ ID NO 318 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 318 cacagcctgc aggatctcgg 20 <210> SEQ ID NO 319 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 319 ccacagcctg caggatctcg 20 <210> SEQ ID NO 320 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 320 cccacagcct gcaggatctc 20 <210> SEQ ID NO 321 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 321 gcccacagcc tgcaggatct 20 <210> SEQ ID NO 322 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 322 cgcccacagc ctgcaggatc 20 <210> SEQ ID NO 323 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 323 ccgcccacag cctgcaggat 20 <210> SEQ ID NO 324 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 324 accgcccaca gcctgcagga 20 <210> SEQ ID NO 325 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 325 caccgcccac agcctgcagg 20 <210> SEQ ID NO 326 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 326 ccaccgccca cagcctgcag 20 <210> SEQ ID NO 327 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 327 cccaccgccc acagcctgca 20 <210> SEQ ID NO 328 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 328 gcccaccgcc cacagcctgc 20 <210> SEQ ID NO 329 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 329 ggcccaccgc ccacagcctg 20 <210> SEQ ID NO 330 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 330 aggcccaccg cccacagcct 20 <210> SEQ ID NO 331 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 331 caggcccacc gcccacagcc 20 <210> SEQ ID NO 332 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 332 ccaggcccac cgcccacagc 20 <210> SEQ ID NO 333 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 333 cccaggccca ccgcccacag 20 <210> SEQ ID NO 334 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 334 tcccaggccc accgcccaca 20 <210> SEQ ID NO 335 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 335 gtcccaggcc caccgcccac 20 <210> SEQ ID NO 336 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 336 tgtcccaggc ccaccgccca 20 <210> SEQ ID NO 337 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 337 ctgtcccagg cccaccgccc 20 <210> SEQ ID NO 338 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 338 cctgtcccag gcccaccgcc 20 <210> SEQ ID NO 339 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 339 gcctgtccca ggcccaccgc 20 <210> SEQ ID NO 340 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 340 tgcctgtccc aggcccaccg 20 <210> SEQ ID NO 341 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 341 ctgcctgtcc caggcccacc 20 <210> SEQ ID NO 342 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 342 gctgcctgtc ccaggcccac 20 <210> SEQ ID NO 343 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 343 agctgcctgt cccaggccca 20 <210> SEQ ID NO 344 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 344 tagctgcctg tcccaggccc 20 <210> SEQ ID NO 345 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 345 gtagctgcct gtcccaggcc 20 <210> SEQ ID NO 346 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 346 cgtagctgcc tgtcccaggc 20 <210> SEQ ID NO 347 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 347 ccgtagctgc ctgtcccagg 20 <210> SEQ ID NO 348 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 348 cccgtagctg cctgtcccag 20 <210> SEQ ID NO 349 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 349 gcccgtagct gcctgtccca 20 <210> SEQ ID NO 350 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 350 ggcccgtagc tgcctgtccc 20 <210> SEQ ID NO 351 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 351 tagaacattt cataggcgaa 20 <210> SEQ ID NO 352 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 352 tctccgccgt ggaatccgcg 20 <210> SEQ ID NO 353 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 353 gtctccgccg tggaatccgc 20 <210> SEQ ID NO 354 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 354 ggtctccgcc gtggaatccg 20 <210> SEQ ID NO 355 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 355 aggtctccgc cgtggaatcc 20 <210> SEQ ID NO 356 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 356 taggtctccg ccgtggaatc 20 <210> SEQ ID NO 357 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 357 ttgtagtgga cgatcttgcc 20 <210> SEQ ID NO 358 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 358 cttgtagtgg acgatcttgc 20 <210> SEQ ID NO 359 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 359 ccttgtagtg gacgatcttg 20 <210> SEQ ID NO 360 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 360 tccttgtagt ggacgatctt 20 <210> SEQ ID NO 361 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 361 ctccttgtag tggacgatct 20 <210> SEQ ID NO 362 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 362 gctccttgta gtggacgatc 20 <210> SEQ ID NO 363 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 363 tgctccttgt agtggacgat 20 <210> SEQ ID NO 364 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 364 gtgctccttg tagtggacga 20 <210> SEQ ID NO 365 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 365 ggtgctcctt gtagtggacg 20 <210> SEQ ID NO 366 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 366 aggtgctcct tgtagtggac 20 <210> SEQ ID NO 367 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 367 gaggtgctcc ttgtagtgga 20 <210> SEQ ID NO 368 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 368 agaggtgctc cttgtagtgg 20 <210> SEQ ID NO 369 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 369 gagaggtgct ccttgtagtg 20 <210> SEQ ID NO 370 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 370 agagaggtgc tccttgtagt 20 <210> SEQ ID NO 371 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 371 gagagaggtg ctccttgtag 20 <210> SEQ ID NO 372 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 372 agagagaggt gctccttgta 20 <210> SEQ ID NO 373 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 373 cagagagagg tgctccttgt 20 <210> SEQ ID NO 374 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 374 ggcagagaga ggtgctcctt 20 <210> SEQ ID NO 375 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 375 cggcagagag aggtgctcct 20 <210> SEQ ID NO 376 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 376 gcggcagaga gaggtgctcc 20 <210> SEQ ID NO 377 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 377 agcggcagag agaggtgctc 20 <210> SEQ ID NO 378 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 378 cagcggcaga gagaggtgct 20 <210> SEQ ID NO 379 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 379 ccagcggcag agagaggtgc 20 <210> SEQ ID NO 380 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 380 ggcccagccg tgtctccggg 20 <210> SEQ ID NO 381 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 381 cggcccagcc gtgtctccgg 20 <210> SEQ ID NO 382 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 382 ccggcccagc cgtgtctccg 20 <210> SEQ ID NO 383 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 383 cccggcccag ccgtgtctcc 20 <210> SEQ ID NO 384 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 384 ccccggccca gccgtgtctc 20 <210> SEQ ID NO 385 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 385 accccggccc agccgtgtct 20 <210> SEQ ID NO 386 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 386 caccccggcc cagccgtgtc 20 <210> SEQ ID NO 387 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 387 ccaccccggc ccagccgtgt 20 <210> SEQ ID NO 388 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 388 tccaccccgg cccagccgtg 20 <210> SEQ ID NO 389 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 389 ctccaccccg gcccagccgt 20 <210> SEQ ID NO 390 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 390 gctccacccc ggcccagccg 20 <210> SEQ ID NO 391 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 391 tgctccaccc cggcccagcc 20 <210> SEQ ID NO 392 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 392 ctgctccacc ccggcccagc 20 <210> SEQ ID NO 393 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 393 aagggatgtg tccggaagtc 20 <210> SEQ ID NO 394 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 394 gaagggatgt gtccggaagt 20 <210> SEQ ID NO 395 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 395 agaagggatg tgtccggaag 20 <210> SEQ ID NO 396 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 396 aagaagggat gtgtccggaa 20 <210> SEQ ID NO 397 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 397 gaagaaggga tgtgtccgga 20 <210> SEQ ID NO 398 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 398 agaagaaggg atgtgtccgg 20 <210> SEQ ID NO 399 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 399 aagaagaagg gatgtgtccg 20 <210> SEQ ID NO 400 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 400 aaagaagaag ggatgtgtcc 20 <210> SEQ ID NO 401 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 401 caaagaagaa gggatgtgtc 20 <210> SEQ ID NO 402 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 402 ccaaagaaga agggatgtgt 20 <210> SEQ ID NO 403 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 403 ggccaaagaa gaagggatgt 20 <210> SEQ ID NO 404 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 404 aggccaaaga agaagggatg 20 <210> SEQ ID NO 405 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 405 gaggccaaag aagaagggat 20 <210> SEQ ID NO 406 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 406 cgaggccaaa gaagaaggga 20 <210> SEQ ID NO 407 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 407 tcgaggccaa agaagaaggg 20 <210> SEQ ID NO 408 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 408 gtcgaggcca aagaagaagg 20 <210> SEQ ID NO 409 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 409 agtcgaggcc aaagaagaag 20 <210> SEQ ID NO 410 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 410 cagtcgaggc caaagaagaa 20 <210> SEQ ID NO 411 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 411 ccagtcgagg ccaaagaaga 20 <210> SEQ ID NO 412 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 412 cccagtcgag gccaaagaag 20 <210> SEQ ID NO 413 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 413 tcccagtcga ggccaaagaa 20 <210> SEQ ID NO 414 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 414 atcccagtcg aggccaaaga 20 <210> SEQ ID NO 415 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 415 catcccagtc gaggccaaag 20 <210> SEQ ID NO 416 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 416 ccatcccagt cgaggccaaa 20 <210> SEQ ID NO 417 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 417 accatcccag tcgaggccaa 20 <210> SEQ ID NO 418 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 418 gaccatccca gtcgaggcca 20 <210> SEQ ID NO 419 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 419 agaccatccc agtcgaggcc 20 <210> SEQ ID NO 420 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 420 gagaccatcc cagtcgaggc 20 <210> SEQ ID NO 421 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 421 ggagaccatc ccagtcgagg 20 <210> SEQ ID NO 422 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 422 ttcgaaatcc ggtgtaaagg 20 <210> SEQ ID NO 423 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 423 cttcgaaatc cggtgtaaag 20 <210> SEQ ID NO 424 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 424 ccttcgaaat ccggtgtaaa 20 <210> SEQ ID NO 425 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 425 accttcgaaa tccggtgtaa 20 <210> SEQ ID NO 426 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 426 caccttcgaa atccggtgta 20 <210> SEQ ID NO 427 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 427 gcaccttcga aatccggtgt 20 <210> SEQ ID NO 428 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 428 ggcaccttcg aaatccggtg 20 <210> SEQ ID NO 429 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 429 tggcaccttc gaaatccggt 20 <210> SEQ ID NO 430 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 430 gtggcacctt cgaaatccgg 20 <210> SEQ ID NO 431 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 431 ggtggcacct tcgaaatccg 20 <210> SEQ ID NO 432 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 432 cggtggcacc ttcgaaatcc 20 <210> SEQ ID NO 433 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 433 tcggtggcac cttcgaaatc 20 <210> SEQ ID NO 434 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 434 gtcggtggca ccttcgaaat 20 <210> SEQ ID NO 435 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 435 tgtcggtggc accttcgaaa 20 <210> SEQ ID NO 436 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 436 gtgtcggtgg caccttcgaa 20 <210> SEQ ID NO 437 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 437 tgtgtcggtg gcaccttcga 20 <210> SEQ ID NO 438 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 438 atgtgtcggt ggcaccttcg 20 <210> SEQ ID NO 439 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 439 catgtgtcgg tggcaccttc 20 <210> SEQ ID NO 440 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 440 gcatgtgtcg gtggcacctt 20 <210> SEQ ID NO 441 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 441 tgcatgtgtc ggtggcacct 20 <210> SEQ ID NO 442 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 442 ttgcatgtgt cggtggcacc 20 <210> SEQ ID NO 443 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 443 gttgcatgtg tcggtggcac 20 <210> SEQ ID NO 444 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 444 agttgcatgt gtcggtggca 20 <210> SEQ ID NO 445 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 445 aagttgcatg tgtcggtggc 20 <210> SEQ ID NO 446 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 446 gaagttgcat gtgtcggtgg 20 <210> SEQ ID NO 447 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 447 cgaagttgca tgtgtcggtg 20 <210> SEQ ID NO 448 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 448 gtcgaagttg catgtgtcgg 20 <210> SEQ ID NO 449 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 449 agtcgaagtt gcatgtgtcg 20 <210> SEQ ID NO 450 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 450 aagtcgaagt tgcatgtgtc 20 <210> SEQ ID NO 451 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 451 caagtcgaag ttgcatgtgt 20 <210> SEQ ID NO 452 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 452 ccaagtcgaa gttgcatgtg 20 <210> SEQ ID NO 453 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 453 accaagtcga agttgcatgt 20 <210> SEQ ID NO 454 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 454 caccaagtcg aagttgcatg 20 <210> SEQ ID NO 455 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 455 ccaccaagtc gaagttgcat 20 <210> SEQ ID NO 456 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 456 tccaccaagt cgaagttgca 20 <210> SEQ ID NO 457 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 457 ctccaccaag tcgaagttgc 20 <210> SEQ ID NO 458 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 458 cctccaccaa gtcgaagttg 20 <210> SEQ ID NO 459 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 459 tcctccacca agtcgaagtt 20 <210> SEQ ID NO 460 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 460 gtcctccacc aagtcgaagt 20 <210> SEQ ID NO 461 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 461 cgtcctccac caagtcgaag 20 <210> SEQ ID NO 462 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 462 ccgtcctcca ccaagtcgaa 20 <210> SEQ ID NO 463 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 463 cccgtcctcc accaagtcga 20 <210> SEQ ID NO 464 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 464 gcccgtcctc caccaagtcg 20 <210> SEQ ID NO 465 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 465 agcccgtcct ccaccaagtc 20 <210> SEQ ID NO 466 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 466 gagcccgtcc tccaccaagt 20 <210> SEQ ID NO 467 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 467 tgagcccgtc ctccaccaag 20 <210> SEQ ID NO 468 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 468 ggttccgagc ctctgcctcg 20 <210> SEQ ID NO 469 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 469 cggttccgag cctctgcctc 20 <210> SEQ ID NO 470 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 470 ccggttccga gcctctgcct 20 <210> SEQ ID NO 471 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 471 cccggttccg agcctctgcc 20 <210> SEQ ID NO 472 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 472 tcccggttcc gagcctctgc 20 <210> SEQ ID NO 473 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 473 gtcccggttc cgagcctctg 20 <210> SEQ ID NO 474 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 474 aggtcccggt tccgagcctc 20 <210> SEQ ID NO 475 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 475 taggtcccgg ttccgagcct 20 <210> SEQ ID NO 476 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 476 ctaggtcccg gttccgagcc 20 <210> SEQ ID NO 477 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 477 tctaggtccc ggttccgagc 20 <210> SEQ ID NO 478 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 478 ctctaggtcc cggttccgag 20 <210> SEQ ID NO 479 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 479 cctctaggtc ccggttccga 20 <210> SEQ ID NO 480 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 480 gcctctaggt cccggttccg 20 <210> SEQ ID NO 481 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 481 catccgctcc tgcaactgcc 20 <210> SEQ ID NO 482 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 482 ccatccgctc ctgcaactgc 20 <210> SEQ ID NO 483 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 483 tccatccgct cctgcaactg 20 <210> SEQ ID NO 484 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 484 ctccatccgc tcctgcaact 20 <210> SEQ ID NO 485 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 485 actccatccg ctcctgcaac 20 <210> SEQ ID NO 486 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 486 aactccatcc gctcctgcaa 20 <210> SEQ ID NO 487 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 487 caactccatc cgctcctgca 20 <210> SEQ ID NO 488 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 488 agcaactcca tccgctcctg 20 <210> SEQ ID NO 489 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 489 cagcaactcc atccgctcct 20 <210> SEQ ID NO 490 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 490 gcagcaactc catccgctcc 20 <210> SEQ ID NO 491 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 491 cagctgtggc tccctctgcc 20 <210> SEQ ID NO 492 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 492 acagctgtgg ctccctctgc 20 <210> SEQ ID NO 493 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 493 gacagctgtg gctccctctg 20 <210> SEQ ID NO 494 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 494 tgacagctgt ggctccctct 20 <210> SEQ ID NO 495 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 495 gtgacagctg tggctccctc 20 <210> SEQ ID NO 496 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 496 cgtgacagct gtggctccct 20 <210> SEQ ID NO 497 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 497 ccgtgacagc tgtggctccc 20 <210> SEQ ID NO 498 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 498 cccgtgacag ctgtggctcc 20 <210> SEQ ID NO 499 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 499 ccccgtgaca gctgtggctc 20 <210> SEQ ID NO 500 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 500 cccccgtgac agctgtggct 20 <210> SEQ ID NO 501 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 501 acccccgtga cagctgtggc 20 <210> SEQ ID NO 502 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 502 gacccccgtg acagctgtgg 20 <210> SEQ ID NO 503 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 503 ggacccccgt gacagctgtg 20 <210> SEQ ID NO 504 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 504 gggacccccg tgacagctgt 20 <210> SEQ ID NO 505 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 505 gaaggtggat ccgtggcccg 20 <210> SEQ ID NO 506 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 506 ggaaggtgga tccgtggccc 20 <210> SEQ ID NO 507 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 507 gggaaggtgg atccgtggcc 20 <210> SEQ ID NO 508 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 508 tgggaaggtg gatccgtggc 20 <210> SEQ ID NO 509 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 509 atgggaaggt ggatccgtgg 20 <210> SEQ ID NO 510 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 510 gatgggaagg tggatccgtg 20 <210> SEQ ID NO 511 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 511 tagatgggaa ggtggatccg 20 <210> SEQ ID NO 512 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 512 ctagatggga aggtggatcc 20 <210> SEQ ID NO 513 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 513 tctagatggg aaggtggatc 20 <210> SEQ ID NO 514 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 514 atctagatgg gaaggtggat 20 <210> SEQ ID NO 515 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 515 ccatctagat gggaaggtgg 20 <210> SEQ ID NO 516 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 516 gccatctaga tgggaaggtg 20 <210> SEQ ID NO 517 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 517 ggccatctag atgggaaggt 20 <210> SEQ ID NO 518 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 518 caccagcggg cactggccca 20 <210> SEQ ID NO 519 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 519 ccaccagcgg gcactggccc 20 <210> SEQ ID NO 520 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 520 cccaccagcg ggcactggcc 20 <210> SEQ ID NO 521 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 521 ccccaccagc gggcactggc 20 <210> SEQ ID NO 522 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 522 ggccccacca gcgggcactg 20 <210> SEQ ID NO 523 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 523 tggccccacc agcgggcact 20 <210> SEQ ID NO 524 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 524 ctggccccac cagcgggcac 20 <210> SEQ ID NO 525 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 525 cctggcccca ccagcgggca 20 <210> SEQ ID NO 526 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 526 gcctggcccc accagcgggc 20 <210> SEQ ID NO 527 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 527 gggcctggcc ccaccagcgg 20 <210> SEQ ID NO 528 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 528 aggtggcggc ggtgcatggg 20 <210> SEQ ID NO 529 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 529 caggtggcgg cggtgcatgg 20 <210> SEQ ID NO 530 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 530 gcaggtggcg gcggtgcatg 20 <210> SEQ ID NO 531 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 531 agcaggtggc ggcggtgcat 20 <210> SEQ ID NO 532 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 532 cagcaggtgg cggcggtgca 20 <210> SEQ ID NO 533 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 533 gcagcaggtg gcggcggtgc 20 <210> SEQ ID NO 534 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 534 agcagcaggt ggcggcggtg 20 <210> SEQ ID NO 535 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 535 gagcagcagg tggcggcggt 20 <210> SEQ ID NO 536 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 536 ggagcagcag gtggcggcgg 20 <210> SEQ ID NO 537 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 537 gggagcagca ggtggcggcg 20 <210> SEQ ID NO 538 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 538 agggagcagc aggtggcggc 20 <210> SEQ ID NO 539 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 539 cagggagcag caggtggcgg 20 <210> SEQ ID NO 540 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 540 gcagggagca gcaggtggcg 20 <210> SEQ ID NO 541 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 541 ggcagggagc agcaggtggc 20 <210> SEQ ID NO 542 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 542 tggcagggag cagcaggtgg 20 <210> SEQ ID NO 543 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 543 ctggcaggga gcagcaggtg 20 <210> SEQ ID NO 544 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 544 ccctggcagg gagcagcagg 20 <210> SEQ ID NO 545 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 545 accctggcag ggagcagcag 20 <210> SEQ ID NO 546 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 546 gaccctggca gggagcagca 20 <210> SEQ ID NO 547 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 547 ggaccctggc agggagcagc 20 <210> SEQ ID NO 548 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 548 ggcctaggga ccctggcagg 20 <210> SEQ ID NO 549 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 549 aggcctaggg accctggcag 20 <210> SEQ ID NO 550 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 550 ccaggcctag ggaccctggc 20 <210> SEQ ID NO 551 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 551 gccaggccta gggaccctgg 20 <210> SEQ ID NO 552 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 552 ggccaggcct agggaccctg 20 <210> SEQ ID NO 553 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 553 aggccaggcc tagggaccct 20 <210> SEQ ID NO 554 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 554 taggccaggc ctagggaccc 20 <210> SEQ ID NO 555 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 555 ataggccagg cctagggacc 20 <210> SEQ ID NO 556 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 556 gataggccag gcctagggac 20 <210> SEQ ID NO 557 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 557 cgataggcca ggcctaggga 20 <210> SEQ ID NO 558 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 558 ccgataggcc aggcctaggg 20 <210> SEQ ID NO 559 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 559 tccgataggc caggcctagg 20 <210> SEQ ID NO 560 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 560 ctccgatagg ccaggcctag 20 <210> SEQ ID NO 561 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 561 cctccgatag gccaggccta 20 <210> SEQ ID NO 562 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 562 gcctccgata ggccaggcct 20 <210> SEQ ID NO 563 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 563 gcgcctccga taggccaggc 20 <210> SEQ ID NO 564 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 564 aacaggagca gggaaagcgc 20 <210> SEQ ID NO 565 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 565 gaacaggagc agggaaagcg 20 <210> SEQ ID NO 566 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 566 cgaacaggag cagggaaagc 20 <210> SEQ ID NO 567 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 567 gcgaacagga gcagggaaag 20 <210> SEQ ID NO 568 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 568 ggcgaacagg agcagggaaa 20 <210> SEQ ID NO 569 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 569 cggcgaacag gagcagggaa 20 <210> SEQ ID NO 570 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 570 acggcgaaca ggagcaggga 20 <210> SEQ ID NO 571 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 571 aacggcgaac aggagcaggg 20 <210> SEQ ID NO 572 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 572 caacggcgaa caggagcagg 20 <210> SEQ ID NO 573 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 573 gggcggcggc acgagacaga 20 <210> SEQ ID NO 574 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 574 agggcggcgg cacgagacag 20 <210> SEQ ID NO 575 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 575 cagggcggcg gcacgagaca 20 <210> SEQ ID NO 576 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 576 ccagggcggc ggcacgagac 20 <210> SEQ ID NO 577 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 577 cccagggcgg cggcacgaga 20 <210> SEQ ID NO 578 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 578 gcccagggcg gcggcacgag 20 <210> SEQ ID NO 579 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 579 agcccagggc ggcggcacga 20 <210> SEQ ID NO 580 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 580 cagcccaggg cggcggcacg 20 <210> SEQ ID NO 581 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 581 gcagcccagg gcggcggcac 20 <210> SEQ ID NO 582 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 582 ctgcggtgag ttggccggcg 20 <210> SEQ ID NO 583 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 583 actgcggtga gttggccggc 20 <210> SEQ ID NO 584 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 584 gactgcggtg agttggccgg 20 <210> SEQ ID NO 585 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 585 agactgcggt gagttggccg 20 <210> SEQ ID NO 586 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 586 cagactgcgg tgagttggcc 20 <210> SEQ ID NO 587 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 587 ccagactgcg gtgagttggc 20 <210> SEQ ID NO 588 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 588 gccagactgc ggtgagttgg 20 <210> SEQ ID NO 589 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 589 cgccagactg cggtgagttg 20 <210> SEQ ID NO 590 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 590 aagacagttc tagggttcag 20 <210> SEQ ID NO 591 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 591 gaagacagtt ctagggttca 20 <210> SEQ ID NO 592 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 592 cgaagacagt tctagggttc 20 <210> SEQ ID NO 593 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 593 tcgaagacag ttctagggtt 20 <210> SEQ ID NO 594 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 594 gtcgaagaca gttctagggt 20 <210> SEQ ID NO 595 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 595 agtcgaagac agttctaggg 20 <210> SEQ ID NO 596 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 596 gagtcgaaga cagttctagg 20 <210> SEQ ID NO 597 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 597 ggagtcgaag acagttctag 20 <210> SEQ ID NO 598 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 598 cggagtcgaa gacagttcta 20 <210> SEQ ID NO 599 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 599 ccggagtcga agacagttct 20 <210> SEQ ID NO 600 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 600 cccggagtcg aagacagttc 20 <210> SEQ ID NO 601 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 601 ccccggagtc gaagacagtt 20 <210> SEQ ID NO 602 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 602 gccccggagt cgaagacagt 20 <210> SEQ ID NO 603 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 603 ggccccggag tcgaagacag 20 <210> SEQ ID NO 604 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 604 gggccccgga gtcgaagaca 20 <210> SEQ ID NO 605 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 605 aggcggtggg cgcggcttct 20 <210> SEQ ID NO 606 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 606 caggcggtgg gcgcggcttc 20 <210> SEQ ID NO 607 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 607 gcaggcggtg ggcgcggctt 20 <210> SEQ ID NO 608 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 608 tggcaggcgg tgggcgcggc 20 <210> SEQ ID NO 609 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 609 actggcaggc ggtgggcgcg 20 <210> SEQ ID NO 610 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 610 gaactggcag gcggtgggcg 20 <210> SEQ ID NO 611 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 611 tgaactggca ggcggtgggc 20 <210> SEQ ID NO 612 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 612 tgtgaactgg caggcggtgg 20 <210> SEQ ID NO 613 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 613 tggagctggg cggagaccca 20 <210> SEQ ID NO 614 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 614 actggagctg ggcggagacc 20 <210> SEQ ID NO 615 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 615 gactggagct gggcggagac 20 <210> SEQ ID NO 616 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 616 aggactggag ctgggcggag 20 <210> SEQ ID NO 617 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 617 acaggactgg agctgggcgg 20 <210> SEQ ID NO 618 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 618 cacaggactg gagctgggcg 20 <210> SEQ ID NO 619 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 619 tcacaggact ggagctgggc 20 <210> SEQ ID NO 620 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 620 gcctcagcct ggccgaaaga 20 <210> SEQ ID NO 621 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 621 ggcctcagcc tggccgaaag 20 <210> SEQ ID NO 622 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 622 tggtggagcc aagccctccc 20 <210> SEQ ID NO 623 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 623 gggcaccctc agagcctgaa 20 <210> SEQ ID NO 624 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 624 accccactgc aagaagtcgg 20 <210> SEQ ID NO 625 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 625 gccccaggat gggaggatct 20 <210> SEQ ID NO 626 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 626 cataggacag agaaatgttg 20 <210> SEQ ID NO 627 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 627 tgctgacctt actctgcccc 20 <210> SEQ ID NO 628 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 628 taagccatgg ctctgagtca 20 <210> SEQ ID NO 629 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 629 agagaggcca tgggaggctg 20 <210> SEQ ID NO 630 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 630 ctggccctcc tggcttgccc 20 <210> SEQ ID NO 631 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 631 agctgcccca tgctggccct 20 <210> SEQ ID NO 632 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 632 gcccctggca gctgccccat 20 <210> SEQ ID NO 633 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 633 ctgtcggctg cgcccctggc 20 <210> SEQ ID NO 634 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 634 cgccgaacac ctgcctgtcg 20 <210> SEQ ID NO 635 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 635 cctcccagtg cctgggcacc 20 <210> SEQ ID NO 636 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 636 gcgcctgtct gcaaagctgg 20 <210> SEQ ID NO 637 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 637 cccaaagttg tccctcctgg 20 <210> SEQ ID NO 638 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 638 acacccagaa gaacccaaag 20 <210> SEQ ID NO 639 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 639 ctgacccaca cggctcatag 20 <210> SEQ ID NO 640 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 640 tggccccagg ccctggaaag 20 <210> SEQ ID NO 641 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 641 gacaaggcag ctggcagaag 20 <210> SEQ ID NO 642 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 642 aagaaaccag tgaccagtga 20 <210> SEQ ID NO 643 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 643 ctgtgaaatg ggaggaggag 20 <210> SEQ ID NO 644 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 644 gaaggttttt ccagaggctg 20 <210> SEQ ID NO 645 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 645 ggccaggaga gtcattaggg 20 <210> SEQ ID NO 646 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 646 ccacaaaagg agtgctcctc 20 <210> SEQ ID NO 647 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 647 ccttttaagg cagcaggaac 20 <210> SEQ ID NO 648 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 648 ctaggactgt ctgcttccca 20 <210> SEQ ID NO 649 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 649 gtcattcatc aatttctaag 20 <210> SEQ ID NO 650 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 650 ggaggagctg cagccggaga 20 <210> SEQ ID NO 651 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 651 gcacccggag gagctgcagc 20 <210> SEQ ID NO 652 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 652 gcacgacacc tgcagggcac 20 <210> SEQ ID NO 653 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 653 agctcaccag gtagttctca 20 <210> SEQ ID NO 654 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 654 gcttcctctc cccacctcct 20 <210> SEQ ID NO 655 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 655 gcagcacccc caatcctaga 20 <210> SEQ ID NO 656 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 656 gcccctcatc cacctgacac 20 <210> SEQ ID NO 657 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 657 ttccaggtaa gagacccccc 20 <210> SEQ ID NO 658 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 658 agaataggtc ccagacactc 20 <210> SEQ ID NO 659 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 659 ctccccctga gatgttctgg 20 <210> SEQ ID NO 660 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 660 ccccagccca gagataacca 20 <210> SEQ ID NO 661 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 661 cctgatccat cacggatggc 20 <210> SEQ ID NO 662 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 662 tactccatga ccaggtactg 20 <210> SEQ ID NO 663 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 663 gctctgacct tccaagaacc 20 <210> SEQ ID NO 664 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 664 ctcccttctg tggtcccacc 20 <210> SEQ ID NO 665 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 665 gtcgggtttg atgtccctgc 20 <210> SEQ ID NO 666 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 666 agggcactgg ctcaccgttc 20 <210> SEQ ID NO 667 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 667 gggccctcct tccaaccact 20 <210> SEQ ID NO 668 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 668 gcccacccct ctgggcccac 20 <210> SEQ ID NO 669 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 669 aggagcagag cgaggcttgg 20 <210> SEQ ID NO 670 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 670 caccttgtag tggacgatct 20 <210> SEQ ID NO 671 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 671 ctaccccgcc cccgctcacc 20 <210> SEQ ID NO 672 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 672 ctaggtcact gctgggtcct 20 <210> SEQ ID NO 673 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 673 ctcagatagc tccccactcc 20 <210> SEQ ID NO 674 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 674 aattctctaa ttctctagac 20 <210> SEQ ID NO 675 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 675 tacctgaggg ccatgcagga 20 <210> SEQ ID NO 676 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 676 gttccaagac tgatcctgca 20 <210> SEQ ID NO 677 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 677 aggagggcgg tggcgcggcg 20 <210> SEQ ID NO 678 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 678 tgacagctgg aaggagaaga 20 <210> SEQ ID NO 679 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 679 catgggaagg tggatccgtg 20 <210> SEQ ID NO 680 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 680 ggaggttatc tagggagatc 20 <210> SEQ ID NO 681 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 681 gaagggacag gtgacccgat 20 <210> SEQ ID NO 682 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 682 cgtaccctgg cagggagcag 20 <210> SEQ ID NO 683 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 683 ggactcgccc cgcctacgcc 20 <210> SEQ ID NO 684 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 684 ctcctgggac tcgccccgcc 20 <210> SEQ ID NO 685 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 685 gctcctggga ctcgccccgc 20 <210> SEQ ID NO 686 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 686 attggctcct gggactcgcc 20 <210> SEQ ID NO 687 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 687 gattggctcc tgggactcgc 20 <210> SEQ ID NO 688 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 688 gcctctgatt ggctcctggg 20 <210> SEQ ID NO 689 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 689 gcatgggcct ctgattggct 20 <210> SEQ ID NO 690 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 690 cacccggcat gggcctctga 20 <210> SEQ ID NO 691 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 691 gccaggccta gggacctgcg 20 <210> SEQ ID NO 692 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 692 ttcctccccc aaccctgatt 20 <210> SEQ ID NO 693 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 693 aagtttgcag caacttttct 20 <210> SEQ ID NO 694 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 694 gcccctcgga attcccggct 20 <210> SEQ ID NO 695 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 695 catctcggcc tgcgctccgc 20 <210> SEQ ID NO 696 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 696 gcaggccccc acattcccca 20 <210> SEQ ID NO 697 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 697 cttctgcacg cctccgtctc 20 <210> SEQ ID NO 698 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 698 tggcccacag ccacggccgg 20 <210> SEQ ID NO 699 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 699 ggcctggccc caccagcggg 20 <210> SEQ ID NO 700 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 700 cctggcaggg agcagcaggt 20 <210> SEQ ID NO 701 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 701 cagccgcact tcggctgaca 20 <210> SEQ ID NO 702 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 702 gcctgggtcc agcaccagct 20 <210> SEQ ID NO 703 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 703 gtcccaggaa gcctgggtcc 20 <210> SEQ ID NO 704 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 704 cgttagcagg tccccgccca 20 <210> SEQ ID NO 705 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 705 gtctatggcc atgacaatct 20 <210> SEQ ID NO 706 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 706 gtagcccagc cggtgcacgg 20 <210> SEQ ID NO 707 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 707 gggtgcccac agccaccagc 20 <210> SEQ ID NO 708 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 708 tggcccgtag ctgcctgccc 20 <210> SEQ ID NO 709 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 709 ggaaatcacc tgccccacct 20 <210> SEQ ID NO 710 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 710 ggatgtttct ggaaatcacc 20 <210> SEQ ID NO 711 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 711 gtggcaccct cgaagtctgg 20 <210> SEQ ID NO 712 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 712 ccccgctcac catggcagtg 20 <210> SEQ ID NO 713 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 713 ggtccgggac ctgattgtct 20 <210> SEQ ID NO 714 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 714 gctgcatgtc tgcccgtccc 20 <210> SEQ ID NO 715 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 715 ggccccagaa ccctagctgc 20 <210> SEQ ID NO 716 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 716 tcacagggcc tggctgcccc 20 <210> SEQ ID NO 717 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 717 ggctgacatg ttgggcaggc 20 <210> SEQ ID NO 718 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 718 tgtccaggcc ccagaaccct 20 <210> SEQ ID NO 719 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 719 ggccaggcct agggatctgc 20 <210> SEQ ID NO 720 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 720 cgcctcggat aggccaggcc 20 <210> SEQ ID NO 721 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 721 ggcttggagt cttagggttc 20 <210> SEQ ID NO 722 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 722 tccccggccg ccaggtggca 20 <210> SEQ ID NO 723 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 723 ggtgctgggc acgagccctg 20 <210> SEQ ID NO 724 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 724 gcccagctgc tgcagcagcg 20 <210> SEQ ID NO 725 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 725 ccgtgtgtgc tggcagaggt 20 <210> SEQ ID NO 726 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 726 ataaataccg aggaatgtcg 20 <210> SEQ ID NO 727 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 727 gggacagaca ataaataccg 20 <210> SEQ ID NO 728 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 728 gtgcagccca gtgtggcggc 20 <210> SEQ ID NO 729 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 729 cctggagaag ttctggttgg 20 <210> SEQ ID NO 730 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 730 ggtgacccga tcggagccca 20 <210> SEQ ID NO 731 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 731 agctggagag agaagggaca 20 <210> SEQ ID NO 732 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 732 gtgagggact cgcctgcggc 20 <210> SEQ ID NO 733 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 733 gcggctgcgg tgccccagcc 20 <210> SEQ ID NO 734 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 734 gggccatcta gctggagaga 20 <210> SEQ ID NO 735 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 735 ccccactgca agaagtcggc 20 <210> SEQ ID NO 736 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 736 ttgagccctt ttaaggcagc 20 <210> SEQ ID NO 737 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 737 tgaccaggta ctgggagcgg 20 <210> SEQ ID NO 738 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 738 cctggagctg gatcagtccc 20 <210> SEQ ID NO 739 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 739 acatgggaag gtggatccgt 20 <210> SEQ ID NO 740 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 740 gtgggacata ccctggcagg 20 <210> SEQ ID NO 741 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 741 gccaggccta gggatctgca 20 <210> SEQ ID NO 742 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 742 ggaagcacga cacctcgcct 20 <210> SEQ ID NO 743 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 743 cctcaccatt ccatcaggct 20 <210> SEQ ID NO 744 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 744 cggcagcgac aagtgttccc 20 <210> SEQ ID NO 745 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 745 gtctctgaag gccatgcagc 20 <210> SEQ ID NO 746 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 746 cagccacttg atccggtggg 20 <210> SEQ ID NO 747 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 747 aggtcggcct cttcagccac 20 <210> SEQ ID NO 748 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 748 gttggctgga gaagttctgg 20 <210> SEQ ID NO 749 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 749 ccccgtgatg gctgcggctc 20 <210> SEQ ID NO 750 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 750 aggccaggcc tagggatcct 20 <210> SEQ ID NO 751 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 751 ggcgcggtgc cccagcctgg 20 <210> SEQ ID NO 752 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 752 gtcctggccc caccagcggg 20 <210> SEQ ID NO 753 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 753 ccaggcctag gaatcctggc 20 <210> SEQ ID NO 754 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 754 gcgcctcgga tagccaggcc 20 <210> SEQ ID NO 755 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 755 cccagtgtgg cgcagcagcc 20 <210> SEQ ID NO 756 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 756 gtgtttcatc ttcaccaccg 20 <210> SEQ ID NO 757 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 757 aggtcagcct cttcagccac 20 <210> SEQ ID NO 758 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 758 ggccatatgg gaaggtggat 20 <210> SEQ ID NO 759 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 759 ggaggatttg gcgagaagca 20 <210> SEQ ID NO 760 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 760 cgaagtctgc cccacctcga 20 <210> SEQ ID NO 761 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 761 gtggcaccct cgaagtctgc 20 <210> SEQ ID NO 762 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 762 gggtccattg taaggaagct 20 <210> SEQ ID NO 763 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 763 ggtgcccaca gccaccaggg 20 <210> SEQ ID NO 764 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 764 tccatggcag tgagccggtc 20 <210> SEQ ID NO 765 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 765 gggaccactt gatccggtgg 20 <210> SEQ ID NO 766 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 766 ggatcagagt tgggaccact 20 <210> SEQ ID NO 767 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 767 ccccgtgatg gctgcggttc 20 <210> SEQ ID NO 768 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 768 gtgtgtcctc ataccccgcc 20 <210> SEQ ID NO 769 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 769 gcaccctcga agtctcgacc 20 <210> SEQ ID NO 770 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 770 gctctgaagg ccatgcagca 20 <210> SEQ ID NO 771 <211> LENGTH: 25 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Primer <400> SEQUENCE: 771 gacatatgcc aagattgtgc actac 25 <210> SEQ ID NO 772 <211> LENGTH: 21 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Primer <400> SEQUENCE: 772 cacgaatgag gtcctgagct t 21 <210> SEQ ID NO 773 <211> LENGTH: 22 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Probe <400> SEQUENCE: 773 aacacttgtc gctgccgctg gc 22 <210> SEQ ID NO 774 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 774 agcgaggctt cacttggcgc 20 <210> SEQ ID NO 775 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 775 gggaagcgag gcttcacttg 20 <210> SEQ ID NO 776 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 776 gcggtcagcg atcccagggt 20 <210> SEQ ID NO 777 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 777 gggtgccagc gcggtgatct 20 <210> SEQ ID NO 778 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 778 tgttacaaag aaagtgactg 20 <210> SEQ ID NO 779 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 779 cgatggcagc aacggaagtt 20 <210> SEQ ID NO 780 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 780 gtcagtttac gatggcagca 20 <210> SEQ ID NO 781 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 781 cagggctttg tttcgaaaaa 20 <210> SEQ ID NO 782 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 782 ccattttctt ccacagggct 20 <210> SEQ ID NO 783 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 783 atgcttcttc aagttttcca 20 <210> SEQ ID NO 784 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 784 cagaatgact ttaatgcttc 20 <210> SEQ ID NO 785 <211> LENGTH: 21 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Primer <400> SEQUENCE: 785 ccaccgcaaa tgcttctaga c 21 <210> SEQ ID NO 786 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Primer <400> SEQUENCE: 786 cccccccatt gagaagattc 20 <210> SEQ ID NO 787 <211> LENGTH: 24 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Probe <400> SEQUENCE: 787 ctccacctcc agcacgcgac ttct 24 <210> SEQ ID NO 788 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 788 gcggtcagcg atcccagggt 20 <210> SEQ ID NO 789 <211> LENGTH: 25 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 789 agcagcagca gcagcagcag cagca 25 <210> SEQ ID NO 790 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 790 agcagcagca gcagcagcag 20 <210> SEQ ID NO 791 <211> LENGTH: 15 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 791 gcagcagcag cagca 15 <210> SEQ ID NO 792 <400> SEQUENCE: 792 000 <210> SEQ ID NO 793 <211> LENGTH: 2611 <212> TYPE: DNA <213> ORGANISM: Mus musculus <400> SEQUENCE: 793 cgggaagacc ccgagctccg gcccggggag gggccatggt gttgcctgcc caacatgtca 60 gccgaagtgc ggctgaggca gctccagcag ctggtgctgg acccaggctt cctgggactg 120 gagcccctgc tcgaccttct cctgggcgtc caccaggagc tgggtgcctc tcacctagcc 180 caggacaagt atgtggccga cttcttgcag tgggtggagc ccattgcagc aaggcttaag 240 gaggtccgac tgcagaggga tgattttgag attttgaagg tgatcgggcg tggggcgttc 300 agcgaggtag cggtggtgaa gatgaaacag acgggccaag tgtatgccat gaagattatg 360 aataagtggg acatgctgaa gagaggcgag gtgtcgtgct tccgggaaga aagggatgta 420 ttagtgaaag gggaccggcg ctggatcaca cagctgcact ttgccttcca ggatgagaac 480 tacctgtacc tggtcatgga atactacgtg ggcggggacc tgctaacgct gctgagcaag 540 tttggggagc ggatccccgc cgagatggct cgcttctacc tggccgagat tgtcatggcc 600 atagactccg tgcaccggct gggctacgtg cacagggaca tcaaaccaga taacattctg 660 ctggaccgat gtgggcacat tcgcctggca gacttcggct cctgcctcaa actgcagcct 720 gatggaatgg tgaggtcgct ggtggctgtg ggcaccccgg actacctgtc tcctgagatt 780 ctgcaggccg ttggtggagg gcctggggca ggcagctacg ggccagagtg tgactggtgg 840 gcactgggcg tgttcaccta tgagatgttc tatgggcaga cccccttcta cgcggactcc 900 acagccgaga catatgccaa gattgtgcac tacagggaac acttgtcgct gccgctggca 960 gacacagttg tccccgagga agctcaggac ctcattcgtg ggctgctgtg tcctgctgag 1020 ataaggctag gtcgaggtgg ggcagacttc gagggtgcca cggacacatg caatttcgat 1080 gtggtggagg accggctcac tgccatggtg agcgggggcg gggagacgct gtcagacatg 1140 caggaagaca tgccccttgg ggtgcgcctg cccttcgtgg gctactccta ctgctgcatg 1200 gccttcagag acaatcaggt cccggacccc acccctatgg aactagaggc cctgcagttg 1260 cctgtgtcag acttgcaagg gcttgacttg cagcccccag tgtccccacc ggatcaagtg 1320 gctgaagagg ctgacctagt ggctgtccct gcccctgtgg ctgaggcaga gaccacggta 1380 acgctgcagc agctccagga agccctggaa gaagaggttc tcacccggca gagcctgagc 1440 cgcgagctgg aggccatccg gaccgccaac cagaacttct ccagccaact acaggaggcc 1500 gaggtccgaa accgagacct ggaggcgcat gttcggcagc tacaggaacg gatggagatg 1560 ctgcaggccc caggagccgc agccatcacg ggggtcccca gtccccgggc cacggatcca 1620 ccttcccatc tagatggccc cccggccgtg gctgtgggcc agtgcccgct ggtggggcca 1680 ggccccatgc accgccgtca cctgctgctc cctgccagga tccctaggcc tggcctatcc 1740 gaggcgcgtt gcctgctcct gttcgccgct gctctggctg ctgccgccac actgggctgc 1800 actgggttgg tggcctatac cggcggtctc accccagtct ggtgtttccc gggagccacc 1860 ttcgccccct gaaccctaag actccaagcc atctttcatt taggcctcct aggaaggtcg 1920 agcgaccagg gagcgaccca aagcgtctct gtgcccatcg cccccccccc cccccccacc 1980 gctccgctcc acacttctgt gagcctgggt ccccacccag ctccgctcct gtgatccagg 2040 cctgccacct ggcggccggg gagggaggaa cagggctcgt gcccagcacc cctggttcct 2100 gcagagctgg tagccaccgc tgctgcagca gctgggcatt cgccgacctt gctttactca 2160 gccccgacgt ggatgggcaa actgctcagc tcatccgatt tcactttttc actctcccag 2220 ccatcagtta caagccataa gcatgagccc cctatttcca gggacatccc attcccatag 2280 tgatggatca gcaagacctc tgccagcaca cacggagtct ttggcttcgg acagcctcac 2340 tcctgggggt tgctgcaact ccttccccgt gtacacgtct gcactctaac aacggagcca 2400 cagctgcact cccccctccc ccaaagcagt gtgggtattt attgatcttg ttatctgact 2460 cactgacaga ctccgggacc cacgttttag atgcattgag actcgacatt cctcggtatt 2520 tattgtctgt ccccacctac gacctccact cccgaccctt gcgaataaaa tacttctggt 2580 ctgccctaaa aaaaaaaaaa aaaaaaaaaa a 2611 <210> SEQ ID NO 794 <211> LENGTH: 988 <212> TYPE: DNA <213> ORGANISM: Mus musculus <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (531)..(531) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (942)..(942) <223> OTHER INFORMATION: n is a, c, g, or t <400> SEQUENCE: 794 gctggaccgg tccggaattc tccggatcgc cagcctttgt gggccatatt cgtcatccct 60 cctggcttct catctgcttt tgtggtccta gctcaagacc tctaattcct ctgctgactt 120 aaatgccctt ccccagaggt cttctcaggc ctagtggaca agcttggagc cttatctgct 180 cctgcccaac attgagccaa agctccagct taccccagct tccttacaat ggaccccatt 240 gcagcaaggc ttaaggaggt ccgactgcag agggatgatt ttgagatttt gaaggtgatc 300 gggcgtgggg cgttcagcga ggtagcggtg gtgaagatga aacagacggg ccaagtgtat 360 gccatgaaga ttatgaataa gtgggacatg ctgaagagag gcgaggtgtc gtgcttccgg 420 gaagaaaggg atgtattagt gaaaggggac cggcgctgga tcacacagct gcactttgcc 480 ttccaggatg agaactacct gtacctggtc atggaatact acgtgggcgg ngacctgcta 540 acgctgctga gcaagttttg gggagcggat ccccgccgag atggctcgct tctacctggc 600 cgagattgtc atggccatag actccgtgca ccggctgggc tacgtgcaca gggacatcaa 660 accagataac attctgctgg accgatgtgg gcacattcgc ctggcagact tcggctcctg 720 gcctcaactg cagcctgatg gaatggtgga gtcccctggt ggctgtgggc acccccggac 780 tacctgtctc ctgaaattct gcagggcctt ggtgggaggc cctggggaag gcaactacgg 840 gccaaaagtt ggaagggggg ggcctggggg gggttcccct atgaaaagtt ctatggggag 900 gacccccttt aagcggaatc ccaggccgaa aaatatgccc angattgggc cctaacaggg 960 aaaacttttc ccctgcccct gggacaat 988 <210> SEQ ID NO 795 <211> LENGTH: 649 <212> TYPE: DNA <213> ORGANISM: Mus musculus <400> SEQUENCE: 795 ggcgtgttcg cctatgagat gttctatggg cagaccccct tctacgcgga ctccacagcc 60 gagacatatg ccaagattgt gcactacagg gaacacttgt cgctgccgct ggcagacaca 120 gttgtccccg aggaagctca ggacctcatt cgtgggctgc tgtgtcctgc tgagataagg 180 ctaggtcgag gtggggcagg tgatttccag aaacatcctt tcttctttgg ccttgattgg 240 gagggtctcc gagacagtgt accccccttt acaccagact tcgagggtgc cacggacaca 300 tgcaatttcg atgtggtgga ggaccggctc actgccatgg agacgctgtc agacatgcag 360 gaagacatgc cccttggggt gcgcctgccc ttcgtgggct actcctactg ctgcatggcc 420 ttcagagaca atcaggtccc ggaccccacc cctatggaac tagaggccct gcagttgcct 480 gtgtcagact tgcaagggct tgacttgcag cccccagtgt ccccaccgga tcaagtggtc 540 ccaactctga tccccaccga caggctgaag aggctgacct agtggctgtc cctgcccctg 600 tggctgaggc agagccacgg taacgctgca gcagctccag gaagccctg 649 <210> SEQ ID NO 796 <211> LENGTH: 527 <212> TYPE: DNA <213> ORGANISM: Mus musculus <400> SEQUENCE: 796 atttcgatgt ggtggaggac cggctcactg ccatggtgag cgggggcggg gagacgctgt 60 cagacatgca ggaagacatg ccccttgggg tgcgcctgcc cttcgtgggc tactcctact 120 gctgcatggc cttcagagac aatcaggtcc cggaccccac ccctatggaa ctagaggccc 180 tgcagttgcc tgtgtcagac ttgcaagggc ttgacttgca gcccccagtg tccccaccgg 240 atcaagtggc tgaagaggct gacctagtgg ctgtccctgc ccctgtggct gaggcagaga 300 ccacggtaac gctgcagcag ctccaggaag ccctggaaga agaggttctc acccggcaga 360 gcctgagccg cgagctggag gccatccgga ccgccaacca gaacttctcc aggaggccga 420 ggtccgaaac cgagacctgg aggcgcatgt tcggcagcta caggaacgga tggagatgct 480 gcaggcccca ggaaccgcag ccatcacggg ggtccccagt cccccgg 527 <210> SEQ ID NO 797 <211> LENGTH: 567 <212> TYPE: DNA <213> ORGANISM: Mus musculus <400> SEQUENCE: 797 atggtgaggt cgctggtggc tgtgggcacc ccggactacc tgtctcctga gattctgcag 60 gccgttggtg gagggcctgg ggcaggcagc tacgggccag agtgtgactg gtgggcactg 120 ggcgtgttcg cctatgagat gttctatggg cagaccccct tctacgcgga ctccacagcc 180 gagacatatg ccaagattgt gcactacagg gaacacttgt cgctgccgct ggcagacaca 240 gttgtccccg aggaagctca ggacctcatt cgtgggctgc tgtgtcctgc tgagataagg 300 ctaggtcgag gtggggcagg tgatttccag aaacatcctt tcttctttgg ccttgattgg 360 gagggtctcc gagacagtgt accccccttt acaccagact tcgagggtgc cacggacaca 420 tgcaatttcg atgtggtgga ggaccggctc actgccatgg tgagcggggg cggggtatga 480 ggacacacag gtgaccagtc cccaagacag tgagtgaggc ttcactcttg gcagtactaa 540 aattgaatgt agggggctgg gctcttg 567 <210> SEQ ID NO 798 <211> LENGTH: 2474 <212> TYPE: DNA <213> ORGANISM: Mus musculus <400> SEQUENCE: 798 ccgggaagaa agggatgtat tagtgaaagg ggaccggcgc tggatcacac agctgcactt 60 tgccttccag gatgagaact acctgtacct ggtcatggaa tactacgtgg gcggggacct 120 gctaacgctg ctgagcaagt ttggggagcg gatccccgcc gagatggctc gcttctacct 180 ggccgagatt gtcatggcca tagactccgt gcaccggctg ggctacgtgc acagggacat 240 caaaccagat aacattctgc tggaccgatg tgggcacatt cgcctggcag acttcggctc 300 ctgcctcaaa ctgcagcctg atggaatggt gaggtcgctg gtggctgtgg gcaccccgga 360 ctacctgtct cctgagattc tgcaggccgt tggtggaggg cctggggcag gcagctacgg 420 gccagagtgt gactggtggg cactgggcgt gttcgcctat gagatgttct atgggcagac 480 ccccttctac gcggactcca cagccgagac atatgccaag attgtgcact acagggaaca 540 cttgtcgctg ccgctggcag acacagttgt ccccgaggaa gctcaggacc tcattcgtgg 600 gctgctgtgt cctgctgaga taaggctagg tcgagacttc gagggtgcca cggacacatg 660 caatttcgat gtggtggagg accggctcac tgccatggtg agcgggggcg gggagacgct 720 gtcagacatg caggaagaca tgccccttgg ggtgcgcctg cccttcgtgg gctactccta 780 ctgctgcatg gccttcagag acaatcaggt cccggacccc acccctatgg aactagaggc 840 cctgcagttg cctgtgtcag acttgcaagg gcttgacttg cagcccccag tgtccccacc 900 ggatcaagtg gctgaagagg ccgacctagt ggctgtccct gcccctgtgg ctgaggcaga 960 gaccacggta acgctgcagc agctccagga agccctggaa gaagaggttc tcacccggca 1020 gagcctgagc cgcgagctgg aggccatccg gaccgccaac cagaacttct ccagccaact 1080 acaggaggcc gaggtccgaa accgagacct ggaggcgcat gttcggcagc tacaggaacg 1140 gatggagatg ctgcaggccc caggagccgc aggcgagtcc ctcacctgct tccagccaag 1200 ggggcactgg gtggagatgg ggggcatgtt gggtgtgtga accctcgggg caggggagga 1260 gtccaggctg gggcaccgca gccgcgccac tgcctttctc ctccatcctc cacactccat 1320 acacctctct cttctccttc cagccatcac gggggtcccc agtccccggg ccacggatcc 1380 accttcccat gcttctcgcc aaatcctccc caagggaact ccctagactc ccgttctggc 1440 ctcgactaga ttcccgcact gcctctcgcc ctgctgctgg gctccgatcg ggtcacctgt 1500 cccttctctc tccagctaga tggccccccg gccgtggctg tgggccagtg cccgctggtg 1560 gggccaggcc ccatgcaccg ccgtcacctg ctgctccctg ccaggatccc taggcctggc 1620 ctatccgagg cgcgttgcct gctcctgttc gccgctgctc tggctgctgc cgccacactg 1680 ggctgcactg ggttggtggc ctataccggc ggtctcaccc cagtctggtg tttcccggga 1740 gccaccttcg ccccctgaac cctaagactc caagccatct ttcatttagg cctcctagga 1800 agatcgagcg accagggagc gacccaaagc gtctctgtgc ccatcgcccc cccccccccc 1860 cccaccgctc cgctccacac ttctgtgagc ctgggtcccc acccagctcc gctcctgtga 1920 tccaggcctg ccacctggcg gccggggagg gaggaacagg gctcgtgccc agcacccctg 1980 gttcctgcag agctggtagc caccgctgct gcagcagctg ggcattcgcc gaccttgctt 2040 tactcagccc tgacgtggat gggctaactg ctcagctcat ccgatttcac tttttcactc 2100 tcccagccat cagttacaag ccataagcat gagcccccta tttccaggga catcccattc 2160 ccatagtgat ggatcagcaa gacctctgcc agcacacacg gagtctttgg cttcggacag 2220 cctcactcct gggggttgct gcaactcctt ccccgtgtac acgtctgcac tctaacaacg 2280 gagccacagc tgcactcccc cctcccccaa agcagtgtgg gtatttattg atcttgttat 2340 ctgactcact gacagactcc gggacccacg ttttagatgc attgagactc gacattcctc 2400 ggtatttatt gtctgtcccc acctacgacc tccactcccg acccttgcga ataaaatact 2460 tctggtctgc ccta 2474 <210> SEQ ID NO 799 <211> LENGTH: 2135 <212> TYPE: DNA <213> ORGANISM: Mus musculus <400> SEQUENCE: 799 ccgggaagaa agggatgtat tagtgaaagg ggaccggcgc tggatcacac agctgcactt 60 tgccttccag gatgagaact acctgtacct ggtcatggaa tactacgtgg gcggggacct 120 gctaacgctg ctgagcaagt ttggggagcg gatccccgcc gagatggctc gcttctacct 180 ggccgagatt gtcatggcca tagactccgt gcaccggctg ggctacgtgc acagggacat 240 caaaccagat aacattctgc tggaccgatg tgggcacatt cgcctggcag acttcggctc 300 ctgcctcaaa ctgcagcctg atggaatggt gaggtcgctg gtggctgtgg gcaccccgga 360 ctacctgtct cctgagattc tgcaggccgt tggtggaggg cctggggcag gcagctacgg 420 gccagagtgt gactggtggg cactgggcgt gttcgcctat gagatgttct atgggcagac 480 ccccttctac gcggactcca cagccgagac atatgccaag attgtgcact acagggaaca 540 cttgtcgctg ccgctggcag acacagttgt ccccgaggaa gctcaggacc tcattcgtgg 600 gctgctgtgt cctgctgaga taaggctagg tcgaggtggg gcaggtgatt tccagaaaca 660 tcctttcttc tttggccttg attgggaggg tctccgagac agtgtacccc cctttacacc 720 agacttcgag ggtgccacgg acacatgcaa tttcgatgtg gtggaggacc ggctcactgc 780 catggagacg ctgtcagaca tgcaggaaga catgcccctt ggggtgcgcc tgcccttcgt 840 gggctactcc tactgctgca tggccttcag agctgaagag gccgacctag tggctgtccc 900 tgcccctgtg gctgaggcag agaccacggt aacgctgcag cagctccagg aagccctgga 960 agaagaggtt ctcacccggc agagcctgag ccgcgagctg gaggccatcc ggaccgccaa 1020 ccagaacttc tccagccaac tacaggaggc cgaggtccga aaccgagacc tggaggcgca 1080 tgttcggcag ctacaggaac ggatggagat gctgcaggcc ccaggagccg cagccatcac 1140 gggggtcccc agtccccggg ccacggatcc accttcccat atggcccccc ggccgtggct 1200 gtgggccagt gcccgctggt ggggccaggc cccatgcacc gccgtcacct gctgctccct 1260 gccaggatcc ctaggcctgg cctatccgag gcgcgttgcc tgctcctgtt cgccgctgct 1320 ctggctgctg ccgccacact gggctgcact gggttggtgg cctataccgg cggtctcacc 1380 ccagtctggt gtttcccggg agccaccttc gccccctgaa ccctaagact ccaagccatc 1440 tttcatttag gcctcctagg aagatcgagc gaccagggag cgacccaaag cgtctctgtg 1500 cccatcgccc cccccccccc ccccaccgct ccgctccaca cttctgtgag cctgggtccc 1560 cacccagctc cgctcctgtg atccaggcct gccacctggc ggccggggag ggaggaacag 1620 ggctcgtgcc cagcacccct ggttcctgca gagctggtag ccaccgctgc tgcagcagct 1680 gggcattcgc cgaccttgct ttactcagcc ctgacgtgga tgggctaact gctcagctca 1740 tccgatttca ctttttcact ctcccagcca tcagttacaa gccataagca tgagccccct 1800 atttccaggg acatcccatt cccatagtga tggatcagca agacctctgc cagcacacac 1860 ggagtctttg gcttcggaca gcctcactcc tgggggttgc tgcaactcct tccccgtgta 1920 cacgtctgca ctctaacaac ggagccacag ctgcactccc ccctccccca aagcagtgtg 1980 ggtatttatt gatcttgtta tctgactcac tgacagactc cgggacccac gttttagatg 2040 cattgagact cgacattcct cggtatttat tgtctgtccc cacctacgac ctccactccc 2100 gacccttgcg aataaaatac ttctggtctg cccta 2135 <210> SEQ ID NO 800 <211> LENGTH: 2873 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <400> SEQUENCE: 800 aggggggctg gaccaagggg tggggagaag gggaggaggc ctcggccggc cgcagagaga 60 agtggccaga gaggcccagg ggacagccag ggacaggcag acatgcagcc agggctccag 120 ggcctggaca ggggctgcca ggccctgtga caggaggacc ccgagccccc ggcccgggga 180 ggggccatgg tgctgcctgt ccaacatgtc agccgaggtg cggctgaggc ggctccagca 240 gctggtgttg gacccgggct tcctggggct ggagcccctg ctcgaccttc tcctgggcgt 300 ccaccaggag ctgggcgcct ccgaactggc ccaggacaag tacgtggccg acttcttgca 360 gtgggcggag cccatcgtgg tgaggcttaa ggaggtccga ctgcagaggg acgacttcga 420 gattctgaag gtgatcggac gcggggcgtt cagcgaggta gcggtagtga agatgaagca 480 gacgggccag gtgtatgcca tgaagatcat gaacaagtgg gacatgctga agaggggcga 540 ggtgtcgtgc ttccgtgagg agagggacgt gttggtgaat ggggaccggc ggtggatcac 600 gcagctgcac ttcgccttcc aggatgagaa ctacctgtac ctggtcatgg agtattacgt 660 gggcggggac ctgctgacac tgctgagcaa gtttggggag cggattccgg ccgagatggc 720 gcgcttctac ctggcggaga ttgtcatggc catagactcg gtgcaccggc ttggctacgt 780 gcacagggac atcaaacccg acaacatcct gctggaccgc tgtggccaca tccgcctggc 840 cgacttcggc tcttgcctca agctgcgggc agatggaacg gtgcggtcgc tggtggctgt 900 gggcacccca gactacctgt cccccgagat cctgcaggct gtgggcggtg ggcctgggac 960 aggcagctac gggcccgagt gtgactggtg ggcgctgggt gtattcgcct atgaaatgtt 1020 ctatgggcag acgcccttct acgcggattc cacggcggag acctatggca agatcgtcca 1080 ctacaaggag cacctctctc tgccgctggt ggacgaaggg gtccctgagg aggctcgaga 1140 cttcattcag cggttgctgt gtcccccgga gacacggctg ggccggggtg gagcaggcga 1200 cttccggaca catcccttct tctttggcct cgactgggat ggtctccggg acagcgtgcc 1260 cccctttaca ccggatttcg aaggtgccac cgacacatgc aacttcgact tggtggagga 1320 cgggctcact gccatggaga cactgtcgga cattcgggaa ggtgcgccgc taggggtcca 1380 cctgcctttt gtgggctact cctactcctg catggccctc agggacagtg aggtcccagg 1440 ccccacaccc atggaactgg aggccgagca gctgcttgag ccacacgtgc aagcgcccag 1500 cctggagccc tcggtgtccc cacaggatga aacagctgaa gtggcagttc cagcggctgt 1560 ccctgcggca gaggctgagg ccgaggtgac gctgcgggag ctccaggaag ccctggagga 1620 ggaggtgctc acccggcaga gcctgagccg ggagatggag gccatccgca cggacaacca 1680 gaacttcgcc agtcaactac gcgaggcaga ggctcggaac cgggacctag aggcacacgt 1740 ccggcagttg caggagcgga tggagttgct gcaggcagag ggagccacag ctgtcacggg 1800 ggtccccagt ccccgggcca cggatccacc ttcccatatg gccccccggc cgtggctgtg 1860 ggccagtgcc cgctggtggg gccaggcccc atgcaccgcc gccacctgct gctccctgcc 1920 agggtcccta ggcctggcct atcggaggcg ctttccctgc tcctgttcgc cgttgttctg 1980 tctcgtgccg ccgccctggg ctgcattggg ttggtggccc acgccggcca actcaccgca 2040 gtctggcgcc gcccaggagc cgcccgcgct ccctgaaccc tagaactgtc ttcgactccg 2100 gggccccgtt ggaagactga gtgcccgggg cacggcacag aagccgcgcc caccgcctgc 2160 cagttcacaa ccgctccgag cgtgggtctc cgcccagctc cagtcctgtg atccgggccc 2220 gccccctagc ggccggggag ggaggggccg ggtccgcggc cggcgaacgg ggctcgaagg 2280 gtccttgtag ccgggaatgc tgctgctgct gctgctgctg ctgctgctgc tgctgctgct 2340 gctgctgctg ctgctgctgg ggggatcaca gaccatttct ttctttcggc caggctgagg 2400 ccctgacgtg gatgggcaaa ctgcaggcct gggaaggcag caagccgggc cgtccgtgtt 2460 ccatcctcca cgcaccccca cctatcgttg gttcgcaaag tgcaaagctt tcttgtgcat 2520 gacgccctgc tctggggagc gtctggcgcg atctctgcct gcttactcgg gaaatttgct 2580 tttgccaaac ccgctttttc ggggatcccg cgcccccctc ctcacttgcg ctgctctcgg 2640 agccccagcc ggctccgccc gcttcggcgg tttggatatt tattgacctc gtcctccgac 2700 tcgctgacag gctacaggac ccccaacaac cccaatccac gttttggatg cactgagacc 2760 ccgacattcc tcggtattta ttgtctgtcc ccacctagga cccccacccc cgaccctcgc 2820 gaataaaagg ccctccatct gcccaaaaaa aaaaaaaaaa aaaaaaaaaa aaa 2873 <210> SEQ ID NO 801 <211> LENGTH: 1509 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <400> SEQUENCE: 801 ccaccgcagc ggacagcgcc aagtgaagcc tcgcttcccc tccgcggcga ccagggcccg 60 agccgagagt agcagttgta gctacccgcc cagaaactag acacaatgtg cgacgaagac 120 gagaccaccg ccctcgtgtg cgacaatggc tccggcctgg tgaaagccgg cttcgccggg 180 gatgacgccc ctagggccgt gttcccgtcc atcgtgggcc gcccccgaca ccagggcgtc 240 atggtcggta tgggtcagaa agattcctac gtgggcgacg aggctcagag caagagaggt 300 atcctgaccc tgaagtaccc tatcgagcac ggcatcatca ccaactggga tgacatggag 360 aagatctggc accacacctt ctacaacgag cttcgcgtgg ctcccgagga gcaccccacc 420 ctgctcaccg aggcccccct caatcccaag gccaaccgcg agaagatgac ccagatcatg 480 tttgagacct tcaacgtgcc cgccatgtac gtggccatcc aggccgtgct gtccctctac 540 gcctccggca ggaccaccgg catcgtgctg gactccggcg acggcgtcac ccacaacgtg 600 cccatttatg agggctacgc gctgccgcac gccatcatgc gcctggacct ggcgggccgc 660 gatctcaccg actacctgat gaagatcctc actgagcgtg gctactcctt cgtgaccaca 720 gctgagcgcg agatcgtgcg cgacatcaag gagaagctgt gctacgtggc cctggacttc 780 gagaacgaga tggcgacggc cgcctcctcc tcctccctgg aaaagagcta cgagctgcca 840 gacgggcagg tcatcaccat cggcaacgag cgcttccgct gcccggagac gctcttccag 900 ccctccttca tcggtatgga gtcggcgggc attcacgaga ccacctacaa cagcatcatg 960 aagtgtgaca tcgacatcag gaaggacctg tatgccaaca acgtcatgtc ggggggcacc 1020 acgatgtacc ctgggatcgc tgaccgcatg cagaaagaga tcaccgcgct ggcacccagc 1080 accatgaaga tcaagatcat cgccccgccg gagcgcaaat actcggtgtg gatcggcggc 1140 tccatcctgg cctcgctgtc caccttccag cagatgtgga tcaccaagca ggagtacgac 1200 gaggccggcc cttccatcgt ccaccgcaaa tgcttctaga cacactccac ctccagcacg 1260 cgacttctca ggacgacgaa tcttctcaat gggggggcgg ctgagctcca gccaccccgc 1320 agtcactttc tttgtaacaa cttccgttgc tgccatcgta aactgacaca gtgtttataa 1380 cgtgtacata cattaactta ttacctcatt ttgttatttt tcgaaacaaa gccctgtgga 1440 agaaaatgga aaacttgaag aagcattaaa gtcattctgt taagctgcgt aaaaaaaaaa 1500 aaaaaaaaa 1509 <210> SEQ ID NO 802 <211> LENGTH: 19 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 802 gcagcagcag cagcagcag 19 <210> SEQ ID NO 803 <211> LENGTH: 19 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 803 gcagcagcag cagcagcag 19 <210> SEQ ID NO 804 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 804 agcagcagca gcagcagcag 20 <210> SEQ ID NO 805 <211> LENGTH: 18 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 805 gcagcagcag cagcagca 18 <210> SEQ ID NO 806 <211> LENGTH: 19 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 806 agcagcagca gcagcagca 19 <210> SEQ ID NO 807 <211> LENGTH: 16 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 807 agcagcagca gcagca 16 <210> SEQ ID NO 808 <211> LENGTH: 16 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 808 ctcccgacaa gctcca 16 <210> SEQ ID NO 809 <211> LENGTH: 14 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 809 tcccgacaag ctcc 14 <210> SEQ ID NO 810 <211> LENGTH: 16 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 810 gcttgcacgt gtggct 16 <210> SEQ ID NO 811 <211> LENGTH: 14 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 811 cttgcacgtg tggc 14 <210> SEQ ID NO 812 <211> LENGTH: 16 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 812 ggttgtgaac tggcag 16 <210> SEQ ID NO 813 <211> LENGTH: 14 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 813 gttgtgaact ggca 14 <210> SEQ ID NO 814 <211> LENGTH: 16 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 814 gagcggttgt gaactg 16 <210> SEQ ID NO 815 <211> LENGTH: 14 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 815 agcggttgtg aact 14 <210> SEQ ID NO 816 <211> LENGTH: 16 <212> TYPE: DNA <213> ORGANISM: Artificial sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 816 gctgccttcc caggcc 16 <210> SEQ ID NO 817 <211> LENGTH: 14 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 817 ctgccttccc aggc 14 <210> SEQ ID NO 818 <211> LENGTH: 16 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 818 gcactttgcg aaccaa 16 <210> SEQ ID NO 819 <211> LENGTH: 14 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 819 cactttgcga acca 14 <210> SEQ ID NO 820 <211> LENGTH: 16 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 820 gaaagctttg cacttt 16 <210> SEQ ID NO 821 <211> LENGTH: 14 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 821 aaagctttgc actt 14 <210> SEQ ID NO 822 <211> LENGTH: 16 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 822 cggaggacga ggtcaa 16 <210> SEQ ID NO 823 <211> LENGTH: 14 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 823 ggaggacgag gtca 14 <210> SEQ ID NO 824 <211> LENGTH: 16 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 824 agcctgtcag cgagtc 16 <210> SEQ ID NO 825 <211> LENGTH: 14 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 825 gcctgtcagc gagt 14 <210> SEQ ID NO 826 <211> LENGTH: 16 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 826 tcctgtagcc tgtcag 16 <210> SEQ ID NO 827 <211> LENGTH: 14 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 827 cctgtagcct gtca 14 <210> SEQ ID NO 828 <211> LENGTH: 16 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 828 gaagcgaggc ttcact 16 <210> SEQ ID NO 829 <211> LENGTH: 14 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 829 aagcgaggct tcac 14 <210> SEQ ID NO 830 <211> LENGTH: 16 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 830 acctgcccgt ctggca 16 <210> SEQ ID NO 831 <211> LENGTH: 14 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 831 cctgcccgtc tggc 14 <210> SEQ ID NO 832 <211> LENGTH: 16 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 832 ggtcagcgat cccagg 16 <210> SEQ ID NO 833 <211> LENGTH: 14 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 833 gtcagcgatc ccag 14 <210> SEQ ID NO 834 <211> LENGTH: 16 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 834 attttcttcc acaggg 16 <210> SEQ ID NO 835 <211> LENGTH: 14 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 835 ttttcttcca cagg 14 <210> SEQ ID NO 836 <211> LENGTH: 16 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 836 gaatgacttt aatgct 16 <210> SEQ ID NO 837 <211> LENGTH: 14 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 837 aatgacttta atgc 14

1 SEQUENCE LISTING <160> NUMBER OF SEQ ID NOS: 837 <210> SEQ ID NO 1 <211> LENGTH: 2877 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <400> SEQUENCE: 1 aggggggctg gaccaagggg tggggagaag gggaggaggc ctcggccggc cgcagagaga 60 agtggccaga gaggcccagg ggacagccag ggacaggcag acatgcagcc agggctccag 120 ggcctggaca ggggctgcca ggccctgtga caggaggacc ccgagccccc ggcccgggga 180 ggggccatgg tgctgcctgt ccaacatgtc agccgaggtg cggctgaggc ggctccagca 240 gctggtgttg gacccgggct tcctggggct ggagcccctg ctcgaccttc tcctgggcgt 300 ccaccaggag ctgggcgcct ccgaactggc ccaggacaag tacgtggccg acttcttgca 360 gtgggcggag cccatcgtgg tgaggcttaa ggaggtccga ctgcagaggg acgacttcga 420 gattctgaag gtgatcggac gcggggcgtt cagcgaggta gcggtagtga agatgaagca 480 gacgggccag gtgtatgcca tgaagatcat gaacaagtgg gacatgctga agaggggcga 540 ggtgtcgtgc ttccgtgagg agagggacgt gttggtgaat ggggaccggc ggtggatcac 600 gcagctgcac ttcgccttcc aggatgagaa ctacctgtac ctggtcatgg agtattacgt 660 gggcggggac ctgctgacac tgctgagcaa gtttggggag cggattccgg ccgagatggc 720 gcgcttctac ctggcggaga ttgtcatggc catagactcg gtgcaccggc ttggctacgt 780 gcacagggac atcaaacccg acaacatcct gctggaccgc tgtggccaca tccgcctggc 840 cgacttcggc tcttgcctca agctgcgggc agatggaacg gtgcggtcgc tggtggctgt 900 gggcacccca gactacctgt cccccgagat cctgcaggct gtgggcggtg ggcctgggac 960 aggcagctac gggcccgagt gtgactggtg ggcgctgggt gtattcgcct atgaaatgtt 1020 ctatgggcag acgcccttct acgcggattc cacggcggag acctatggca agatcgtcca 1080 ctacaaggag cacctctctc tgccgctggt ggacgaaggg gtccctgagg aggctcgaga 1140 cttcattcag cggttgctgt gtcccccgga gacacggctg ggccggggtg gagcaggcga 1200 cttccggaca catcccttct tctttggcct cgactgggat ggtctccggg acagcgtgcc 1260 cccctttaca ccggatttcg aaggtgccac cgacacatgc aacttcgact tggtggagga 1320 cgggctcact gccatggaga cactgtcgga cattcgggaa ggtgcgccgc taggggtcca 1380 cctgcctttt gtgggctact cctactcctg catggccctc agggacagtg aggtcccagg 1440 ccccacaccc atggaactgg aggccgagca gctgcttgag ccacacgtgc aagcgcccag 1500 cctggagccc tcggtgtccc cacaggatga aacagctgaa gtggcagttc cagcggctgt 1560 ccctgcggca gaggctgagg ccgaggtgac gctgcgggag ctccaggaag ccctggagga 1620 ggaggtgctc acccggcaga gcctgagccg ggagatggag gccatccgca cggacaacca 1680 gaacttcgcc agtcaactac gcgaggcaga ggctcggaac cgggacctag aggcacacgt 1740 ccggcagttg caggagcgga tggagttgct gcaggcagag ggagccacag ctgtcacggg 1800 ggtccccagt ccccgggcca cggatccacc ttcccatcta gatggccccc cggccgtggc 1860 tgtgggccag tgcccgctgg tggggccagg ccccatgcac cgccgccacc tgctgctccc 1920 tgccagggtc cctaggcctg gcctatcgga ggcgctttcc ctgctcctgt tcgccgttgt 1980 tctgtctcgt gccgccgccc tgggctgcat tgggttggtg gcccacgccg gccaactcac 2040 cgcagtctgg cgccgcccag gagccgcccg cgctccctga accctagaac tgtcttcgac 2100 tccggggccc cgttggaaga ctgagtgccc ggggcacggc acagaagccg cgcccaccgc 2160 ctgccagttc acaaccgctc cgagcgtggg tctccgccca gctccagtcc tgtgatccgg 2220 gcccgccccc tagcggccgg ggagggaggg gccgggtccg cggccggcga acggggctcg 2280 aagggtcctt gtagccggga atgctgctgc tgctgctgct gctgctgctg ctgctgctgc 2340 tgctgctgct gctgctgctg ctggggggat cacagaccat ttctttcttt cggccaggct 2400 gaggccctga cgtggatggg caaactgcag gcctgggaag gcagcaagcc gggccgtccg 2460 tgttccatcc tccacgcacc cccacctatc gttggttcgc aaagtgcaaa gctttcttgt 2520 gcatgacgcc ctgctctggg gagcgtctgg cgcgatctct gcctgcttac tcgggaaatt 2580 tgcttttgcc aaacccgctt tttcggggat cccgcgcccc cctcctcact tgcgctgctc 2640 tcggagcccc agccggctcc gcccgcttcg gcggtttgga tatttattga cctcgtcctc 2700 cgactcgctg acaggctaca ggacccccaa caaccccaat ccacgttttg gatgcactga 2760 gaccccgaca ttcctcggta tttattgtct gtccccacct aggaccccca cccccgaccc 2820 tcgcgaataa aaggccctcc atctgcccaa aaaaaaaaaa aaaaaaaaaa aaaaaaa 2877 <210> SEQ ID NO 2 <211> LENGTH: 14411 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <400> SEQUENCE: 2 ctcccagccc agcgcctccc accccttttc atagcaggaa aagccggagc ccagggaggg 60 aacggacctg cgagtcacac aactggtgac ccacaccagc ggctggagca ggaccctctt 120 ggggagaaga gcatcctgcc cgcagccagg gcccctcatc aaagtcctcg gtgtttttta 180 aattatcaga actgcccagg accacgtttc ccaggccctg cccagctggg actcctcggt 240 ccttgcctcc tagtttctca ggcctggccc tctcaaggcc caggcacccc aggccggttg 300 gaggccccga cttccactct ggagaaccgt ccaccctgga aagaagagct cagattcctc 360 ttggctctcg gagccgcagg gagtgtgtct tcccgcgcca ccctccaccc cccgaaatgt 420 ttctgtttct aatcccagcc tgggcaggaa tgtggctccc cggccagggg ccaaggagct 480 attttggggt ctcgtttgcc cagggagggc ttggctccac cactttcctc ccccagcctt 540 tgggcagcag gtcacccctg ttcaggctct gagggtgccc cctcctggtc ctgtcctcac 600 caccccttcc ccacctcctg ggaaaaaaaa aaaaaaaaaa aaaaaaagct ggtataaagc 660 agagagcctg agggctaaat ttaactgtcc gagtcggaat ccatctctga gtcacccaag 720 aagctgccct ggcctcccgt ccccttccca ggcctcaacc cctttctccc acccagcccc 780 aacccccagc cctcaccccc tagcccccag ttctggagct tgtcgggagc aagggggtgg 840 ttgctactgg gtcactcagc ctcaattggc cctgtttcag caatgggcag gttcttcttg 900 aaattcatca cacctgtggc ttcctctgtg ctctaccttt ttattggggt gacagtgtga 960 cagctgagat tctccatgca ttccccctac tctagcactg aagggttctg aagggccctg 1020 gaaggaggga gcttgggggg ctggcttgtg aggggttaag gctgggaggc gggagggggg 1080 ctggaccaag gggtggggag aaggggagga ggcctcggcc ggccgcagag agaagtggcc 1140 agagaggccc aggggacagc cagggacagg cagacatgca gccagggctc cagggcctgg 1200 acaggggctg ccaggccctg tgacaggagg accccgagcc cccggcccgg ggaggggcca 1260 tggtgctgcc tgtccaacat gtcagccgag gtgcggctga ggcggctcca gcagctggtg 1320 ttggacccgg gcttcctggg gctggagccc ctgctcgacc ttctcctggg cgtccaccag 1380 gagctgggcg cctccgaact ggcccaggac aagtacgtgg ccgacttctt gcagtggggt 1440 gagtgcctac cctcggggct cctgcagatg gggtgggggt ggggcaggag acaggtctgg 1500 gcacagaggc ctggctgttg ggggggcagg atggcaggat gggcatgggg agatcctccc 1560 atcctggggc tcagagtgtg gacctgggcc ctggggcaac atttctctgt cctatgccac 1620 cactctggag gggcagagta aggtcagcag aggctagggt ggctgtgact cagagccatg 1680 gcttaggagt cacagcaggc taggctgcca acagcctccc atggcctctc tgcaccccgc 1740 ctcagggtca gggtcagggt catgctggga gctccctctc ctaggaccct ccccccaaaa 1800 gtgggctcta tggccctctc ccctggtttc ctgtggcctg gggcaagcca ggagggccag 1860 catggggcag ctgccagggg cgcagccgac aggcaggtgt tcggcgccag cctctccagc 1920 tgccccaaca ggtgcccagg cactgggagg gcggtgactc acgcgggccc tgtgggagaa 1980 ccagctttgc agacaggcgc caccagtgcc ccctcctctg cgatccagga gggacaactt 2040 tgggttcttc tgggtgtgtc tccttctttt gtaggttctg cacccacccc cacccccagc 2100 cccaaagtct cggttcctat gagccgtgtg ggtcagccac cattcccgcc accccgggtc 2160 cctgcgtcct ttagttctcc tggcccaggg cctccaacct tccagctgtc ccacaaaacc 2220 ccttcttgca agggctttcc agggcctggg gccagggctg gaaggaggat gcttccgctt 2280 ctgccagctg ccttgtctgc ccacctcctc cccaagccca ggactcgggc tcactggtca 2340 ctggtttctt tcattcccag caccctgccc ctctggccct catatgtctg gccctcagtg 2400 actggtgttt ggtttttggc ctgtgtgtaa caaactgtgt gtgacacttg tttcctgttt 2460 ctccgccttc ccctgcttcc tcttgtgtcc atctctttct gacccaggcc tggttccttt 2520 ccctcctcct cccatttcac agatgggaag gtggaggcca agaagggcca ggccattcag 2580 cctctggaaa aaccttctcc caacctccca cagcccctaa tgactctcct ggcctccctt 2640 tagtagagga tgaagttggg ttggcagggt aaactgagac cgggtggggt aggggtctgg 2700 cgctcccggg aggagcactc cttttgtggc ccgagctgca tctcgcggcc cctcccctgc 2760 caggcctggg gcgggggagg gggccagggt tcctgctgcc ttaaaagggc tcaatgtctt 2820 ggctctctcc tccctccccc gtcctcagcc ctggctggtt cgtccctgct ggcccactct 2880 cccggaaccc cccggaaccc ctctctttcc tccagaaccc actgtctcct ctccttccct 2940 cccctcccat acccatccct ctctccatcc tgcctccact tcttccaccc ccgggagtcc 3000 aggcctccct gtccccacag tccctgagcc acaagcctcc accccagctg gtcccccacc 3060 caggctgccc agtttaacat tcctagtcat aggaccttga cttctgagag gcctgattgt 3120 catctgtaaa taaggggtag gactaaagca ctcctcctgg aggactgaga gatgggctgg 3180 accggagcac ttgagtctgg gatatgtgac catgctacct ttgtctccct gtcctgttcc 3240 ttcccccagc cccaaatcca gggttttcca aagtgtggtt caagaaccac ctgcatctga 3300 atctagaggt actggataca accccacgtc tgggccgtta cccaggacat tctacatgag 3360 aacgtggggg tggggccctg gctgcacctg aactgtcacc tggagtcagg gtggaaggtg 3420 gaagaactgg gtcttatttc cttctcccct tgttctttag ggtctgtcct tctgcagact 3480 ccgttacccc accctaacca tcctgcacac ccttggagcc ctctgggcca atgccctgtc 3540 ccgcaaaggg cttctcaggc atctcacctc tatgggaggg catttttggc ccccagaacc 3600 ttacacggtg tttatgtggg gaagcccctg ggaagcagac agtcctaggg tgaagctgag 3660 aggcagagag aaggggagac agacagaggg tggggctttc ccccttgtct ccagtgccct 3720 ttctggtgac cctcggttct tttcccccac caccccccca gcggagccca tcgtggtgag 3780 gcttaaggag gtccgactgc agagggacga cttcgagatt ctgaaggtga tcggacgcgg 3840 ggcgttcagc gaggtaagcc gaaccgggcg ggagcctgac ttgactcgtg gtgggcgggg 3900 cataggggtt ggggcggggc cttagaaatt gatgaatgac cgagccttag aacctagggc 3960 tgggctggag gcggggcttg ggaccaatgg gcgtggtgtg gcaggtgggg cggggccacg 4020

gctgggtgca gaagcgggtg gagttgggtc tgggcgagcc cttttgtttt cccgccgtct 4080 ccactctgtc tcactatctc gacctcaggt agcggtagtg aagatgaagc agacgggcca 4140 ggtgtatgcc atgaagatca tgaacaagtg ggacatgctg aagaggggcg aggtgagggg 4200 ctgggcggac gtggggggct ttgaggatcc gcgccccgtc tccggctgca gctcctccgg 4260 gtgccctgca ggtgtcgtgc ttccgtgagg agagggacgt gttggtgaat ggggaccggc 4320 ggtggatcac gcagctgcac ttcgccttcc aggatgagaa ctacctggtg agctccgggc 4380 cggggtgact aggaagaggg acaagagccc gtgctgtcac tggacgagga ggtggggaga 4440 ggaagctcta ggattggggg tgctgcccgg aaacgtctgt gggaaagtct gtgtgcggta 4500 agagggtgtg tcaggtggat gaggggcctt ccctatctga gacggggatg gtgtccttca 4560 ctgcccgttt ctggggtgat ctgggggact cttataaaga tgtctctgtt gcggggggtc 4620 tcttacctgg aatgggatag gtcttcagga attctaacgg ggccactgcc tagggaagga 4680 gtgtctggga cctattctct gggtgttggg tggcctctgg gttctctttc ccagaacatc 4740 tcagggggag tgaatctgcc cagtgacatc ccaggaaagt ttttttgttt gtgttttttt 4800 ttgaggggcg ggggcggggg ccgcaggtgg tctctgattt ggcccggcag atctctatgg 4860 ttatctctgg gctggggctg caggtctctg cccaaggatg gggtgtctct gggaggggtt 4920 gtcccagcca tccgtgatgg atcagggcct caggggacta ccaaccaccc atgacgaacc 4980 ccttctcagt acctggtcat ggagtattac gtgggcgggg acctgctgac actgctgagc 5040 aagtttgggg agcggattcc ggccgagatg gcgcgcttct acctggcgga gattgtcatg 5100 gccatagact cggtgcaccg gcttggctac gtgcacaggt gggtgcagca tggccgaggg 5160 gatagcaagc ttgttccctg gccgggttct tggaaggtca gagcccagag aggccagggc 5220 ctggagaggg accttcttgg ttggggccca ccggggggtg cctgggagta ggggtcagaa 5280 ctgtagaagc cctacagggg cggaacccga ggaagtgggg tcccaggtgg cactgcccgg 5340 aggggcggag cctggtggga ccacagaagg gaggttcatt tatcccaccc ttctcttttc 5400 ctccgtgcag ggacatcaaa cccgacaaca tcctgctgga ccgctgtggc cacatccgcc 5460 tggccgactt cggctcttgc ctcaagctgc gggcagatgg aacggtgagc cagtgccctg 5520 gccacagagc aactggggct gctgatgagg gatggaaggc acagagtgtg ggagcgggac 5580 tggatttgga ggggaaaaga ggtggtgtga cccaggctta agtgtgcatc tgtgtggcgg 5640 agtattagac caggcagagg gaggggctaa gcatttgggg agtggttgga aggagggccc 5700 agagctggtg ggcccagagg ggtgggccca agcctcgctc tgctcctttt ggtccaggtg 5760 cggtcgctgg tggctgtggg caccccagac tacctgtccc ccgagatcct gcaggctgtg 5820 ggcggtgggc ctgggacagg cagctacggg cccgagtgtg actggtgggc gctgggtgta 5880 ttcgcctatg aaatgttcta tgggcagacg cccttctacg cggattccac ggcggagacc 5940 tatggcaaga tcgtccacta caaggtgagc acggccgcag ggagacctgg cctctcccgg 6000 taggcgctcc caggctatcg cctcctctcc ctctgagcag gagcacctct ctctgccgct 6060 ggtggacgaa ggggtccctg aggaggctcg agacttcatt cagcggttgc tgtgtccccc 6120 ggagacacgg ctgggccggg gtggagcagg cgacttccgg acacatccct tcttctttgg 6180 cctcgactgg gatggtctcc gggacagcgt gccccccttt acaccggatt tcgaaggtgc 6240 caccgacaca tgcaacttcg acttggtgga ggacgggctc actgccatgg tgagcggggg 6300 cggggtaggt acctgtggcc cctgctcggc tgcgggaacc tccccatgct ccctccataa 6360 agttggagta aggacagtgc ctaccttctg gggtcctgaa tcactcattc cccagagcac 6420 ctgctctgtg cccatctact actgaggacc cagcagtgac ctagacttac agtccagtgg 6480 gggaacacag agcagtcttc agacagtaag gccccagagt gatcagggct gagacaatgg 6540 agtgcagggg gtgggggact cctgactcag caaggaaggt cctggagggc tttctggagt 6600 ggggagctat ctgagctgag acttggaggg atgagaagca ggagaggact cctcctccct 6660 taggccgtct ctcttcaccg tgtaacaagc tgtcatggca tgcttgctcg gctctgggtg 6720 cccttttgct gaacaatact ggggatccag cacggaccag atgagctctg gtccctgccc 6780 tcatccagtt gcagtctaga gaattagaga attatggaga gtgtggcagg tgccctgaag 6840 ggaagcaaca ggatacaaga aaaaatgatg gggccaggca cggtggctca cgcctgtaac 6900 cccagcaatt tggcaggccg aagtgggtgg attgcttgag cccaggagtt cgagaccagc 6960 ctgggcaatg tggtgagacc cccgtctcta caaaaatgtt ttaaaaattg gttgggcgtg 7020 gtggcgcatg cctgtatact cagctactag ggtggccgac gtgggcttga gcccaggagg 7080 tcaaggctgc agtgagctgt gattgtgcca ctgcactcca gcctgggcaa cggagagaga 7140 ctctgtctca aaaataagat aaactgaaat taaaaaatag gctgggctgg ccgggcgtgg 7200 tggctcacgc ctgtaatctc agcactttgg gaggccgagg cgggtggatc acgaggtcag 7260 gagatcgaga ccatcttggc taacacggtg aaaccccatc tctcctaaaa atacaaaaaa 7320 ttagccaggc gtggtggcgg gcgcctgtag tcccagctac tcaggaggct gaggcaggag 7380 aatggcgtga acccgggagg cagagtttgc agtgagccga gatcgtgcca ctgcactcca 7440 gcctgggcga cagagcgaga ctctgtctca gaaaaaaaaa aaaaaaaaaa aaaaaatagg 7500 ctggaccgcg gccgggcgct gtggctcatg cctgtaatcc cagcactttg ggagtccaag 7560 gccggtgggt catgagatca ggagttttga gactaggctg gccaacacgg tgaaaccccg 7620 tctctactaa aaatacaaga aaattagctg ggtgtggtct cgggtgcctg taattccagt 7680 tactggggaa gctgaggcag gagaattgct tgaacctggg aggcagagtt tgcagtgagc 7740 caagatcatg ccactacact ccagtctggg tgacagagtg agactctgtc tcaaaaaaaa 7800 aaaaaaaaaa aagggttggg caaggtggtt cacgcctgta atcccagaac tttgggaggc 7860 tgaggcaggc agatcactgg aagtcaggag ttcaagacca gcctggccaa catggtgaaa 7920 ccctgtgtct actaaaaata caaaatttag ccaggcttgg tggcgtatgc ctgtaatgcc 7980 agctactcag gaggctgagg caggagaatc gcttgattga acctgggagg cagagtttgc 8040 agtgggctgg ggttgtgcca ctgcactcta ggctgggaga cagcaagact ccatctaaaa 8100 aaaaaaaaca gaactgggct gggcacagtg gcttatattt gtaatcccag cactttggga 8160 ggctgaggtt ggaggactgc ttgagcccag agtttgggac tacaacagct gaggtaggcg 8220 gatcacttga ggtcagaaga tggagaccag cctggccagc gtggcgaaac cccgtctcta 8280 ccaaaaatat aaaaaattag ccaggcgtgg tagagggcgc ctgtaatctc agctactcag 8340 gacgctgagg caggagaatc gcctgaacct gggaggcgga ggttgcagtg agctgagatt 8400 gcaccactgc actccagcct gggtaacaga gcgagactcc gtatcaaaga aaaagaaaaa 8460 agaaaaaatg ctggaggggc cactttagat aagccctgag ttggggctgg tttgggggga 8520 acatgtaagc caagatcaaa aagcagtgag gggcccgccc tgacgactgc tgctcacatc 8580 tgtgtgtctt gcgcaggaga cactgtcgga cattcgggaa ggtgcgccgc taggggtcca 8640 cctgcctttt gtgggctact cctactcctg catggccctc aggtaagcac tgccctggac 8700 ggcctccagg ggccacgagg ctgcttgagc ttcctgggtc ctgctccttg gcagccaatg 8760 gagttgcagg atcagtcttg gaaccttact gttttgggcc caaagactcc taagaggcca 8820 gagttggagg accttaaatt ttcagatcta tgtacttcaa aatgttagat tgaattttaa 8880 aacctcagag tcacagactg ggcttcccag aatcttgtaa ccattaactt ttacgtctgt 8940 agtacacaga gccacaggac ttcagaactt ggaaaatatg aagtttagac ttttacaatc 9000 agttgtaaaa gaatgcaaat tctttgaatc agccatataa caataaggcc atttaaaagt 9060 attaatttag gcgggccgcg gtggctcacg cctgtaatcc tagcactttg ggaggccaag 9120 gcaggtggat catgaggtca ggagatcgag accatcctgg ctaacacggt gaaaccccgt 9180 ctctactaaa aatacaaaaa aattagccgg gcatggtggc gggcgcttgc ggtcccagct 9240 acttgggagg cgaggcagga gaatggcatg aacccgggag gcggagcttg cagtgagccg 9300 agatcatgcc actgcactcc agcctgggcg acagagcaag actccgtctc aaaaaaaaaa 9360 aaaaaaaagt atttatttag gccgggtgtg gtggctcacg cctgtaattc cagtgctttg 9420 ggaggatgag gtgggtggat cacctgaggt caggagttcg agaccagcct gaccaacgtg 9480 gagaaacctc atctctacta aaaaacaaaa ttagccaggc gtggtggcat atacctgtaa 9540 tcccagctac tcaggaggct gaggcaggag aatcagaacc caggaggggg aggttgtggt 9600 gagctgagat cgtgccattg cattccagcc tgggcaacaa gagtgaaact tcatctcaaa 9660 aaaaaaaaaa aaaaagtact aatttacagg ctgggcatgg tggctcacgc ttggaatccc 9720 agcactttgg gaggctgaag tggacggatt gcttcagccc aggagttcaa gaccagcctg 9780 agcaacataa tgagaccctg tctctacaaa aaattgaaaa aatcgtgcca ggcatggtgg 9840 tctgtgcctg cagtcctagc tactcaggag tctgaagtag gagaatcact tgagcctgga 9900 gtttgaggct tcagtgagcc atgatagatt ccagcctagg caacaaagtg agacctggtc 9960 tcaacaaaag tattaattac acaaataatg cattgcttat cacaagtaaa ttagaaaata 10020 cagataagga aaaggaagtt gatatctcgt gagctcacca gatggcagtg gtccctggct 10080 cacacgtgta ctgacacatg tttaaatagt ggagaacagg tgtttttttg gtttgttttt 10140 ttccccttcc tcatgctact ttgtctaaga gaacagttgg ttttctagtc agcttttatt 10200 actggacaac attacacata ctatacctta tcattaatga actccagctt gattctgaac 10260 cgctgcgggg cctgaacggt gggtcaggat tgaacccatc ctctattaga acccaggcgc 10320 atgtccagga tagctaggtc ctgagccgtg ttcccacagg agggactgct gggttggagg 10380 ggacagccac ttcatacccc agggaggagc tgtccccttc ccacagctga gtggggtgtg 10440 ctgacctcaa gttgccatct tggggtccca tgcccagtct taggaccaca tctgtggagg 10500 tggccagagc caagcagtct ccccatcagg tcggcctccc tgtcctgagg ccctgagaag 10560 aggggtctgc agcggtcaca tgtcaaggga ggagatgagc tgaccctaga acatgggggt 10620 ctggacccca agtccctgca gaaggtttag aaagagcagc tcccaggggc ccaaggccag 10680 gagaggggca gggcttttcc taagcagagg aggggctatt ggcctacctg ggactctgtt 10740 ctcttcgctc tgctgctccc cttcctcaaa tcaggaggtc ttggaagcag ctgcccctac 10800 ccacaggcca gaagttctgg ttctccacca gagaatcagc attctgtctc cctccccact 10860 ccctcctcct ctccccaggg acagtgaggt cccaggcccc acacccatgg aactggaggc 10920 cgagcagctg cttgagccac acgtgcaagc gcccagcctg gagccctcgg tgtccccaca 10980 ggatgaaaca gtaagttggt ggaggggagg gggtccgtca gggacaattg ggagagaaaa 11040 ggtgagggct tcccgggtgg cgtgcactgt agagccctct agggacttcc tgaacagaag 11100 cagacagaaa ccacggagag acgaggttac ttcagacatg ggacggtctc tgtagttaca 11160 gtggggcatt aagtaagggt gtgtgtgttg ctggggatct gagaagtcga tctttgagct 11220 gagcgctggt gaaggagaaa caagccatgg aaggaaaggt gccaagtggt caggcgagag 11280 cctccagggc aaaggccttg ggcaggtggg aatcctgatt tgttcctgaa aggtagtttg 11340 gctgaatcat tcctgagaag gctggagagg ccagcaggaa acaaaaccca gcaaggcctt 11400 ttgtcgtgag ggcattaggg agctggaggg attttgagca gcagagggac ataggttgtg 11460 ttagtgtttg agcaccagcc ctctggtccc tgtgtagatt tagaggacca gactcaggga 11520

tggggctgag ggaggtaggg aagggagggg gcttggatca ttgcaggagc tatggggatt 11580 ccagaaatgt tgaggggacg gaggagtagg ggataaacaa ggattcctag cctggaacca 11640 gtgcccaagt cctgagtctt ccaggagcca caggcagcct taagcctggt ccccatacac 11700 aggctgaagt ggcagttcca gcggctgtcc ctgcggcaga ggctgaggcc gaggtgacgc 11760 tgcgggagct ccaggaagcc ctggaggagg aggtgctcac ccggcagagc ctgagccggg 11820 agatggaggc catccgcacg gacaaccaga acttcgccag gtcgggatcg gggccggggc 11880 cggggccggg atgcgggccg gtggcaaccc ttggcatccc ctctcgtccg gcccggacgg 11940 actcaccgtc cttacctccc cacagtcaac tacgcgaggc agaggctcgg aaccgggacc 12000 tagaggcaca cgtccggcag ttgcaggagc ggatggagtt gctgcaggca gagggagcca 12060 caggtgagtc cctcatgtgt ccccttcccc ggaggaccgg gaggaggtgg gccgtctgct 12120 ccgcggggcg tgtatagaca cctggaggag ggaagggacc cacgctgggg cacgccgcgc 12180 caccgccctc cttcgcccct ccacgcgccc tatgcctctt tcttctcctt ccagctgtca 12240 cgggggtccc cagtccccgg gccacggatc caccttccca tgtaagaccc ctctctttcc 12300 cctgcctcag acctgctgcc cattctgcag atcccctccc tggctcctgg tctccccgtc 12360 cagatatagg gctcacccta cgtctttgcg actttagagg gcagaagccc tttattcagc 12420 cccagatctc cctccgttca ggcctcacca gattccctcc gggatctccc tagataacct 12480 ccccaacctc gattcccctc gctgtctctc gccccaccgc tgagggctgg gctgggctcc 12540 gatcgggtca cctgtccctt ctctctccag ctagatggcc ccccggccgt ggctgtgggc 12600 cagtgcccgc tggtggggcc aggccccatg caccgccgcc acctgctgct ccctgccagg 12660 gtacgtccgg ctgcccacgc ccccctccgc cgtcgcgccc cgcgctccac ccgccccttg 12720 ccacccgctt agctgcgcat ttgcggggct gggcccacgg caggagggcg gatcttcggg 12780 cagccaatca acacaggccg ctaggaagca gccaatgacg agttcggacg ggattcgagg 12840 cgtgcgagtg gactaacaac agctgtaggc tgttggggcg ggggcggggc gcagggaaga 12900 gtgcgggccc acctatgggc gtaggcgggg cgagtcccag gagccaatca gaggcccatg 12960 ccgggtgttg acctcgccct ctccccgcag gtccctaggc ctggcctatc ggaggcgctt 13020 tccctgctcc tgttcgccgt tgttctgtct cgtgccgccg ccctgggctg cattgggttg 13080 gtggcccacg ccggccaact caccgcagtc tggcgccgcc caggagccgc ccgcgctccc 13140 tgaaccctag aactgtcttc gactccgggg ccccgttgga agactgagtg cccggggcac 13200 ggcacagaag ccgcgcccac cgcctgccag ttcacaaccg ctccgagcgt gggtctccgc 13260 ccagctccag tcctgtgatc cgggcccgcc ccctagcggc cggggaggga ggggccgggt 13320 ccgcggccgg cgaacggggc tcgaagggtc cttgtagccg ggaatgctgc tgctgctgct 13380 gctgctgctg ctgctgctgc tgctgctgct gctgctgctg ctgctggggg gatcacagac 13440 catttctttc tttcggccag gctgaggccc tgacgtggat gggcaaactg caggcctggg 13500 aaggcagcaa gccgggccgt ccgtgttcca tcctccacgc acccccacct atcgttggtt 13560 cgcaaagtgc aaagctttct tgtgcatgac gccctgctct ggggagcgtc tggcgcgatc 13620 tctgcctgct tactcgggaa atttgctttt gccaaacccg ctttttcggg gatcccgcgc 13680 ccccctcctc acttgcgctg ctctcggagc cccagccggc tccgcccgct tcggcggttt 13740 ggatatttat tgacctcgtc ctccgactcg ctgacaggct acaggacccc caacaacccc 13800 aatccacgtt ttggatgcac tgagaccccg acattcctcg gtatttattg tctgtcccca 13860 cctaggaccc ccacccccga ccctcgcgaa taaaaggccc tccatctgcc caaagctctg 13920 gactccacag tgtccgcggt ttgcgttgtg ggccggaggc tccgcagcgg gccaatccgg 13980 aggcgtgtgg aggcggccga aggtctggga ggagctagcg ggatgcgaag cggccgaatc 14040 agggttgggg gaggaaaagc cacggggcgg ggctttggcg tccggccaat aggagggcga 14100 gcgggccacc cggaggcacc gcccccgccc agctgtggcc cagctgtgcc accgagcgtc 14160 gagaagaggg ggctgggctg gcagcgcgcg cggccatcct ccttccactg cgcctgcgca 14220 cgccacgcgc atccgctcct gggacgcaag ctcgagaaaa gttgctgcaa actttctagc 14280 ccgttccccg cccctcctcc cggccagacc cgccccccct gcggagccgg gaattccgag 14340 gggcggagcg caggccgaga tggggaatgt gggggcctgc agaggaccct ggagacggag 14400 gcgtgcagaa g 14411 <210> SEQ ID NO 3 <211> LENGTH: 15000 <212> TYPE: DNA <213> ORGANISM: Mus musculus <400> SEQUENCE: 3 cagtgtcccc actgcccaag gctggctcca tcacgtaccg ctttggctca gctggccagg 60 acacacagtt ctgcctgtgg gacctcacag aagatgtgct ctcccctcat ccgtctctgg 120 cccgtacccg cacccttccg ggcacacctg gtgccacccc accagcttct ggtagttctc 180 gggccggaga gacaggtgca ggccccctgc cccgctccct gtctcgttcc aacagtctcc 240 cacacccagc tggtggtggc aaggctggtg ggcctagtgc atcgatggag cctggcatac 300 cattcagcat tggccgcttt gccacactga ccctgcagga gcggcgggac cggggagctg 360 agaaggaaca caaacgctac catagcctgg gaaacatcag ccgcggtggc agtgggggca 420 atagcagcaa tgacaagctc agtggtcctg ccccccgaag ccgattggac ccagctaagg 480 tgctgggcac ggcactgtgc cctcggatcc atgaggtgcc actgctggag cctctcgtgt 540 gcaagaagat tgctcaggaa cgcctgaccg tgctactgtt cctggaggat tgtatcatca 600 ctgcctgcca agagggcctc atctgcacct gggcccggcc aggcaaggcg gtgagtccgc 660 acctgcccaa gcgctgaggg gcaccagttc tgtccctacc ggatgccagt tatccgtcag 720 cagaaaggtc aggtatagga gacagaatgg ggggaaccac agctaacgtc tttagagcct 780 ctgctggccc atatggctca tccttagtac ttcacactca aggcagaacc tgtgtttata 840 ggaaatctga agtgtagatg gtgaaacttt attcaggtct agggatgtga ttgagctggg 900 ggcccacttc tggcctgcct cttagacact gtttctgagc cagctgctga aggcctggat 960 gggaattagc cagggtccag gcctgcactt cctcttgctg ctgtgtggtc ctggtcattg 1020 ggtctcacag atgggctgtg cagtggctgt gctcttagtt ggtgaggtgc aggcctgtca 1080 cctggtcagg cttgagcatg tggtctcagt gtctaggacc ctactctgcc ctcagtcctt 1140 cagtcccttg ctttggaagg ctagagtcca gaagccttag aacgtcaggc agttgcagag 1200 ccactgccag gctagtaggg ctgcgggagt tgactgagtt ctcacagaca cccctctgtc 1260 tccctagttc acagacgagg agaccgaggc ccaggcaggg caagcaagtt ggcccaggtc 1320 acccagcaag tcagttgtag aggtaggaca acccctgaag ctgcaagtgg accccagttt 1380 cttttctctc cactgtcgtc ccctgtatgc ccaggacacc tggggccaca ttactgtgga 1440 agtgctactc tgggtcagtg gagacggccg agctgtttgt tcctagctag gacagcagct 1500 ttaggcctgg ggggcagatc ccagctgggg cagcagctcc aaggcctttg ggtggctcct 1560 tctccgggtt ctggcagaag cccaggtgct gtctaatcca cctttctcct cttgttctcc 1620 ccagggcatc tcctcccaac caggcagctc ccccagtggc actgtggtgt gaaatgtgga 1680 tgtcccatgt tcccggcctc ctagccataa ccctccccgc tgacctcaag aatcactgta 1740 ttaacaagac taatcatgat ggaaggactg ctccaagccc cacgctgcac acatactggg 1800 ggtcccctag gttggcccag ccatggggat gtagtgtcct gtgtggcctt ggccctgtcc 1860 tccacccact gccaagtaca atgacctgtt ctctgaaaca tcagtgttaa ccatatccct 1920 gtcccagcat gtgactgttc actcctggga gagacttagc ccacagtacc cctgggtgag 1980 agggcagggc aggggccatc cccactcctg cccaaactcc accccttgct atggtctgtg 2040 attttgaaag tgttaaatta tggaagccct gagggccctc cttgttcccc tggacctctt 2100 atttatacta aagtccttgt ttgcacagtg tttctgttcc ctggggcagg gtagggtggg 2160 ggttgcagta cttggcctcc aagctgtgct ctgaccaaag gaagcccaat cttagctgtt 2220 tccccatccc tagccccgag cagagagccc tctgaaagat gagtctcgac ccccaaagtc 2280 aagaggctga gatggccttc ctactaggtc cttggagatg tttgaaactt gttttaaaca 2340 ccaggactat ccaagcatgc tctccttggg gagaggagga tgctggaatt gactgcactc 2400 cctgcctcct ctgaacatgc ctttgcagtc tgctgcccct ggcccattta tgactggcca 2460 tctagtgcca gctggaggtc atgatttcct ccccagagaa ctggccaccc tagaaagaag 2520 ctaacttgtc gcctggcttg ctgtccaggc agctccgccc tcaaccccta aaatgtttct 2580 gtctctaatc ctagcccagg caggaatgtg gctgccccgg cctgtggcca aggagctatt 2640 ttggggttct cttttgctta aggagggcct ggatccacca cttgcctccc ccaggctggg 2700 gccagcaggt cacccctggc cctggcggct gagcaaactc tctcctgatc ttccttctac 2760 ctcctgccaa aaaatggggg ggcgggtaat acagcaggca caggggctaa atttaactgt 2820 cccaaagtcg gaatccattg ctgagtcacg aagaagctgc ccctggcctt tgcccccccc 2880 actaccccct caccccctgt tgcccaggca tcagcccttt cccccaaccc ctcccagctc 2940 tgagtctata gactggctct cctgggcact gacacctccc acctgtaact ccctgtgctc 3000 tctttatggg tgggtagagt caatgggggg gggcaaccct ggagtattac tctgtcccct 3060 gacattgggc tctgaagagt tttgaggggc cctggaagaa gggagttggg gtgttggctc 3120 aggaggggtt aaaaactggg aggcgggagg ggggctgggc caaggggtgg agaaaagagg 3180 aggaggcctt aagcatagaa ctggccagag agacccaagg gatagtcagg gacgggcaga 3240 catgcagcta gggttctggg gcctggacag gggcagccag gccctgtgac gggaagaccc 3300 cgagctccgg cccggggagg ggccatggtg ttgcctgccc aacatgtcag ccgaagtgcg 3360 gctgaggcag ctccagcagc tggtgctgga cccaggcttc ctgggactgg agcccctgct 3420 cgaccttctc ctgggcgtcc accaggagct gggtgcctct cacctagccc aggacaagta 3480 tgtggccgac ttcttgcagt ggggtgagta tggataggaa gcctggggtt gggtgcaagg 3540 cagaggtggg tctacagggc aagaatgggc tatggagggg caggagggcc tggaaagggc 3600 tttttgtaag ggagccaagc agagctcatg acctgacccc aagctcccct ggtgaggcac 3660 cagggtcagt gaggccacct atgactcagc cagtgcaggc tggggtgggc atagcctcct 3720 gctatctcag cacccacact aggacctggc agctttctct tttaggaccc ttggctcctc 3780 aaactggctt catagccctc cccagtttcc cagagtgtgg ggagggacag cgtggggcag 3840 ctgccagggt gtggcccata ggcaggtgtt tggcgtctgc ctccccagct gccctgacag 3900 gtgtccagga gctatgaggg cactgtgact cacagaggcc ctgggggaga accagcccgg 3960 cagacaggcg ccaccgagca ccctttctgt tccccaaatt aagaggaagg aacaacttca 4020 gcttctgagt gtgcccatcc ctagcactct gatcccgccc agcctttgtg ggccagattg 4080 gtcatccctc ctggcttctc atctgctttt gtggttctag ctcaagacct ctaattcctc 4140 tgctgactta aatgcccttc cccagaggtc ttctcaggcc tagtggacaa gcttggagcc 4200 ttatctgctc ctgcccaaca ttgagccaaa gctccagctt accccagctt ccttacaagt 4260 aacgacctgt tttgttgctc tgtgcctatt attaagggtc caggtcttga ttcttggctg 4320 tctgcccatg tgtgtgaccc tagtgcattc tcccctcctc ccccgtttca cagatggaaa 4380

ggttgaggcc atcggttaga ctgctaagcc tgtgaaagac tttttctcct ctccagtctt 4440 tagtgtctcc ctcaaccttt cttttgaagg atggggtttg ggctggcagg gtaaactgag 4500 aactggggtg ggggcagggg gtctgaccct ctgggaagga gcagtccttt tgtggcctga 4560 gcagcatcct gtgggcccct cccctgccag gcctgggcgg gggagggggc ctgggttccc 4620 gctgccttaa aagggctcaa cgccttggct ctctcctcct ccccaccccc cagccttggc 4680 cctagctgta tcttccccgg ctgcccactt tcccaaaccc ctttcttctc tgtgacccca 4740 tctccccgct tccccacacg tccctcctcc atccttactc cccggcctta gaacttccct 4800 aagggagatc tgacctccct ctgcccaccc cgcaccccca gtcgccagcc tcagacctag 4860 ctgctctccc ctctggctga accaccctag cacaggacct tataccctgg agctttggtt 4920 ataagaagac tctccttcac cctttggaaa ccaagaaagc ccttccaaca gtgtccagga 4980 tgctggaggg cagtgaccct cccccacttc ttcttcgtgc tggctgtgct gacacagctc 5040 cagttcgagg ttgtggcccg agacattaag tgagagcccc gggtgacctg acttagcacc 5100 ctgatcatca catgggagtg aaaggcctga tgcgccagct tctcccactg cctccctttc 5160 tgccctgcaa ccctgtggaa acaggcagtt ctgggtccca caaacatcac agaggttttg 5220 aaagcagaat cctaaagccg atttaagggg cagaaggaag gaggctataa agtcactacc 5280 cttaccgcta gtgttctgat gacccttggt tcttcttccc ccacccccgc ccagtggagc 5340 ccattgcagc aaggcttaag gaggtccgac tgcagaggga tgattttgag attttgaagg 5400 tgatcgggcg tggggcgttc agcgaggtga gtcttcagtg gcctgggaat ggaactttac 5460 ttgatgtggg tggggcataa cagctggggc agagccttaa aaattgatga atgagcttga 5520 atttaaggct ggaggggtgg gggcggagct tgtggtcagt gggcggtgtg cacgtgaggg 5580 cggggctaag gttgggtgga gataagggtg gagtcctgtc tgggtgagcc ttgctggttt 5640 tccctgccac ctcttgctgt catctcggtt ccgtatttag gtagcggtgg tgaagatgaa 5700 acagacgggc caagtgtatg ccatgaagat tatgaataag tgggacatgc tgaagagagg 5760 cgaggtgagg gccagggatt agggcagcgc cctcatctct ccaactcacc tcctgtagct 5820 tctctcctac ctcacaggtg tcgtgcttcc gggaagaaag ggatgtatta gtgaaagggg 5880 accggcgctg gatcacacag ctgcactttg ccttccagga tgagaactac ctggtaagct 5940 ccgggttcag gtgactagga aagagtgaca gttacatcgc cccaagtcaa gaaggctgga 6000 gaagggagaa gctgctgtag atcggggggg tgggggtggg ggggacacac acaggggatg 6060 ggggacgggg gtaggattgt gtctcaagta taggagagac cttccttgag acaggagtga 6120 tatctggttt ggcctttgga tggggcgctc tctcactgtg cgggggtcct ctgtgcttgg 6180 gaacggggtg tctttgggag tcttgggggc taccaaaccc ctgtgacaca cccgctccca 6240 gtacctggtc atggaatact acgtgggcgg ggacctgcta acgctgctga gcaagtttgg 6300 ggagcggatc cccgccgaga tggctcgctt ctacctggcc gagattgtca tggccataga 6360 ctccgtgcac cggctgggct acgtgcacag gtgggcgtgg cggggccctt ggagggttag 6420 cagaatttgt gtgggaagga agggtacctg aaggtcagat cccattgggg acagaatcgg 6480 ggtctagaat tgtagaatcc tgggtggggt ggaagtggat cgagctgacg ggccctaaga 6540 gggaaggttt tcaagaaagc acactttccc tcttctctct atgcacaggg acatcaaacc 6600 agataacatt ctgctggacc gatgtgggca cattcgcctg gcagacttcg gctcctgcct 6660 caaactgcag cctgatggaa tggtaagaag agcctggcga aactctcctc attggtgaag 6720 gaccggatta gggggcgggg ctgggttgag gagcaggagg ggagcttggt ctgggatgtc 6780 ctgcgcacca tatttggaca gtcaagggaa aggttttaag cattcaggtc tgattggcac 6840 aggtgaggtc gctggtggct gtgggcaccc cggactacct gtctcctgag attctgcagg 6900 ccgttggtgg agggcctggg gcaggcagct acgggccaga gtgtgactgg tgggcactgg 6960 gcgtgttcgc ctatgagatg ttctatgggc agaccccctt ctacgcggac tccacagccg 7020 agacatatgc caagattgtg cactacaggg tgagcacaag caccatgcag gggggctgac 7080 ttagtggctt gtgctcccag actgtctttt ttaaaagata tttatttata tgtgtgtgtt 7140 ttctgtgtat gtatatctgt gcactgagta ggtgtgcgaa ggtcagaggg catgggatcc 7200 cctggaactg gagtcacaga ctattgtgtg ctgccatgct gagtgctggg aaacagaacc 7260 ttgatcactc tgcaagagca gccagtgcac tgaaacgaca gagccagctc tgcagcccag 7320 ggctaactgt tgcttttctt tctaaatagg aacacttgtc gctgccgctg gcagacacag 7380 ttgtccccga ggaagctcag gacctcattc gtgggctgct gtgtcctgct gagataaggc 7440 taggtcgagg tggggcaggt gatttccaga aacatccttt cttctttggc cttgattggg 7500 agggtctccg agacagtgta ccccccttta caccagactt cgagggtgcc acggacacat 7560 gcaatttcga tgtggtggag gaccggctca ctgccatggt gagcgggggc ggggtacgta 7620 cctgcagttc ctgatccgtt gaggggactt ccctagcctc ttccataaaa ttggggtgat 7680 tggccaggtg tggtggtgca tacctttaat cgtagaactt cataggcaga ggcaggtggc 7740 tctctggtaa atcaaggcca tcttggtcta catagtgact tctaggccag tcaggagtga 7800 gatcctccct tgaaaaataa aaaagggggt gttgaccttc ctgggtccca aattattatc 7860 ctagagcact gctatgtatc cactcaggta tgaggacaca caggtgacca gtcccaaaga 7920 cagtgagtga ggcctcactc ttggcagtac taaaattgat tgtagggggc tgggctcttg 7980 acccagcctg gaaagtgctg gagggcttcc tggaggagga gactagctga gcccagaagg 8040 atgcaggaga tcctttctcg ggtgagtgct ctcagcattt taacaagctc taggccctgc 8100 agagagaagt ctggtgtggg cagagcccca atagaaagca acaagataga agagaaaatg 8160 gtggagtttg ttagtggggg cagttatgcc gtgaacatag aggggcgaag ggccatctcg 8220 gataactgct agccacaaga gccctgtctg tcttcctagg agacgctgtc agacatgcag 8280 gaagacatgc cccttggggt gcgcctgccc ttcgtgggct actcctactg ctgcatggcc 8340 ttcaggtgag cacgactgcc ccctgctggg gcctgtgtgc aggcccacca cagccactca 8400 attgaaggct cagtcttcaa accaagtatt cctaggagct gtctaagtta ggctttctgc 8460 tgctgcgatg aaccctgact aaaagcaagc tggggaggaa aaggcttatc gggcttacgt 8520 ttccacatgg gagcccatca ctgaaggaag ccaggacagg aactcacagc ggggcaggaa 8580 cgtggagctg atgcagaggc aatggagggg agctgcttac tgacttgatc cttatgtctt 8640 cctcagcctg tttccttgta gagcccagga ccaccaggcc agtgagggct ccactcacaa 8700 tgggctgagc tctcatctat gatcactagt tatgaaaatg cccgataggc ttgcctgcag 8760 cttcagtttt tgaggcactt tccttccttc cttccttcct tccttccttc cttccttcct 8820 ttctttcttt ctttctttct ttctttcttt ctttctttct ttctttcttt ctttctttct 8880 tagtctttta gagacagggt ctttctatgt agctctggct gtcttggaat tcattctgta 8940 gaccaggctg gtcttattta tttattttat gtatgtgagt ccactatcac tgtcctcaga 9000 cacaccagaa gagggcatca gatcccatta cagatggctg tgagccacca tgtggttgct 9060 gggaattgaa ctcaggacct ctggaagagc agccagtgct cctgccctgt agaggcattt 9120 tcttcatgaa ggctgtctcc tctctgatga cttgatgact ctagcttgtt gtgtcaagtg 9180 gacataagac taggaaagca gctacacatg cactttgttt atttttgttt tgctttttga 9240 gactgggtct ctccatctca tagctctggc catcctgcct ggtgacattc cagtccagtt 9300 gtataaccta agaatctgag actcagcctt gcagaatcct gctattaacg ggtctaggac 9360 actccataga atccaggatc ttagaaaaac aaacctgaag tgtgacagtt tattttaaga 9420 acacaattgg agcacataac aataatacaa cttttcagtt ttaaaaagtt ttctgtcttg 9480 ttttttgagg caggagctcc ttaatatagt ctaagccgcc ctgcgagtgc tgtgattgat 9540 gggcatgtac caccatgcct agtcaataaa gcctttaaaa agcatccgtt atgctggctg 9600 tggtgccaca aacctgtaat cccagcactt agaaggtaga ggcaagatta tcagaaattc 9660 aaggccatcc tgggctatac agtaatctaa ggctagcctg gtctacaaga gactctgtct 9720 aaagaaacaa aagataaata gcacccacta ttgctaggca atataaccct ataaccccac 9780 cattgaggag gctgaggctg gagcatcact gcaaatttga ggccaggatg gtcaacaaat 9840 aagtcccaga gctggcatag aggaactctg tctcaacaat aaagagaact tatctagcat 9900 ttatgagggt aaataaaaat ttaccattgc cacaaaaaat gtaaatgaag agactgcttt 9960 taggagtgaa ctgggaagca gggaacactt agaggatgct cactcacaca ggtatccacc 10020 atcaggcatg cctcaggcct gcacagggaa ggacaacttg tttcatgatt tgcaagcagc 10080 atcccatgct ccttagagcg ggttgggccc agcccaccct ctgtggagtt atcgctcagc 10140 caggcagcaa ggcagccaag gtgctgaggc cctggcagtc tgctctcttc tctgctctga 10200 acctccttta gctttagcct aggagcctgg cctggtgccc acaggctagg gagtccctag 10260 cctcttcctc ttctcagaga caatcaggtc ccggacccca cccctatgga actagaggcc 10320 ctgcagttgc ctgtgtcaga cttgcaaggg cttgacttgc agcccccagt gtccccaccg 10380 gatcaagtgg tgagtagact gagaggtggg caaagcttcc tgggtgggtg tacctgcagt 10440 gccaactgcc aggctgttaa ttcagtagga cactgtcccc aactggccca actgcacatc 10500 ctgtagtcag gaggcacagg cagaaaaatc ccaaattcaa ggcttgctcc cgttatgtaa 10560 tgagatcctg tcttggagta aaaaacaaag aagagaacta gggatagctc agaggtagat 10620 gctctcctgg catgggggtg gggtcagaaa gcaacaccaa ccggggcctg ggagggaggg 10680 actgccaacc acctggagga gtctggggta gacttggtga acaaagttca gaggccatca 10740 ggtgggatgc tggtttctta aaagccacag ataggtgggt agcattggaa agaggagtgg 10800 ggggttgcag aaagtgacaa gacacaaact ggggaggcct aagggtaaag ccagggttgt 10860 ctgaagcact gtggagctgg gaggaacacg ctaaacttct gacttcagcc cttcagttcc 10920 cctgttgact acactgtccc cagggaccca gggatgggga gaggtggacg ggggagggaa 10980 gtacgggact gatccagctc caggtcccaa ctctgatccc caccgacagg ctgaagaggc 11040 tgacctagtg gctgtccctg cccctgtggc tgaggcagag accacggtaa cgctgcagca 11100 gctccaggaa gccctggaag aagaggttct cacccggcag agcctgagcc gcgagctgga 11160 ggccatccgg accgccaacc agaacttctc caggtcaggg tcacagtgct ggggtgaggg 11220 gagaggagag cagcaaccct cgcagtctcc tcaccgatag gtcggctcac tcccctatct 11280 ttcccagcca actacaggag gccgaggtcc gaaaccgaga cctggaggcg catgttcggc 11340 agctacagga acggatggag atgctgcagg ccccaggagc cgcaggcgag tccctcacct 11400 gcttccagcc aagggggcac tgggtggaga tggggggcat gttgggtgtg tgaaccctcg 11460 gggcagggga ggagtccagg ctggggcacc gcagccgcgc cactgccttt ctcctccatc 11520 ctccacactc catacacctc tctcttctcc ttccagccat cacgggggtc cccagtcccc 11580 gggccacgga tccaccttcc catgtaagac ccctctctcc cctccccgat ccccatctta 11640 gatatgctac ccacagccct tctcccgtcc acgtttaggg tccattctcc ttgggggttc 11700 cagaagaaag ctgcccttca ctcatccatt cagcatgcac tatctaccag ctctccctcg 11760 tttcaggctt ctcgccaaat cctccccaag ggaactccct atactcccgt tctggcctcg 11820 actagattcc cgcactgcct ctcgccctgc tgctgggctc cgatcgggtc acctgtccct 11880

tctctctcca gctagatggc cccccggccg tggctgtggg ccagtgcccg ctggtggggc 11940 caggccccat gcaccgccgt cacctgctgc tccctgccag ggtatgtccc acgtccgccc 12000 accacgggcc tctgcctagc tctgcccact gagtgtcacc actgcttgct gtgcctctgt 12060 ggagctcggc ccaccgcagg gagggggggt attcgggcgg ccaatcaaca caggctgctg 12120 ctaagtagcc aatgacgagt tccaacagga gctctttctt gcgagcagac caactttagc 12180 tgcgggctgt ggggaccaga gatgcgctca gaggcccatc tatgggtata ggctgggcgg 12240 ctcccaggag ccagtgggcc cctgtagcct agtgctaatc caaccttctc tcctgcagat 12300 ccctaggcct ggcctatccg aggcgcgttg cctgctcctg ttcgccgctg ctctggctgc 12360 tgccgccaca ctgggctgca ctgggttggt ggcctatacc ggcggtctca ccccagtctg 12420 gtgtttcccg ggagccacct tcgccccctg aaccctaaga ctccaagcca tctttcattt 12480 aggcctccta ggaaggtcga gcgaccaggg agcgacccaa agcgtctctg tgcccatcgc 12540 gccccccccc cccccccacc gctccgctcc acacttctgt gagcctgggt ccccacccag 12600 ctccgctcct gtgatccagg cctgccacct ggcggccggg gagggaggaa cagggctcgt 12660 gcccagcacc cctggttcct gcagagctgg tagccaccgc tgctgcagca gctgggcatt 12720 cgccgacctt gctttactca gccccgacgt ggatgggcaa actgctcagc tcatccgatt 12780 tcactttttc actctcccag ccatcagtta caagccataa gcatgagccc cctatttcca 12840 gggacatccc attcccatag tgatggatca gcaagacctc tgccagcaca cacggagtct 12900 ttggcttcgg acagcctcac tcctgggggt tgctgcaact ccttccccgt gtacacgtct 12960 gcactctaac aacggagcca cagctgcact cccccctccc ccaaagcagt gtgggtattt 13020 attgatcttg ttatctgact cactgacaga ctccgggacc cacgttttag atgcattgag 13080 actcgacatt cctcggtatt tattgtctgt ccccacctac gacctccact cccgaccctt 13140 gcgaataaaa tacttctggt ctgccctaaa tcccgcgcaa tatctctgtt gtggaaagga 13200 aaccgccccg caggccaatg gagagtccaa tagagacaac caatggcttg agtgggagct 13260 agaggggagg caaagcgcac gaatcaggtt gaagggtggg gcttaggcat ccagccagta 13320 ggagagaagc aacaagccac cagagacacc accgcccccc accctccccc ccagctgtga 13380 cccagctgtg ccactcaagt ttggaaaaaa gtagggggtt gggccagcag cgggcacacc 13440 atcttcccac tgcgcctgcg caagccacgc gcatccgctt tttggaccga cactccagaa 13500 aagttgctgc aaactttcta gcgcgattcc ccgcccctcc tcccagctag atccaccgcc 13560 tacccgcggg gccgggaatt ccgaggggcg gagcacggcg cggagatggg aagggagggg 13620 gcccttcaag ggacccggga gatgggagcg gcttcgcgcc cttaaccctc cggacggccc 13680 attaccttct ccgttgctct gatagggaaa ctgaggccct gagtcagagg cacacaaggg 13740 gggaaggcca aaagcgcggc cagagacgga gggaaaacaa agaatcctga cagcccggga 13800 ggggggcgga cacacaggga caaggacaga cccgagtgca gagctgggtc tagtctttgg 13860 gagggggcca gaagactgca aggggaccgg gggggggggc ggcgaggagg actgggcgga 13920 ggagggggct ggggaagccc gcgggaggcg gcaaaggagg gaggaacttt ccaaagttgc 13980 caaacatggc tacctcgcct gcggagccga gcgcggggcc cgcggctcgg ggggaggcgg 14040 cggcggcgac cgaggagcag gaggaggaag cgcgccagct tctgcagact ctgcaggcag 14100 ccgaggggga ggcggcggcg gccggggcgg gagatgcggc ggcggcggcg gactctgggt 14160 ccccgagtgg cccggggtct ccccgggaga ccgtgaccga ggtgcccact ggccttcgct 14220 tctcgcccga acaggtggca tgcgtgtgcg aggcgctgct gcaggcgggc cacgccggcc 14280 gcttgagccg cttcctgggc gcgctgcccc cggccgagcg cctacgtggc agcgatccgg 14340 tgctgcgcgc gcgggcccta gtggccttcc agcggggtga atacgccgag ctctaccaac 14400 ttctcgagag ccgccctttc cccgccgccc accacgcctt cctgcaggac ctctacctgc 14460 gcgcgcgcta ccacgaggcc gagcgggccc gtggccgtgc gctgggcgct gtggacaaat 14520 accggctgcg caagaagttc cctctgccca agaccatctg ggatggcgag gagaccgtct 14580 attgcttcaa ggagcgctcg cgagcggcgc tcaaggcctg ctaccgcggc aaccgctatc 14640 ccacgcctga cgagaagcgc cgcctggcca cgctcaccgg cctctcgctt acacaggtca 14700 gcaactggtt caagaaccgg cgacagcgcg accgcactgg gaccggcggt ggagcgcctt 14760 gcaaaaggtg aggggggaac cgaccctcct tcctcggtgg ccgctggagt ctgcgcaagt 14820 gacccttcac atccctcttc ggtggcgtcg gcgagtgcat aggctgagcg tggagagacc 14880 aggcacaccc tgggttctct gggcatcact gcctcagggg cagaggttgt tccagctact 14940 tctaagctgg gaacgcagtg ccaggaatgg gggggggggc gggggcggga cgggcagtga 15000 <210> SEQ ID NO 4 <211> LENGTH: 1896 <212> TYPE: DNA <213> ORGANISM: Mus musculus <400> SEQUENCE: 4 atgtcagccg aagtgcggct gaggcagctc cagcagctgg tgctggaccc aggcttcctg 60 ggactggagc ccctgctcga ccttctcctg ggcgtccacc aggagctggg tgcctctcac 120 ctagcccagg acaagtatgt ggccgacttc ttgcagtggg tggagcccat tgcagcaagg 180 cttaaggagg tccgactgca gagggatgat tttgagattt tgaaggtgat cgggcgtggg 240 gcgttcagcg aggtagcggt ggtgaagatg aaacagacgg gccaagtgta tgccatgaag 300 attatgaata agtgggacat gctgaagaga ggcgaggtgt cgtgcttccg ggaagaaagg 360 gatgtattag tgaaagggga ccggcgctgg atcacacagc tgcactttgc cttccaggat 420 gagaactacc tgtacctggt catggaatac tacgtgggcg gggacctgct aacgctgctg 480 agcaagtttg gggagcggat ccccgccgag atggctcgct tctacctggc cgagattgtc 540 atggccatag actccgtgca ccggctgggc tacgtgcaca gggacatcaa accagataac 600 attctgctgg accgatgtgg gcacattcgc ctggcagact tcggctcctg cctcaaactg 660 cagcctgatg gaatggtgag gtcgctggtg gctgtgggca ccccggacta cctgtctcct 720 gagattctgc aggccgttgg tggagggcct ggggcaggca gctacgggcc agagtgtgac 780 tggtgggcac tgggcgtgtt cgcctatgag atgttctatg ggcagacccc cttctacgcg 840 gactccacag ccgagacata tgccaagatt gtgcactaca gggaacactt gtcgctgccg 900 ctggcagaca cagttgtccc cgaggaagct caggacctca ttcgtgggct gctgtgtcct 960 gctgagataa ggctaggtcg aggtggggca ggtgatttcc agaaacatcc tttcttcttt 1020 ggccttgatt gggagggtct ccgagacagt gtacccccct ttacaccaga cttcgagggt 1080 gccacggaca catgcaattt cgatgtggtg gaggaccggc tcactgccat ggtgagcggg 1140 ggcggggaga cgctgtcaga catgcaggaa gacatgcccc ttggggtgcg cctgcccttc 1200 gtgggctact cctactgctg catggccttc agagacaatc aggtcccgga ccccacccct 1260 atggaactag aggccctgca gttgcctgtg tcagacttgc aagggcttga cttgcagccc 1320 ccagtgtccc caccggatca agtggctgaa gaggccgacc tagtggctgt ccctgcccct 1380 gtggctgagg cagagaccac ggtaacgctg cagcagctcc aggaagccct ggaagaagag 1440 gttctcaccc ggcagagcct gagccgcgag ctggaggcca tccggaccgc caaccagaac 1500 ttctccagcc aactacagga ggccgaggtc cgaaaccgag acctggaggc gcatgttcgg 1560 cagctacagg aacggatgga gatgctgcag gccccaggag ccgcagccat cacgggggtc 1620 cccagtcccc gggccacgga tccaccttcc catctagatg gccccccggc cgtggctgtg 1680 ggccagtgcc cgctggtggg gccaggcccc atgcaccgcc gtcacctgct gctccctgcc 1740 aggatcccta ggcctggcct atccgaggcg cgttgcctgc tcctgttcgc cgctgctctg 1800 gctgctgccg ccacactggg ctgcactggg ttggtggcct ataccggcgg tctcacccca 1860 gtctggtgtt tcccgggagc caccttcgcc ccctga 1896 <210> SEQ ID NO 5 <211> LENGTH: 771 <212> TYPE: DNA <213> ORGANISM: Mus musculus <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (89)..(89) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (238)..(238) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (506)..(506) <223> OTHER INFORMATION: n is a, c, g, or t <400> SEQUENCE: 5 cctgcccctg tggctgaggc agagaccacg gtaacgctgc agcagctcca ggaagccctg 60 gaagaagagg ttctcacccg gcagagctng agccgcgagc tggaggccat ccggaccgcc 120 aaccagaact tctccagcca actacaggag gccgaggtcc gaaaccgaga cctggaggcg 180 catgttcggc agctacagga acggatggag atgctgcagg ccccaggagc cgccggantc 240 cctcacctgc ttccagccaa gggggcactg ggtggagatg gggggcatgt tgggtgtgtg 300 aaccctcggg gcaggggagg agtccaggct ggggcaccgc gccgcgccac tgcctttctc 360 ctccatcctc cacactccat acacctctct cttctccttc cagccatcac gggggtccca 420 gtccccgggc cacggatcca ccttcccatc tagatggccc cccggcggtg gctgtgggcc 480 agtgcccgct ggtggggcca ggacantgtc accgccgtca cctgctgctc cctgccagga 540 ttcctaggcc tggctatccg aggcgcgttg ctgctcctgt tcgccgctgc tctggctgct 600 gcgccacact gggctgcact gggttggttg gctataccgg cggtcttcac ccagtctggt 660 gtttcccgtg agcacccttc gcccctgaaa cctaagactt caagccatct ttcatttagg 720 ccttctagga aggtcgagcg acaggggagc gacccaaagc gtctctgtgc c 771 <210> SEQ ID NO 6 <211> LENGTH: 434 <212> TYPE: DNA <213> ORGANISM: Mus musculus <400> SEQUENCE: 6 gagagaccca aggggtagtc agggacgggc agacatgcag ctagggttct ggggcctgga 60 caggggcagc caggccctgt gacgggaaga ccccgagctc cggcccgggg aggggccatg 120 gtgttgcctg cccaacatgt cagccgaagt gcggctgagg cagctccagc agctggtgct 180 ggacccaggc ttcctgggac tggagcccct gctcgacctt ctcctgggcg tccaccagga 240 gctgggtgcc tctcacctag cccaggacaa gtatgtggcc gacttcttgc agtgggtgga 300 gcccattgca gcaaggctta aggaggtccg actgcagagg gatgattttg agattttgaa 360 ggtgatcggg cgtggggcgt tcagcgaggt agcggtggtg aagatgaaac acacggagtc 420 tttggcttcg gaca 434 <210> SEQ ID NO 7 <211> LENGTH: 2688 <212> TYPE: DNA <213> ORGANISM: Mus musculus

<400> SEQUENCE: 7 ccacgcgtcc gcccacgcgt ccggggcaga catgcagcta gggttctggg gcctggacag 60 gggcagccag gccctgtgac gggaagaccc cgagctccgg cccggggagg ggccatggtg 120 ttgcctgccc aacatgtcag ccgaagtgcg gctgaggcag ctccagcagc tggtgctgga 180 cccaggcttc ctgggactgg agcccctgct cgaccttctc ctgggcgtcc accaggagct 240 gggtgcctct cacctagccc aggacaagta tgtggccgac ttcttgcagt gggtggagcc 300 cattgcagca aggcttaagg aggtccgact gcagagggat gattttgaga ttttgaaggt 360 gatcgggcgt ggggcgttca gcgaggtagc ggtggtgaag atgaaacaga cgggccaagt 420 gtatgccatg aagattatga ataagtggga catgctgaag agaggcgagg tgtcgtgctt 480 ccgggaagaa agggatgtat tagtgaaagg ggaccggcgc tggatcacac agctgcactt 540 tgccttccag gatgagaact acctgtacct ggtcatggaa tactacgtgg gcggggacct 600 gctaacgctg ctgagcaagt ttggggagcg gatccccgcc gagatggctc gcttctacct 660 ggccgagatt gtcatggcca tagactccgt gcaccggctg ggctacgtgc acagggacat 720 caaaccagat aacattctgc tggaccgatg tgggcacatt cgcctggcag acttcggctc 780 ctgcctcaaa ctgcagcctg atggaatggt gaggtcgctg gtggctgtgg gcaccccgga 840 ctacctgtct cctgagattc tgcaggccgt tggtggaggg cctggggcag gcagctacgg 900 gccagagtgt gactggtggg cactgggcgt gttcacctat gagatgttct atgggcagac 960 ccccttctac gcggactcca cagccgagac atatgccaag attgtgcact acagggaaca 1020 cttgtcgctg ccgctggcag acacagttgt ccccgaggaa gctcaggacc tcattcgtgg 1080 gctgctgtgt cctgctgaga taaggctagg tcgaggtggg gcaggtgatt tccagaaaca 1140 tcctttcttc tttggccttg attgggaggg tctccgagac agtgtacccc cctttacacc 1200 agacttcgag ggtgccacgg acacatgcaa tttcgatgtg gtggaggacc ggctcactgc 1260 catggtgagc gggggcgggg agacgctgtc agacatgcag gaagacatgc cccttggggt 1320 gcgcctgccc ttcgtgggct actcctactg ctgcatggcc ttcagagaca atcaggtccc 1380 ggaccccacc cctatggaac tagaggccct gcagttgcct gtgtcagact tgcaagggct 1440 tgacttgcag cccccagtgt ccccaccgga tcaagtggct gaagaggctg acctagtggc 1500 tgtccctgcc cctgtggctg aggcagagac cacggtaacg ctgcagcagc tccaggaagc 1560 cctggaagaa gaggttctca cccggcagag cctgagccgc gagctggagg ccatccggac 1620 cgccaaccag aacttctcca gccaactaca ggaggccgag gtccgaaacc gagacctgga 1680 ggcgcatgtt cggcagctac aggaacggat ggagatgctg caggccccag gagccgcaga 1740 tccctaggcc tggcctatcc gaggcgcgtt gcctgctcct gttcgccgct gctctggctg 1800 ctgccgccac actgggctgc actgggttgg tggcctatac cggcggtctc accccagtct 1860 ggtgtttccc gggagccacc ttcgccccct gaaccctaag actccaagcc atctttcatt 1920 taggcctcct aggaaggtcg agcgaccagg gagcgaccca aagcgtctct gtgcccatcg 1980 cccccccccc cccccccacc gctccgctcc acacttctgt gagcctgggt ccccacccag 2040 ctccgctcct gtgatccagg cctgccacct ggcggccggg gagggaggaa cagggctcgt 2100 gcccagcacc cctggttcct gcagagctgg tagccaccgc tgctgcagca gctgggcatt 2160 cgccgacctt gctttactca gccccgacgt ggatgggcaa actgctcagc tcatccgatt 2220 tcactttttc actctcccag ccatcagtta caagccataa gcatgagccc cctatttcca 2280 gggacatccc attcccatag tgatggatca gcaagacctc tgccagcaca cacggagtct 2340 ttggcttcgg acagcctcac tcctgggggt tgctgcaact ccttccccgt gtacacgtct 2400 gcactctaac aacggagcca cagctgcact cccccctccc ccaaagcagt gtgggtattt 2460 attgatcttg ttatctgact cactgacaga ctccgggacc cacgttttag atgcattgag 2520 actcgacatt cctcggtatt tattgtctgt ccccacctac gacctccact cccgaccctt 2580 gcgaataaaa tacttctggt ctgccctaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 2640 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaa 2688 <210> SEQ ID NO 8 <211> LENGTH: 2862 <212> TYPE: DNA <213> ORGANISM: Mus musculus <400> SEQUENCE: 8 gggatagtca gggacgggca gacatgcagc tagggttctg gggcctggac aggggcagcc 60 aggccctgtg acgggaagac cccgagctcc ggcccgggga ggggccatgg tgttgcctgc 120 ccaacatgtc agccgaagtg cggctgaggc agctccagca gctggtgctg gacccaggct 180 tcctgggact ggagcccctg ctcgaccttc tcctgggcgt ccaccaggag ctgggtgcct 240 ctcacctagc ccaggacaag tatgtggccg acttcttgca gtgggtggag cccattgcag 300 caaggcttaa ggaggtccga ctgcagaggg atgattttga gattttgaag gtgatcgggc 360 gtggggcgtt cagcgaggta gcggtggtga agatgaaaca gacgggccaa gtgtatgcca 420 tgaagattac gaataagtgg gacatgctga agagaggcga ggtgtcgtgc ttccgggaag 480 aaagggatgt attagtgaaa ggggaccggc gctggatcac acagctgcac tttgccttcc 540 aggatgagaa ctacctgtac ctggtcatgg aatactacgt gggcggggac ctgctaacgc 600 tgctgagcaa gtttggggag cggatccccg ccgagatggc tcgcttctac ctggccgaga 660 ttgtcatggc catagactcc gtgcaccggc tgggctacgt gcacagggac atcaaaccag 720 ataacattct gctggaccga tgtgggcaca ttcgcctggc agacttcggc tcctgcctca 780 aactgcagcc tgatggaatg gtgaggtcgc tggtggctgt gggcaccccg gactacctgt 840 ctcctgagat tctgcaggcc gttggtggag ggcctggggc aggcagctac gggccagagt 900 gtgactggtg ggcactgggc gtgttcacct atgagatgtt ctatgggcag acccccttct 960 acgcggactc cacagccgag acatatgcca agattgtgca ctacagggaa cacttgtcgc 1020 tgccgctggc agacacagtt gtccccgagg aagctcagga cctcattcgt gggctgctgt 1080 gtcctgctga gataaggcta ggtcgaggtg gggcaggtga tttccagaaa catcctttct 1140 tctttggcct tgattgggag ggtctccgag acagtgtacc cccctttaca ccagacttcg 1200 agggtgccac ggacacatgc aatttcgatg tggtggagga ccggctcact gccatggaga 1260 cgctgtcaga catgcaggaa gacatgcccc ttggggtgcg cctgcccttc gtgggctact 1320 cctactgctg catggccttc agagacaatc aggtcccgga ccccacccct atggaactag 1380 aggccctgca gttgcctgtg tcagacttgc aagggcttga cttgcagccc ccagtgtccc 1440 caccggatca agtggctgaa gaggctgacc tagtggctgt ccctgcccct gtggctgagg 1500 cagagaccac ggtaacgctg cagcagctcc aggaagccct ggaagaagag gttctcaccc 1560 ggcagagcct gagccgcgag ctggaggcca tccggaccgc caaccagaac ttctccagcc 1620 aactacagga ggccgaggtc cgaaaccgag acctggaggc gcatgttcgg cagctacagg 1680 aacggatgga gatgctgcag gccccaggag ccgcagccat cacgggggtc cccagtcccc 1740 gggccacgga tccaccttcc catgcttctc gccaaatcct ccccaaggga actccctaga 1800 ctcccgttct ggcctcgact agattcccgc actgcctctc gccctgctgc tgggctccga 1860 tcgggtcacc tgtcccttct ctctccagct agatggcccc ccggccgtgg ctgtgggcca 1920 gtgcccgctg gtggggccag gccccatgca ccgccgtcac ctgctgctcc ctgccaggat 1980 ccctaggcct ggcctatccg aggcgcgttg cctgctcctg ttcgccgctg ctctggctgc 2040 tgccgccaca ctgggctgca ctgggttggt ggcctatacc ggcggtctca ccccagtctg 2100 gtgtttcccg ggagccacct tcgccccctg aaccctaaga ctccaagcca tctttcattt 2160 aggcctccta ggaaggtcga gcgaccaggg agcgacccaa agcgtctctg tgcccatcgc 2220 cccccccccc ccccccaccg ctccgctcca cacttctgtg agcctgggtc cccacccagc 2280 tccgctcctg tgatccaggc ctgccacctg gcggccgggg agggaggaac agggctcgtg 2340 cccagcaccc ctggttcctg cagagctggt agccaccgct gctgcagcag ctgggcattc 2400 gccgaccttg ctttactcag ccccgacgtg gatgggcaaa ctgctcagct catccgattt 2460 cactttttca ctctcccagc catcagttac aagccataag catgagcccc ctatttccag 2520 ggacatccca ttcccatagt gatggatcag caagacctct gccagcacac acggagtctt 2580 tggcttcgga cagcctcact cctgggggtt gctgcaactc cttccccgtg tacacgtctg 2640 cactctaaca acggagccac agctgcactc ccccctcccc caaagcagtg tgggtattta 2700 ttgatcttgt tatctgactc actgacagac tccgggaccc acgttttaga tgcattgaga 2760 ctcgacattc ctcggtattt attgtctgtc cccacctacg acctccactc ccgacccttg 2820 cgaataaaat acttctggtc tgccctaaaa aaaaaaaaaa aa 2862 <210> SEQ ID NO 9 <211> LENGTH: 18 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Primer <400> SEQUENCE: 9 agcctgagcc gggagatg 18 <210> SEQ ID NO 10 <211> LENGTH: 21 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Primer <400> SEQUENCE: 10 gcgtagttga ctggcgaagt t 21 <210> SEQ ID NO 11 <211> LENGTH: 21 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Probe <400> SEQUENCE: 11 aggccatccg cacggacaac c 21 <210> SEQ ID NO 12 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 12 ctggctgcat gtctgcctgt 20 <210> SEQ ID NO 13 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE:

<223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 13 ccaggagaag gtcgagcagg 20 <210> SEQ ID NO 14 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 14 tctatggcca tgacaatctc 20 <210> SEQ ID NO 15 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 15 atgtccctgt gcacgtagcc 20 <210> SEQ ID NO 16 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 16 atgtgtccgg aagtcgcctg 20 <210> SEQ ID NO 17 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 17 ctcaggctct gccgggtgag 20 <210> SEQ ID NO 18 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 18 ggcactggcc cacagccacg 20 <210> SEQ ID NO 19 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 19 cctggccgaa agaaagaaat 20 <210> SEQ ID NO 20 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 20 aaagaaatgg tctgtgatcc 20 <210> SEQ ID NO 21 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 21 aagaaagaaa tggtctgtga 20 <210> SEQ ID NO 22 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 22 ggccgaaaga aagaaatggt 20 <210> SEQ ID NO 23 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 23 cctcagcctg gccgaaagaa 20 <210> SEQ ID NO 24 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 24 gggcctcagc ctggccgaaa 20 <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 tcagggcctc agcctggccg 20 <210> SEQ ID NO 26 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 26 ctgcagtttg cccatccacg 20 <210> SEQ ID NO 27 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 27 ggcctgcagt ttgcccatcc 20 <210> SEQ ID NO 28 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 28 ccaggcctgc agtttgccca 20 <210> SEQ ID NO 29 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 29 gccttcccag gcctgcagtt 20 <210> SEQ ID NO 30 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 30 gctgccttcc caggcctgca 20 <210> SEQ ID NO 31 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 31 cttgctgcct tcccaggcct 20 <210> SEQ ID NO 32 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 32 gcccggcttg ctgccttccc 20 <210> SEQ ID NO 33 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 33 acggcccggc ttgctgcctt 20 <210> SEQ ID NO 34 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence

<220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 34 cggacggccc ggcttgctgc 20 <210> SEQ ID NO 35 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 35 acacggacgg cccggcttgc 20 <210> SEQ ID NO 36 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 36 gatggaacac ggacggcccg 20 <210> SEQ ID NO 37 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 37 gaggatggaa cacggacggc 20 <210> SEQ ID NO 38 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 38 gtggaggatg gaacacggac 20 <210> SEQ ID NO 39 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 39 gcgaaccaac gataggtggg 20 <210> SEQ ID NO 40 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 40 tttgcgaacc aacgataggt 20 <210> SEQ ID NO 41 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 41 ttgcactttg cgaaccaacg 20 <210> SEQ ID NO 42 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 42 gctttgcact ttgcgaacca 20 <210> SEQ ID NO 43 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 43 aaagctttgc actttgcgaa 20 <210> SEQ ID NO 44 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 44 aagaaagctt tgcactttgc 20 <210> SEQ ID NO 45 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 45 cacaagaaag ctttgcactt 20 <210> SEQ ID NO 46 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 46 gtcatgcaca agaaagcttt 20 <210> SEQ ID NO 47 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 47 acgctcccca gagcagggcg 20 <210> SEQ ID NO 48 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 48 gcagagatcg cgccagacgc 20 <210> SEQ ID NO 49 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 49 caggcagaga tcgcgccaga 20 <210> SEQ ID NO 50 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 50 aagcaggcag agatcgcgcc 20 <210> SEQ ID NO 51 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 51 ccgagtaagc aggcagagat 20 <210> SEQ ID NO 52 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 52 ttcccgagta agcaggcaga 20 <210> SEQ ID NO 53 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 53 gcaaatttcc cgagtaagca 20 <210> SEQ ID NO 54 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 54 aaagcaaatt tcccgagtaa 20 <210> SEQ ID NO 55 <211> LENGTH: 20 <212> TYPE: DNA

<213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 55 ttggcaaaag caaatttccc 20 <210> SEQ ID NO 56 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 56 ggtttggcaa aagcaaattt 20 <210> SEQ ID NO 57 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 57 gcgggtttgg caaaagcaaa 20 <210> SEQ ID NO 58 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 58 aaagcgggtt tggcaaaagc 20 <210> SEQ ID NO 59 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 59 cccgaaaaag cgggtttggc 20 <210> SEQ ID NO 60 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 60 atccccgaaa aagcgggttt 20 <210> SEQ ID NO 61 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 61 cgggatcccc gaaaaagcgg 20 <210> SEQ ID NO 62 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 62 gcgcgggatc cccgaaaaag 20 <210> SEQ ID NO 63 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 63 gagagcagcg caagtgagga 20 <210> SEQ ID NO 64 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 64 tccgagagca gcgcaagtga 20 <210> SEQ ID NO 65 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 65 ggctccgaga gcagcgcaag 20 <210> SEQ ID NO 66 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 66 aagcgggcgg agccggctgg 20 <210> SEQ ID NO 67 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 67 ccgaagcggg cggagccggc 20 <210> SEQ ID NO 68 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 68 aaaccgccga agcgggcgga 20 <210> SEQ ID NO 69 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 69 tccaaaccgc cgaagcgggc 20 <210> SEQ ID NO 70 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 70 atatccaaac cgccgaagcg 20 <210> SEQ ID NO 71 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 71 taaatatcca aaccgccgaa 20 <210> SEQ ID NO 72 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 72 caataaatat ccaaaccgcc 20 <210> SEQ ID NO 73 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 73 cgaggtcaat aaatatccaa 20 <210> SEQ ID NO 74 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 74 ggacgaggtc aataaatatc 20 <210> SEQ ID NO 75 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 75 ggaggacgag gtcaataaat 20 <210> SEQ ID NO 76 <211> LENGTH: 20

<212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 76 gtcggaggac gaggtcaata 20 <210> SEQ ID NO 77 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 77 cgagtcggag gacgaggtca 20 <210> SEQ ID NO 78 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 78 tgtcagcgag tcggaggacg 20 <210> SEQ ID NO 79 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 79 gcctgtcagc gagtcggagg 20 <210> SEQ ID NO 80 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 80 gtagcctgtc agcgagtcgg 20 <210> SEQ ID NO 81 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 81 cctgtagcct gtcagcgagt 20 <210> SEQ ID NO 82 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 82 ggtcctgtag cctgtcagcg 20 <210> SEQ ID NO 83 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 83 aaataccgag gaatgtcggg 20 <210> SEQ ID NO 84 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 84 aataaatacc gaggaatgtc 20 <210> SEQ ID NO 85 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 85 gacaataaat accgaggaat 20 <210> SEQ ID NO 86 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 86 cggggccccg gagtcgaaga 20 <210> SEQ ID NO 87 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 87 ccaacggggc cccggagtcg 20 <210> SEQ ID NO 88 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 88 ttccaacggg gccccggagt 20 <210> SEQ ID NO 89 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 89 gtcttccaac ggggccccgg 20 <210> SEQ ID NO 90 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 90 cagtcttcca acggggcccc 20 <210> SEQ ID NO 91 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 91 ctcagtcttc caacggggcc 20 <210> SEQ ID NO 92 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 92 gcactcagtc ttccaacggg 20 <210> SEQ ID NO 93 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 93 ccccgggcac tcagtcttcc 20 <210> SEQ ID NO 94 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 94 tgccccgggc actcagtctt 20 <210> SEQ ID NO 95 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 95 cgtgccccgg gcactcagtc 20 <210> SEQ ID NO 96 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 96 gtgccgtgcc ccgggcactc 20 <210> SEQ ID NO 97

<211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 97 tctgtgccgt gccccgggca 20 <210> SEQ ID NO 98 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 98 gcttctgtgc cgtgccccgg 20 <210> SEQ ID NO 99 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 99 gcggcttctg tgccgtgccc 20 <210> SEQ ID NO 100 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 100 gcgcggcttc tgtgccgtgc 20 <210> SEQ ID NO 101 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 101 gggcgcggct tctgtgccgt 20 <210> SEQ ID NO 102 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 102 ggcggtgggc gcggcttctg 20 <210> SEQ ID NO 103 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 103 ggcaggcggt gggcgcggct 20 <210> SEQ ID NO 104 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 104 ctggcaggcg gtgggcgcgg 20 <210> SEQ ID NO 105 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 105 aactggcagg cggtgggcgc 20 <210> SEQ ID NO 106 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 106 gtgaactggc aggcggtggg 20 <210> SEQ ID NO 107 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 107 ggttgtgaac tggcaggcgg 20 <210> SEQ ID NO 108 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 108 gcggttgtga actggcaggc 20 <210> SEQ ID NO 109 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 109 cggagcggtt gtgaactggc 20 <210> SEQ ID NO 110 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 110 cgctcggagc ggttgtgaac 20 <210> SEQ ID NO 111 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 111 cccacgctcg gagcggttgt 20 <210> SEQ ID NO 112 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 112 agacccacgc tcggagcggt 20 <210> SEQ ID NO 113 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 113 cggagaccca cgctcggagc 20 <210> SEQ ID NO 114 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 114 gggcggagac ccacgctcgg 20 <210> SEQ ID NO 115 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 115 gctgggcgga gacccacgct 20 <210> SEQ ID NO 116 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 116 ggagctgggc ggagacccac 20 <210> SEQ ID NO 117 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 117 ctggagctgg gcggagaccc 20

<210> SEQ ID NO 118 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 118 ggactggagc tgggcggaga 20 <210> SEQ ID NO 119 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 119 caggactgga gctgggcgga 20 <210> SEQ ID NO 120 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 120 atcacaggac tggagctggg 20 <210> SEQ ID NO 121 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 121 gggcgggccc ggatcacagg 20 <210> SEQ ID NO 122 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 122 gggggcgggc ccggatcaca 20 <210> SEQ ID NO 123 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 123 aggcagcacc atggcccctc 20 <210> SEQ ID NO 124 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 124 ggtccaacac cagctgctgg 20 <210> SEQ ID NO 125 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 125 cgatcacctt cagaatctcg 20 <210> SEQ ID NO 126 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 126 cttgttcatg atcttcatgg 20 <210> SEQ ID NO 127 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 127 ccccattcac caacacgtcc 20 <210> SEQ ID NO 128 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 128 gcgtgatcca ccgccggtcc 20 <210> SEQ ID NO 129 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 129 gtaatactcc atgaccaggt 20 <210> SEQ ID NO 130 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 130 gcagtgtcag caggtccccg 20 <210> SEQ ID NO 131 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 131 caccgagtct atggccatga 20 <210> SEQ ID NO 132 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 132 acgtagccaa gccggtgcac 20 <210> SEQ ID NO 133 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 133 atgtggccac agcggtccag 20 <210> SEQ ID NO 134 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 134 cttcgtccac cagcggcaga 20 <210> SEQ ID NO 135 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 135 gaccccttcg tccaccagcg 20 <210> SEQ ID NO 136 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 136 cctgctccac cccggcccag 20 <210> SEQ ID NO 137 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 137 cggaagtcgc ctgctccacc 20 <210> SEQ ID NO 138 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 138 cggagaccat cccagtcgag 20

<210> SEQ ID NO 139 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 139 tgagggccat gcaggagtag 20 <210> SEQ ID NO 140 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 140 ctccagttcc atgggtgtgg 20 <210> SEQ ID NO 141 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 141 gcgcttgcac gtgtggctca 20 <210> SEQ ID NO 142 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 142 gccacttcag ctgtttcatc 20 <210> SEQ ID NO 143 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 143 gcctcagcct ctgccgcagg 20 <210> SEQ ID NO 144 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 144 gcagcgtcac ctcggcctca 20 <210> SEQ ID NO 145 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 145 ggctcaggct ctgccgggtg 20 <210> SEQ ID NO 146 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 146 ttccgagcct ctgcctcgcg 20 <210> SEQ ID NO 147 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 147 ggtcccggtt ccgagcctct 20 <210> SEQ ID NO 148 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 148 atccgctcct gcaactgccg 20 <210> SEQ ID NO 149 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 149 gcaactccat ccgctcctgc 20 <210> SEQ ID NO 150 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 150 aggtggatcc gtggcccggg 20 <210> SEQ ID NO 151 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 151 cgcggcttct gtgccgtgcc 20 <210> SEQ ID NO 152 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 152 ttgctgcctt cccaggcctg 20 <210> SEQ ID NO 153 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 153 tgctcccgac aagctccaga 20 <210> SEQ ID NO 154 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 154 agaacctgcc cattgctgaa 20 <210> SEQ ID NO 155 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 155 cactgagggc cagacatatg 20 <210> SEQ ID NO 156 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 156 ctctagattc agatgcaggt 20 <210> SEQ ID NO 157 <211> LENGTH: 15 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Primer <400> SEQUENCE: 157 cgggccgtcc gtgtt 15 <210> SEQ ID NO 158 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Primer <400> SEQUENCE: 158 ctttgcactt tgcgaaccaa 20 <210> SEQ ID NO 159 <211> LENGTH: 21 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Probe <400> SEQUENCE: 159 catcctccac gcacccccac c 21

<210> SEQ ID NO 160 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 160 gcctggcagc ccctgtccag 20 <210> SEQ ID NO 161 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 161 ggcctggcag cccctgtcca 20 <210> SEQ ID NO 162 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 162 gggcctggca gcccctgtcc 20 <210> SEQ ID NO 163 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 163 atggcccctc cccgggccgg 20 <210> SEQ ID NO 164 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 164 catggcccct ccccgggccg 20 <210> SEQ ID NO 165 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 165 ccatggcccc tccccgggcc 20 <210> SEQ ID NO 166 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 166 accatggccc ctccccgggc 20 <210> SEQ ID NO 167 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 167 caccatggcc cctccccggg 20 <210> SEQ ID NO 168 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 168 gcaccatggc ccctccccgg 20 <210> SEQ ID NO 169 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 169 agcaccatgg cccctccccg 20 <210> SEQ ID NO 170 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 170 cagcaccatg gcccctcccc 20 <210> SEQ ID NO 171 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 171 gcagcaccat ggcccctccc 20 <210> SEQ ID NO 172 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 172 ggcagcacca tggcccctcc 20 <210> SEQ ID NO 173 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 173 caggcagcac catggcccct 20 <210> SEQ ID NO 174 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 174 acaggcagca ccatggcccc 20 <210> SEQ ID NO 175 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 175 ggacaggcag caccatggcc 20 <210> SEQ ID NO 176 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 176 tggacaggca gcaccatggc 20 <210> SEQ ID NO 177 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 177 ttggacaggc agcaccatgg 20 <210> SEQ ID NO 178 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 178 gttggacagg cagcaccatg 20 <210> SEQ ID NO 179 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 179 tgttggacag gcagcaccat 20 <210> SEQ ID NO 180 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 180

atgttggaca ggcagcacca 20 <210> SEQ ID NO 181 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 181 catgttggac aggcagcacc 20 <210> SEQ ID NO 182 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 182 acatgttgga caggcagcac 20 <210> SEQ ID NO 183 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 183 gacatgttgg acaggcagca 20 <210> SEQ ID NO 184 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 184 tgacatgttg gacaggcagc 20 <210> SEQ ID NO 185 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 185 ctgacatgtt ggacaggcag 20 <210> SEQ ID NO 186 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 186 gctgacatgt tggacaggca 20 <210> SEQ ID NO 187 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 187 ggctgacatg ttggacaggc 20 <210> SEQ ID NO 188 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 188 cggctgacat gttggacagg 20 <210> SEQ ID NO 189 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 189 tcggctgaca tgttggacag 20 <210> SEQ ID NO 190 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 190 ctcggctgac atgttggaca 20 <210> SEQ ID NO 191 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 191 cctcggctga catgttggac 20 <210> SEQ ID NO 192 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 192 acctcggctg acatgttgga 20 <210> SEQ ID NO 193 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 193 cacctcggct gacatgttgg 20 <210> SEQ ID NO 194 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 194 gcacctcggc tgacatgttg 20 <210> SEQ ID NO 195 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 195 cgcacctcgg ctgacatgtt 20 <210> SEQ ID NO 196 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 196 ccgcacctcg gctgacatgt 20 <210> SEQ ID NO 197 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 197 gccgcacctc ggctgacatg 20 <210> SEQ ID NO 198 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 198 agccgcacct cggctgacat 20 <210> SEQ ID NO 199 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 199 cagccgcacc tcggctgaca 20 <210> SEQ ID NO 200 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 200 tcagccgcac ctcggctgac 20 <210> SEQ ID NO 201 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 201

ctcagccgca cctcggctga 20 <210> SEQ ID NO 202 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 202 cctcagccgc acctcggctg 20 <210> SEQ ID NO 203 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 203 gcctcagccg cacctcggct 20 <210> SEQ ID NO 204 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 204 ccaacaccag ctgctggagc 20 <210> SEQ ID NO 205 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 205 tccaacacca gctgctggag 20 <210> SEQ ID NO 206 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 206 gtccaacacc agctgctgga 20 <210> SEQ ID NO 207 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 207 gggtccaaca ccagctgctg 20 <210> SEQ ID NO 208 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 208 ggctccagcc ccaggaagcc 20 <210> SEQ ID NO 209 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 209 gggctccagc cccaggaagc 20 <210> SEQ ID NO 210 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 210 caggagaagg tcgagcaggg 20 <210> SEQ ID NO 211 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 211 cccaggagaa ggtcgagcag 20 <210> SEQ ID NO 212 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 212 gcccaggaga aggtcgagca 20 <210> SEQ ID NO 213 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 213 cgcccaggag aaggtcgagc 20 <210> SEQ ID NO 214 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 214 acgcccagga gaaggtcgag 20 <210> SEQ ID NO 215 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 215 tcctgggcca gttcggaggc 20 <210> SEQ ID NO 216 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 216 gtcctgggcc agttcggagg 20 <210> SEQ ID NO 217 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 217 tgtcctgggc cagttcggag 20 <210> SEQ ID NO 218 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 218 ttgtcctggg ccagttcgga 20 <210> SEQ ID NO 219 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 219 cttgtcctgg gccagttcgg 20 <210> SEQ ID NO 220 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 220 acttgtcctg ggccagttcg 20 <210> SEQ ID NO 221 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 221 tacttgtcct gggccagttc 20 <210> SEQ ID NO 222 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide

<400> SEQUENCE: 222 gtacttgtcc tgggccagtt 20 <210> SEQ ID NO 223 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 223 cgtacttgtc ctgggccagt 20 <210> SEQ ID NO 224 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 224 actgcaagaa gtcggccacg 20 <210> SEQ ID NO 225 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 225 ccactgcaag aagtcggcca 20 <210> SEQ ID NO 226 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 226 cccactgcaa gaagtcggcc 20 <210> SEQ ID NO 227 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 227 gcccactgca agaagtcggc 20 <210> SEQ ID NO 228 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 228 cgcccactgc aagaagtcgg 20 <210> SEQ ID NO 229 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 229 ccgcccactg caagaagtcg 20 <210> SEQ ID NO 230 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 230 tccgcccact gcaagaagtc 20 <210> SEQ ID NO 231 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 231 ctccgcccac tgcaagaagt 20 <210> SEQ ID NO 232 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 232 gctccgccca ctgcaagaag 20 <210> SEQ ID NO 233 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 233 ggctccgccc actgcaagaa 20 <210> SEQ ID NO 234 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 234 gggctccgcc cactgcaaga 20 <210> SEQ ID NO 235 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 235 tgggctccgc ccactgcaag 20 <210> SEQ ID NO 236 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 236 atgggctccg cccactgcaa 20 <210> SEQ ID NO 237 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 237 gatgggctcc gcccactgca 20 <210> SEQ ID NO 238 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 238 cgatgggctc cgcccactgc 20 <210> SEQ ID NO 239 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 239 acgatgggct ccgcccactg 20 <210> SEQ ID NO 240 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 240 cacgatgggc tccgcccact 20 <210> SEQ ID NO 241 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 241 ccacgatggg ctccgcccac 20 <210> SEQ ID NO 242 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 242 accacgatgg gctccgccca 20 <210> SEQ ID NO 243 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide

<400> SEQUENCE: 243 caccacgatg ggctccgccc 20 <210> SEQ ID NO 244 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 244 tcaccacgat gggctccgcc 20 <210> SEQ ID NO 245 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 245 ctcaccacga tgggctccgc 20 <210> SEQ ID NO 246 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 246 cctcaccacg atgggctccg 20 <210> SEQ ID NO 247 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 247 gcctcaccac gatgggctcc 20 <210> SEQ ID NO 248 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 248 agcctcacca cgatgggctc 20 <210> SEQ ID NO 249 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 249 aagcctcacc acgatgggct 20 <210> SEQ ID NO 250 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 250 taagcctcac cacgatgggc 20 <210> SEQ ID NO 251 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 251 ttaagcctca ccacgatggg 20 <210> SEQ ID NO 252 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 252 cttaagcctc accacgatgg 20 <210> SEQ ID NO 253 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 253 ccttaagcct caccacgatg 20 <210> SEQ ID NO 254 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 254 tccttaagcc tcaccacgat 20 <210> SEQ ID NO 255 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 255 ctccttaagc ctcaccacga 20 <210> SEQ ID NO 256 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 256 cctccttaag cctcaccacg 20 <210> SEQ ID NO 257 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 257 acctccttaa gcctcaccac 20 <210> SEQ ID NO 258 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 258 gacctcctta agcctcacca 20 <210> SEQ ID NO 259 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 259 ggacctcctt aagcctcacc 20 <210> SEQ ID NO 260 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 260 cggacctcct taagcctcac 20 <210> SEQ ID NO 261 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 261 tcggacctcc ttaagcctca 20 <210> SEQ ID NO 262 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 262 gtcggacctc cttaagcctc 20 <210> SEQ ID NO 263 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 263 cagtcggacc tccttaagcc 20 <210> SEQ ID NO 264 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE:

<223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 264 gcagtcggac ctccttaagc 20 <210> SEQ ID NO 265 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 265 tgcagtcgga cctccttaag 20 <210> SEQ ID NO 266 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 266 ccttcagaat ctcgaagtcg 20 <210> SEQ ID NO 267 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 267 accttcagaa tctcgaagtc 20 <210> SEQ ID NO 268 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 268 tcaccttcag aatctcgaag 20 <210> SEQ ID NO 269 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 269 atcaccttca gaatctcgaa 20 <210> SEQ ID NO 270 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 270 gatcaccttc agaatctcga 20 <210> SEQ ID NO 271 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 271 ccgatcacct tcagaatctc 20 <210> SEQ ID NO 272 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 272 tccgatcacc ttcagaatct 20 <210> SEQ ID NO 273 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 273 gtccgatcac cttcagaatc 20 <210> SEQ ID NO 274 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 274 cgtccgatca ccttcagaat 20 <210> SEQ ID NO 275 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 275 cccgtctgct tcatcttcac 20 <210> SEQ ID NO 276 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 276 gcccgtctgc ttcatcttca 20 <210> SEQ ID NO 277 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 277 ggcccgtctg cttcatcttc 20 <210> SEQ ID NO 278 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 278 tggcccgtct gcttcatctt 20 <210> SEQ ID NO 279 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 279 ctggcccgtc tgcttcatct 20 <210> SEQ ID NO 280 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 280 cctggcccgt ctgcttcatc 20 <210> SEQ ID NO 281 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 281 acctggcccg tctgcttcat 20 <210> SEQ ID NO 282 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 282 cacctggccc gtctgcttca 20 <210> SEQ ID NO 283 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 283 acacctggcc cgtctgcttc 20 <210> SEQ ID NO 284 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 284 tacacctggc ccgtctgctt 20 <210> SEQ ID NO 285 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence

<220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 285 ttgttcatga tcttcatggc 20 <210> SEQ ID NO 286 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 286 acttgttcat gatcttcatg 20 <210> SEQ ID NO 287 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 287 cacttgttca tgatcttcat 20 <210> SEQ ID NO 288 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 288 ccacttgttc atgatcttca 20 <210> SEQ ID NO 289 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 289 cccacttgtt catgatcttc 20 <210> SEQ ID NO 290 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 290 tcccacttgt tcatgatctt 20 <210> SEQ ID NO 291 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 291 gtcccacttg ttcatgatct 20 <210> SEQ ID NO 292 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 292 tgtcccactt gttcatgatc 20 <210> SEQ ID NO 293 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 293 atgtcccact tgttcatgat 20 <210> SEQ ID NO 294 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 294 catgtcccac ttgttcatga 20 <210> SEQ ID NO 295 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 295 gcatgtccca cttgttcatg 20 <210> SEQ ID NO 296 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 296 agcatgtccc acttgttcat 20 <210> SEQ ID NO 297 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 297 cagcatgtcc cacttgttca 20 <210> SEQ ID NO 298 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 298 tcagcatgtc ccacttgttc 20 <210> SEQ ID NO 299 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 299 ttcagcatgt cccacttgtt 20 <210> SEQ ID NO 300 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 300 cttcagcatg tcccacttgt 20 <210> SEQ ID NO 301 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 301 tcttcagcat gtcccacttg 20 <210> SEQ ID NO 302 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 302 cctcttcagc atgtcccact 20 <210> SEQ ID NO 303 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 303 ccctcttcag catgtcccac 20 <210> SEQ ID NO 304 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 304 cccctcttca gcatgtccca 20 <210> SEQ ID NO 305 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 305 gcccctcttc agcatgtccc 20 <210> SEQ ID NO 306 <211> LENGTH: 20 <212> TYPE: DNA

<213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 306 cgcccctctt cagcatgtcc 20 <210> SEQ ID NO 307 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 307 tcgcccctct tcagcatgtc 20 <210> SEQ ID NO 308 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 308 ctcgcccctc ttcagcatgt 20 <210> SEQ ID NO 309 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 309 cctcgcccct cttcagcatg 20 <210> SEQ ID NO 310 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 310 acctcgcccc tcttcagcat 20 <210> SEQ ID NO 311 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 311 cacctcgccc ctcttcagca 20 <210> SEQ ID NO 312 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 312 acacctcgcc cctcttcagc 20 <210> SEQ ID NO 313 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 313 gacacctcgc ccctcttcag 20 <210> SEQ ID NO 314 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 314 gccaggcgga tgtggccaca 20 <210> SEQ ID NO 315 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 315 accgcaccgt tccatctgcc 20 <210> SEQ ID NO 316 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 316 gaccgcaccg ttccatctgc 20 <210> SEQ ID NO 317 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 317 acagcctgca ggatctcggg 20 <210> SEQ ID NO 318 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 318 cacagcctgc aggatctcgg 20 <210> SEQ ID NO 319 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 319 ccacagcctg caggatctcg 20 <210> SEQ ID NO 320 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 320 cccacagcct gcaggatctc 20 <210> SEQ ID NO 321 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 321 gcccacagcc tgcaggatct 20 <210> SEQ ID NO 322 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 322 cgcccacagc ctgcaggatc 20 <210> SEQ ID NO 323 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 323 ccgcccacag cctgcaggat 20 <210> SEQ ID NO 324 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 324 accgcccaca gcctgcagga 20 <210> SEQ ID NO 325 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 325 caccgcccac agcctgcagg 20 <210> SEQ ID NO 326 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 326 ccaccgccca cagcctgcag 20 <210> SEQ ID NO 327 <211> LENGTH: 20

<212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 327 cccaccgccc acagcctgca 20 <210> SEQ ID NO 328 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 328 gcccaccgcc cacagcctgc 20 <210> SEQ ID NO 329 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 329 ggcccaccgc ccacagcctg 20 <210> SEQ ID NO 330 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 330 aggcccaccg cccacagcct 20 <210> SEQ ID NO 331 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 331 caggcccacc gcccacagcc 20 <210> SEQ ID NO 332 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 332 ccaggcccac cgcccacagc 20 <210> SEQ ID NO 333 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 333 cccaggccca ccgcccacag 20 <210> SEQ ID NO 334 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 334 tcccaggccc accgcccaca 20 <210> SEQ ID NO 335 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 335 gtcccaggcc caccgcccac 20 <210> SEQ ID NO 336 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 336 tgtcccaggc ccaccgccca 20 <210> SEQ ID NO 337 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 337 ctgtcccagg cccaccgccc 20 <210> SEQ ID NO 338 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 338 cctgtcccag gcccaccgcc 20 <210> SEQ ID NO 339 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 339 gcctgtccca ggcccaccgc 20 <210> SEQ ID NO 340 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 340 tgcctgtccc aggcccaccg 20 <210> SEQ ID NO 341 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 341 ctgcctgtcc caggcccacc 20 <210> SEQ ID NO 342 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 342 gctgcctgtc ccaggcccac 20 <210> SEQ ID NO 343 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 343 agctgcctgt cccaggccca 20 <210> SEQ ID NO 344 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 344 tagctgcctg tcccaggccc 20 <210> SEQ ID NO 345 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 345 gtagctgcct gtcccaggcc 20 <210> SEQ ID NO 346 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 346 cgtagctgcc tgtcccaggc 20 <210> SEQ ID NO 347 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 347 ccgtagctgc ctgtcccagg 20 <210> SEQ ID NO 348

<211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 348 cccgtagctg cctgtcccag 20 <210> SEQ ID NO 349 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 349 gcccgtagct gcctgtccca 20 <210> SEQ ID NO 350 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 350 ggcccgtagc tgcctgtccc 20 <210> SEQ ID NO 351 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 351 tagaacattt cataggcgaa 20 <210> SEQ ID NO 352 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 352 tctccgccgt ggaatccgcg 20 <210> SEQ ID NO 353 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 353 gtctccgccg tggaatccgc 20 <210> SEQ ID NO 354 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 354 ggtctccgcc gtggaatccg 20 <210> SEQ ID NO 355 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 355 aggtctccgc cgtggaatcc 20 <210> SEQ ID NO 356 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 356 taggtctccg ccgtggaatc 20 <210> SEQ ID NO 357 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 357 ttgtagtgga cgatcttgcc 20 <210> SEQ ID NO 358 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 358 cttgtagtgg acgatcttgc 20 <210> SEQ ID NO 359 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 359 ccttgtagtg gacgatcttg 20 <210> SEQ ID NO 360 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 360 tccttgtagt ggacgatctt 20 <210> SEQ ID NO 361 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 361 ctccttgtag tggacgatct 20 <210> SEQ ID NO 362 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 362 gctccttgta gtggacgatc 20 <210> SEQ ID NO 363 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 363 tgctccttgt agtggacgat 20 <210> SEQ ID NO 364 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 364 gtgctccttg tagtggacga 20 <210> SEQ ID NO 365 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 365 ggtgctcctt gtagtggacg 20 <210> SEQ ID NO 366 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 366 aggtgctcct tgtagtggac 20 <210> SEQ ID NO 367 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 367 gaggtgctcc ttgtagtgga 20 <210> SEQ ID NO 368 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 368 agaggtgctc cttgtagtgg 20

<210> SEQ ID NO 369 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 369 gagaggtgct ccttgtagtg 20 <210> SEQ ID NO 370 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 370 agagaggtgc tccttgtagt 20 <210> SEQ ID NO 371 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 371 gagagaggtg ctccttgtag 20 <210> SEQ ID NO 372 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 372 agagagaggt gctccttgta 20 <210> SEQ ID NO 373 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 373 cagagagagg tgctccttgt 20 <210> SEQ ID NO 374 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 374 ggcagagaga ggtgctcctt 20 <210> SEQ ID NO 375 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 375 cggcagagag aggtgctcct 20 <210> SEQ ID NO 376 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 376 gcggcagaga gaggtgctcc 20 <210> SEQ ID NO 377 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 377 agcggcagag agaggtgctc 20 <210> SEQ ID NO 378 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 378 cagcggcaga gagaggtgct 20 <210> SEQ ID NO 379 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 379 ccagcggcag agagaggtgc 20 <210> SEQ ID NO 380 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 380 ggcccagccg tgtctccggg 20 <210> SEQ ID NO 381 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 381 cggcccagcc gtgtctccgg 20 <210> SEQ ID NO 382 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 382 ccggcccagc cgtgtctccg 20 <210> SEQ ID NO 383 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 383 cccggcccag ccgtgtctcc 20 <210> SEQ ID NO 384 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 384 ccccggccca gccgtgtctc 20 <210> SEQ ID NO 385 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 385 accccggccc agccgtgtct 20 <210> SEQ ID NO 386 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 386 caccccggcc cagccgtgtc 20 <210> SEQ ID NO 387 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 387 ccaccccggc ccagccgtgt 20 <210> SEQ ID NO 388 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 388 tccaccccgg cccagccgtg 20 <210> SEQ ID NO 389 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 389 ctccaccccg gcccagccgt 20

<210> SEQ ID NO 390 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 390 gctccacccc ggcccagccg 20 <210> SEQ ID NO 391 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 391 tgctccaccc cggcccagcc 20 <210> SEQ ID NO 392 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 392 ctgctccacc ccggcccagc 20 <210> SEQ ID NO 393 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 393 aagggatgtg tccggaagtc 20 <210> SEQ ID NO 394 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 394 gaagggatgt gtccggaagt 20 <210> SEQ ID NO 395 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 395 agaagggatg tgtccggaag 20 <210> SEQ ID NO 396 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 396 aagaagggat gtgtccggaa 20 <210> SEQ ID NO 397 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 397 gaagaaggga tgtgtccgga 20 <210> SEQ ID NO 398 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 398 agaagaaggg atgtgtccgg 20 <210> SEQ ID NO 399 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 399 aagaagaagg gatgtgtccg 20 <210> SEQ ID NO 400 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 400 aaagaagaag ggatgtgtcc 20 <210> SEQ ID NO 401 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 401 caaagaagaa gggatgtgtc 20 <210> SEQ ID NO 402 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 402 ccaaagaaga agggatgtgt 20 <210> SEQ ID NO 403 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 403 ggccaaagaa gaagggatgt 20 <210> SEQ ID NO 404 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 404 aggccaaaga agaagggatg 20 <210> SEQ ID NO 405 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 405 gaggccaaag aagaagggat 20 <210> SEQ ID NO 406 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 406 cgaggccaaa gaagaaggga 20 <210> SEQ ID NO 407 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 407 tcgaggccaa agaagaaggg 20 <210> SEQ ID NO 408 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 408 gtcgaggcca aagaagaagg 20 <210> SEQ ID NO 409 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 409 agtcgaggcc aaagaagaag 20 <210> SEQ ID NO 410 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 410 cagtcgaggc caaagaagaa 20

<210> SEQ ID NO 411 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 411 ccagtcgagg ccaaagaaga 20 <210> SEQ ID NO 412 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 412 cccagtcgag gccaaagaag 20 <210> SEQ ID NO 413 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 413 tcccagtcga ggccaaagaa 20 <210> SEQ ID NO 414 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 414 atcccagtcg aggccaaaga 20 <210> SEQ ID NO 415 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 415 catcccagtc gaggccaaag 20 <210> SEQ ID NO 416 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 416 ccatcccagt cgaggccaaa 20 <210> SEQ ID NO 417 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 417 accatcccag tcgaggccaa 20 <210> SEQ ID NO 418 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 418 gaccatccca gtcgaggcca 20 <210> SEQ ID NO 419 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 419 agaccatccc agtcgaggcc 20 <210> SEQ ID NO 420 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 420 gagaccatcc cagtcgaggc 20 <210> SEQ ID NO 421 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 421 ggagaccatc ccagtcgagg 20 <210> SEQ ID NO 422 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 422 ttcgaaatcc ggtgtaaagg 20 <210> SEQ ID NO 423 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 423 cttcgaaatc cggtgtaaag 20 <210> SEQ ID NO 424 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 424 ccttcgaaat ccggtgtaaa 20 <210> SEQ ID NO 425 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 425 accttcgaaa tccggtgtaa 20 <210> SEQ ID NO 426 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 426 caccttcgaa atccggtgta 20 <210> SEQ ID NO 427 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 427 gcaccttcga aatccggtgt 20 <210> SEQ ID NO 428 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 428 ggcaccttcg aaatccggtg 20 <210> SEQ ID NO 429 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 429 tggcaccttc gaaatccggt 20 <210> SEQ ID NO 430 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 430 gtggcacctt cgaaatccgg 20 <210> SEQ ID NO 431 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 431

ggtggcacct tcgaaatccg 20 <210> SEQ ID NO 432 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 432 cggtggcacc ttcgaaatcc 20 <210> SEQ ID NO 433 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 433 tcggtggcac cttcgaaatc 20 <210> SEQ ID NO 434 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 434 gtcggtggca ccttcgaaat 20 <210> SEQ ID NO 435 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 435 tgtcggtggc accttcgaaa 20 <210> SEQ ID NO 436 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 436 gtgtcggtgg caccttcgaa 20 <210> SEQ ID NO 437 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 437 tgtgtcggtg gcaccttcga 20 <210> SEQ ID NO 438 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 438 atgtgtcggt ggcaccttcg 20 <210> SEQ ID NO 439 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 439 catgtgtcgg tggcaccttc 20 <210> SEQ ID NO 440 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 440 gcatgtgtcg gtggcacctt 20 <210> SEQ ID NO 441 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 441 tgcatgtgtc ggtggcacct 20 <210> SEQ ID NO 442 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 442 ttgcatgtgt cggtggcacc 20 <210> SEQ ID NO 443 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 443 gttgcatgtg tcggtggcac 20 <210> SEQ ID NO 444 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 444 agttgcatgt gtcggtggca 20 <210> SEQ ID NO 445 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 445 aagttgcatg tgtcggtggc 20 <210> SEQ ID NO 446 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 446 gaagttgcat gtgtcggtgg 20 <210> SEQ ID NO 447 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 447 cgaagttgca tgtgtcggtg 20 <210> SEQ ID NO 448 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 448 gtcgaagttg catgtgtcgg 20 <210> SEQ ID NO 449 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 449 agtcgaagtt gcatgtgtcg 20 <210> SEQ ID NO 450 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 450 aagtcgaagt tgcatgtgtc 20 <210> SEQ ID NO 451 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 451 caagtcgaag ttgcatgtgt 20 <210> SEQ ID NO 452 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 452

ccaagtcgaa gttgcatgtg 20 <210> SEQ ID NO 453 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 453 accaagtcga agttgcatgt 20 <210> SEQ ID NO 454 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 454 caccaagtcg aagttgcatg 20 <210> SEQ ID NO 455 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 455 ccaccaagtc gaagttgcat 20 <210> SEQ ID NO 456 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 456 tccaccaagt cgaagttgca 20 <210> SEQ ID NO 457 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 457 ctccaccaag tcgaagttgc 20 <210> SEQ ID NO 458 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 458 cctccaccaa gtcgaagttg 20 <210> SEQ ID NO 459 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 459 tcctccacca agtcgaagtt 20 <210> SEQ ID NO 460 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 460 gtcctccacc aagtcgaagt 20 <210> SEQ ID NO 461 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 461 cgtcctccac caagtcgaag 20 <210> SEQ ID NO 462 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 462 ccgtcctcca ccaagtcgaa 20 <210> SEQ ID NO 463 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 463 cccgtcctcc accaagtcga 20 <210> SEQ ID NO 464 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 464 gcccgtcctc caccaagtcg 20 <210> SEQ ID NO 465 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 465 agcccgtcct ccaccaagtc 20 <210> SEQ ID NO 466 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 466 gagcccgtcc tccaccaagt 20 <210> SEQ ID NO 467 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 467 tgagcccgtc ctccaccaag 20 <210> SEQ ID NO 468 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 468 ggttccgagc ctctgcctcg 20 <210> SEQ ID NO 469 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 469 cggttccgag cctctgcctc 20 <210> SEQ ID NO 470 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 470 ccggttccga gcctctgcct 20 <210> SEQ ID NO 471 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 471 cccggttccg agcctctgcc 20 <210> SEQ ID NO 472 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 472 tcccggttcc gagcctctgc 20 <210> SEQ ID NO 473 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide

<400> SEQUENCE: 473 gtcccggttc cgagcctctg 20 <210> SEQ ID NO 474 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 474 aggtcccggt tccgagcctc 20 <210> SEQ ID NO 475 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 475 taggtcccgg ttccgagcct 20 <210> SEQ ID NO 476 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 476 ctaggtcccg gttccgagcc 20 <210> SEQ ID NO 477 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 477 tctaggtccc ggttccgagc 20 <210> SEQ ID NO 478 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 478 ctctaggtcc cggttccgag 20 <210> SEQ ID NO 479 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 479 cctctaggtc ccggttccga 20 <210> SEQ ID NO 480 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 480 gcctctaggt cccggttccg 20 <210> SEQ ID NO 481 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 481 catccgctcc tgcaactgcc 20 <210> SEQ ID NO 482 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 482 ccatccgctc ctgcaactgc 20 <210> SEQ ID NO 483 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 483 tccatccgct cctgcaactg 20 <210> SEQ ID NO 484 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 484 ctccatccgc tcctgcaact 20 <210> SEQ ID NO 485 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 485 actccatccg ctcctgcaac 20 <210> SEQ ID NO 486 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 486 aactccatcc gctcctgcaa 20 <210> SEQ ID NO 487 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 487 caactccatc cgctcctgca 20 <210> SEQ ID NO 488 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 488 agcaactcca tccgctcctg 20 <210> SEQ ID NO 489 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 489 cagcaactcc atccgctcct 20 <210> SEQ ID NO 490 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 490 gcagcaactc catccgctcc 20 <210> SEQ ID NO 491 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 491 cagctgtggc tccctctgcc 20 <210> SEQ ID NO 492 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 492 acagctgtgg ctccctctgc 20 <210> SEQ ID NO 493 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 493 gacagctgtg gctccctctg 20 <210> SEQ ID NO 494 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide

<400> SEQUENCE: 494 tgacagctgt ggctccctct 20 <210> SEQ ID NO 495 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 495 gtgacagctg tggctccctc 20 <210> SEQ ID NO 496 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 496 cgtgacagct gtggctccct 20 <210> SEQ ID NO 497 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 497 ccgtgacagc tgtggctccc 20 <210> SEQ ID NO 498 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 498 cccgtgacag ctgtggctcc 20 <210> SEQ ID NO 499 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 499 ccccgtgaca gctgtggctc 20 <210> SEQ ID NO 500 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 500 cccccgtgac agctgtggct 20 <210> SEQ ID NO 501 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 501 acccccgtga cagctgtggc 20 <210> SEQ ID NO 502 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 502 gacccccgtg acagctgtgg 20 <210> SEQ ID NO 503 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 503 ggacccccgt gacagctgtg 20 <210> SEQ ID NO 504 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 504 gggacccccg tgacagctgt 20 <210> SEQ ID NO 505 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 505 gaaggtggat ccgtggcccg 20 <210> SEQ ID NO 506 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 506 ggaaggtgga tccgtggccc 20 <210> SEQ ID NO 507 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 507 gggaaggtgg atccgtggcc 20 <210> SEQ ID NO 508 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 508 tgggaaggtg gatccgtggc 20 <210> SEQ ID NO 509 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 509 atgggaaggt ggatccgtgg 20 <210> SEQ ID NO 510 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 510 gatgggaagg tggatccgtg 20 <210> SEQ ID NO 511 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 511 tagatgggaa ggtggatccg 20 <210> SEQ ID NO 512 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 512 ctagatggga aggtggatcc 20 <210> SEQ ID NO 513 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 513 tctagatggg aaggtggatc 20 <210> SEQ ID NO 514 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 514 atctagatgg gaaggtggat 20 <210> SEQ ID NO 515 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE:

<223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 515 ccatctagat gggaaggtgg 20 <210> SEQ ID NO 516 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 516 gccatctaga tgggaaggtg 20 <210> SEQ ID NO 517 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 517 ggccatctag atgggaaggt 20 <210> SEQ ID NO 518 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 518 caccagcggg cactggccca 20 <210> SEQ ID NO 519 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 519 ccaccagcgg gcactggccc 20 <210> SEQ ID NO 520 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 520 cccaccagcg ggcactggcc 20 <210> SEQ ID NO 521 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 521 ccccaccagc gggcactggc 20 <210> SEQ ID NO 522 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 522 ggccccacca gcgggcactg 20 <210> SEQ ID NO 523 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 523 tggccccacc agcgggcact 20 <210> SEQ ID NO 524 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 524 ctggccccac cagcgggcac 20 <210> SEQ ID NO 525 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 525 cctggcccca ccagcgggca 20 <210> SEQ ID NO 526 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 526 gcctggcccc accagcgggc 20 <210> SEQ ID NO 527 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 527 gggcctggcc ccaccagcgg 20 <210> SEQ ID NO 528 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 528 aggtggcggc ggtgcatggg 20 <210> SEQ ID NO 529 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 529 caggtggcgg cggtgcatgg 20 <210> SEQ ID NO 530 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 530 gcaggtggcg gcggtgcatg 20 <210> SEQ ID NO 531 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 531 agcaggtggc ggcggtgcat 20 <210> SEQ ID NO 532 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 532 cagcaggtgg cggcggtgca 20 <210> SEQ ID NO 533 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 533 gcagcaggtg gcggcggtgc 20 <210> SEQ ID NO 534 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 534 agcagcaggt ggcggcggtg 20 <210> SEQ ID NO 535 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 535 gagcagcagg tggcggcggt 20 <210> SEQ ID NO 536 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence

<220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 536 ggagcagcag gtggcggcgg 20 <210> SEQ ID NO 537 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 537 gggagcagca ggtggcggcg 20 <210> SEQ ID NO 538 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 538 agggagcagc aggtggcggc 20 <210> SEQ ID NO 539 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 539 cagggagcag caggtggcgg 20 <210> SEQ ID NO 540 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 540 gcagggagca gcaggtggcg 20 <210> SEQ ID NO 541 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 541 ggcagggagc agcaggtggc 20 <210> SEQ ID NO 542 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 542 tggcagggag cagcaggtgg 20 <210> SEQ ID NO 543 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 543 ctggcaggga gcagcaggtg 20 <210> SEQ ID NO 544 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 544 ccctggcagg gagcagcagg 20 <210> SEQ ID NO 545 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 545 accctggcag ggagcagcag 20 <210> SEQ ID NO 546 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 546 gaccctggca gggagcagca 20 <210> SEQ ID NO 547 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 547 ggaccctggc agggagcagc 20 <210> SEQ ID NO 548 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 548 ggcctaggga ccctggcagg 20 <210> SEQ ID NO 549 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 549 aggcctaggg accctggcag 20 <210> SEQ ID NO 550 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 550 ccaggcctag ggaccctggc 20 <210> SEQ ID NO 551 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 551 gccaggccta gggaccctgg 20 <210> SEQ ID NO 552 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 552 ggccaggcct agggaccctg 20 <210> SEQ ID NO 553 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 553 aggccaggcc tagggaccct 20 <210> SEQ ID NO 554 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 554 taggccaggc ctagggaccc 20 <210> SEQ ID NO 555 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 555 ataggccagg cctagggacc 20 <210> SEQ ID NO 556 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 556 gataggccag gcctagggac 20 <210> SEQ ID NO 557 <211> LENGTH: 20 <212> TYPE: DNA

<213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 557 cgataggcca ggcctaggga 20 <210> SEQ ID NO 558 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 558 ccgataggcc aggcctaggg 20 <210> SEQ ID NO 559 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 559 tccgataggc caggcctagg 20 <210> SEQ ID NO 560 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 560 ctccgatagg ccaggcctag 20 <210> SEQ ID NO 561 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 561 cctccgatag gccaggccta 20 <210> SEQ ID NO 562 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 562 gcctccgata ggccaggcct 20 <210> SEQ ID NO 563 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 563 gcgcctccga taggccaggc 20 <210> SEQ ID NO 564 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 564 aacaggagca gggaaagcgc 20 <210> SEQ ID NO 565 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 565 gaacaggagc agggaaagcg 20 <210> SEQ ID NO 566 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 566 cgaacaggag cagggaaagc 20 <210> SEQ ID NO 567 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 567 gcgaacagga gcagggaaag 20 <210> SEQ ID NO 568 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 568 ggcgaacagg agcagggaaa 20 <210> SEQ ID NO 569 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 569 cggcgaacag gagcagggaa 20 <210> SEQ ID NO 570 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 570 acggcgaaca ggagcaggga 20 <210> SEQ ID NO 571 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 571 aacggcgaac aggagcaggg 20 <210> SEQ ID NO 572 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 572 caacggcgaa caggagcagg 20 <210> SEQ ID NO 573 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 573 gggcggcggc acgagacaga 20 <210> SEQ ID NO 574 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 574 agggcggcgg cacgagacag 20 <210> SEQ ID NO 575 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 575 cagggcggcg gcacgagaca 20 <210> SEQ ID NO 576 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 576 ccagggcggc ggcacgagac 20 <210> SEQ ID NO 577 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 577 cccagggcgg cggcacgaga 20 <210> SEQ ID NO 578 <211> LENGTH: 20

<212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 578 gcccagggcg gcggcacgag 20 <210> SEQ ID NO 579 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 579 agcccagggc ggcggcacga 20 <210> SEQ ID NO 580 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 580 cagcccaggg cggcggcacg 20 <210> SEQ ID NO 581 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 581 gcagcccagg gcggcggcac 20 <210> SEQ ID NO 582 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 582 ctgcggtgag ttggccggcg 20 <210> SEQ ID NO 583 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 583 actgcggtga gttggccggc 20 <210> SEQ ID NO 584 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 584 gactgcggtg agttggccgg 20 <210> SEQ ID NO 585 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 585 agactgcggt gagttggccg 20 <210> SEQ ID NO 586 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 586 cagactgcgg tgagttggcc 20 <210> SEQ ID NO 587 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 587 ccagactgcg gtgagttggc 20 <210> SEQ ID NO 588 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 588 gccagactgc ggtgagttgg 20 <210> SEQ ID NO 589 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 589 cgccagactg cggtgagttg 20 <210> SEQ ID NO 590 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 590 aagacagttc tagggttcag 20 <210> SEQ ID NO 591 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 591 gaagacagtt ctagggttca 20 <210> SEQ ID NO 592 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 592 cgaagacagt tctagggttc 20 <210> SEQ ID NO 593 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 593 tcgaagacag ttctagggtt 20 <210> SEQ ID NO 594 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 594 gtcgaagaca gttctagggt 20 <210> SEQ ID NO 595 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 595 agtcgaagac agttctaggg 20 <210> SEQ ID NO 596 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 596 gagtcgaaga cagttctagg 20 <210> SEQ ID NO 597 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 597 ggagtcgaag acagttctag 20 <210> SEQ ID NO 598 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 598 cggagtcgaa gacagttcta 20 <210> SEQ ID NO 599

<211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 599 ccggagtcga agacagttct 20 <210> SEQ ID NO 600 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 600 cccggagtcg aagacagttc 20 <210> SEQ ID NO 601 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 601 ccccggagtc gaagacagtt 20 <210> SEQ ID NO 602 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 602 gccccggagt cgaagacagt 20 <210> SEQ ID NO 603 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 603 ggccccggag tcgaagacag 20 <210> SEQ ID NO 604 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 604 gggccccgga gtcgaagaca 20 <210> SEQ ID NO 605 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 605 aggcggtggg cgcggcttct 20 <210> SEQ ID NO 606 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 606 caggcggtgg gcgcggcttc 20 <210> SEQ ID NO 607 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 607 gcaggcggtg ggcgcggctt 20 <210> SEQ ID NO 608 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 608 tggcaggcgg tgggcgcggc 20 <210> SEQ ID NO 609 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 609 actggcaggc ggtgggcgcg 20 <210> SEQ ID NO 610 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 610 gaactggcag gcggtgggcg 20 <210> SEQ ID NO 611 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 611 tgaactggca ggcggtgggc 20 <210> SEQ ID NO 612 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 612 tgtgaactgg caggcggtgg 20 <210> SEQ ID NO 613 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 613 tggagctggg cggagaccca 20 <210> SEQ ID NO 614 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 614 actggagctg ggcggagacc 20 <210> SEQ ID NO 615 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 615 gactggagct gggcggagac 20 <210> SEQ ID NO 616 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 616 aggactggag ctgggcggag 20 <210> SEQ ID NO 617 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 617 acaggactgg agctgggcgg 20 <210> SEQ ID NO 618 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 618 cacaggactg gagctgggcg 20 <210> SEQ ID NO 619 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 619 tcacaggact ggagctgggc 20

<210> SEQ ID NO 620 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 620 gcctcagcct ggccgaaaga 20 <210> SEQ ID NO 621 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 621 ggcctcagcc tggccgaaag 20 <210> SEQ ID NO 622 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 622 tggtggagcc aagccctccc 20 <210> SEQ ID NO 623 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 623 gggcaccctc agagcctgaa 20 <210> SEQ ID NO 624 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 624 accccactgc aagaagtcgg 20 <210> SEQ ID NO 625 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 625 gccccaggat gggaggatct 20 <210> SEQ ID NO 626 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 626 cataggacag agaaatgttg 20 <210> SEQ ID NO 627 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 627 tgctgacctt actctgcccc 20 <210> SEQ ID NO 628 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 628 taagccatgg ctctgagtca 20 <210> SEQ ID NO 629 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 629 agagaggcca tgggaggctg 20 <210> SEQ ID NO 630 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 630 ctggccctcc tggcttgccc 20 <210> SEQ ID NO 631 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 631 agctgcccca tgctggccct 20 <210> SEQ ID NO 632 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 632 gcccctggca gctgccccat 20 <210> SEQ ID NO 633 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 633 ctgtcggctg cgcccctggc 20 <210> SEQ ID NO 634 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 634 cgccgaacac ctgcctgtcg 20 <210> SEQ ID NO 635 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 635 cctcccagtg cctgggcacc 20 <210> SEQ ID NO 636 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 636 gcgcctgtct gcaaagctgg 20 <210> SEQ ID NO 637 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 637 cccaaagttg tccctcctgg 20 <210> SEQ ID NO 638 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 638 acacccagaa gaacccaaag 20 <210> SEQ ID NO 639 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 639 ctgacccaca cggctcatag 20 <210> SEQ ID NO 640 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 640 tggccccagg ccctggaaag 20

<210> SEQ ID NO 641 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 641 gacaaggcag ctggcagaag 20 <210> SEQ ID NO 642 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 642 aagaaaccag tgaccagtga 20 <210> SEQ ID NO 643 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 643 ctgtgaaatg ggaggaggag 20 <210> SEQ ID NO 644 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 644 gaaggttttt ccagaggctg 20 <210> SEQ ID NO 645 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 645 ggccaggaga gtcattaggg 20 <210> SEQ ID NO 646 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 646 ccacaaaagg agtgctcctc 20 <210> SEQ ID NO 647 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 647 ccttttaagg cagcaggaac 20 <210> SEQ ID NO 648 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 648 ctaggactgt ctgcttccca 20 <210> SEQ ID NO 649 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 649 gtcattcatc aatttctaag 20 <210> SEQ ID NO 650 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 650 ggaggagctg cagccggaga 20 <210> SEQ ID NO 651 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 651 gcacccggag gagctgcagc 20 <210> SEQ ID NO 652 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 652 gcacgacacc tgcagggcac 20 <210> SEQ ID NO 653 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 653 agctcaccag gtagttctca 20 <210> SEQ ID NO 654 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 654 gcttcctctc cccacctcct 20 <210> SEQ ID NO 655 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 655 gcagcacccc caatcctaga 20 <210> SEQ ID NO 656 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 656 gcccctcatc cacctgacac 20 <210> SEQ ID NO 657 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 657 ttccaggtaa gagacccccc 20 <210> SEQ ID NO 658 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 658 agaataggtc ccagacactc 20 <210> SEQ ID NO 659 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 659 ctccccctga gatgttctgg 20 <210> SEQ ID NO 660 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 660 ccccagccca gagataacca 20 <210> SEQ ID NO 661 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 661 cctgatccat cacggatggc 20

<210> SEQ ID NO 662 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 662 tactccatga ccaggtactg 20 <210> SEQ ID NO 663 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 663 gctctgacct tccaagaacc 20 <210> SEQ ID NO 664 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 664 ctcccttctg tggtcccacc 20 <210> SEQ ID NO 665 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 665 gtcgggtttg atgtccctgc 20 <210> SEQ ID NO 666 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 666 agggcactgg ctcaccgttc 20 <210> SEQ ID NO 667 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 667 gggccctcct tccaaccact 20 <210> SEQ ID NO 668 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 668 gcccacccct ctgggcccac 20 <210> SEQ ID NO 669 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 669 aggagcagag cgaggcttgg 20 <210> SEQ ID NO 670 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 670 caccttgtag tggacgatct 20 <210> SEQ ID NO 671 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 671 ctaccccgcc cccgctcacc 20 <210> SEQ ID NO 672 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 672 ctaggtcact gctgggtcct 20 <210> SEQ ID NO 673 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 673 ctcagatagc tccccactcc 20 <210> SEQ ID NO 674 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 674 aattctctaa ttctctagac 20 <210> SEQ ID NO 675 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 675 tacctgaggg ccatgcagga 20 <210> SEQ ID NO 676 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 676 gttccaagac tgatcctgca 20 <210> SEQ ID NO 677 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 677 aggagggcgg tggcgcggcg 20 <210> SEQ ID NO 678 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 678 tgacagctgg aaggagaaga 20 <210> SEQ ID NO 679 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 679 catgggaagg tggatccgtg 20 <210> SEQ ID NO 680 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 680 ggaggttatc tagggagatc 20 <210> SEQ ID NO 681 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 681 gaagggacag gtgacccgat 20 <210> SEQ ID NO 682 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 682

cgtaccctgg cagggagcag 20 <210> SEQ ID NO 683 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 683 ggactcgccc cgcctacgcc 20 <210> SEQ ID NO 684 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 684 ctcctgggac tcgccccgcc 20 <210> SEQ ID NO 685 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 685 gctcctggga ctcgccccgc 20 <210> SEQ ID NO 686 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 686 attggctcct gggactcgcc 20 <210> SEQ ID NO 687 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 687 gattggctcc tgggactcgc 20 <210> SEQ ID NO 688 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 688 gcctctgatt ggctcctggg 20 <210> SEQ ID NO 689 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 689 gcatgggcct ctgattggct 20 <210> SEQ ID NO 690 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 690 cacccggcat gggcctctga 20 <210> SEQ ID NO 691 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 691 gccaggccta gggacctgcg 20 <210> SEQ ID NO 692 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 692 ttcctccccc aaccctgatt 20 <210> SEQ ID NO 693 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 693 aagtttgcag caacttttct 20 <210> SEQ ID NO 694 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 694 gcccctcgga attcccggct 20 <210> SEQ ID NO 695 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 695 catctcggcc tgcgctccgc 20 <210> SEQ ID NO 696 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 696 gcaggccccc acattcccca 20 <210> SEQ ID NO 697 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 697 cttctgcacg cctccgtctc 20 <210> SEQ ID NO 698 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 698 tggcccacag ccacggccgg 20 <210> SEQ ID NO 699 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 699 ggcctggccc caccagcggg 20 <210> SEQ ID NO 700 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 700 cctggcaggg agcagcaggt 20 <210> SEQ ID NO 701 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 701 cagccgcact tcggctgaca 20 <210> SEQ ID NO 702 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 702 gcctgggtcc agcaccagct 20 <210> SEQ ID NO 703 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 703

gtcccaggaa gcctgggtcc 20 <210> SEQ ID NO 704 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 704 cgttagcagg tccccgccca 20 <210> SEQ ID NO 705 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 705 gtctatggcc atgacaatct 20 <210> SEQ ID NO 706 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 706 gtagcccagc cggtgcacgg 20 <210> SEQ ID NO 707 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 707 gggtgcccac agccaccagc 20 <210> SEQ ID NO 708 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 708 tggcccgtag ctgcctgccc 20 <210> SEQ ID NO 709 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 709 ggaaatcacc tgccccacct 20 <210> SEQ ID NO 710 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 710 ggatgtttct ggaaatcacc 20 <210> SEQ ID NO 711 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 711 gtggcaccct cgaagtctgg 20 <210> SEQ ID NO 712 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 712 ccccgctcac catggcagtg 20 <210> SEQ ID NO 713 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 713 ggtccgggac ctgattgtct 20 <210> SEQ ID NO 714 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 714 gctgcatgtc tgcccgtccc 20 <210> SEQ ID NO 715 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 715 ggccccagaa ccctagctgc 20 <210> SEQ ID NO 716 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 716 tcacagggcc tggctgcccc 20 <210> SEQ ID NO 717 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 717 ggctgacatg ttgggcaggc 20 <210> SEQ ID NO 718 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 718 tgtccaggcc ccagaaccct 20 <210> SEQ ID NO 719 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 719 ggccaggcct agggatctgc 20 <210> SEQ ID NO 720 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 720 cgcctcggat aggccaggcc 20 <210> SEQ ID NO 721 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 721 ggcttggagt cttagggttc 20 <210> SEQ ID NO 722 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 722 tccccggccg ccaggtggca 20 <210> SEQ ID NO 723 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 723 ggtgctgggc acgagccctg 20 <210> SEQ ID NO 724 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide

<400> SEQUENCE: 724 gcccagctgc tgcagcagcg 20 <210> SEQ ID NO 725 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 725 ccgtgtgtgc tggcagaggt 20 <210> SEQ ID NO 726 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 726 ataaataccg aggaatgtcg 20 <210> SEQ ID NO 727 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 727 gggacagaca ataaataccg 20 <210> SEQ ID NO 728 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 728 gtgcagccca gtgtggcggc 20 <210> SEQ ID NO 729 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 729 cctggagaag ttctggttgg 20 <210> SEQ ID NO 730 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 730 ggtgacccga tcggagccca 20 <210> SEQ ID NO 731 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 731 agctggagag agaagggaca 20 <210> SEQ ID NO 732 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 732 gtgagggact cgcctgcggc 20 <210> SEQ ID NO 733 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 733 gcggctgcgg tgccccagcc 20 <210> SEQ ID NO 734 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 734 gggccatcta gctggagaga 20 <210> SEQ ID NO 735 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 735 ccccactgca agaagtcggc 20 <210> SEQ ID NO 736 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 736 ttgagccctt ttaaggcagc 20 <210> SEQ ID NO 737 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 737 tgaccaggta ctgggagcgg 20 <210> SEQ ID NO 738 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 738 cctggagctg gatcagtccc 20 <210> SEQ ID NO 739 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 739 acatgggaag gtggatccgt 20 <210> SEQ ID NO 740 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 740 gtgggacata ccctggcagg 20 <210> SEQ ID NO 741 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 741 gccaggccta gggatctgca 20 <210> SEQ ID NO 742 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 742 ggaagcacga cacctcgcct 20 <210> SEQ ID NO 743 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 743 cctcaccatt ccatcaggct 20 <210> SEQ ID NO 744 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 744 cggcagcgac aagtgttccc 20 <210> SEQ ID NO 745 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide

<400> SEQUENCE: 745 gtctctgaag gccatgcagc 20 <210> SEQ ID NO 746 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 746 cagccacttg atccggtggg 20 <210> SEQ ID NO 747 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 747 aggtcggcct cttcagccac 20 <210> SEQ ID NO 748 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 748 gttggctgga gaagttctgg 20 <210> SEQ ID NO 749 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 749 ccccgtgatg gctgcggctc 20 <210> SEQ ID NO 750 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 750 aggccaggcc tagggatcct 20 <210> SEQ ID NO 751 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 751 ggcgcggtgc cccagcctgg 20 <210> SEQ ID NO 752 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 752 gtcctggccc caccagcggg 20 <210> SEQ ID NO 753 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 753 ccaggcctag gaatcctggc 20 <210> SEQ ID NO 754 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 754 gcgcctcgga tagccaggcc 20 <210> SEQ ID NO 755 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 755 cccagtgtgg cgcagcagcc 20 <210> SEQ ID NO 756 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 756 gtgtttcatc ttcaccaccg 20 <210> SEQ ID NO 757 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 757 aggtcagcct cttcagccac 20 <210> SEQ ID NO 758 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 758 ggccatatgg gaaggtggat 20 <210> SEQ ID NO 759 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 759 ggaggatttg gcgagaagca 20 <210> SEQ ID NO 760 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 760 cgaagtctgc cccacctcga 20 <210> SEQ ID NO 761 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 761 gtggcaccct cgaagtctgc 20 <210> SEQ ID NO 762 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 762 gggtccattg taaggaagct 20 <210> SEQ ID NO 763 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 763 ggtgcccaca gccaccaggg 20 <210> SEQ ID NO 764 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 764 tccatggcag tgagccggtc 20 <210> SEQ ID NO 765 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 765 gggaccactt gatccggtgg 20 <210> SEQ ID NO 766 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE:

<223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 766 ggatcagagt tgggaccact 20 <210> SEQ ID NO 767 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 767 ccccgtgatg gctgcggttc 20 <210> SEQ ID NO 768 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 768 gtgtgtcctc ataccccgcc 20 <210> SEQ ID NO 769 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 769 gcaccctcga agtctcgacc 20 <210> SEQ ID NO 770 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 770 gctctgaagg ccatgcagca 20 <210> SEQ ID NO 771 <211> LENGTH: 25 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Primer <400> SEQUENCE: 771 gacatatgcc aagattgtgc actac 25 <210> SEQ ID NO 772 <211> LENGTH: 21 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Primer <400> SEQUENCE: 772 cacgaatgag gtcctgagct t 21 <210> SEQ ID NO 773 <211> LENGTH: 22 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Probe <400> SEQUENCE: 773 aacacttgtc gctgccgctg gc 22 <210> SEQ ID NO 774 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 774 agcgaggctt cacttggcgc 20 <210> SEQ ID NO 775 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 775 gggaagcgag gcttcacttg 20 <210> SEQ ID NO 776 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 776 gcggtcagcg atcccagggt 20 <210> SEQ ID NO 777 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 777 gggtgccagc gcggtgatct 20 <210> SEQ ID NO 778 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 778 tgttacaaag aaagtgactg 20 <210> SEQ ID NO 779 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 779 cgatggcagc aacggaagtt 20 <210> SEQ ID NO 780 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 780 gtcagtttac gatggcagca 20 <210> SEQ ID NO 781 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 781 cagggctttg tttcgaaaaa 20 <210> SEQ ID NO 782 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 782 ccattttctt ccacagggct 20 <210> SEQ ID NO 783 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 783 atgcttcttc aagttttcca 20 <210> SEQ ID NO 784 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 784 cagaatgact ttaatgcttc 20 <210> SEQ ID NO 785 <211> LENGTH: 21 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Primer <400> SEQUENCE: 785 ccaccgcaaa tgcttctaga c 21 <210> SEQ ID NO 786 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Primer <400> SEQUENCE: 786 cccccccatt gagaagattc 20 <210> SEQ ID NO 787 <211> LENGTH: 24 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence

<220> FEATURE: <223> OTHER INFORMATION: Probe <400> SEQUENCE: 787 ctccacctcc agcacgcgac ttct 24 <210> SEQ ID NO 788 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 788 gcggtcagcg atcccagggt 20 <210> SEQ ID NO 789 <211> LENGTH: 25 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 789 agcagcagca gcagcagcag cagca 25 <210> SEQ ID NO 790 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 790 agcagcagca gcagcagcag 20 <210> SEQ ID NO 791 <211> LENGTH: 15 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 791 gcagcagcag cagca 15 <210> SEQ ID NO 792 <400> SEQUENCE: 792 000 <210> SEQ ID NO 793 <211> LENGTH: 2611 <212> TYPE: DNA <213> ORGANISM: Mus musculus <400> SEQUENCE: 793 cgggaagacc ccgagctccg gcccggggag gggccatggt gttgcctgcc caacatgtca 60 gccgaagtgc ggctgaggca gctccagcag ctggtgctgg acccaggctt cctgggactg 120 gagcccctgc tcgaccttct cctgggcgtc caccaggagc tgggtgcctc tcacctagcc 180 caggacaagt atgtggccga cttcttgcag tgggtggagc ccattgcagc aaggcttaag 240 gaggtccgac tgcagaggga tgattttgag attttgaagg tgatcgggcg tggggcgttc 300 agcgaggtag cggtggtgaa gatgaaacag acgggccaag tgtatgccat gaagattatg 360 aataagtggg acatgctgaa gagaggcgag gtgtcgtgct tccgggaaga aagggatgta 420 ttagtgaaag gggaccggcg ctggatcaca cagctgcact ttgccttcca ggatgagaac 480 tacctgtacc tggtcatgga atactacgtg ggcggggacc tgctaacgct gctgagcaag 540 tttggggagc ggatccccgc cgagatggct cgcttctacc tggccgagat tgtcatggcc 600 atagactccg tgcaccggct gggctacgtg cacagggaca tcaaaccaga taacattctg 660 ctggaccgat gtgggcacat tcgcctggca gacttcggct cctgcctcaa actgcagcct 720 gatggaatgg tgaggtcgct ggtggctgtg ggcaccccgg actacctgtc tcctgagatt 780 ctgcaggccg ttggtggagg gcctggggca ggcagctacg ggccagagtg tgactggtgg 840 gcactgggcg tgttcaccta tgagatgttc tatgggcaga cccccttcta cgcggactcc 900 acagccgaga catatgccaa gattgtgcac tacagggaac acttgtcgct gccgctggca 960 gacacagttg tccccgagga agctcaggac ctcattcgtg ggctgctgtg tcctgctgag 1020 ataaggctag gtcgaggtgg ggcagacttc gagggtgcca cggacacatg caatttcgat 1080 gtggtggagg accggctcac tgccatggtg agcgggggcg gggagacgct gtcagacatg 1140 caggaagaca tgccccttgg ggtgcgcctg cccttcgtgg gctactccta ctgctgcatg 1200 gccttcagag acaatcaggt cccggacccc acccctatgg aactagaggc cctgcagttg 1260 cctgtgtcag acttgcaagg gcttgacttg cagcccccag tgtccccacc ggatcaagtg 1320 gctgaagagg ctgacctagt ggctgtccct gcccctgtgg ctgaggcaga gaccacggta 1380 acgctgcagc agctccagga agccctggaa gaagaggttc tcacccggca gagcctgagc 1440 cgcgagctgg aggccatccg gaccgccaac cagaacttct ccagccaact acaggaggcc 1500 gaggtccgaa accgagacct ggaggcgcat gttcggcagc tacaggaacg gatggagatg 1560 ctgcaggccc caggagccgc agccatcacg ggggtcccca gtccccgggc cacggatcca 1620 ccttcccatc tagatggccc cccggccgtg gctgtgggcc agtgcccgct ggtggggcca 1680 ggccccatgc accgccgtca cctgctgctc cctgccagga tccctaggcc tggcctatcc 1740 gaggcgcgtt gcctgctcct gttcgccgct gctctggctg ctgccgccac actgggctgc 1800 actgggttgg tggcctatac cggcggtctc accccagtct ggtgtttccc gggagccacc 1860 ttcgccccct gaaccctaag actccaagcc atctttcatt taggcctcct aggaaggtcg 1920 agcgaccagg gagcgaccca aagcgtctct gtgcccatcg cccccccccc cccccccacc 1980 gctccgctcc acacttctgt gagcctgggt ccccacccag ctccgctcct gtgatccagg 2040 cctgccacct ggcggccggg gagggaggaa cagggctcgt gcccagcacc cctggttcct 2100 gcagagctgg tagccaccgc tgctgcagca gctgggcatt cgccgacctt gctttactca 2160 gccccgacgt ggatgggcaa actgctcagc tcatccgatt tcactttttc actctcccag 2220 ccatcagtta caagccataa gcatgagccc cctatttcca gggacatccc attcccatag 2280 tgatggatca gcaagacctc tgccagcaca cacggagtct ttggcttcgg acagcctcac 2340 tcctgggggt tgctgcaact ccttccccgt gtacacgtct gcactctaac aacggagcca 2400 cagctgcact cccccctccc ccaaagcagt gtgggtattt attgatcttg ttatctgact 2460 cactgacaga ctccgggacc cacgttttag atgcattgag actcgacatt cctcggtatt 2520 tattgtctgt ccccacctac gacctccact cccgaccctt gcgaataaaa tacttctggt 2580 ctgccctaaa aaaaaaaaaa aaaaaaaaaa a 2611 <210> SEQ ID NO 794 <211> LENGTH: 988 <212> TYPE: DNA <213> ORGANISM: Mus musculus <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (531)..(531) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (942)..(942) <223> OTHER INFORMATION: n is a, c, g, or t <400> SEQUENCE: 794 gctggaccgg tccggaattc tccggatcgc cagcctttgt gggccatatt cgtcatccct 60 cctggcttct catctgcttt tgtggtccta gctcaagacc tctaattcct ctgctgactt 120 aaatgccctt ccccagaggt cttctcaggc ctagtggaca agcttggagc cttatctgct 180 cctgcccaac attgagccaa agctccagct taccccagct tccttacaat ggaccccatt 240 gcagcaaggc ttaaggaggt ccgactgcag agggatgatt ttgagatttt gaaggtgatc 300 gggcgtgggg cgttcagcga ggtagcggtg gtgaagatga aacagacggg ccaagtgtat 360 gccatgaaga ttatgaataa gtgggacatg ctgaagagag gcgaggtgtc gtgcttccgg 420 gaagaaaggg atgtattagt gaaaggggac cggcgctgga tcacacagct gcactttgcc 480 ttccaggatg agaactacct gtacctggtc atggaatact acgtgggcgg ngacctgcta 540 acgctgctga gcaagttttg gggagcggat ccccgccgag atggctcgct tctacctggc 600 cgagattgtc atggccatag actccgtgca ccggctgggc tacgtgcaca gggacatcaa 660 accagataac attctgctgg accgatgtgg gcacattcgc ctggcagact tcggctcctg 720 gcctcaactg cagcctgatg gaatggtgga gtcccctggt ggctgtgggc acccccggac 780 tacctgtctc ctgaaattct gcagggcctt ggtgggaggc cctggggaag gcaactacgg 840 gccaaaagtt ggaagggggg ggcctggggg gggttcccct atgaaaagtt ctatggggag 900 gacccccttt aagcggaatc ccaggccgaa aaatatgccc angattgggc cctaacaggg 960 aaaacttttc ccctgcccct gggacaat 988 <210> SEQ ID NO 795 <211> LENGTH: 649 <212> TYPE: DNA <213> ORGANISM: Mus musculus <400> SEQUENCE: 795 ggcgtgttcg cctatgagat gttctatggg cagaccccct tctacgcgga ctccacagcc 60 gagacatatg ccaagattgt gcactacagg gaacacttgt cgctgccgct ggcagacaca 120 gttgtccccg aggaagctca ggacctcatt cgtgggctgc tgtgtcctgc tgagataagg 180 ctaggtcgag gtggggcagg tgatttccag aaacatcctt tcttctttgg ccttgattgg 240 gagggtctcc gagacagtgt accccccttt acaccagact tcgagggtgc cacggacaca 300 tgcaatttcg atgtggtgga ggaccggctc actgccatgg agacgctgtc agacatgcag 360 gaagacatgc cccttggggt gcgcctgccc ttcgtgggct actcctactg ctgcatggcc 420 ttcagagaca atcaggtccc ggaccccacc cctatggaac tagaggccct gcagttgcct 480 gtgtcagact tgcaagggct tgacttgcag cccccagtgt ccccaccgga tcaagtggtc 540 ccaactctga tccccaccga caggctgaag aggctgacct agtggctgtc cctgcccctg 600 tggctgaggc agagccacgg taacgctgca gcagctccag gaagccctg 649 <210> SEQ ID NO 796 <211> LENGTH: 527 <212> TYPE: DNA <213> ORGANISM: Mus musculus <400> SEQUENCE: 796 atttcgatgt ggtggaggac cggctcactg ccatggtgag cgggggcggg gagacgctgt 60 cagacatgca ggaagacatg ccccttgggg tgcgcctgcc cttcgtgggc tactcctact 120 gctgcatggc cttcagagac aatcaggtcc cggaccccac ccctatggaa ctagaggccc 180

tgcagttgcc tgtgtcagac ttgcaagggc ttgacttgca gcccccagtg tccccaccgg 240 atcaagtggc tgaagaggct gacctagtgg ctgtccctgc ccctgtggct gaggcagaga 300 ccacggtaac gctgcagcag ctccaggaag ccctggaaga agaggttctc acccggcaga 360 gcctgagccg cgagctggag gccatccgga ccgccaacca gaacttctcc aggaggccga 420 ggtccgaaac cgagacctgg aggcgcatgt tcggcagcta caggaacgga tggagatgct 480 gcaggcccca ggaaccgcag ccatcacggg ggtccccagt cccccgg 527 <210> SEQ ID NO 797 <211> LENGTH: 567 <212> TYPE: DNA <213> ORGANISM: Mus musculus <400> SEQUENCE: 797 atggtgaggt cgctggtggc tgtgggcacc ccggactacc tgtctcctga gattctgcag 60 gccgttggtg gagggcctgg ggcaggcagc tacgggccag agtgtgactg gtgggcactg 120 ggcgtgttcg cctatgagat gttctatggg cagaccccct tctacgcgga ctccacagcc 180 gagacatatg ccaagattgt gcactacagg gaacacttgt cgctgccgct ggcagacaca 240 gttgtccccg aggaagctca ggacctcatt cgtgggctgc tgtgtcctgc tgagataagg 300 ctaggtcgag gtggggcagg tgatttccag aaacatcctt tcttctttgg ccttgattgg 360 gagggtctcc gagacagtgt accccccttt acaccagact tcgagggtgc cacggacaca 420 tgcaatttcg atgtggtgga ggaccggctc actgccatgg tgagcggggg cggggtatga 480 ggacacacag gtgaccagtc cccaagacag tgagtgaggc ttcactcttg gcagtactaa 540 aattgaatgt agggggctgg gctcttg 567 <210> SEQ ID NO 798 <211> LENGTH: 2474 <212> TYPE: DNA <213> ORGANISM: Mus musculus <400> SEQUENCE: 798 ccgggaagaa agggatgtat tagtgaaagg ggaccggcgc tggatcacac agctgcactt 60 tgccttccag gatgagaact acctgtacct ggtcatggaa tactacgtgg gcggggacct 120 gctaacgctg ctgagcaagt ttggggagcg gatccccgcc gagatggctc gcttctacct 180 ggccgagatt gtcatggcca tagactccgt gcaccggctg ggctacgtgc acagggacat 240 caaaccagat aacattctgc tggaccgatg tgggcacatt cgcctggcag acttcggctc 300 ctgcctcaaa ctgcagcctg atggaatggt gaggtcgctg gtggctgtgg gcaccccgga 360 ctacctgtct cctgagattc tgcaggccgt tggtggaggg cctggggcag gcagctacgg 420 gccagagtgt gactggtggg cactgggcgt gttcgcctat gagatgttct atgggcagac 480 ccccttctac gcggactcca cagccgagac atatgccaag attgtgcact acagggaaca 540 cttgtcgctg ccgctggcag acacagttgt ccccgaggaa gctcaggacc tcattcgtgg 600 gctgctgtgt cctgctgaga taaggctagg tcgagacttc gagggtgcca cggacacatg 660 caatttcgat gtggtggagg accggctcac tgccatggtg agcgggggcg gggagacgct 720 gtcagacatg caggaagaca tgccccttgg ggtgcgcctg cccttcgtgg gctactccta 780 ctgctgcatg gccttcagag acaatcaggt cccggacccc acccctatgg aactagaggc 840 cctgcagttg cctgtgtcag acttgcaagg gcttgacttg cagcccccag tgtccccacc 900 ggatcaagtg gctgaagagg ccgacctagt ggctgtccct gcccctgtgg ctgaggcaga 960 gaccacggta acgctgcagc agctccagga agccctggaa gaagaggttc tcacccggca 1020 gagcctgagc cgcgagctgg aggccatccg gaccgccaac cagaacttct ccagccaact 1080 acaggaggcc gaggtccgaa accgagacct ggaggcgcat gttcggcagc tacaggaacg 1140 gatggagatg ctgcaggccc caggagccgc aggcgagtcc ctcacctgct tccagccaag 1200 ggggcactgg gtggagatgg ggggcatgtt gggtgtgtga accctcgggg caggggagga 1260 gtccaggctg gggcaccgca gccgcgccac tgcctttctc ctccatcctc cacactccat 1320 acacctctct cttctccttc cagccatcac gggggtcccc agtccccggg ccacggatcc 1380 accttcccat gcttctcgcc aaatcctccc caagggaact ccctagactc ccgttctggc 1440 ctcgactaga ttcccgcact gcctctcgcc ctgctgctgg gctccgatcg ggtcacctgt 1500 cccttctctc tccagctaga tggccccccg gccgtggctg tgggccagtg cccgctggtg 1560 gggccaggcc ccatgcaccg ccgtcacctg ctgctccctg ccaggatccc taggcctggc 1620 ctatccgagg cgcgttgcct gctcctgttc gccgctgctc tggctgctgc cgccacactg 1680 ggctgcactg ggttggtggc ctataccggc ggtctcaccc cagtctggtg tttcccggga 1740 gccaccttcg ccccctgaac cctaagactc caagccatct ttcatttagg cctcctagga 1800 agatcgagcg accagggagc gacccaaagc gtctctgtgc ccatcgcccc cccccccccc 1860 cccaccgctc cgctccacac ttctgtgagc ctgggtcccc acccagctcc gctcctgtga 1920 tccaggcctg ccacctggcg gccggggagg gaggaacagg gctcgtgccc agcacccctg 1980 gttcctgcag agctggtagc caccgctgct gcagcagctg ggcattcgcc gaccttgctt 2040 tactcagccc tgacgtggat gggctaactg ctcagctcat ccgatttcac tttttcactc 2100 tcccagccat cagttacaag ccataagcat gagcccccta tttccaggga catcccattc 2160 ccatagtgat ggatcagcaa gacctctgcc agcacacacg gagtctttgg cttcggacag 2220 cctcactcct gggggttgct gcaactcctt ccccgtgtac acgtctgcac tctaacaacg 2280 gagccacagc tgcactcccc cctcccccaa agcagtgtgg gtatttattg atcttgttat 2340 ctgactcact gacagactcc gggacccacg ttttagatgc attgagactc gacattcctc 2400 ggtatttatt gtctgtcccc acctacgacc tccactcccg acccttgcga ataaaatact 2460 tctggtctgc ccta 2474 <210> SEQ ID NO 799 <211> LENGTH: 2135 <212> TYPE: DNA <213> ORGANISM: Mus musculus <400> SEQUENCE: 799 ccgggaagaa agggatgtat tagtgaaagg ggaccggcgc tggatcacac agctgcactt 60 tgccttccag gatgagaact acctgtacct ggtcatggaa tactacgtgg gcggggacct 120 gctaacgctg ctgagcaagt ttggggagcg gatccccgcc gagatggctc gcttctacct 180 ggccgagatt gtcatggcca tagactccgt gcaccggctg ggctacgtgc acagggacat 240 caaaccagat aacattctgc tggaccgatg tgggcacatt cgcctggcag acttcggctc 300 ctgcctcaaa ctgcagcctg atggaatggt gaggtcgctg gtggctgtgg gcaccccgga 360 ctacctgtct cctgagattc tgcaggccgt tggtggaggg cctggggcag gcagctacgg 420 gccagagtgt gactggtggg cactgggcgt gttcgcctat gagatgttct atgggcagac 480 ccccttctac gcggactcca cagccgagac atatgccaag attgtgcact acagggaaca 540 cttgtcgctg ccgctggcag acacagttgt ccccgaggaa gctcaggacc tcattcgtgg 600 gctgctgtgt cctgctgaga taaggctagg tcgaggtggg gcaggtgatt tccagaaaca 660 tcctttcttc tttggccttg attgggaggg tctccgagac agtgtacccc cctttacacc 720 agacttcgag ggtgccacgg acacatgcaa tttcgatgtg gtggaggacc ggctcactgc 780 catggagacg ctgtcagaca tgcaggaaga catgcccctt ggggtgcgcc tgcccttcgt 840 gggctactcc tactgctgca tggccttcag agctgaagag gccgacctag tggctgtccc 900 tgcccctgtg gctgaggcag agaccacggt aacgctgcag cagctccagg aagccctgga 960 agaagaggtt ctcacccggc agagcctgag ccgcgagctg gaggccatcc ggaccgccaa 1020 ccagaacttc tccagccaac tacaggaggc cgaggtccga aaccgagacc tggaggcgca 1080 tgttcggcag ctacaggaac ggatggagat gctgcaggcc ccaggagccg cagccatcac 1140 gggggtcccc agtccccggg ccacggatcc accttcccat atggcccccc ggccgtggct 1200 gtgggccagt gcccgctggt ggggccaggc cccatgcacc gccgtcacct gctgctccct 1260 gccaggatcc ctaggcctgg cctatccgag gcgcgttgcc tgctcctgtt cgccgctgct 1320 ctggctgctg ccgccacact gggctgcact gggttggtgg cctataccgg cggtctcacc 1380 ccagtctggt gtttcccggg agccaccttc gccccctgaa ccctaagact ccaagccatc 1440 tttcatttag gcctcctagg aagatcgagc gaccagggag cgacccaaag cgtctctgtg 1500 cccatcgccc cccccccccc ccccaccgct ccgctccaca cttctgtgag cctgggtccc 1560 cacccagctc cgctcctgtg atccaggcct gccacctggc ggccggggag ggaggaacag 1620 ggctcgtgcc cagcacccct ggttcctgca gagctggtag ccaccgctgc tgcagcagct 1680 gggcattcgc cgaccttgct ttactcagcc ctgacgtgga tgggctaact gctcagctca 1740 tccgatttca ctttttcact ctcccagcca tcagttacaa gccataagca tgagccccct 1800 atttccaggg acatcccatt cccatagtga tggatcagca agacctctgc cagcacacac 1860 ggagtctttg gcttcggaca gcctcactcc tgggggttgc tgcaactcct tccccgtgta 1920 cacgtctgca ctctaacaac ggagccacag ctgcactccc ccctccccca aagcagtgtg 1980 ggtatttatt gatcttgtta tctgactcac tgacagactc cgggacccac gttttagatg 2040 cattgagact cgacattcct cggtatttat tgtctgtccc cacctacgac ctccactccc 2100 gacccttgcg aataaaatac ttctggtctg cccta 2135 <210> SEQ ID NO 800 <211> LENGTH: 2873 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <400> SEQUENCE: 800 aggggggctg gaccaagggg tggggagaag gggaggaggc ctcggccggc cgcagagaga 60 agtggccaga gaggcccagg ggacagccag ggacaggcag acatgcagcc agggctccag 120 ggcctggaca ggggctgcca ggccctgtga caggaggacc ccgagccccc ggcccgggga 180 ggggccatgg tgctgcctgt ccaacatgtc agccgaggtg cggctgaggc ggctccagca 240 gctggtgttg gacccgggct tcctggggct ggagcccctg ctcgaccttc tcctgggcgt 300 ccaccaggag ctgggcgcct ccgaactggc ccaggacaag tacgtggccg acttcttgca 360 gtgggcggag cccatcgtgg tgaggcttaa ggaggtccga ctgcagaggg acgacttcga 420 gattctgaag gtgatcggac gcggggcgtt cagcgaggta gcggtagtga agatgaagca 480 gacgggccag gtgtatgcca tgaagatcat gaacaagtgg gacatgctga agaggggcga 540 ggtgtcgtgc ttccgtgagg agagggacgt gttggtgaat ggggaccggc ggtggatcac 600 gcagctgcac ttcgccttcc aggatgagaa ctacctgtac ctggtcatgg agtattacgt 660 gggcggggac ctgctgacac tgctgagcaa gtttggggag cggattccgg ccgagatggc 720 gcgcttctac ctggcggaga ttgtcatggc catagactcg gtgcaccggc ttggctacgt 780 gcacagggac atcaaacccg acaacatcct gctggaccgc tgtggccaca tccgcctggc 840 cgacttcggc tcttgcctca agctgcgggc agatggaacg gtgcggtcgc tggtggctgt 900

gggcacccca gactacctgt cccccgagat cctgcaggct gtgggcggtg ggcctgggac 960 aggcagctac gggcccgagt gtgactggtg ggcgctgggt gtattcgcct atgaaatgtt 1020 ctatgggcag acgcccttct acgcggattc cacggcggag acctatggca agatcgtcca 1080 ctacaaggag cacctctctc tgccgctggt ggacgaaggg gtccctgagg aggctcgaga 1140 cttcattcag cggttgctgt gtcccccgga gacacggctg ggccggggtg gagcaggcga 1200 cttccggaca catcccttct tctttggcct cgactgggat ggtctccggg acagcgtgcc 1260 cccctttaca ccggatttcg aaggtgccac cgacacatgc aacttcgact tggtggagga 1320 cgggctcact gccatggaga cactgtcgga cattcgggaa ggtgcgccgc taggggtcca 1380 cctgcctttt gtgggctact cctactcctg catggccctc agggacagtg aggtcccagg 1440 ccccacaccc atggaactgg aggccgagca gctgcttgag ccacacgtgc aagcgcccag 1500 cctggagccc tcggtgtccc cacaggatga aacagctgaa gtggcagttc cagcggctgt 1560 ccctgcggca gaggctgagg ccgaggtgac gctgcgggag ctccaggaag ccctggagga 1620 ggaggtgctc acccggcaga gcctgagccg ggagatggag gccatccgca cggacaacca 1680 gaacttcgcc agtcaactac gcgaggcaga ggctcggaac cgggacctag aggcacacgt 1740 ccggcagttg caggagcgga tggagttgct gcaggcagag ggagccacag ctgtcacggg 1800 ggtccccagt ccccgggcca cggatccacc ttcccatatg gccccccggc cgtggctgtg 1860 ggccagtgcc cgctggtggg gccaggcccc atgcaccgcc gccacctgct gctccctgcc 1920 agggtcccta ggcctggcct atcggaggcg ctttccctgc tcctgttcgc cgttgttctg 1980 tctcgtgccg ccgccctggg ctgcattggg ttggtggccc acgccggcca actcaccgca 2040 gtctggcgcc gcccaggagc cgcccgcgct ccctgaaccc tagaactgtc ttcgactccg 2100 gggccccgtt ggaagactga gtgcccgggg cacggcacag aagccgcgcc caccgcctgc 2160 cagttcacaa ccgctccgag cgtgggtctc cgcccagctc cagtcctgtg atccgggccc 2220 gccccctagc ggccggggag ggaggggccg ggtccgcggc cggcgaacgg ggctcgaagg 2280 gtccttgtag ccgggaatgc tgctgctgct gctgctgctg ctgctgctgc tgctgctgct 2340 gctgctgctg ctgctgctgg ggggatcaca gaccatttct ttctttcggc caggctgagg 2400 ccctgacgtg gatgggcaaa ctgcaggcct gggaaggcag caagccgggc cgtccgtgtt 2460 ccatcctcca cgcaccccca cctatcgttg gttcgcaaag tgcaaagctt tcttgtgcat 2520 gacgccctgc tctggggagc gtctggcgcg atctctgcct gcttactcgg gaaatttgct 2580 tttgccaaac ccgctttttc ggggatcccg cgcccccctc ctcacttgcg ctgctctcgg 2640 agccccagcc ggctccgccc gcttcggcgg tttggatatt tattgacctc gtcctccgac 2700 tcgctgacag gctacaggac ccccaacaac cccaatccac gttttggatg cactgagacc 2760 ccgacattcc tcggtattta ttgtctgtcc ccacctagga cccccacccc cgaccctcgc 2820 gaataaaagg ccctccatct gcccaaaaaa aaaaaaaaaa aaaaaaaaaa aaa 2873 <210> SEQ ID NO 801 <211> LENGTH: 1509 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <400> SEQUENCE: 801 ccaccgcagc ggacagcgcc aagtgaagcc tcgcttcccc tccgcggcga ccagggcccg 60 agccgagagt agcagttgta gctacccgcc cagaaactag acacaatgtg cgacgaagac 120 gagaccaccg ccctcgtgtg cgacaatggc tccggcctgg tgaaagccgg cttcgccggg 180 gatgacgccc ctagggccgt gttcccgtcc atcgtgggcc gcccccgaca ccagggcgtc 240 atggtcggta tgggtcagaa agattcctac gtgggcgacg aggctcagag caagagaggt 300 atcctgaccc tgaagtaccc tatcgagcac ggcatcatca ccaactggga tgacatggag 360 aagatctggc accacacctt ctacaacgag cttcgcgtgg ctcccgagga gcaccccacc 420 ctgctcaccg aggcccccct caatcccaag gccaaccgcg agaagatgac ccagatcatg 480 tttgagacct tcaacgtgcc cgccatgtac gtggccatcc aggccgtgct gtccctctac 540 gcctccggca ggaccaccgg catcgtgctg gactccggcg acggcgtcac ccacaacgtg 600 cccatttatg agggctacgc gctgccgcac gccatcatgc gcctggacct ggcgggccgc 660 gatctcaccg actacctgat gaagatcctc actgagcgtg gctactcctt cgtgaccaca 720 gctgagcgcg agatcgtgcg cgacatcaag gagaagctgt gctacgtggc cctggacttc 780 gagaacgaga tggcgacggc cgcctcctcc tcctccctgg aaaagagcta cgagctgcca 840 gacgggcagg tcatcaccat cggcaacgag cgcttccgct gcccggagac gctcttccag 900 ccctccttca tcggtatgga gtcggcgggc attcacgaga ccacctacaa cagcatcatg 960 aagtgtgaca tcgacatcag gaaggacctg tatgccaaca acgtcatgtc ggggggcacc 1020 acgatgtacc ctgggatcgc tgaccgcatg cagaaagaga tcaccgcgct ggcacccagc 1080 accatgaaga tcaagatcat cgccccgccg gagcgcaaat actcggtgtg gatcggcggc 1140 tccatcctgg cctcgctgtc caccttccag cagatgtgga tcaccaagca ggagtacgac 1200 gaggccggcc cttccatcgt ccaccgcaaa tgcttctaga cacactccac ctccagcacg 1260 cgacttctca ggacgacgaa tcttctcaat gggggggcgg ctgagctcca gccaccccgc 1320 agtcactttc tttgtaacaa cttccgttgc tgccatcgta aactgacaca gtgtttataa 1380 cgtgtacata cattaactta ttacctcatt ttgttatttt tcgaaacaaa gccctgtgga 1440 agaaaatgga aaacttgaag aagcattaaa gtcattctgt taagctgcgt aaaaaaaaaa 1500 aaaaaaaaa 1509 <210> SEQ ID NO 802 <211> LENGTH: 19 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 802 gcagcagcag cagcagcag 19 <210> SEQ ID NO 803 <211> LENGTH: 19 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 803 gcagcagcag cagcagcag 19 <210> SEQ ID NO 804 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 804 agcagcagca gcagcagcag 20 <210> SEQ ID NO 805 <211> LENGTH: 18 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 805 gcagcagcag cagcagca 18 <210> SEQ ID NO 806 <211> LENGTH: 19 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 806 agcagcagca gcagcagca 19 <210> SEQ ID NO 807 <211> LENGTH: 16 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 807 agcagcagca gcagca 16 <210> SEQ ID NO 808 <211> LENGTH: 16 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 808 ctcccgacaa gctcca 16 <210> SEQ ID NO 809 <211> LENGTH: 14 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 809 tcccgacaag ctcc 14 <210> SEQ ID NO 810 <211> LENGTH: 16 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 810 gcttgcacgt gtggct 16 <210> SEQ ID NO 811 <211> LENGTH: 14 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 811 cttgcacgtg tggc 14 <210> SEQ ID NO 812 <211> LENGTH: 16 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence

<220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 812 ggttgtgaac tggcag 16 <210> SEQ ID NO 813 <211> LENGTH: 14 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 813 gttgtgaact ggca 14 <210> SEQ ID NO 814 <211> LENGTH: 16 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 814 gagcggttgt gaactg 16 <210> SEQ ID NO 815 <211> LENGTH: 14 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 815 agcggttgtg aact 14 <210> SEQ ID NO 816 <211> LENGTH: 16 <212> TYPE: DNA <213> ORGANISM: Artificial sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 816 gctgccttcc caggcc 16 <210> SEQ ID NO 817 <211> LENGTH: 14 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 817 ctgccttccc aggc 14 <210> SEQ ID NO 818 <211> LENGTH: 16 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 818 gcactttgcg aaccaa 16 <210> SEQ ID NO 819 <211> LENGTH: 14 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 819 cactttgcga acca 14 <210> SEQ ID NO 820 <211> LENGTH: 16 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 820 gaaagctttg cacttt 16 <210> SEQ ID NO 821 <211> LENGTH: 14 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 821 aaagctttgc actt 14 <210> SEQ ID NO 822 <211> LENGTH: 16 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 822 cggaggacga ggtcaa 16 <210> SEQ ID NO 823 <211> LENGTH: 14 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 823 ggaggacgag gtca 14 <210> SEQ ID NO 824 <211> LENGTH: 16 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 824 agcctgtcag cgagtc 16 <210> SEQ ID NO 825 <211> LENGTH: 14 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 825 gcctgtcagc gagt 14 <210> SEQ ID NO 826 <211> LENGTH: 16 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 826 tcctgtagcc tgtcag 16 <210> SEQ ID NO 827 <211> LENGTH: 14 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 827 cctgtagcct gtca 14 <210> SEQ ID NO 828 <211> LENGTH: 16 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 828 gaagcgaggc ttcact 16 <210> SEQ ID NO 829 <211> LENGTH: 14 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 829 aagcgaggct tcac 14 <210> SEQ ID NO 830 <211> LENGTH: 16 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 830 acctgcccgt ctggca 16 <210> SEQ ID NO 831 <211> LENGTH: 14 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 831 cctgcccgtc tggc 14 <210> SEQ ID NO 832 <211> LENGTH: 16 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 832 ggtcagcgat cccagg 16 <210> SEQ ID NO 833 <211> LENGTH: 14 <212> TYPE: DNA

<213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 833 gtcagcgatc ccag 14 <210> SEQ ID NO 834 <211> LENGTH: 16 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 834 attttcttcc acaggg 16 <210> SEQ ID NO 835 <211> LENGTH: 14 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 835 ttttcttcca cagg 14 <210> SEQ ID NO 836 <211> LENGTH: 16 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 836 gaatgacttt aatgct 16 <210> SEQ ID NO 837 <211> LENGTH: 14 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic oligonucleotide <400> SEQUENCE: 837 aatgacttta atgc 14

Claims

1.-22. (canceled)

23. A compound comprising a modified oligonucleotide consisting of 10 to 30 linked nucleosides and having a nucleobase sequence comprising at least 8 contiguous nucleobases of sequence recited in SEQ ID NOs: 44 or 76.

24. The compound of claim 23, wherein the modified oligonucleotide is a single-stranded oligonucleotide.

25. The compound of claim 23, wherein the nucleobase sequence of the modified oligonucleotide is 100% complementary to SEQ ID NO: 2.

26. The compound of claim 23, wherein at least one internucleoside linkage is a modified internucleoside linkage.

27. The compound of claim 26, wherein each internucleoside linkage is a phosphorothioate internucleoside linkage.

28. The compound of claim 23, wherein at least one nucleoside comprises a modified sugar.

29. The compound of claim 28, wherein at least one modified sugar is a bicyclic sugar.

30. The compound of claim 28, wherein at least one modified sugar comprises a 2'-O-methoxyethyl.

31. The compound of claim 23, wherein at least one nucleoside comprises a modified nucleobase.

32. The compound of claim 31, wherein the modified nucleobase is a 5-methylcytosine.

33. The compound of claim 23, wherein the modified oligonucleotide comprises: a gap segment consisting of linked deoxynucleosides; a 5' wing segment consisting of linked nucleosides; a 3' wing segment consisting of linked nucleosides; wherein the gap segment is positioned between the 5' wing segment and the 3' wing segment and wherein each nucleoside of each wing segment comprises a modified sugar.

34. The compound of claim 23, wherein the modified oligonucleotide consists of 20 linked nucleosides and comprises: a gap segment consisting of ten linked deoxynucleosides; a 5' wing segment consisting of five linked nucleosides; a 3' wing segment consisting of five linked nucleosides; wherein the gap segment is positioned between the 5' wing segment and the 3' wing segment, wherein each nucleoside of each wing segment comprises a 2'-O-methoxyethyl sugar; and wherein each internucleoside linkage is a phosphorothioate linkage.

35. The compound of claim 23, wherein the modified oligonucleotide consists of 20 linked nucleosides.