Patent application title: POLYNUCLEOTIDES AND POLYPEPTIDE SEQUENCES INVOLVED IN CANCER
Inventors:
IPC8 Class: AC07K1628FI
USPC Class:
1 1
Class name:
Publication date: 2018-12-06
Patent application number: 20180346563
Abstract:
The present invention relates to polynucleotide and polypeptide sequences
which are differentially expressed in cancer cells compared to normal
cells. The present invention more particularly relates to the use of
these sequences in the diagnosis, prognosis or treatment of cancer and in
the detection of cancer cells.Claims:
1-93. (canceled)
94. An isolated or purified antibody or an antigen-binding fragment thereof capable of specifically binding to a polypeptide selected from the group consisting of; a) a polypeptide comprising the amino acid sequence set forth in SEQ ID NO.:70 (KAAG1), and; b) a polypeptide comprising a sequence encoded by SEQ ID NO.:24 or a fragment of at least 6 amino acids of said polypeptide.
95-96. (canceled)
97. An hybridoma cell producing the antibody or antigen binding fragment thereof of claim 94.
98-99. (canceled)
100. A composition comprising the antibody or antigen binding fragment thereof of claim 94.
101. A method of making an antibody comprising immunizing a non-human animal with an immunogenic fragment of a polypeptide selected from the group consisting of a. a polypeptide comprising the amino acid sequence set forth in SEQ ID NO.:70 (KAAG1), and; b. a polypeptide comprising a sequence encoded by SEQ ID NO.:24.
102-124. (canceled)
125. A method of treating cancer comprising administering an antibody or an antigen binding fragment thereof capable of specific binding to a polypeptide selected from the group consisting of a. a polypeptide comprising the amino acid sequence set forth in SEQ ID NO.:70 (KAAG1) b. a polypeptide encoded by SEQ ID NO.:24, c. a fragment of any one of a) or b), d. a derivative of any one of a) or b) and; e. an analog of any one of a) or b). to a mammal in need.
126. (canceled)
127. The antibody or antigen binding fragment thereof of claim 94, wherein the antibody or antigen binding fragment thereof is linked to a toxin.
128. The composition of claim 100, wherein the antibody or antigen binding fragment thereof is linked to a toxin.
129. A method of treating cancer, the method comprising administering a toxin-linked antibody or antigen binding fragment thereof that specifically binds to a polypeptide having the amino acid sequence set forth in SEQ ID NO.:70 (KAAG1) to a cancer patient having a) ovarian cancer, prostate cancer, renal cancer, lung cancer, colon cancer, breast cancer, central nervous system cancer, leukemia or melanoma comprising cancer cells expressing the polypeptide and b) normal kidney cells that do not express KAAG1, wherein the toxin-linked antibody or antigen binding fragment thereof comprises complementarity determining regions identical to those of a monoclonal antibody, chimeric antibody, humanized antibody, human antibody or of a Fab fragment thereof that specifically binds to the polypeptide and wherein the toxin is toxic to the cancer cells.
130. The method of claim 129, wherein the cancer patient is selected prior to administration for having a) ovarian cancer, prostate cancer, renal cancer, lung cancer, colon cancer, breast cancer, central nervous system cancer, leukemia or melanoma comprising cancer cells expressing a polypeptide having the amino acid sequence set forth in SEQ ID NO.:70 (KAAG1) and b) normal kidney cells that do not express KAAG1.
131. The method of claim 129, wherein the method is for treating ovarian cancer in a cancer patient suffering from ovarian cancer.
132. The method of claim 131, wherein the ovarian cancer is late stage ovarian cancer.
133. A method of inhibiting the growth or survival of cancer cells, the method comprising administering a toxin-linked antibody or antigen binding fragment thereof that specifically binds to a polypeptide having the amino acid sequence set forth in SEQ ID NO.:70 (KAAG1) to a cancer patient having a) a cancer comprising cancer cells expressing the polypeptide and b) normal kidney cells that do not express KAAG1, wherein the toxin-linked antibody or antigen binding fragment thereof comprises complementarity determining regions identical to those of a monoclonal antibody, chimeric antibody, humanized antibody, human antibody or of a Fab fragment thereof that specifically binds to the polypeptide and wherein the toxin is toxic to the cancer cells.
Description:
PRIORITY CLAIM
[0001] This patent application is a continuation of U.S. Ser. No. 14/690,562 filed Apr. 20, 2015, which is a continuation of U.S. Ser. No. 13/490,857 filed on Jun. 7, 2012, which is a divisional of U.S. Ser. No. 12/305,648 filed on Nov. 6, 2009 now U.S. Pat. No. 8,216,582 which is a national stage filing under 35 U.S.C. .sctn. 371 of international application No. PCT/CA2007/001134 filed on Jun. 22, 2007 which claimed priority to U.S. provisional application No. 60/815,829 filed Jun. 23, 2006 and U.S. provisional application No. 60/874,471 filed on Dec. 13, 2006. The entire contents of each of these priority applications are incorporated herein by reference.
SEQUENCE LISTING
[0002] In accordance with 37 C.F.R. .sctn. 1.52(e)(5), a Sequence Listing in the form of a computer readable text file, submitted on a compact disk (in accordance to 37 C.F.R. .sctn. 1.52(e)) entitled: "ADC_11504_220C1_SEQUENCELISTING_ST25.txt", created on Aug. 21, 2018 of 281,730 bytes) and is incorporated herein by reference in its entirety.
FIELD OF THE INVENTION
[0003] The present invention relates to polynucleotide and polypeptide sequences which are differentially expressed in cancer compared to normal cells. The present invention more particularly relates to the use of these sequences in the diagnosis, prognosis or treatment of cancer and in the detection of cancer cells.
BACKGROUND OF THE INVENTION
[0004] Among gynecologic malignancies, ovarian cancer accounts for the highest tumor-related mortality in women in the United States (Jemal et al., 2005). It is the fourth leading cause of cancer-related death in women in the U.S (Menon et al., 2005). The American Cancer Society estimated a total of 22,220 new cases in 2005 and attributed 16,210 deaths to the disease (Bonome et al., 2005). For the past 30 years, the statistics have remained largely the same--the majority of women who develop ovarian cancer will die of this disease (Chambers and Vanderhyden, 2006). The disease carries a 1:70 lifetime risk and a mortality rate of >60% (Chambers and Vanderhyden, 2006). The high mortality rate is due to the difficulties with the early detection of ovarian cancer when the malignancy has already spread beyond the ovary. Indeed, >80% of patients are diagnosed with advanced staged disease (stage III or IV) (Bonome et al., 2005). These patients have a poor prognosis that is reflected in <45% 5-year survival rate, although 80% to 90% will initially respond to chemotherapy (Berek et al., 2000). This increased success compared to 20% 5-year survival rate years earlier is, at least in part, due to the ability to optimally debulk tumor tissue when it is confined to the ovaries, which is a significant prognostic factor for ovarian cancer (Bristow R. E., 2000 and Brown et al., 2004). In patients who are diagnosed with early disease (stage I), the 5-yr survival ranges from >90 (Chambers and Vanderhyden, 2006).
[0005] Ovarian cancer comprises a heterogeneous group of tumors that are derived from the surface epithelium of the ovary or from surface inclusions. They are classified into serous, mucinous, endometrioid, clear cell, and Brenner (transitional) types corresponding to the different types of epithelia in the organs of the female reproductive tract (Shih and Kurman, 2005). Of these, serous tumors account for .about.60% of the ovarian cancer cases diagnosed. Each histologic subcategory is further divided into three groups: benign, intermediate (borderline tumor or low malignancy potential (LMP)), and malignant, reflecting their clinical behavior (Seidman et al., 2002). LMP represents 10% to 15% of tumors diagnosed as serous and is a conundrum as they display atypical nuclear structure and metastatic behavior, yet they are considerably less aggressive than high-grade serous tumors. The 5-year survival for patients with LMP tumors is 95% in contrast to a <45% survival for advanced high-grade disease over the same period (Berek et al., 2000).
[0006] Despite improved knowledge of the etiology of the disease, aggressive cytoreductive surgery, and modern combination chemotherapy, there has been only little change in mortality. Poor outcomes have been attributed to (1) lack of adequate screening tests for early disease detection, in combination with only subtle presentation of symptoms at this stage--diagnosis is frequently being made only after progression to later stages, at which point the peritoneal dissemination of the cancer limits effective treatment and (2) the frequent development of resistance to standard chemotherapeutic strategies limiting improvement in the 5-year survival rate of patients. The initial chemotherapy regimen for ovarian cancer includes the combination of carboplatin (Paraplatin) and paclitaxel (taxol). Years of clinical trials have proved this combination to be most effective after effective surgery--reduces tumor volume in about 80% of the women with newly diagnosed ovarian cancer and 40% to 50% will have complete regression--but studies continue to look for ways to improve it. Recent abdominal infusion of chemotherapeutics to target hard-to-reach cells in combination with intravenous delivery has increased the effectiveness. However, severe side effects often lead to an incomplete course of treatment. Some other chemotherapeutic agents include doxorubicin, cisplatin, cyclophosphamide, bleomycin, etoposide, vinblastine, topotecan hydrochloride, ifosfamide, 5-fluorouracil and melphalan. The excellent survival rates for women with early stage disease receiving chemotherapy provide a strong rationale for research efforts to develop strategies to improve the detection of ovarian cancer. Furthermore, the discovery of new ovarian cancer-related biomarkers will lead to the development of more effective therapeutic strategies with minimal side effects for the future treatment of ovarian cancer.
[0007] Presently, the diagnosis of ovarian cancer is accomplished, in part, through routine analysis of the medical history of patients and by performing physical, ultrasound and x-ray examinations, and hematological screening. Two alternative strategies have been reported for early hematological detection of serum biomarkers. One approach is the analysis of serum samples by mass spectrometry to find proteins or protein fragments of unknown identity that detect the presence or absence of cancer (Mor et al., 2005 and Kozak et al., 2003). However, this strategy is expensive and not broadly available. Alternatively, the presence or absence of known proteins/peptides in the serum is being detected using antibody microarrays, ELISA, or other similar approaches. Serum testing for a protein biomarker called CA-125 (cancer antigen-125) has long been widely performed as a marker for ovarian cancer. However, although ovarian cancer cells may produce an excess of these protein molecules, there are some other cancers, including cancer of the fallopian tube or endometrial cancer (cancer of the lining of the uterus), 60% of people with pancreatic cancer, and 20%-25% of people with other malignancies with elevated levels of CA-125. The CA-125 test only returns a true positive result for about 50% of Stage I ovarian cancer patients and has a80% chance of returning true positive results from stage II, III, and IV ovarian cancer patients. The other 20% of ovarian cancer patients do not show any increase in CA-125 concentrations. In addition, an elevated CA-125 test may indicate other benign activity not associated with cancer, such as menstruation, pregnancy, or endometriosis. Consequently, this test has very limited clinical application for the detection of early stage disease when it is still treatable, exhibiting a positive predictive value (PPV) of <10%. And, even with the addition of ultrasound screening to CA-125, the PPV only improves to around 20% (Kozak et al., 2003). Thus, this test is not an effective screening test.
[0008] Other studies have yielded a number of biomarker combinations with increased specificity and sensitivity for ovarian cancer relative to CA-125 alone (McIntosh et al., 2004, Woolas et al., 1993, Schorge et., 2004). Serum biomarkers that are often elevated in women with epithelial ovarian cancer, but not exclusively, include carcinoembryonic antigen, ovarian cystadenocarcinoma antigen, lipidassociated sialic acid, NB/70, TAG72.3, CA-15.3, and CA-125. Unfortunately, although this approach has increased the sensitivity and specificity of early detection, published biomarker combinations still fail to detect a significant percentage of stage I/II epithelial ovarian cancer. Another study (Elieser et al., 2005) measured serum concentrations of 46 biomarkers including CA-125 and amongst these, 20 proteins in combination correctly recognized more than 98% of serum samples of women with ovarian cancer compared to other benign pelvic disease. Although other malignancies were not included in this study, this multimarker panel assay provided the highest diagnostic power for early detection of ovarian cancer thus far.
[0009] Additionally, with the advent of differential gene expression analysis technologies, for example DNA microarrays and subtraction methods, many groups have now reported large collections of genes that are upregulated in epithelial ovarian cancer (United States Patent Application published under numbers; 20030124579, 20030087250, 20060014686, 20060078941, 20050095592, 20050214831, 20030219760, 20060078941, 20050214826). However, the clinical utilities with respect to ovarian cancer of one or combinations of these genes are not as yet fully determined.
[0010] There is a need for new tumor biomarkers for improving diagnosis and/or prognosis of cancer. In addition, due to the genetic diversity of tumors, and the development of chemoresistance by many patients, there exists further need for better and more universal therapeutic approaches for the treatment of cancer. Molecular targets for the development of such therapeutics may preferably show a high degree of specificity for the tumor tissues compared to other somatic tissues, which will serve to minimize or eliminate undesired side effects, and increase the efficacy of the therapeutic candidates.
[0011] This present invention tries to address these needs and other needs.
SUMMARY OF THE INVENTION
[0012] In accordance with the present invention, there is provided new polynucleotide sequences and new polypeptide sequences as well as compositions, antibodies specific for these sequences, vectors and cells comprising a recombinant form of these new sequences.
[0013] The present invention also provides methods of detecting cancer cells using single or multiple polynucleotides and/or polypeptide sequences which are specific to these tumor cells. Some of the polynucleotides and/or polypeptides sequences provided herein are differentially expressed in ovarian cancer compared to normal cells and may also be used to distinguish between malignant ovarian cancer and an ovarian cancer of a low malignancy potential and/or a normal state (individual free of ovarian cancer).
[0014] Also encompassed by the present invention are diagnostic methods, prognostic methods, methods of detection, kits, arrays, libraries and assays which comprises one or more polypeptide and/or polynucleotide sequences or antibodies described herein as well as new therapeutic avenues for cancer treatment.
[0015] The Applicant has come to the surprising discovery that polynucleotide and/or polypeptide sequences described herein are preferentially upregulated in malignant ovarian cancer compared to low malignancy potential ovarian cancer and/or compared to normal cells. More interestingly, some of these sequences appear to be overexpressed in late stage ovarian cancer.
[0016] The Applicant has also come to the surprising discovery that some of the sequences described herein are not only expressed in ovarian cancer cells but in other cancer cells such as cells from breast cancer, prostate cancer, renal cancer, colon cancer, lung cancer, melanoma, leukemia and from cancer of the central nervous system. As such, several of these sequences, either alone or in combination may represent universal tumor markers. Therefore, some NSEQs and PSEQs described herein not only find utility in the field of ovarian cancer detection and treatment but also in the detection and treatment of other types of tumors
[0017] Therefore, using NSEQs or PSEQs of the present invention, one may readily identify a cell as being cancerous. As such NSEQs or PSEQs may be used to identify a cell as being a ovarian cancer cell, a prostate cancer cell, a breast cancer cell, a lung cancer cell, a colon cancer cell, a renal cancer cell, a cell from a melanoma, a leukemia cell or a cell from a cancer of the central nervous system.
[0018] Even more particularly, NSEQs or PSEQs described herein may be used to identify a cell as being a malignant ovarian cancer or a low malignant potential ovarian cancer.
[0019] The presence of some NSEQs or PSEQs in ovarian cancer cell may preferentially be indicative that the ovarian cancer is of the malignant type. Some NSEQs or PSEQs of the present invention may also more particularly indicate that the cancer is a late-stage malignant ovarian cancer.
[0020] The NSEQs or PSEQs may further be used to treat cancer or to identify compounds useful in the treatment of cancer including, ovarian cancer (i.e., LMP and/or malignant ovarian cancer), prostate cancer, breast cancer, lung cancer, colon cancer, renal cancer, melanoma, leukemia or cancer of the central nervous system.
[0021] As used herein and in some embodiments of the invention, the term "NSEQ" refers generally to polynucleotides sequences comprising or consisting of any one of SEQ. ID. NOs:1 to 49, and 169 (e.g., an isolated form) or comprising or consisting of a fragment of any one of SEQ. ID. NOs: 1 to 49 and 169. The term "NSEQ" more particularly refers to a polynucleotide sequence comprising or consisting of a transcribed portion of any one of SEQ. ID. NOs:1 to 49 and 169, which may be, for example, free of untranslated or untranslatable portion(s) (i.e., a coding portion of any one of SEQ ID Nos.: 1-49 and 169). The term "NSEQ" additionally refers to a sequence substantially identical to any one of the above and more particularly substantially identical to polynucleotide sequence comprising or consisting of a transcribed portion of any one of SEQ. ID. NOs:1 to 49 and 169, which may be, for example, free of untranslated or untranslatable portion(s). The term "NSEQ" additionally refers to a nucleic acid sequence region of any one of SEQ. ID. NOs:1 to 49 and 169 which encodes or is able to encode a polypeptide. The term "NSEQ" also refers to a polynucleotide sequence able to encode any one of the polypeptides described herein or a polypeptide fragment of any one of the above. Finally, the term "NSEQ" refers to a sequence substantially complementary to any one of the above.
[0022] In other embodiments of the invention such as those which relate to detection and/or treatment of cancers other than ovarian cancer, NSEQ may also relates to SEQ ID NO.:50 including any polynucleotide comprising or consisting of SEQ. ID. NO:50 (e.g., an isolated form) or comprising or consisting of a fragment of any one of SEQ. ID. NO:50, such as a polynucleotide sequence comprising or consisting of a transcribed portion of any one of SEQ. ID. NO:50, which may be, for example, free of untranslated or untranslatable portion(s) (i.e., a coding portion of SEQ. ID. NO:50). The term "NSEQ" additionally refers to a sequence substantially identical to any one of the above and more particularly substantially identical to polynucleotide sequence comprising or consisting of a transcribed portion of SEQ. ID. NO:50, which may be, for example, free of untranslated or untranslatable portion(s). The term "NSEQ" additionally refers to a nucleic acid sequence region of SEQ. ID. NO:50 which encodes or is able to encode a polypeptide. Finally, the term "NSEQ" refers to a sequence substantially complementary to any one of the above.
[0023] As such, in embodiments of the invention NSEQ encompasses, for example, SEQ. ID. NOs:1 to 49, 50 and 169 and also encompasses polynucleotide sequences which comprises, are designed or derived from SEQ. ID. NOs:1 to 49, 50 or 169. Non-limiting examples of such sequences includes, for example, SEQ ID NOs.: 103-150 or 151-152.
[0024] The term "inhibitory NSEQ" generally refers to a sequence substantially complementary to any one of SEQ. ID. NOs:1 to 49, 50 or 169, substantially complementary to a fragment of any one of SEQ. ID. Nos: 1 to 49, 50 or 169, substantially complementary to a sequence substantially identical to SEQ. ID. NOs:1 to 49, 50 or 169 and more particularly, substantially complementary to a transcribed portion of any one of SEQ. ID. NOs:1 to 49, 50 or 169 (e.g., which may be free of unstranslated or untranslatable portion) and which may have attenuating or even inhibitory action against the transcription of a mRNA or against expression of a polypeptide encoded by a corresponding SEQ ID NOs.:1 to 49, 50 or 169. Suitable "inhibitory NSEQ" may have for example and without limitation from about 10 to about 30 nucleotides, from about 10 to about 25 nucleotides or from about 15 to about 20 nucleotides.
[0025] As used herein the term "PSEQ" refers generally to each and every polypeptide sequences mentioned herein such as, for example, any polypeptide sequences encoded (putatively encoded) by any one of NSEQ described herein (e.g., any one of SEQ. ID. NOs:1 to 49 or 169) including their isolated or substantially purified form. Therefore, in embodiments of the invention, a polypeptide comprising or consisting of any one of SEQ. ID. NOs:51 to 88 or 170 including variants (e.g., an isolated natural protein variant), analogs, derivatives and fragments thereof are collectively referred to herein as "PSEQ". In other embodiments of the invention, such as those related to detection and/or treatment of cancers other than ovarian cancer, PSEQ also refers to polypeptide comprising or consisting of SEQ ID NO.:89 including variants (e.g., an isolated natural protein variant), analogs, derivatives and fragments.
[0026] Some of the NSEQs or PSEQs described herein have been previously characterized for purposes other than those described herein. As such diagnostics and therapeutics which are known to target those NSEQs or PSEQs (e.g., antibodies and/or inhibitors) may thus now be applied for inhibition of these NSEQ or PSEQ in the context of treatment of ovarian cancer, prostate cancer, renal cancer, colon cancer, lung cancer, melanoma, leukemia or cancer of the central nervous system. The use of these known therapeutics and diagnostics for previously undisclosed utility such as those described herein is encompassed by the present invention.
[0027] For example, antibodies capable of binding to folate receptor-1 may thus be used for specific binding of tumor cells other than ovarian cancer cells, such as breast cancer, prostate cancer, renal cancer, colon cancer, lung cancer, melanoma, leukemia and from cancer of the central nervous system. As such the use of antibodies and/or inhibitors of folate receptor-1 (e.g., CB300638, CB300945 which are Cyclopenta[g]quinazoline-based Thymidylate Synthase Inhibitor, those described in US20040242606, US20050009851, etc.) in the use of treatment of prostate cancer, renal cancer, colon cancer, lung cancer, melanoma, leukemia and cancer of the central nervous system is encompassed by the present invention.
Non-Limitative Exemplary Embodiments of the Invention
Use of NSEQ as a Screening Tool
[0028] The NSEQ described herein may be used either directly or in the development of tools for the detection and isolation of expression products (mRNA, mRNA precursor, hnRNA, etc.), of genomic DNA or of synthetic products (cDNA, PCR fragments, vectors comprising NSEQ etc.). NSEQs may also be used to prepare suitable tools for detecting an encoded polypeptide or protein. NSEQ may thus be used to provide an encoded polypeptide and to generate an antibody specific for the polypeptide.
[0029] Those skilled in the art will also recognize that short oligonucleotides sequences may be prepared based on the polynucleotide sequences described herein. For example, oligonucleotides having 10 to 20 nucleotides or more may be prepared for specifically hybridizing to a NSEQ having a substantially complementary sequence and to allow detection, identification and isolation of nucleic sequences by hybridization. Probe sequences of for example, at least 10-20 nucleotides may be prepared based on a sequence found in any one of SEQ ID NO.:1 to 49, 50 or 169 and more particularly selected from regions that lack homology to undesirable sequences. Probe sequences of 20 or more nucleotides that lack such homology may show an increased specificity toward the target sequence. Useful hybridization conditions for probes and primers are readily determinable by those of skill in the art. Stringent hybridization conditions encompassed herewith are those that may allow hybridization of nucleic acids that are greater than 90% homologous but which may prevent hybridization of nucleic acids that are less than 70% homologous. The specificity of a probe may be determined by whether it is made from a unique region, a regulatory region, or from a conserved motif. Both probe specificity and the stringency of diagnostic hybridization or amplification (maximal, high, intermediate, or low) reactions depend on whether or not the probe identifies exactly complementary sequences, allelic variants, or related sequences. Probes designed to detect related sequences may have, for example, at least 50% sequence identity to any of the selected polynucleotides.
[0030] Furthermore, a probe may be labelled by any procedure known in the art, for example by incorporation of nucleotides linked to a "reporter molecule". A "reporter molecule", as used herein, may be a molecule that provides an analytically identifiable signal allowing detection of a hybridized probe. Detection may be either qualitative or quantitative. Commonly used reporter molecules include fluorophores, enzymes, biotin, chemiluminescent molecules, bioluminescent molecules, digoxigenin, avidin, streptavidin or radioisotopes. Commonly used enzymes include horseradish peroxidase, alkaline phosphatase, glucose oxidase and .beta.-galactosidase, among others. Enzymes may be conjugated to avidin or streptavidin for use with a biotinylated probe. Similarly, probes may be conjugated to avidin or streptavidin for use with a biotinylated enzyme. Incorporation of a reporter molecule into a DNA probe may be effected by any method known to the skilled artisan, for example by nick translation, primer extension, random oligo priming, by 3' or 5' end labeling or by other means. In addition, hybridization probes include the cloning of nucleic acid sequences into vectors for the production of mRNA probes. Such vectors are known in the art, are commercially available, and may be used to synthesize RNA probes in vitro. The labelled polynucleotide sequences may be used in Southern or northern analysis, dot blot, or other membrane-based technologies; in PCR technologies; and in micro arrays utilizing samples from subjects to detect altered expression. Oligonucleotides useful as probes for screening of samples by hybridization assays or as primers for amplification may be packaged into kits. Such kits may contain the probes or primers in a pre-measured or predetermined amount, as well as other suitably packaged reagents and materials needed for the particular hybridization or amplification protocol.
[0031] The expression of mRNAs identical or substantially identical to the NSEQs of the present invention may thus be detected and/or isolated using methods which are known in the art. Exemplary embodiment of such methods includes, for example and without limitation, hybridization analysis using oligonucleotide probes, reverse transcription and in vitro nucleic acid amplification methods.
[0032] Such procedures may therefore, permit detection of mRNAs in ovarian cells (e.g., ovarian cancer cells) or in any other cells expressing such mRNAs. Expression of mRNA in a tissue-specific or a disease-specific manner may be useful for defining the tissues and/or particular disease state. One of skill in the art may readily adapt the NSEQs for these purposes.
[0033] It is to be understood herein that the NSEQs may hybridize to a substantially complementary sequence found in a test sample (e.g., cell, tissue, etc.). Additionally, a sequence substantially complementary to NSEQ (including fragments) may bind a NSEQ and substantially identical sequences found in a test sample (e.g., cell, tissue, etc.).
[0034] Polypeptide encoded by an isolated NSEQ, polypeptide variants, polypeptide analogs or polypeptide fragments thereof are also encompassed herewith. The polypeptides whether in a premature, mature or fused form, may be isolated from lysed cells, or from the culture medium, and purified to the extent needed for the intended use. One of skill in the art may readily purify these proteins, polypeptides and peptides by any available procedure. For example, purification may be accomplished by salt fractionation, size exclusion chromatography, ion exchange chromatography, reverse phase chromatography, affinity chromatography and the like. Alternatively, PSEQ may be made by chemical synthesis.
[0035] Natural variants may be identified through hybridization screening of a nucleic acid library or polypeptide library from different tissue, cell type, population, species, etc using the NSEQ and derived tools.
[0036] Use of NSEQ for Development of an Expression System
[0037] In order to express a polypeptide, a NSEQ able to encode any one of a PSEQ described herein may be inserted into an expression vector, i.e., a vector that contains the elements for transcriptional and translational control of the inserted coding sequence in a particular host. These elements may include regulatory sequences, such as enhancers, constitutive and inducible promoters, and 5' and 3' un-translated regions. Methods that are well known to those skilled in the art may be used to construct such expression vectors. These methods include in vitro recombinant DNA techniques, synthetic techniques, and in vivo genetic recombination.
[0038] A variety of expression vector/host cell systems known to those of skill in the art may be utilized to express a polypeptide or RNA from NSEQ. These include, but are not limited to, microorganisms such as bacteria transformed with recombinant bacteriophage, plasmid, or cosmid DNA expression vectors; yeast transformed with yeast expression vectors; insect cell systems infected with baculovirus vectors; plant cell systems transformed with viral or bacterial expression vectors; or animal cell systems. For long-term production of recombinant proteins in mammalian systems, stable expression in cell lines may be effected. For example, NSEQ may be transformed into cell lines using expression vectors that may contain viral origins of replication and/or endogenous expression elements and a selectable or visible marker gene on the same or on a separate vector. The invention is not to be limited by the vector or host cell employed.
[0039] Alternatively, RNA and/or polypeptide may be expressed from a vector comprising NSEQ using an in vitro transcription system or a coupled in vitro transcription/translation system respectively.
[0040] In general, host cells that contain NSEQ and/or that express a polypeptide encoded by the NSEQ, or a portion thereof, may be identified by a variety of procedures known to those of skill in the art. These procedures include, but are not limited to, DNA/DNA or DNA/RNA hybridizations, PCR amplification, and protein bioassay or immunoassay techniques that include membrane, solution, or chip based technologies for the detection and/or quantification of nucleic acid or amino acid sequences. Immunological methods for detecting and measuring the expression of polypeptides using either specific polyclonal or monoclonal antibodies are known in the art. Examples of such techniques include enzyme-linked immunosorbent assays (ELISAs), radioimmunoassays (RIAs), and fluorescence activated cell sorting (FACS). Those of skill in the art may readily adapt these methodologies to the present invention.
[0041] Host cells comprising NSEQ may thus be cultured under conditions for the transcription of the corresponding RNA (mRNA, siRNA, shRNA etc.) and/or the expression of the polypeptide from cell culture. The polypeptide produced by a cell may be secreted or may be retained intracellularly depending on the sequence and/or the vector used. As will be understood by those of skill in the art, expression vectors containing NSEQ may be designed to contain signal sequences that direct secretion of the polypeptide through a prokaryotic or eukaryotic cell membrane. Due to the inherent degeneracy of the genetic code, other DNA sequences that encode the same, substantially the same or a functionally equivalent amino acid sequence may be produced and used, for example, to express a polypeptide encoded by NSEQ. The nucleotide sequences of the present invention may be engineered using methods generally known in the art in order to alter the nucleotide sequences for a variety of purposes including, but not limited to, modification of the cloning, processing, and/or expression of the gene product. DNA shuffling by random fragmentation and PCR reassembly of gene fragments and synthetic oligonucleotides may be used to engineer the nucleotide sequences. For example, oligonucleotide-mediated site-directed mutagenesis may be used to introduce mutations that create new restriction sites, alter glycosylation patterns, change codon preference, produce splice variants, and so forth. In addition, a host cell strain may be chosen for its ability to modulate expression of the inserted sequences or to process the expressed polypeptide in the desired fashion. Such modifications of the polypeptide include, but are not limited to, acetylation, carboxylation, glycosylation, phosphorylation, lipidation, and acylation. Post-translational processing, which cleaves a "prepro" form of the polypeptide, may also be used to specify protein targeting, folding, and/or activity. Different host cells that have specific cellular machinery and characteristic mechanisms for post-translational activities (e.g., CHO, HeLa, MDCK, HEK293, and W138) are available commercially and from the American Type Culture Collection (ATCC) and may be chosen to ensure the correct modification and processing of the expressed polypeptide.
[0042] Those of skill in the art will readily appreciate that natural, modified, or recombinant nucleic acid sequences may be ligated to a heterologous sequence resulting in translation of a fusion polypeptide containing heterologous polypeptide moieties in any of the aforementioned host systems. Such heterologous polypeptide moieties may facilitate purification of fusion polypeptides using commercially available affinity matrices. Such moieties include, but are not limited to, glutathione S-transferase (GST), maltose binding protein, thioredoxin, calmodulin binding peptide, 6-His (His), FLAG, c-myc, hemaglutinin (HA), and antibody epitopes such as monoclonal antibody epitopes.
[0043] In yet a further aspect, the present invention relates to a polynucleotide which may comprise a nucleotide sequence encoding a fusion protein, the fusion protein may comprise a fusion partner fused to a peptide fragment of a protein encoded by, or a naturally occurring allelic variant polypeptide encoded by, the polynucleotide sequence described herein.
[0044] Those of skill in the art will also readily recognize that the nucleic acid and polypeptide sequences may be synthesized, in whole or in part, using chemical or enzymatic methods well known in the art. For example, peptide synthesis may be performed using various solid-phase techniques and machines such as the ABI 431A Peptide synthesizer (PE Biosystems) may be used to automate synthesis. If desired, the amino acid sequence may be altered during synthesis and/or combined with sequences from other proteins to produce a variant protein.
[0045] The present invention additionally relates to a bioassay for evaluating compounds as potential antagonists of the polypeptide described herein, the bioassay may comprise:
[0046] a) culturing test cells in culture medium containing increasing concentrations of at least one compound whose ability to inhibit the action of a polypeptide described herein is sought to be determined, wherein the test cells may contain a polynucleotide sequence described herein (for example, in a form having improved trans-activation transcription activity, relative to wild-type polynucleotide, and comprising a response element operatively linked to a reporter gene); and thereafter
[0047] b) monitoring in the cells the level of expression of the product of the reporter gene (encoding a reporter molecule) as a function of the concentration of the potential antagonist compound in the culture medium, thereby indicating the ability of the potential antagonist compound to inhibit activation of the polypeptide encoded by, the polynucleotide sequence described herein.
[0048] The present invention further relates to a bioassay for evaluating compounds as potential agonists for a polypeptide encoded by the polynucleotide sequence described herein, the bioassay may comprise:
[0049] a) culturing test cells in culture medium containing increasing concentrations of at least one compound whose ability to promote the action of the polypeptide encoded by the polynucleotide sequence described herein is sought to be determined, wherein the test cells may contain a polynucleotide sequence described herein (for example, in a form having improved trans-activation transcription activity, relative to wild-type polynucleotide, and comprising a response element operatively linked to a reporter gene); and thereafter
[0050] b) monitoring in the cells the level of expression of the product of the reporter gene as a function of the concentration of the potential agonist compound in the culture medium, thereby indicating the ability of the potential agonist compound to promote activation of a polypeptide encoded by the polynucleotide sequence described herein.
Use of NSEQ as a Identification Tool or as a Diagnostic Screening Tool
[0051] The skilled artisan will readily recognize that NSEQ may be used to identify a particular cell, cell type, tissue, disease and thus may be used for diagnostic purposes to determine the absence, presence, or altered expression (i.e. increased or decreased compared to normal) of the expression product of a gene. Suitable NSEQ may be for example, between 10 and 20 or longer, i.e., at least 10 nucleotides long or at least 12 nucleotides long, or at least 15 nucleotides long up to any desired length and may comprise, for example, RNA, DNA, branched nucleic acids, and/or peptide nucleic acids (PNAs). In one alternative, the polynucleotides may be used to detect and quantify gene expression in samples in which expression of NSEQ is correlated with disease. In another alternative, NSEQ may be used to detect genetic polymorphisms associated with a disease. These polymorphisms may be detected, for example, in the transcript, cDNA or genomic DNA.
[0052] The invention provides for the use of at least one of the NSEQ described herein on an array and for the use of that array in a method of detection of a particular cell, cell type, tissue, disease for the prognosis or diagnosis of cancer. The method may comprise hybridizing the array with a patient sample (putatively comprising or comprising a target polynucleotide sequence substantially complementary to a NSEQ) under conditions to allow complex formation (between NSEQ and target polynucleotide), detecting complex formation, wherein the complex formation is indicative of the presence of the polynucleotide and wherein the absence of complex formation is indicative of the absence of the polynucleotide in the patient sample. The presence or absence of the polynucleotide may be indicative of cancer such as, for example, ovarian cancer or other cancer as indicated herein.
[0053] The method may also comprise the step of quantitatively or qualitatively comparing (e.g., with a computer system, apparatus) the level of complex formation in the patient sample to that of standards for normal cells or individual or other type, origin or grade of cancer.
[0054] The present invention provides one or more compartmentalized kits for detection of a polynucleotide and/or polypeptide for the diagnosis or prognosis of ovarian cancer. A first kit may have a receptacle containing at least one isolated NSEQ or probe comprising NSEQ. Such a probe may bind to a nucleic acid fragment which is present/absent in normal cells but which is absent/present in affected or diseased cells. Such a probe may be specific for a nucleic acid site that is normally active/inactive but which may be inactive/active in certain cell types. Similarly, such a probe may be specific for a nucleic acid site that may be abnormally expressed in certain cell types. Finally, such a probe may identify a specific mutation. The probe may be capable of hybridizing to the nucleic acid sequence which is mutated (not identical to the normal nucleic acid sequence), or may be capable of hybridizing to nucleic acid sequences adjacent to the mutated nucleic acid sequences. The probes provided in the present kits may have a covalently attached reporter molecule. Probes and reporter molecules may be readily prepared as described above by those of skill in the art.
[0055] Antibodies (e.g., isolated antibody) that may specifically bind to a protein or polypeptide described herein (a PSEQ) as well as nucleic acids encoding such antibodies are also encompassed by the present invention.
[0056] As used herein the term "antibody" means a monoclonal antibody, a polyclonal antibody, a single chain antibody, a chimeric antibody, a humanized antibody, a deimmunized antibody, an antigen-binding fragment, an Fab fragment; an F(ab').sub.2 fragment, and Fv fragment; CDRs, or a single-chain antibody comprising an antigen-binding fragment (e.g., a single chain Fv).
[0057] The antibody may originate for example, from a mouse, rat or any other mammal or from other sources such as through recombinant DNA technologies.
[0058] The antibody may also be a human antibody which may be obtained, for example, from a transgenic non-human mammal capable of expressing human Ig genes. The antibody may also be a humanised antibody which may comprise, for example, one or more complementarity determining regions of non-human origin. It may also comprise a surface residue of a human antibody and/or framework regions of a human antibody. The antibody may also be a chimeric antibody which may comprise, for example, variable domains of a non-human antibody and constant domains of a human antibody.
[0059] The antibody of the present invention may be mutated and selected based on an increased affinity, solubility, stability, specificity and/or for one of a polypeptide described herein and/or based on a reduced immunogenicity in a desired host or for other desirable characteristics.
[0060] Suitable antibodies may bind to unique antigenic regions or epitopes in the polypeptides, or a portion thereof. Epitopes and antigenic regions useful for generating antibodies may be found within the proteins, polypeptides or peptides by procedures available to one of skill in the art. For example, short, unique peptide sequences may be identified in the proteins and polypeptides that have little or no homology to known amino acid sequences. Preferably the region of a protein selected to act as a peptide epitope or antigen is not entirely hydrophobic; hydrophilic regions are preferred because those regions likely constitute surface epitopes rather than internal regions of the proteins and polypeptides. These surface epitopes are more readily detected in samples tested for the presence of the proteins and polypeptides. Such antibodies may include, but are not limited to, polyclonal, monoclonal, chimeric, and single chain antibodies, Fab fragments, and fragments produced by a Fab expression library. The production of antibodies is well known to one of skill in the art and is not intended to be limited herein.
[0061] Peptides may be made by any procedure known to one of skill in the art, for example, by using in vitro translation or chemical synthesis procedures or by introducing a suitable expression vector into cells. Short peptides which provide an antigenic epitope but which by themselves are too small to induce an immune response may be conjugated to a suitable carrier. Suitable carriers and methods of linkage are well known in the art. Suitable carriers are typically large macromolecules such as proteins, polysaccharides and polymeric amino acids. Examples include serum albumins, keyhole limpet hemocyanin, ovalbumin, polylysine and the like. One of skill in the art may use available procedures and coupling reagents to link the desired peptide epitope to such a carrier. For example, coupling reagents may be used to form disulfide linkages or thioether linkages from the carrier to the peptide of interest. If the peptide lacks a disulfide group, one may be provided by the addition of a cysteine residue. Alternatively, coupling may be accomplished by activation of carboxyl groups.
[0062] The minimum size of peptides useful for obtaining antigen specific antibodies may vary widely. The minimum size must be sufficient to provide an antigenic epitope that is specific to the protein or polypeptide. The maximum size is not critical unless it is desired to obtain antibodies to one particular epitope. For example, a large polypeptide may comprise multiple epitopes, one epitope being particularly useful and a second epitope being immunodominant, etc. Typically, antigenic peptides selected from the present proteins and polypeptides will range without limitation, from 5 to about 100 amino acids in length. More typically, however, such an antigenic peptide will be a maximum of about 50 amino acids in length, and preferably a maximum of about 30 amino acids. It is usually desirable to select a sequence of about 6, 8, 10, 12 or 15 amino acids, up to about 20 or 25 amino acids (and any number therebetween).
[0063] Amino acid sequences comprising useful epitopes may be identified in a number of ways. For example, preparing a series of short peptides that taken together span the entire protein sequence may be used to screen the entire protein sequence. One of skill in the art may routinely test a few large polypeptides for the presence of an epitope showing a desired reactivity and also test progressively smaller and overlapping fragments to identify a preferred epitope with the desired specificity and reactivity.
[0064] As mentioned herein, antigenic polypeptides and peptides are useful for the production of monoclonal and polyclonal antibodies. Antibodies to a polypeptide encoded by the polynucleotides of NSEQ, polypeptide analogs or portions thereof, may be generated using methods that are well known in the art. For example, monoclonal antibodies may be prepared using any technique that provides for the production of antibody molecules by continuous cell lines in culture. These include, but are not limited to, the hybridoma, the human B-cell hybridoma, and the EBV-hybridoma techniques. In addition, techniques developed for the production of chimeric antibodies may be used. Alternatively, techniques described for the production of single chain antibodies may be employed. Fabs that may contain specific binding sites for a polypeptide encoded by the polynucleotides of NSEQ, or a portion thereof, may also be generated. Various immunoassays may be used to identify antibodies having the desired specificity. Numerous protocols for competitive binding or immunoradiometric assays using either polyclonal or monoclonal antibodies with established specificities are well known in the art.
[0065] To obtain polyclonal antibodies, a selected animal may be immunized with a protein or polypeptide. Serum from the animal may be collected and treated according to known procedures. Polyclonal antibodies to the protein or polypeptide of interest may then be purified by affinity chromatography. Techniques for producing polyclonal antisera are well known in the art.
[0066] Monoclonal antibodies (MAbs) may be made by one of several procedures available to one of skill in the art, for example, by fusing antibody producing cells with immortalized cells and thereby making a hybridoma. The general methodology for fusion of antibody producing B cells to an immortal cell line is well within the province of one skilled in the art. Another example is the generation of MAbs from mRNA extracted from bone marrow and spleen cells of immunized animals using combinatorial antibody library technology.
[0067] One drawback of MAbs derived from animals or from derived cell lines is that although they may be administered to a patient for diagnostic or therapeutic purposes, they are often recognized as foreign antigens by the immune system and are unsuitable for continued use. Antibodies that are not recognized as foreign antigens by the human immune system have greater potential for both diagnosis and treatment. Methods for generating human and humanized antibodies are now well known in the art.
[0068] Chimeric antibodies may be constructed in which regions of a non-human MAb are replaced by their human counterparts. A preferred chimeric antibody is one that has amino acid sequences that comprise one or more complementarity determining regions (CDRs) of a non-human Mab that binds to a polypeptide encoded by the polynucleotides of NSEQ, or a portion thereof, grafted to human framework (FW) regions. Methods for producing such antibodies are well known in the art. Amino acid residues corresponding to CDRs and FWs are known to one of average skill in the art.
[0069] A variety of methods have been developed to preserve or to enhance affinity for antigen of antibodies comprising grafted CDRs. One way is to include in the chimeric antibody the foreign framework residues that influence the conformation of the CDR regions. A second way is to graft the foreign CDRs onto human variable domains with the closest homology to the foreign variable region. Thus, grafting of one or more non-human CDRs onto a human antibody may also involve the substitution of amino acid residues which are adjacent to a particular CDR sequence or which are not contiguous with the CDR sequence but which are packed against the CDR in the overall antibody variable domain structure and which affect the conformation of the CDR. Humanized antibodies of the invention therefore include human antibodies which comprise one or more non-human CDRs as well as such antibodies in which additional substitutions or replacements have been made to preserve or enhance binding characteristics.
[0070] Chimeric antibodies of the invention also include antibodies that have been humanized by replacing surface-exposed residues to make the MAb appear human. Because the internal packing of amino acid residues in the vicinity of the antigen-binding site remains unchanged, affinity is preserved. Substitution of surface-exposed residues of a polypeptide encoded by the polynucleotides of NSEQ (or a portion thereof)-antibody according to the invention for the purpose of humanization does not mean substitution of CDR residues or adjacent residues that influence affinity for a polypeptide encoded by the polynucleotides of NSEQ, or a portion thereof.
[0071] Chimeric antibodies may also include antibodies where some or all non-human constant domains have been replaced with human counterparts. This approach has the advantage that the antigen-binding site remains unaffected. However, significant amounts of non-human sequences may be present where variable domains are derived entirely from non-human antibodies.
[0072] Antibodies of the invention include human antibodies that are antibodies consisting essentially of human sequences. Human antibodies may be obtained from phage display libraries wherein combinations of human heavy and light chain variable domains are displayed on the surface of filamentous phage. Combinations of variable domains are typically displayed on filamentous phage in the form of Fab's or scFvs. The library may be screened for phage bearing combinations of variable domains having desired antigen-binding characteristics. Preferred variable domain combinations are characterized by high affinity for a polypeptide encoded by the polynucleotides of NSEQ, or a portion thereof. Preferred variable domain combinations may also be characterized by high specificity for a polypeptide encoded by the polynucleotides of NSEQ, or a portion thereof, and little cross-reactivity to other related antigens. By screening from very large repertoires of antibody fragments, (2-10.times.10.sup.10) a good diversity of high affinity Mabs may be isolated, with many expected to have sub-nanomolar affinities for a polypeptide encoded by the polynucleotides of NSEQ, or a portion thereof.
[0073] Antibodies of the invention may include complete anti-polypeptide antibodies as well as antibody fragments and derivatives that comprise a binding site for a polypeptide encoded by the polynucleotides of NSEQ, or a portion thereof. Derivatives are macromolecules that comprise a binding site linked to a functional domain. Functional domains may include, but are not limited to signalling domains, toxins, enzymes and cytokines.
[0074] Alternatively, human antibodies may be obtained from transgenic animals into which un-rearranged human Ig gene segments have been introduced and in which the endogenous mouse Ig genes have been inactivated. Preferred transgenic animals contain very large contiguous Ig gene fragments that are over 1 Mb in size but human polypeptide-specific Mabs of moderate affinity may be raised from transgenic animals containing smaller gene loci. Transgenic animals capable of expressing only human Ig genes may also be used to raise polyclonal antiserum comprising antibodies solely of human origin.
[0075] Antibodies of the invention may include those for which binding characteristics have been improved by direct mutation or by methods of affinity maturation. Affinity and specificity may be modified or improved by mutating CDRs and screening for antigen binding sites having the desired characteristics. CDRs may be mutated in a variety of ways. One way is to randomize individual residues or combinations of residues so that in a population of otherwise identical antigen binding sites, all twenty amino acids may be found at particular positions. Alternatively, mutations may be induced over a range of CDR residues by error prone PCR methods. Phage display vectors containing heavy and light chain variable region gene may be propagated in mutator strains of E. coli. These methods of mutagenesis are illustrative of the many methods known to one of skill in the art.
[0076] The antibody may further comprise a detectable label (reporter molecule) attached thereto.
[0077] There is provided also methods of producing antibodies able to specifically bind to one of a polypeptide, polypeptide fragments, or polypeptide analogs described herein, the method may comprise:
[0078] a) immunizing a mammal (e.g., mouse, a transgenic mammal capable of producing human Ig, etc.) with a suitable amount of a PSEQ described herein including, for example, a polypeptide fragment comprising at least 6 (e.g., 8, 10, 12 etc.) consecutive amino acids of a PSEQ;
[0079] b) collecting the serum from the mammal; and
[0080] c) isolating the polypeptide-specific antibodies from the serum of the mammal.
[0081] The method may further comprise the step of administering a second dose to the mammal (e.g., animal).
[0082] Methods of producing a hybridoma which secretes an antibody that specifically binds to a polypeptide are also encompassed herewith and are known in the art.
[0083] The method may comprise:
[0084] a) immunizing a mammal (e.g., mouse, a transgenic mammal capable of producing human Ig, etc.) with a suitable amount of a PSEQ thereof;
[0085] b) obtaining lymphoid cells from the immunized animal obtained from (a);
[0086] c) fusing the lymphoid cells with an immortalizing cell to produce hybrid cells; and
[0087] d) selecting hybrid cells which produce antibody that specifically binds to a PSEQ thereof.
[0088] Also encompassed by the present invention is a method of producing an antibody that specifically binds to one of the polypeptide described herein, the method may comprise:
[0089] a) synthesizing a library of antibodies (e.g., antigen binding fragment) on phage or ribosomes;
[0090] b) panning the library against a sample by bringing the phage or ribosomes into contact with a composition comprising a polypeptide or polypeptide fragment described herein;
[0091] c) isolating phage which binds to the polypeptide or polypeptide fragment, and;
[0092] d) obtaining an antibody from the phage or ribosomes.
[0093] The antibody of the present invention may thus be obtained, for example, from a library (e.g., bacteriophage library) which may be prepared, for example, by
[0094] a) extracting cells which are responsible for production of antibodies from a host mammal;
[0095] b) isolating RNA from the cells of (a);
[0096] c) reverse transcribing mRNA to produce cDNA;
[0097] d) amplifying the cDNA using a (antibody-specific) primer; and
[0098] e) inserting the cDNA of (d) into a phage display vector or ribosome display cassette such that antibodies are expressed on the phage or ribosomes.
[0099] In order to generate antibodies, the host animal may be immunized with polypeptide and/or a polypeptide fragment and/or analog described herein to induce an immune response prior to extracting the cells which are responsible for production of antibodies.
[0100] The antibodies obtained by the means described herein may be useful for detecting proteins, variant and derivative polypeptides in specific tissues or in body fluids. Moreover, detection of aberrantly expressed proteins or protein fragments is probative of a disease state. For example, expression of the present polypeptides encoded by the polynucleotides of NSEQ, or a portion thereof, may indicate that the protein is being expressed at an inappropriate rate or at an inappropriate developmental stage. Hence, the present antibodies may be useful for detecting diseases associated with protein expression from NSEQs disclosed herein.
[0101] For in vivo detection purposes, antibodies may be those which preferably recognize an epitope present at the surface of a tumor cell.
[0102] A variety of protocols for measuring polypeptides, including ELISAs, RIAs, and FACS, are well known in the art and provide a basis for diagnosing altered or abnormal levels of expression. Standard values for polypeptide expression are established by combining samples taken from healthy subjects, preferably human, with antibody to the polypeptide under conditions for complex formation. The amount of complex formation may be quantified by various methods, such as photometric means. Quantities of polypeptide expressed in disease samples may be compared with standard values. Deviation between standard and subject values may establish the parameters for diagnosing or monitoring disease.
[0103] Design of immunoassays is subject to a great deal of variation and a variety of these are known in the art. Immunoassays may use a monoclonal or polyclonal antibody reagent that is directed against one epitope of the antigen being assayed. Alternatively, a combination of monoclonal or polyclonal antibodies may be used which are directed against more than one epitope. Protocols may be based, for example, upon competition where one may use competitive drug screening assays in which neutralizing antibodies capable of binding a polypeptide encoded by the polynucleotides of NSEQ, or a portion thereof, specifically compete with a test compound for binding the polypeptide. Alternatively one may use, direct antigen-antibody reactions or sandwich type assays and protocols may, for example, make use of solid supports or immunoprecipitation. Furthermore, antibodies may be labelled with a reporter molecule for easy detection. Assays that amplify the signal from a bound reagent are also known. Examples include immunoassays that utilize avidin and biotin, or which utilize enzyme-labelled antibody or antigen conjugates, such as ELISA assays.
[0104] Kits suitable for immunodiagnosis and containing the appropriate labelled reagents include antibodies directed against the polypeptide protein epitopes or antigenic regions, packaged appropriately with the remaining reagents and materials required for the conduct of the assay, as well as a suitable set of assay instructions.
[0105] The present invention therefore provides a kit for specifically detecting a polypeptide described herein, the kit may comprise, for example, an antibody or antibody fragment capable of binding specifically to the polypeptide described herein.
[0106] In accordance with the present invention, the kit may be a diagnostic kit, which may comprise:
[0107] a) one or more antibodies described herein; and
[0108] b) a detection reagent which may comprise a reporter group.
[0109] In accordance with the present invention, the antibodies may be immobilized on a solid support. The detection reagent may comprise, for example, an anti-immunoglobulin, protein G, protein A or lectin etc. The reporter group may be selected, without limitation, from the group consisting of radioisotopes, fluorescent groups, luminescent groups, enzymes, biotin and dye particles
Use of NSEQ, PSEQ as a Therapeutic or Therapeutic Targets
[0110] One of skill in the art will readily appreciate that the NSEQ, PSEQ, expression systems, assays, kits and array discussed above may also be used to evaluate the efficacy of a particular therapeutic treatment regimen, in animal studies, in clinical trials, or to monitor the treatment of an individual subject. Once the presence of disease is established and a treatment protocol is initiated, hybridization or amplification assays may be repeated on a regular basis to determine if the level of mRNA or protein in the patient (patient's blood, tissue, cell etc.) begins to approximate the level observed in a healthy subject. The results obtained from successive assays may be used to show the efficacy of treatment over a period ranging from several days to many years.
[0111] In yet another aspect of the invention, NSEQ may be used therapeutically for the purpose of expressing mRNA and polypeptide, or conversely to block transcription and/or translation of the mRNA. Expression vectors may be constructed using elements from retroviruses, adenoviruses, herpes or vaccinia viruses, or bacterial plasmids, and the like. These vectors may be used for delivery of nucleotide sequences to a particular target organ, tissue, or cell population. Methods well known to those skilled in the art may be used to construct vectors to express nucleic acid sequences or their complements.
[0112] Alternatively, NSEQ may be used for somatic cell or stem cell gene therapy. Vectors may be introduced in vivo, in vitro, and ex vivo. For ex vivo therapy, vectors are introduced into stem cells taken from the subject, and the resulting transgenic cells are clonally propagated for autologous transplant back into that same subject. Delivery of NSEQ by transfection, liposome injections, or polycationic amino polymers may be achieved using methods that are well known in the art. Additionally, endogenous NSEQ expression may be inactivated using homologous recombination methods that insert an inactive gene sequence into the coding region or other targeted region of NSEQ.
[0113] Depending on the specific goal to be achieved, vectors containing NSEQ may be introduced into a cell or tissue to express a missing polypeptide or to replace a non-functional polypeptide. Of course, when one wishes to express PSEQ in a cell or tissue, one may use a NSEQ able to encode such PSEQ for that purpose or may directly administer PSEQ to that cell or tissue.
[0114] On the other hand, when one wishes to attenuate or inhibit the expression of PSEQ, one may use a NSEQ (e.g., an inhibitory NSEQ) which is substantially complementary to at least a portion of a NSEQ able to encode such PSEQ.
[0115] The expression of an inhibitory NSEQ may be done by cloning the inhibitory NSEQ into a vector and introducing the vector into a cell to down-regulate the expression of a polypeptide encoded by the target NSEQ. Complementary or anti-sense sequences may also comprise an oligonucleotide derived from the transcription initiation site; nucleotides between about positions -10 and +10 from the ATG may be used. Therefore, inhibitory NSEQ may encompass a portion which is substantially complementary to a desired nucleic acid molecule to be inhibited and a portion (sequence) which binds to an untranslated portion of the nucleic acid.
[0116] Similarly, inhibition may be achieved using triple helix base-pairing methodology. Triple helix pairing is useful because it causes inhibition of the ability of the double helix to open sufficiently for the binding of polymerases, transcription factors, or regulatory molecules. Recent therapeutic advances using triplex DNA have been described in the literature. (See, e.g., Gee et al. 1994)
[0117] Ribozymes, enzymatic RNA molecules, may also be used to catalyze the cleavage of mRNA and decrease the levels of particular mRNAs, such as those comprising the polynucleotide sequences of the invention. Ribozymes may cleave mRNA at specific cleavage sites. Alternatively, ribozymes may cleave mRNAs at locations dictated by flanking regions that form complementary base pairs with the target mRNA. The construction and production of ribozymes is well known in the art.
[0118] RNA molecules may be modified to increase intracellular stability and half-life. Possible modifications include, but are not limited to, the addition of flanking sequences at the 5' and/or 3' ends of the molecule, or the use of phosphorothioate or 2' O-methyl rather than phosphodiester linkages within the backbone of the molecule. Alternatively, nontraditional bases such as inosine, queosine, and wybutosine, as well as acetyl-, methyl-, thio-, and similarly modified forms of adenine, cytidine, guanine, thymine, and uridine which are not as easily recognized by endogenous endonucleases, may be included.
[0119] Pharmaceutical compositions are also encompassed by the present invention. The pharmaceutical composition may comprise at least one NSEQ or PSEQ and a pharmaceutically acceptable carrier.
[0120] As it will be appreciated form those of skill in the art, the specificity of expression NSEQ and/or PSEQ in tumor cells may advantageously be used for inducing an immune response (through their administration) in an individual having, or suspected of having a tumor expressing such sequence. Administration of NSEQ and/or PSEQ in individuals at risk of developing a tumor expressing such sequence is also encompassed herewith.
[0121] In addition to the active ingredients, a pharmaceutical composition may contain pharmaceutically acceptable carriers comprising excipients and auxiliaries that facilitate processing of the active compounds into preparations that may be used pharmaceutically.
[0122] For any compound, the therapeutically effective dose may be estimated initially either in cell culture assays or in animal models such as mice, rats, rabbits, dogs, or pigs. An animal model may also be used to determine the concentration range and route of administration. Such information may then be used to determine useful doses and routes for administration in humans. These techniques are well known to one skilled in the art and a therapeutically effective dose refers to that amount of active ingredient that ameliorates the symptoms or condition. Therapeutic efficacy and toxicity may be determined by standard pharmaceutical procedures in cell cultures or with experimental animals, such as by calculating and contrasting the ED.sub.50 (the dose therapeutically effective in 50% of the population) and LD.sub.50 (the dose lethal to 50% of the population) statistics. Any of the therapeutic compositions described above may be applied to any subject in need of such therapy, including, but not limited to, mammals such as dogs, cats, cows, horses, rabbits, monkeys, and most preferably, humans.
[0123] The pharmaceutical compositions utilized in this invention may be administered by any number of routes including, but not limited to, oral, intravenous, intramuscular, intra-arterial, intramedullary, intrathecal, intraventricular, transdermal, subcutaneous, intraperitoneal, intranasal, enteral, topical, sublingual, or rectal means.
[0124] The term "treatment" for purposes of this disclosure refers to both therapeutic treatment and prophylactic or preventative measures, wherein the object is to prevent or slow down (lessen) the targeted pathologic condition or disorder. Those in need of treatment include those already with the disorder as well as those prone to have the disorder or those in whom the disorder is to be prevented.
Use of NSEQ in General Research
[0125] The invention also provides products, compositions, processes and methods that utilize a NSEQ described herein, a polypeptide encoded by a NSEQ described herein, a PSEQ described herein for research, biological, clinical and therapeutic purposes. For example, to identify splice variants, mutations, and polymorphisms and to generate diagnostic and prognostic tools.
[0126] NSEQ may be extended utilizing a partial nucleotide sequence and employing various PCR-based methods known in the art to detect upstream sequences such as promoters and other regulatory elements. Additionally, one may use an XL-PCR kit (PE Biosystems, Foster City Calif.), nested primers, and commercially available cDNA libraries (Life Technologies, Rockville Md.) or genomic libraries (Clontech, Palo Alto Calif.) to extend the sequence.
[0127] The polynucleotides (NSEQ) may also be used as targets in a microarray. The microarray may be used to monitor the expression patterns of large numbers of genes simultaneously and to identify splice variants, mutations, and polymorphisms. Information derived from analyses of the expression patterns may be used to determine gene function, to identify a particular cell, cell type or tissue, to understand the genetic basis of a disease, to diagnose a disease, and to develop and monitor the activities of therapeutic agents used to treat a disease. Microarrays may also be used to detect genetic diversity, single nucleotide polymorphisms which may characterize a particular population, at the genomic level.
[0128] The polynucleotides (NSEQ) may also be used to generate hybridization probes useful in mapping the naturally occurring genomic sequence. Fluorescent in situ hybridization (FISH) may be correlated with other physical chromosome mapping techniques and genetic map data.
[0129] It is to be understood herein that a sequence which is upregulated in an ovarian cancer cell (e.g., malignant ovarian cancer cell) may represent a sequence which is involved in or responsible for the growth, development, maligancy and so on, of the cancer cell (referred herein as a positive regulator of ovarian cancer). It is also to be understood that a sequence which is downregulated (unexpressed or expressed at low levels) in a malignant ovarian cancer cell may represent a sequence which is responsible for the maintenance of the normal status (untransformed) of an ovarian cell (referred herein as a negative regulator of ovarian cancer). Therefore, both the presence or absence of some sequences may be indicative of the disease or may be indicative of the disease, probability of having a disease, degree of severity of the disease (staging).
[0130] Therefore, the present invention relates in an aspect thereof to an isolated polynucleotide (e.g., exogenous form of) which may comprise a member selected from the group consisting of;
[0131] a) a polynucleotide which may comprise or consist of any one of SEQ ID NO.:1 to SEQ ID NO. 49 and SEQ ID NO. 169,
[0132] b) a polynucleotide which may comprise the open reading frame of any one of SEQ ID NO.:1 to SEQ ID NO. 49 and SEQ ID NO. 169,
[0133] c) a polynucleotide which may comprise a transcribed or transcribable portion of any one of SEQ. ID. NOs:1 to 49 and 169, which may be, for example, free of untranslated or untranslatable portion(s),
[0134] d) a polynucleotide which may comprise a translated or translatable portion of any one of SEQ. ID. NOs:1 to 49 and 169 (e.g., coding portion),
[0135] e) a polynucleotide which may comprise a sequence substantially identical (e.g., from about 50 to 100%, or about 60 to 100% or about 70 to 100% or about 80 to 100% or about 85, 90, 95 to 100% identical over the entire sequence or portion of sequences) to a), b), c), or d);
[0136] f) a polynucleotide which may comprise a sequence substantially complementary (e.g., from about 50 to 100%, or about 60 to 100% or about 70 to 100% or about 80 to 100% or about 85, 90, 95 to 100% complementarity over the entire sequence or portion of sequences) to a), b), c), or d) and;
[0137] g) a fragment of any one of a) to f) including polynucleotides which consist in the above.
[0138] More specifically, the present invention relates to expressed polynucleotides which are selected from the group consisting of;
[0139] a) a polynucleotide which may comprise or consist of any one of SEQ ID NO.: 1, SEQ ID NO.:14, SEQ ID NO.:16, SEQ ID NO.:19, SEQ ID NO.:20, SEQ ID NO.:22, SEQ ID NO.:28, SEQ ID NO.:37, SEQ ID NO.:41, SEQ ID NO.:45, SEQ ID NO.:46, SEQ ID NO.:47 and SEQ ID NO.:49 and even more specifically those which are selected from the group consisting of SEQ ID NO.: 14, SEQ ID NO.:19, SEQ ID NO.: 22, SEQ ID NO.:37, SEQ ID NO.:41, SEQ ID NO.:45, SEQ ID NO.:46 and SEQ ID NO.:49,
[0140] b) a polynucleotide which may comprise the open reading frame of any one of SEQ ID NO.: 1, SEQ ID NO.:14, SEQ ID NO.:16, SEQ ID NO.:19, SEQ ID NO.:20, SEQ ID NO.:22, SEQ ID NO.:28, SEQ ID NO.:37, SEQ ID NO.:41, SEQ ID NO.:45, SEQ ID NO.:46, SEQ ID NO.:47 and SEQ ID NO.:49 and even more specifically those which are selected from the group consisting of SEQ ID NO.: 14, SEQ ID NO.:19, SEQ ID NO.: 22, SEQ ID NO.:37, SEQ ID NO.:41, SEQ ID NO.:45, SEQ ID NO.:46 and SEQ ID NO.:49,
[0141] c) a polynucleotide which may comprise a transcribed or transcribable portion of any one of SEQ ID NO.: 1, SEQ ID NO.:14, SEQ ID NO.:16, SEQ ID NO.:19, SEQ ID NO.:20, SEQ ID NO.:22, SEQ ID NO.:28, SEQ ID NO.:37, SEQ ID NO.:41, SEQ ID NO.:45, SEQ ID NO.:46, SEQ ID NO.:47 and SEQ ID NO.:49 and even more specifically those which are selected from the group consisting of SEQ ID NO.: 14, SEQ ID NO.:19, SEQ ID NO.: 22, SEQ ID NO.:37, SEQ ID NO.:41, SEQ ID NO.:45, SEQ ID NO.:46 and SEQ ID NO.:49, which may be, for example, free of untranslated or untranslatable portion(s),
[0142] d) a polynucleotide which may comprise a translated or translatable portion of any one of SEQ ID NO.: 1, SEQ ID NO.:14, SEQ ID NO.:16, SEQ ID NO.:19, SEQ ID NO.:20, SEQ ID NO.:22, SEQ ID NO.:28, SEQ ID NO.:37, SEQ ID NO.:41, SEQ ID NO.:45, SEQ ID NO.:46, SEQ ID NO.:47 and SEQ ID NO.:49 and even more specifically those which are selected from the group consisting of SEQ ID NO.: 14, SEQ ID NO.:19, SEQ ID NO.: 22, SEQ ID NO.:37, SEQ ID NO.:41, SEQ ID NO.:45, SEQ ID NO.:46 and SEQ ID NO.:49, (e.g., coding portion),
[0143] e) a polynucleotide which may comprise a sequence substantially identical (e.g., from about 50 to 100%, or about 60 to 100% or about 70 to 100% or about 80 to 100% or about 85, 90, 95 to 100% identical over the entire sequence or portion of sequences) to a), b), c), or d);
[0144] f) a polynucleotide which may comprise a sequence substantially complementary (e.g., from about 50 to 100%, or about 60 to 100% or about 70 to 100% or about 80 to 100% or about 85, 90, 95 to 100% complementarity over the entire sequence or portion of sequences) to a), b), c), or d) and;
[0145] g) a fragment of any one of a) to f) including polynucleotides which consist in the above.
[0146] Vectors (e.g., a viral vector, a mammalian vector, a plasmid, a cosmid, etc.) which may comprise the polynucleotides described herein are also encompassed by the present invention. The vector may be, for example, an expression vector.
[0147] The present invention also provides a library of polynucleotide comprising at least one polynucleotide (e.g., at least two, etc.) described herein (may include SEQ ID NO.:50). The library may be, for example, an expression library. Some or all of the polynucleotides described herein may be contained within an expression vector. The present invention also relates to a polypeptide library which may comprise at least one (e.g., at least two, etc.) polypeptide as described herein.
[0148] In another aspect, the present invention provides arrays which may comprise at least one polynucleotide (e.g., at least two, etc.) described herein. The present invention also provides an isolated cell (e.g., an isolated live cell such as an isolated mammalian cell, a bacterial cell, a yeast cell, an insect cell, etc.) which may comprise the polynucleotide, the vector or the polypeptide described herein.
[0149] In yet a further aspect the present invention relates to a composition comprising the polynucleotide and/or polypeptide described herein.
[0150] In accordance with the present invention, the composition may be, for example, a pharmaceutical composition which may comprise a polynucleotide and/or a polypeptide described herein and a pharmaceutically acceptable carrier. More specifically, the pharmaceutical composition may be used for the treatment of ovarian cancer and/or for inhibiting the growth of an ovarian cancer cell.
[0151] Polynucleotides fragments of those listed above includes polynucleotides comprising at least 10 nucleic acids which may be identical to a corresponding portion of any one of a) to e) and more particularly a coding portion of any one of SEQ ID NO.:1 to 49, 50 or 169.
[0152] Another exemplary embodiment of polynucleotide fragments encompassed by the present invention includes polynucleotides comprising at least 10 nucleic acids which may be substantially complementary to a corresponding portion of a coding portion of any one of SEQ ID NO.:1 to 49, 50 or 169 and encompasses, for example, fragments selected from the group consisting of any one of SEQ ID NO.: 103 to 150.
[0153] These above sequences may represent powerful markers of cancer and more particularly of, ovarian cancer, breast cancer, prostate cancer, leukemia, melanoma, renal cancer, colon cancer, lung cancer, cancer of the central nervous system and any combination thereof.
[0154] Based on the results presented herein and upon reading the present description, a person skilled in the art will understand that the appearance of a positive signal upon testing (hybridization, PCR amplification etc.) for the presence of a given sequence amongst those expressed in a cancer cell, indicates that such sequence is specifically expressed in that type of cancer cell. A person skilled in the art will also understand that, sequences which are specifically expressed in a certain types of cancer cell may be used for developing tools for the detection of this specific type of cancer cell and may also be used as targets in the development of anticancer drugs.
[0155] A positive signal may be in the form of a band in a gel following electrophoresis, Northern blot or Western blot, a PCR fragment detected by emission of fluorescence, etc.
[0156] As it will be understood, sequences which are particularly useful for the development of tools for the detection of cancer cell may preferably be expressed at lower levels in at least some normal cells (non-cancerous cells).
[0157] For example, in FIG. 57 and related description, the appearance of a band upon RT-PCR amplification of mRNAs obtained from ovarian cancer cells, renal cancer cells, lung cancer cells, breast cancer cells and melanoma cells indicates that SEQ ID NO.:1 is expressed in such cancer cells and that SEQ ID NO.:1 may therefore represent a valid marker and target for these types of cancer cells. Similar conclusions may be derived from the results obtained from other Figures and related description.
[0158] NSEQs chosen among those which are substantially complementary to those listed in Table 2, or to fragments of those of Table 2, may be used for the treatment of cancer.
[0159] The present invention therefore relates to a method for identifying a cancer cell. The method may comprise contacting a cell, a cell sample (cell lysate), a body fluid (blood, urine, plasma, saliva etc.) or a tissue with a reagent which may be, for example, capable of specifically binding at least one NSEQ or PSEQ described herein. The method may more particularly comprise contacting a sequence isolated or derived such cell, sample, fluid or tissue. The complex formed may be detected using methods known in the art.
[0160] In accordance with the present invention, the presence of the above mentioned complex may be indicative (a positive indication of the presence) of the presence of a cancer cell.
[0161] The present invention also relates in an additional aspect thereof to a method for the diagnosis or prognosis of cancer. The method may comprise, for example, detecting, in a cell, tissue, sample, body fluid, etc., at least one NSEQ or PSEQ described herein.
[0162] The cell, cell sample, body fluid or tissue may originate, for example, from an individual which has or is suspected of having a cancer and more particularly ovarian cancer, breast cancer, prostate cancer, leukemia, melanoma, renal cancer, colon cancer, lung cancer and/or cancer of the central nervous system Any of the above mentioned methods may further comprise comparing the level obtained with at least one reference level or value.
[0163] Detection of NSEQ may require an amplification (e.g., PCR) step in order to have sufficient material for detection purposes.
[0164] In accordance with the present invention, the polynucleotide described herein may comprise, for example, a RNA molecule, a DNA molecule, including those which are partial or complete, single-stranded or double-stranded, hybrids, modified by a group etc.
[0165] Other aspects of the present invention which are encompassed herewith comprises the use of at least one NSEQ or PSEQ described herein and derived antibodies in the manufacture of a composition for identification or detection of a cancer cell (e.g., a tumor cell) or for inhibiting or lowering the growth of cancer cell (e.g., for treatment of ovarian cancer or other cancer).
[0166] As some NSEQ and PSEQ are expressed at higher levels in malignant ovarian cancer than in LMP detection of such NSEQ or PSEQ in a sample from an individual (or in vivo) one may rule-out a low malignant potential ovarian cancer and may therefore conclude in a diagnostic of a malignant ovarian cancer. Furthermore, detection of the NSEQ or PSEQ in a cell, tissue, sample or body fluid from an individual may also be indicative of a late-stage malignant ovarian cancer. As such, therapies adapted for the treatment of a malignant ovarian cancer or a late-stage malignant ovarian cancer may be commenced.
[0167] In accordance with an embodiment of the present invention, the method may also comprise a step of qualitatively or quantitatively comparing the level (amount, presence) of at least one complex present in the test cell, test sample, test fluid or test tissue with the level of complex in a normal cell, a normal cell sample, a normal body fluid, a normal tissue or a reference value (e.g., for a non-cancerous condition).
[0168] The normal cell may be any cell which does not substantially express the desired sequence to be detected. Examples of such normal cells are included for example, in the description of the drawings section. A normal cell sample or tissue thus include, for example, a normal (non-cancerous) ovarian cell, a normal breast cell, a normal prostate cell, a normal lymphocyte, a normal skin cell, a normal renal cell, a normal colon cell, a normal lung cell and/or a normal cell of the central nervous system. For comparison purposes, a normal cell may be chosen from those of identical or similar cell type.
[0169] Of course, the presence of more than one complex may be performed in order to increase the precision of the diagnostic method. As such, at least two complexes (e.g., formed by a first reagent and a first polynucleotide and a second reagent or a second polynucleotide) or multiple complexes may be detected.
[0170] An exemplary embodiment of a reagent which may be used for detecting a NSEQ described herein is a polynucleotide which may comprise a sequence substantially complementary to the NSEQ.
[0171] A suitable reference level or value may be, for example, derived from the level of expression of a specified sequence in a low malignant potential ovarian cancer and/or from a normal cell.
[0172] It will be understood herein that a higher level of expression measured in a cancer cell, tissue or sample in comparison with a reference value or sample is a indicative of the presence of cancer in the tested individual.
[0173] For example, the higher level measured in an ovarian cell, ovarian tissue or a sample of ovarian origin compared to a reference level or value for a normal cell (normal ovarian cell or normal non-ovarian cell) may be indicative of an ovarian cancer. For comparison purpose, the presence or level of expression of a desired NSEQ or PSEQ to be detected or identified may be compared with the presence, level of expression, found in a normal cell which has been shown herein not to express the desired sequence.
[0174] Therapeutic uses and methods are also encompassed herewith.
[0175] The invention therefore provides polynucleotides which may be able to lower or inhibit the growth of an ovarian cancer cell (e.g., in a mammal or mammalian cell thereof).
[0176] The present invention therefore relates in a further aspect to the use of a polynucleotide sequence which may be selected from the group consisting of
[0177] a) a polynucleotide which may comprise a sequence substantially complementary to any of SEQ ID NO.:1 to SEQ ID NO. 49, 50 or 169
[0178] b) a polynucleotide which may comprise a sequence substantially complementary to a transcribed or transcribable portion of any one of SEQ. ID. NOs:1 to 49, 50 or 169,
[0179] c) a polynucleotide which may comprise a sequence substantially complementary to a translated or translatable portion of any one of SEQ. ID. NOs:1 to 49, 50 or 169, and;
[0180] d) a fragment of any one of a) to c) for reducing, lowering or inhibiting the growth of a cancer cell.
[0181] The polynucleotide may be selected, for example, from the group consisting of polynucleotides which may comprise a sequence of at least 10 nucleotides which is complementary to the nucleic acid sequence of any one of SEQ ID NO.: 1 to 49, 50 and 169 (to a translated portion which may be free, for example, of untranslated portions).
[0182] Of course, the present invention encompasses immunizing an individual by administering a NSEQ (e.g., in an expression vector) or a PSEQ.
[0183] The present invention also relates to a method of reducing or slowing the growth of an ovarian cancer cell in an individual in need thereof. The method may comprise administering to the individual a polynucleotide sequence which may be selected from the group consisting of
[0184] a) a polynucleotide which may comprise a sequence substantially complementary (also including 100% complementary over a portion, e.g., a perfect match) to any of SEQ ID NO.:1 to SEQ ID NO. 49 and 169 or 50,
[0185] b) a polynucleotide which may comprise a sequence substantially complementary (also including 100% complementary over a portion, e.g., a perfect match) to a transcribed or transcribable portion of any one of SEQ. ID. NOs:1 to 49 and 169 or 50,
[0186] c) a polynucleotide which may comprise a sequence substantially complementary (also including 100% complementary over a portion, e.g., a perfect match) to a translated or translatable portion of any one of SEQ. ID. NOs:1 to 49 and 169 or 50, and;
[0187] d) a fragment of any one of a) to c).
[0188] The present invention therefore provides in yet another aspect thereof, a siRNA or shRNA molecule that is able to lower the expression of a nucleic acid selected from the group consisting of
[0189] a) a polynucleotide which may comprise any one of SEQ ID NO.:1 to SEQ ID NO.:49 and SEQ ID NO.:169, or SEQ ID NO.:50,
[0190] b) a polynucleotide which may comprise a transcribed or transcribable portion of any one of SEQ. ID. NOs:1 to 49 and 169, or SEQ ID NO.:50,
[0191] c) a polynucleotide which may comprise a translated or translatable portion of any one of SEQ. ID. NOs:1 to 49 and 169 or SEQ ID NO.:50, and;
[0192] d) a polynucleotide which may comprise a sequence substantially identical to a), b), or c).
[0193] Exemplary embodiment of polynucleotides are those which, for example, may be able to inhibit the growth of an ovarian cancer cell, such as, for example, a polynucleotide having or comprising a sequence selected from the group consisting of any one of SEQ ID NO. 103 to 150. These specific sequences are provided as guidance only and are not intended to limit the scope of the invention.
[0194] The present invention also provides a kit for the diagnosis of cancer. The kit may comprise at least one polynucleotide as described herein and/or a reagent capable of specifically binding at least one polynucleotide described herein.
[0195] In a further aspect, the present invention relates to an isolated polypeptide encoded by the polynucleotide described herein.
[0196] The present invention more particularly provides an isolated polypeptide which may be selected from the group consisting of
[0197] a) a polypeptide which may comprise any one of SEQ ID NO.:51 to 88 and 170
[0198] b) a polypeptide which may be encoded by any one of the polynucleotide described herein,
[0199] c) a fragment of any one of a) or b),
[0200] d) a derivative of any one of a) or b) and;
[0201] e) an analog of any one of a) or b).
[0202] In accordance with the present invention, the analog may comprise, for example, at least one amino acid substitution, deletion or insertion in its amino acid sequence.
[0203] The substitution may be conservative or non-conservative. The polypeptide analog may be a biologically active analog or an immunogenic analog which may comprise, for example, at least one amino acid substitution (conservative or non conservative), for example, 1 to 5, 1 to 10, 1 to 15, 1 to 20, 1 to 50 etc. (including any number there between) compared to the original sequence. An immunogenic analog may comprise, for example, at least one amino acid substitution compared to the original sequence and may still be bound by an antibody specific for the original sequence.
[0204] In accordance with the present invention, a polypeptide fragment may comprise, for example, at least 6 consecutive amino acids, at least 8 consecutive amino acids or more of an amino acid sequence selected from the group consisting of polypeptides encoded by a polynucleotide selected from the group consisting of SEQ ID NO.: 1 to 49 and 169 or any one of SEQ. ID. NOs:51 to 88 and 170, including variants and analogs thereof. The fragment may be immunogenic and may be used for the purpose, for example, of generating antibodies.
[0205] Exemplary embodiments of polypeptide encompassed by the present invention are those which may be encoded by any one of SEQ ID NO.:1-49 and 169, more particularly those encoded by any one of SEQ ID NO.:1, 14, 16, 19, 20, 22, 28, 37, 41, 45, 46, 47 or 49 and even more particularly those encoded by any one of SEQ ID NO.: 14, 19, 22, 37, 41, 45, 46 or 49.
[0206] In a further aspect the present invention relates to a polypeptide which may be encoded by the isolated differentially expressed sequence of the present invention. The present invention as well relates to the polypeptide encoded by the non-human ortholog polynucleotide, analogs, derivatives and fragments thereof.
[0207] A person skilled in the art may easily determine the possible peptide sequence encoded by a particular nucleic acid sequence as generally, a maximum of 6 possible open-reading frames exist in a particular coding sequence. The first possible open-reading frame may start at the first nucleotide (5'-3') of the sequence, therefore using in a 5' to 3' direction nucleotides No. 1 to 3 as the first codon, using nucleotides 4 to 6 as the second codon, etc. The second possible open-reading frame may start at the second nucleotide (5'-3') of the sequence, therefore using in a 5' to 3' direction nucleotides No. 2 to 4 as the first codon, using nucleotides 5 to 7 as the second codon, etc. Finally, the third possible open-reading frame may start at the third nucleotide (5'-3') of the sequence, therefore using in a 5' to 3' direction nucleotides No. 3 to 5 as the first codon, using nucleotides 6 to 8 as the second codon, etc. The fourth possible open-reading frame may start at the first nucleotide of the sequence in a 3' to 5' direction, therefore using in 3' to 5' direction, nucleotides No. 1 to 3 as the first codon, using nucleotides 4 to 6 as the second codon, etc. The fifth possible open-reading frame may start at the second nucleotide of the sequence in a 3' to 5' direction, therefore using in a 3' to 5' direction, nucleotides No. 2 to 4 as the first codon, using nucleotides 5 to 7 as the second codon, etc. Finally, the sixth possible open-reading frame may start at the third nucleotide of the sequence in a 3' to 5' direction, therefore using in a 3' to 5' direction nucleotides No. 3 to 5 as the first codon, using nucleotides 6 to 8 as the second codon, etc.
[0208] In an additional aspect, the present invention relates to the use of at least one polypeptide in the manufacture of a composition for the identification or detection of a cancer cell (tumor cell). The polypeptide may be used, for example, as a standard in an assay and/or for detecting antibodies specific for the particular polypeptide, etc. In yet an additional aspect, the present invention relates to the use of at least one polypeptide described herein in the identification or detection of a cancer cell, such as for example, an ovarian cancer cell or any other cancer cell as described herein.
[0209] The present invention therefore relates in a further aspect, to the use of at least one polypeptide described herein in the prognosis or diagnosis of cancer, such as, for example, a malignant ovarian cancer or a low malignant potential ovarian cancer.
[0210] As such and in accordance with the present invention, detection of the polypeptide in a cell (e.g., ovarian cell), tissue (e.g., ovarian tissue), sample or body fluid from an individual may preferentially be indicative of a malignant ovarian cancer diagnosis over a low malignant potential ovarian cancer diagnosis and therefore may preferentially be indicative of a malignant ovarian cancer rather than a low malignant potential ovarian cancer.
[0211] Further in accordance with the present invention, the presence of the polypeptide in a cell, tissue, sample or body fluid from an individual may preferentially be indicative of a late-stage malignant ovarian cancer.
[0212] There is also provided by the present invention, methods for identifying a cancer cell, which may comprise, for example, contacting a test cell, a test cell sample (cell lysate), a test body fluid (blood, urine, plasma, saliva etc.) or a test tissue with a reagent which may be capable of specifically binding the polypeptide described herein, and detecting the complex formed by the polypeptide and reagent. The presence of a complex may be indicative (a positive indication of the presence) of a cancer cell such as for example, an ovarian cancer cell, a breast cancer cell, a prostate cancer cell, leukemia, melanoma, a renal cancer cell, a colon cancer cell, a lung cancer cell, a cancer cell of the central nervous system and any combination thereof.
[0213] The presence of a complex formed by the polypeptide and the specific reagent may be indicative, for example, of ovarian cancer including, for example, a low malignant potential ovarian cancer or a malignant ovarian cancer.
[0214] However, the method is more particularly powerful for the detection of ovarian cancer of the malignant type. Therefore, the presence of a complex may preferentially be indicative of a malignant ovarian cancer relative (rather than) to a low malignant potential ovarian cancer.
[0215] Detection of the complex may also be indicative of a late stage malignant ovarian cancer.
[0216] In accordance with the present invention, the method may also comprise a step of qualitatively or quantitatively comparing the level (amount, presence) of at least one complex present in a test cell, a test sample, a test fluid or a test tissue with the level of complex in a normal cell, a normal cell sample, a normal body fluid, a normal tissue or a reference value (e.g., for a non-cancerous condition).
[0217] Of course, the presence of more than one polypeptide or complex (two complexes or more (multiple complexes)) may be determined, e.g., one formed by a first specific reagent and a first polypeptide and another formed by a second specific reagent and a second polypeptide may be detected. Detection of more than one polypeptide or complex may help in the determination of the tumorigenicity of the cell.
[0218] An exemplary embodiment of a reagent, which may be used for the detection of the polypeptide described herein, is an antibody and antibody fragment thereof.
[0219] The present invention also relates to a kit which may comprise at least one of the polypeptide described herein and/or a reagent capable of specifically binding to at least one of the polypeptide described herein.
[0220] As one skill in the art will understand, compositions which comprises a polypeptide may be used, for example, for generating antibodies against the particular polypeptide, may be used as a reference for assays and kits, etc.
[0221] Additional aspects of the invention relates to isolated or purified antibodies (including an antigen-binding fragment thereof) which may be capable of specifically binding to a polypeptide selected from the group consisting of;
[0222] a) a polypeptide comprising or consisting of any one of SEQ ID NO.:51 to 89 or 170, and;
[0223] b) a polypeptide comprising a polypeptide sequence encoded by any one of the polynucleotide sequence described herein (e.g., a fragment of at least 6 amino acids of the polypeptide).
[0224] More particularly, exemplary embodiments of the present invention relates to antibodies which may be capable of specifically binding a polypeptide comprising a polypeptide sequence encoded by any one of SEQ ID NO.: 1, 14, 16, 19, 20, 22, 28, 37, 41, 45, 46, 47 or 49, or a fragment of at least 6 amino acids of the polypeptide.
[0225] Even more particular exemplary embodiments of the present invention relates to antibodies which may be capable of specifically binding a polypeptide comprising a polypeptide sequence encoded by any one of SEQ ID NO.: 14, 19, 22, 37, 41, 45, 46 or 49, or a fragment of at least 6 amino acids of the polypeptide.
[0226] In yet an additional aspect, the present invention relates to a hybridoma cell which is capable of producing an antibody which may specifically bind to a polypeptide selected from the group consisting of;
[0227] a) a polypeptide which may comprise any one of SEQ ID NO.:51 to 88, 89 and 170, and;
[0228] b) a polypeptide which may comprise a polypeptide sequence encoded by any one of the polynucleotide sequence described herein or a fragment of at least 6 amino acids of the polypeptide.
[0229] Exemplary hybridoma which are more particularly encompassed by the present invention are those which may produce an antibody which may be capable of specifically binding a polypeptide comprising a polypeptide sequence encoded by any one of SEQ ID NO.: 1, 14, 16, 19, 20, 22, 28, 37, 41, 45, 46, 47 or 49 or a fragment of at least 6 amino acids of the polypeptide.
[0230] Exemplary embodiments of hybridoma which are even more particularly encompassed by the present invention are those which may produce an antibody which is capable of specifically binding a polypeptide comprising a polypeptide sequence encoded by any one of SEQ ID NO.: 14, 19, 22, 37, 41, 45, 46 or 49 or a fragment of at least 6 amino acids of the polypeptide.
[0231] The present invention also relates to a composition which may comprise an antibody described herein.
[0232] In a further aspect the present invention provides a method of making an antibody which may comprise immunizing a non-human animal with an immunogenic fragment (at least 6 amino acids, at least 8 amino acids, etc.) of a polypeptide which may be selected, for example, from the group consisting of;
[0233] a) a polypeptide which may comprise or consist in any one of SEQ ID NO.:51 to 88, 89 and 170 or a fragment thereof, and;
[0234] b) a polypeptide which may comprise a polypeptide sequence encoded by any one of the polynucleotide sequence described herein or a portion thereof.
[0235] Exemplary polypeptides which may, more particularly, be used for generating antibodies are those which are encoded by any one of SEQ ID NO.: 1, 14, 16, 19, 20, 22, 28, 37, 41, 45, 46, 47 or 49 (and polypeptide comprising a polypeptide fragment of these particular PSEQ). Even more particular polypeptides encompassed by the present invention are those which are encoded by any one of SEQ ID NO.: 14, 19, 22, 37, 41, 45, 46 or 49.
[0236] In a further aspect, the present invention relates to a method of identifying a compound which is capable of inhibiting the activity or function of a polypeptide which may be selected, for example from the group consisting of any one of SEQ ID NO.:51 to 88 and 170 or a polypeptide comprising a polypeptide sequence encoded by any one of SEQ ID NO.:1 to 49 and 169 (e.g., a transcribed portion, a translated portion, a fragment, substantially identical and even substantially complementary sequences). The method may comprise contacting the polypeptide with a putative compound an isolating or identifying a compound which is capable of specifically binding any one of the above mentioned polypeptide. The compound may originate from a combinatorial library.
[0237] The method may also further comprise determining whether the activity or function of the polypeptide (e.g., such as a function indicated at Table 2) is affected by the binding of the compound. Those compounds which capable of binding to the polypeptide and which and/or which are capable of altering the function or activity of the polypeptide represents a desirable compound to be used in cancer therapy.
[0238] The method may also further comprise a step of determining the effect of the putative compound on the growth of a cancer cell such as an ovarian cancer cell.
[0239] The present invention also relates to an assay and method for identifying a nucleic acid sequence and/or protein involved in the growth or development of ovarian cancer. The assay and method may comprise silencing an endogenous gene of a cancer cell such as an ovarian cancer cell and providing the cell with a candidate nucleic acid (or protein). A candidate gene (or protein) positively involved in inducing cancer cell death (e.g., apoptosis) (e.g., ovarian cancer cell) may be identified by its ability to complement the silenced endogenous gene. For example, a candidate nucleic acid involved in ovarian cancer provided to a cell for which an endogenous gene has been silenced, may enable the cell to undergo apoptosis more so in the presence of an inducer of apoptosis.
[0240] Alternatively, an assay or method may comprise silencing an endogenous gene (gene expression) corresponding to the candidate nucleic acid or protein sequence to be evaluated and determining the effect of the candidate nucleic acid or protein on cancer growth (e.g., ovarian cancer cell growth). A sequence involved in the promotion or inhibition of cancer growth, development or malignancy may change the viability of the cell, may change the ability of the cell to grow or to form colonies, etc. The activity of a polypeptide may be impaired by targeting such polypeptide with an antibody molecule or any other type of compound. Again, such compound may be identified by screening combinatorial libraries, phage libraries, etc.
[0241] The present invention also provides a method for identifying an inhibitory compound (inhibitor, antagonist) able to impair the function (activity) or expression of a polypeptide described herein. The method may comprise, for example, contacting the (substantially purified or isolated) polypeptide or a cell expressing the polypeptide with a candidate compound and measuring the function (activity) or expression of the polypeptide. A reduction in the function or activity of the polypeptide (compared to the absence of the candidate compound) may thus positively identify a suitable inhibitory compound.
[0242] In accordance with the present invention, the impaired function or activity may be associated, for example, with a reduced ability of the polypeptide to reduce growth of an ovarian cancer cell or a reduced enzymatic activity or function identified for example in Table 2.
[0243] The cell used to carry the screening test may not naturally (endogenously) express the polypeptide or analogs, or alternatively the expression of a naturally expressed polypeptide analog may be repressed.
[0244] As used herein the term "sequence identity" relates to (consecutive) nucleotides of a nucleotide sequence with reference to an original nucleotide sequence which when compared are the same or have a specified percentage of nucleotides which are the same.
[0245] The identity may be compared over a region or over the total sequence of a nucleic acid sequence. Thus, "identity" may be compared, for example, over a region of 10, 19, 20 nucleotides or more (and any number therebetween) and more preferably over a longer region or over the entire region of a polynucleotide sequence described at Table 4 (e.g., any one of SEQ ID NO.:1 to 49 and 169). It is to be understood herein that gaps of non-identical nucleotides may be found between identical nucleic acids regions (identical nucleotides). For example, a polynucleotide may have 100% identity with another polynucleotide over a portion thereof. However, when the entire sequence of both polynucleotides is compared, the two polynucleotides may have 50% of their overall (total) sequence identity to one another.
[0246] Percent identity may be determined, for example, with n algorithm GAP, BESTFIT, or FASTA in the Wisconsin Genetics Software Package Release 7.0, using default gap weights.
[0247] Polynucleotides of the present invention or portion thereof having from about 50 to about 100% and any range therebetween, or about 60 to about 100% or about 70 to about 100% or about 80 to about 100% or about 85% to about 100%, about 90% to about 100%, about 95% to about 100% sequence identity with an original polynucleotide are encompassed herewith. It is known by those of skill in the art, that a polynucleotide having from about 50% to 100% identity may function (e.g., anneal to a substantially complementary sequence) in a manner similar to an original polynucleotide and therefore may be used in replacement of an original polynucleotide. For example a polynucleotide (a nucleic acid sequence) may comprise or have from about 50% to about 100% identity with an original polynucleotide over a defined region and may still work as efficiently or sufficiently to achieve the present invention. The term "substantially identical" used to define the polynucleotides of the present invention refers to polynucleotides which have, for example, from 50% to 100% sequence identity and any range therebetween but preferably at least 80%, at least 85%, at least 90%, at least 95% sequence identity and also include 100% identity with that of an original sequence (including sequences 100% identical over the entire length of the polynucleotide sequence).
[0248] "Substantially identical" polynucleotide sequences may be identified by providing a probe of about 10 to about 25, or more or about 10 to about 20 nucleotides long (or longer) based on the sequence of any one of SEQ ID NOs.:1 to 49 and 169 (more particularly, a transcribed and/or translated portion of any one of SEQ ID NOs.: 1 to 49 and 169) and complementary sequence thereof and hybridizing a library of polynucleotide (e.g., cDNA or else) originating from another species, tissue, cell, individual etc. A polynucleotide which hybridizes under highly stringent conditions (e.g., 6.times.SCC, 65.degree. C.) to the probe may be isolated and identified using methods known in the art. A sequence "substantially identical" includes for example, an isolated allelic variant, an isolated splice variant, an isolated non-human ortholog, a modified NSEQ etc.
[0249] As used herein the terms "sequence complementarity" refers to (consecutive) nucleotides of a nucleotide sequence which are complementary to a reference (original) nucleotide sequence. The complementarity may be compared over a region or over the total sequence of a nucleic acid sequence.
[0250] Polynucleotides of the present invention or portion thereof having from about 50 to about 100%, or about 60 to about 100% or about 70 to about 100% or about 80 to about 100% or about 85%, about 90%, about 95% to about 100% sequence complementarity with an original polynucleotide are thus encompassed herewith. It is known by those of skill in the art, that a polynucleotide having from about 50% to 100% complementarity with an original sequence may anneal to that sequence in a manner sufficient to carry out the present invention (e.g., inhibit expression of the original polynucleotide).
[0251] The term "substantially complementary" used to define the polynucleotides of the present invention refers to polynucleotides which have, for example, from 50% to 100% sequence complementarity and any range therebetween but preferably at least 80%, at least 85%, at least 90%, at least 95% sequence complementarity and also include 100% complementarity with that of an original sequence (including sequences 100% complementarity over the entire length of the polynucleotide sequence).
[0252] As used herein the term "polynucleotide" generally refers to any polyribonucleotide or polydeoxyribo-nucleotide, which may be unmodified RNA or DNA, or modified RNA or DNA. "Polynucleotides" include, without limitation single- and double-stranded DNA, DNA that is a mixture of single- and double-stranded regions, single- and double-stranded RNA, and RNA that is a mixture of single- and double-stranded regions, hybrid molecules comprising DNA and RNA that may be single-stranded or, more typically, double-stranded or a mixture of single- and double-stranded regions. In addition, "polynucleotide" refers to triple-stranded regions comprising RNA or DNA or both RNA and DNA. The term polynucleotide also includes DNAs or RNAs containing one or more modified bases and DNAs or RNAs with backbones modified for stability or for other reasons. "Modified" bases include, for example, tritylated bases and unusual bases such as inosine. A variety of modifications may be made to DNA and RNA; thus "polynucleotide" embraces chemically, enzymatically or metabolically modified forms of polynucleotides as typically found or not in nature, as well as the chemical forms of DNA and RNA characteristic of viruses and cells. "Polynucleotide" includes but is not limited to linear and end-closed molecules. "Polynucleotide" also embraces relatively short polynucleotides, often referred to as oligonucleotides.
[0253] "Polypeptides" refers to any peptide or protein comprising two or more amino acids joined to each other by peptide bonds or modified peptide bonds (i.e., peptide isosteres). "Polypeptide" refers to both short chains, commonly referred as peptides, oligopeptides or oligomers, and to longer chains generally referred to as proteins. As described above, polypeptides may contain amino acids other than the 20 gene-encoded amino acids.
[0254] As used herein the term "polypeptide analog" or "analog" relates to mutants, chimeras, fusions, a polypeptide comprising at least one amino acid deletion, a polypeptide comprising at least one amino acid insertion or addition, a polypeptide comprising at least one amino acid substitutions, and any other type of modifications made relative to a given polypeptide.
[0255] An "analog" is thus to be understood herein as a molecule having a biological activity and/or chemical structure similar to that of a polypeptide described herein. An "analog" may have sequence similarity with that of an original sequence or a portion of an original sequence and may also have a modification of its structure as discussed herein. For example, an "analog" may have at least 80% or 85% or 90% sequence similarity with an original sequence or a portion of an original sequence. An "analog" may also have, for example; at least 70% or even 50% sequence similarity with an original sequence or a portion of an original sequence and may function in a suitable manner.
[0256] A "derivative" is to be understood herein as a polypeptide originating from an original sequence or from a portion of an original sequence and which may comprise one or more modification; for example, one or more modification in the amino acid sequence (e.g., an amino acid addition, deletion, insertion, substitution etc.), one or more modification in the backbone or side-chain of one or more amino acid, or an addition of a group or another molecule to one or more amino acids (side-chains or backbone). Biologically active derivatives of the carrier described herein are encompassed by the present invention. Also, an "derivative" may have, for example, at least 50%, 70%, 80%, 90% sequence similarity to an original sequence with a combination of one or more modification in a backbone or side-chain of an amino acid, or an addition of a group or another molecule, etc.
[0257] As used herein the term "biologically active" refers to an analog which retains some or all of the biological activity of the original polypeptide, i.e., to have some of the activity or function associated with the polypeptide described at Table 2, or to be able to promote or inhibit the growth ovarian cancer.
[0258] Therefore, any polypeptide having a modification compared to an original polypeptide which does not destroy significantly a desired activity, function or immunogenicity is encompassed herein. It is well known in the art, that a number of modifications may be made to the polypeptides of the present invention without deleteriously affecting their biological activity. These modifications may, on the other hand, keep or increase the biological activity of the original polypeptide or may optimize one or more of the particularity (e.g. stability, bioavailability, etc.) of the polypeptides of the present invention which, in some instance might be desirable. Polypeptides of the present invention may comprise for example, those containing amino acid sequences modified either by natural processes, such as posttranslational processing, or by chemical modification techniques which are known in the art. Modifications may occur anywhere in a polypeptide including the polypeptide backbone, the amino acid side-chains and the amino- or carboxy-terminus. It will be appreciated that the same type of modification may be present in the same or varying degrees at several sites in a given polypeptide. Also, a given polypeptide may contain many types of modifications. It is to be understood herein that more than one modification to the polypeptides described herein are encompassed by the present invention to the extent that the biological activity is similar to the original (parent) polypeptide.
[0259] As discussed above, polypeptide modification may comprise, for example, amino acid insertion, deletion and substitution (i.e., replacement), either conservative or non-conservative (e.g., D-amino acids, desamino acids) in the polypeptide sequence where such changes do not substantially alter the overall biological activity of the polypeptide.
[0260] Example of substitutions may be those, which are conservative (i.e., wherein a residue is replaced by another of the same general type or group) or when wanted, non-conservative (i.e., wherein a residue is replaced by an amino acid of another type). In addition, a non-naturally occurring amino acid may substitute for a naturally occurring amino acid (i.e., non-naturally occurring conservative amino acid substitution or a non-naturally occurring non-conservative amino acid substitution).
[0261] As is understood, naturally occurring amino acids may be sub-classified as acidic, basic, neutral and polar, or neutral and non-polar. Furthermore, three of the encoded amino acids are aromatic. It may be of use that encoded polypeptides differing from the determined polypeptide of the present invention contain substituted codons for amino acids, which are from the same type or group as that of the amino acid to be replaced. Thus, in some cases, the basic amino acids Lys, Arg and His may be interchangeable; the acidic amino acids Asp and Glu may be interchangeable; the neutral polar amino acids Ser, Thr, Cys, Gln, and Asn may be interchangeable; the non-polar aliphatic amino acids Gly, Ala, Val, Ile, and Leu are interchangeable but because of size Gly and Ala are more closely related and Val, Ile and Leu are more closely related to each other, and the aromatic amino acids Phe, Trp and Tyr may be interchangeable.
[0262] It should be further noted that if the polypeptides are made synthetically, substitutions by amino acids, which are not naturally encoded by DNA (non-naturally occurring or unnatural amino acid) may also be made.
[0263] A non-naturally occurring amino acid is to be understood herein as an amino acid which is not naturally produced or found in a mammal. A non-naturally occurring amino acid comprises a D-amino acid, an amino acid having an acetylaminomethyl group attached to a sulfur atom of a cysteine, a pegylated amino acid, etc. The inclusion of a non-naturally occurring amino acid in a defined polypeptide sequence will therefore generate a derivative of the original polypeptide. Non-naturally occurring amino acids (residues) include also the omega amino acids of the formula NH.sub.2(CH.sub.2).sub.nCOOH wherein n is 2-6, neutral nonpolar amino acids, such as sarcosine, t-butyl alanine, t-butyl glycine, N-methyl isoleucine, norleucine, etc. Phenylglycine may substitute for Trp, Tyr or Phe; citrulline and methionine sulfoxide are neutral nonpolar, cysteic acid is acidic, and ornithine is basic. Proline may be substituted with hydroxyproline and retain the conformation conferring properties.
[0264] It is known in the art that analogs may be generated by substitutional mutagenesis and retain the biological activity of the polypeptides of the present invention. These analogs have at least one amino acid residue in the protein molecule removed and a different residue inserted in its place. For example, one site of interest for substitutional mutagenesis may include but are not restricted to sites identified as the active site(s), or immunological site(s). Other sites of interest may be those, for example, in which particular residues obtained from various species are identical. These positions may be important for biological activity. Examples of substitutions identified as "conservative substitutions" are shown in Table A. If such substitutions result in a change not desired, then other type of substitutions, denominated "exemplary substitutions" in Table A, or as further described herein in reference to amino acid classes, are introduced and the products screened.
[0265] In some cases it may be of interest to modify the biological activity of a polypeptide by amino acid substitution, insertion, or deletion. For example, modification of a polypeptide may result in an increase in the polypeptide's biological activity, may modulate its toxicity, may result in changes in bioavailability or in stability, or may modulate its immunological activity or immunological identity. Substantial modifications in function or immunological identity are accomplished by selecting substitutions that differ significantly in their effect on maintaining (a) the structure of the polypeptide backbone in the area of the substitution, for example, as a sheet or helical conformation. (b) the charge or hydrophobicity of the molecule at the target site, or (c) the bulk of the side chain. Naturally occurring residues are divided into groups based on common side chain properties:
(1) hydrophobic: norleucine, methionine (Met), Alanine (Ala), Valine (Val), Leucine (Leu), Isoleucine (Ile) (2) neutral hydrophilic: Cysteine (Cys), Serine (Ser), Threonine (Thr) (3) acidic: Aspartic acid (Asp), Glutamic acid (Glu) (4) basic: Asparagine (Asn), Glutamine (Gin), Histidine (His), Lysine (Lys), Arginine (Arg) (5) residues that influence chain orientation: Glycine (Gly), Proline (Pro); and aromatic: Tryptophan (Trp), Tyrosine (Tyr), Phenylalanine (Phe)
[0266] Non-conservative substitutions will entail exchanging a member of one of these classes for another.
TABLE-US-00001 TABLE A Examplary amino acid substitution Original Conservative residue Exemplary substitution substitution Ala (A) Val, Leu, Ile Val Arg (R) Lys, Gln, Asn Lys Asn (N) Gln, His, Lys, Arg Gln Asp (D) Glu Glu Cys (C) Ser Ser Gln (Q) Asn Asn Glu (E) Asp Asp Gly (G) Pro Pro His (H) Asn, Gln, Lys, Arg Arg Ile (I) Leu, Val, Met, Ala, Phe, Leu norleucine Leu (L) Norleucine, Ile, Val, Met, Ile Ala, Phe Lys (K) Arg, Gln, Asn Arg Met (M) Leu, Phe, Ile Leu Phe (F) Leu, Val, Ile, Ala Leu Pro (P) Gly Gly Ser (S) Thr Thr Thr (T) Ser Ser Trp (W) Tyr Tyr Tyr (Y) Trp, Phe, Thr, Ser Phe Val (V) Ile, Leu, Met, Phe, Ala, Leu norleucine
[0267] It is to be understood herein, that if a "range" or "group" of substances (e.g. amino acids), substituents" or the like is mentioned or if other types of a particular characteristic (e.g. temperature, pressure, chemical structure, time, etc.) is mentioned, the present invention relates to and explicitly incorporates herein each and every specific member and combination of sub-ranges or sub-groups therein whatsoever. Thus, any specified range or group is to be understood as a shorthand way of referring to each and every member of a range or group individually as well as each and every possible sub-ranges or sub-groups encompassed therein; and similarly with respect to any sub-ranges or sub-groups therein. Thus, for example, with respect to a percentage (%) of identity of from about 80 to 100%, it is to be understood as specifically incorporating herein each and every individual %, as well as sub-range, such as for example 80%, 81%, 84.78%, 93%, 99% etc. with respect to a length of "about 10 to about 25" it is to be understood as specifically incorporating each and every individual number such as for example 10, 11, 12, 13, 14, 15 up to and including 25; and similarly with respect to other parameters such as, concentrations, elements, etc.
[0268] Other objects, features, advantages, and aspects of the present invention will become apparent to those skilled in the art from the following description. It should be understood, however, that the following description and the specific examples, while indicating preferred embodiments of the invention, are given by way of illustration only. Various changes and modifications within the spirit and scope of the disclosed invention will become readily apparent to those skilled in the art from reading the following description and from reading the other parts of the present disclosure.
BRIEF DESCRIPTION OF THE DRAWINGS
[0269] In the appended drawings:
[0270] FIG. 1 to FIG. 31, FIG. 33, FIG. 34, FIG. 36, FIG. 37, FIG. 39, FIG. 40, FIG. 42, FIG. 43, FIG. 46, FIG. 47, FIG. 49, FIG. 50 and FIG. 56 are pictures of macroarray hybridization results showing the differential expression data for STAR selected ovarian cancer-related human sequences. Macroarrays were prepared using RAMP amplified RNA from six human LMP samples (A-F 1) and twenty malignant ovarian tumor samples (Table B) (A-F 2 and A-G 3-4), and 30 different normal human tissues (adrenal (A7), breast (B7), jejunum (C7), trachea (D7), liver (E7), placenta (F7), aorta (G7), brain (H7), lung (A8), adrenal cortex (B8), esophagus (C8), colon (D8), ovary (E8), kidney (F8), prostate (G8), thymus (H8), skeletal muscle (A9), vena cava (B9), stomach (C9), small intestine (D9), heart (E9), fallopian tube (F9), spleen (G9), bladder (H9), cervix (A10), pancreas (B10), ileum (010), duodenum (D10), thyroid (E10) and testicle (F10)). Also included on the RNA macroarray were breast cancer cell lines (MDA (A5), MCF7 (B5) and MCF7+estradiol (C5)) and LCM microdissected prostate normal epithelium (A-C 6) and prostate cancer (D-F 6), prostate cancer cell line, LNCap (G6) and LNCap+androgen (H6). In these figures, the probe labeling reaction was also spiked with a dsDNA sequence for Arabidopsis, which hybridizes to the same sequence spotted on the macroarray (M) in order to serve as a control for the labeling reaction.
[0271] FIG. 32, FIG. 35, FIG. 38, FIG. 41, FIG. 44, FIG. 45 and FIG. 48 are pictures of RT-PCR results showing the differential expression data for STAR selected ovarian cancer-related human sequences. Complimentary DNAs were prepared using random hexamers from RAMP amplified RNA from six human LMP samples and at least twenty malignant ovarian tumor samples (Table B) as indicated in the figures. The cDNAs were quantified and used as templates for PCR with gene-specific primers using standard methods known to those skilled in the art.
[0272] FIG. 57 to FIG. 105 are pictures of RT-PCR results showing the differential expression data for STAR selected cancer-related human sequences in RNA samples derived from the NCI-60 panel of cancer cell lines. These 59 cell lines are derived from tumors that encompass 9 human cancer types that include leukemia, the central nervous system, breast, colon, lung, melanoma, ovarian, prostate, and renal. Complimentary DNAs were prepared using random hexamers from RAMP amplified RNA from 59 human cancer cell lines (Table C). The cDNAs were quantified and used as templates for PCR with gene-specific primers using standard methods known to those skilled in the art. For each PCR result depicted in FIG. 57 to FIG. 105, equal amounts of template cDNA used in each PCR reaction was confirmed by reamplifying GAPDH with a specific primer pair, OGS 315 (TGAAGGTCGGAGTCAACGGATTTGGT; SEQ. ID. NO. 167) and OGS 316 (CATGTGGGCCATGAGGTCCACCAC; SEQ. ID. NO. 168) for this housekeeping gene.
[0273] More particularly,
[0274] FIG. 1 is a picture of the macroarray hybridization results showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 1. The STAR dsDNA clone representing SEQ. ID. NO. 1 was labeled with .sup.32P and hybridized to the macroarray. The hybridization results obtained confirm its upregulation in a majority of malignant ovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F 1). Expression of this sequence was only observed in one (placenta (F7)) of the 30 normal tissues and the breast cancer cell line, MCF7 (B-C 5);
[0275] FIG. 2 is a picture of the macroarray hybridization results showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 2. The STAR dsDNA clone representing SEQ. ID. NO. 2 was labeled with .sup.32P and hybridized to the macroarray. The hybridization results obtained confirm its upregulation in a majority of malignant ovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F 1). Expression of this sequence was also evident in six (breast (B7), placenta (F7), aorta (G7), colon (D8), ovary (E8) and thymus (H8)) of the 30 normal tissues;
[0276] FIG. 3 is a picture of the macroarray hybridization results showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 3. The STAR dsDNA clone representing SEQ. ID. NO. 3 was labeled with .sup.32P and hybridized to the macroarray. The hybridization results obtained confirm its upregulation in a majority of malignant ovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F 1) but overall, only low levels of expression. No significant expression was seen in any of the normal tissues;
[0277] FIG. 4 is a picture of the macroarray hybridization results showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 4. The STAR dsDNA clone representing SEQ. ID. NO. 4 was labeled with .sup.32P and hybridized to the macroarray. The hybridization results obtained confirm its upregulation in a majority of malignant ovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F 1). Expression of this sequence was also evident in two (esophagus (C8) and fallopian tube (F9)) of the 30 normal tissues;
[0278] FIG. 5 is a picture of the macroarray hybridization results showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 5. The STAR dsDNA clone representing SEQ. ID. NO. 5 was labeled with .sup.32P and hybridized to the macroarray. The hybridization results obtained confirm its upregulation in a majority of malignant ovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F 1). Weak expression of this sequence similar to that of LMPs was also observed in many of the normal tissues;
[0279] FIG. 6 is a picture of the macroarray hybridization results showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 6. The STAR dsDNA clone representing SEQ. ID. NO. 6 was labeled with .sup.32P and hybridized to the macroarray. The hybridization results obtained confirm its upregulation in a majority of malignant ovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F 1). Expression of this sequence was also evident in three (liver (E7), placenta (F7) and kidney (F8)) of the 30 normal tissues;
[0280] FIG. 7 is a picture of the macroarray hybridization results showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 7. The STAR dsDNA clone representing SEQ. ID. NO. 7 was labeled with .sup.32P and hybridized to the macroarray. The hybridization results obtained confirm its upregulation in several malignant ovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F 1). Expression of this sequence was only evident in one (testicle (F10)) of the 30 normal tissues;
[0281] FIG. 8 is a picture of the macroarray hybridization results showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 8. The STAR dsDNA clone representing SEQ. ID. NO. 8 was labeled with .sup.32P and hybridized to the macroarray. The hybridization results obtained confirm its upregulation in a majority of malignant ovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F 1). Expression of this sequence was only evident in two (esophagus (C8) and stomach (C9)) of the 30 normal tissues and the breast and prostate cancer cell lines, MDA (A5) and LNCap (G6 and H6), respectively;
[0282] FIG. 9 is a picture of the macroarray hybridization results showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 9. The STAR dsDNA clone representing SEQ. ID. NO. 9 was labeled with .sup.32P and hybridized to the macroarray. The hybridization results obtained confirm its upregulation in a majority of malignant ovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F 1). Expression of this sequence was only evident in one (placenta (F7)) of the 30 normal tissues, the breast cancer cell line, MCF7 (B-C 5) and LCM microdissected prostate cancer samples (D6 and F6);
[0283] FIG. 10 is a picture of the macroarray hybridization results showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 10. The STAR dsDNA clone representing SEQ. ID. NO. 10 was labeled with .sup.32P and hybridized to the macroarray. The hybridization results obtained confirm its upregulation in a majority of malignant ovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F 1). Expression of this sequence was only evident in one (testicle (F10)) of the 30 normal tissues, the breast cancer cell lines, MDA (A5) and MCF7 (B-C 5) and prostate cancer cell line, LNCap (G-H 6);
[0284] FIG. 11 is a picture of the macroarray hybridization results showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 11. The STAR dsDNA clone representing SEQ. ID. NO. 11 was labeled with .sup.32P and hybridized to the macroarray. The hybridization results obtained confirm its upregulation in a majority of malignant ovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F 1). Significant expression of this sequence was only evident in the breast cancer cell lines, MDA (A5) and MCF7 (B-C 5);
[0285] FIG. 12 is a picture of the macroarray hybridization results showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 12. The STAR dsDNA clone representing SEQ. ID. NO. 12 was labeled with .sup.32P and hybridized to the macroarray. The hybridization results obtained confirm its upregulation in the majority of malignant ovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F 1). Significant expression of this sequence was only evident in one (testicle (F10)) of the 30 normal tissues and the prostate cancer cell line, LNCap (G-H 6). Weaker expression was also observed in normal ovary (E8);
[0286] FIG. 13 is a picture of the macroarray hybridization results showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 13. The STAR dsDNA clone representing SEQ. ID. NO. 13 was labeled with .sup.32P and hybridized to the macroarray. The hybridization results obtained confirm its upregulation in a majority of malignant ovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F 1). Significant expression of this sequence was only evident in the breast cancer cell lines, MDA (A5) and MCF7 (B-C 5). Weaker expression was also observed in some normal tissues and the prostate cancer cell line, LNCap (G-H 6);
[0287] FIG. 14 is a picture of the macroarray hybridization results showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 14. The STAR dsDNA clone representing SEQ. ID. NO. 14 was labeled with .sup.32P and hybridized to the macroarray. The hybridization results obtained confirm its upregulation in a majority of malignant ovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F 1). Weaker expression of this sequence was only observed in the normal kidney (F8) tissue;
[0288] FIG. 15 is a picture of the macroarray hybridization results showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 15. The STAR dsDNA clone representing SEQ. ID. NO. 15 was labeled with .sup.32P and hybridized to the macroarray. The hybridization results obtained confirm its upregulation in the majority of malignant ovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F 1). Weaker expression of this sequence similar to that of the LMPs was noted in many of the normal tissues as well;
[0289] FIG. 16 is a picture of the macroarray hybridization results showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 16. The STAR dsDNA clone representing SEQ. ID. NO. 16 was labeled with .sup.32P and hybridized to the macroarray. The hybridization results obtained confirm its upregulation in the majority of malignant ovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F 1). Significant expression of this sequence was also evident in the breast cancer cell lines, MDA (A5) and MCF7 (B-C 5). Weaker expression similar to that of the LMPs was seen in prostate and some normal tissue samples;
[0290] FIG. 17 is a picture of the macroarray hybridization results showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 17. The STAR dsDNA clone representing SEQ. ID. NO. 17 was labeled with .sup.32P and hybridized to the macroarray. The hybridization results obtained confirm its upregulation in the majority of malignant ovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F 1). Significant expression of this sequence was only evident in two (breast (B7) and bladder (H9)) of the 30 normal tissues;
[0291] FIG. 18 is a picture of the macroarray hybridization results showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 18. The STAR dsDNA clone representing SEQ. ID. NO. 18 was labeled with .sup.32P and hybridized to the macroarray. The hybridization results obtained confirm its upregulation in a majority of malignant ovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F 1). Significant expression of this sequence was also evident in the breast cancer cell lines, MDA (A5) and MCF7 (B-C 5), and somewhat lower expression in prostate cancer cell line, LNCap (G-H 6) and eight normal tissues (adrenal (A7), placenta (F7), lung (A8), adrenal cortex (B8), esophagus (C8), colon (D8), ovary (E8) and testicle (F10));
[0292] FIG. 19A is a picture of the macroarray hybridization results showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 19. The STAR dsDNA clone representing SEQ. ID. NO. 19 was labeled with .sup.32P and hybridized to the macroarray. The hybridization results obtained confirm its upregulation in several malignant ovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F 1). Significant expression of this sequence was also only evident in the breast cancer cell line, MCF7 (B-C 5);
[0293] FIG. 19B (panels A and B) is a picture of RT-PCR data showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 19 and KCNMB2 gene belonging to Unigene cluster, Hs.478368. Primer pairs specific to either the STAR clone sequence for SEQ. ID. NO. 19 or the KCNMB2 gene were used to perform RT-PCR on normal ovarian tissue, and benign and different stages/grades of ovarian cancer. As indicated by the expected PCR amplicon product (FIG. 19B, panel A), compared to normal (Lane 1), benign (Lanes 2-3) and LMPs (Lanes 4-7) samples, increased expression of SEQ. ID. NO. 19 mRNA was evident in clear cell carcinoma (Lanes 8-9), late stage endometrioid (Lane 12) and malignant serous (Lanes 15-17). These results confirm the upregulation of the gene expression for SEQ. ID. NO. 19 in malignant ovarian cancer. However, the expression of KCNMB2 was markedly different from that of SEQ. ID. NO. 19 showing essentially no difference in its expression amongst the different ovarian samples (FIG. 19B, panel B);
[0294] FIG. 20 is a picture of the macroarray hybridization results showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 20. The STAR dsDNA clone representing SEQ. ID. NO. 20 was labeled with .sup.32P and hybridized to the macroarray. The hybridization results obtained confirm its upregulation in several malignant ovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F 1). Significant expression of this sequence was also evident in the four (jejunum (C7), trachea (D7), colon (D8) and thymus (H8)) of the 30 normal tissues;
[0295] FIG. 21 is a picture of the macroarray hybridization results showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 21. The STAR dsDNA clone representing SEQ. ID. NO. 21 was labeled with .sup.32P and hybridized to the macroarray. The hybridization results obtained confirm its upregulation in a majority of malignant ovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F 1). Significant expression of this sequence was also evident in the three (adrenal (A7), breast (B7) and aorta (G7)) of the 30 normal tissues;
[0296] FIG. 22 is a picture of the macroarray hybridization results showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 22. The STAR dsDNA clone representing SEQ. ID. NO. 22 was labeled with .sup.32P and hybridized to the macroarray. The hybridization results obtained confirm its upregulation in a majority of malignant ovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F 1). Significant expression of this sequence was also evident in the breast cancer cell line, MCF7 (B-C 5). Weaker expression similar to that of the LMPs was seen in a majority of the normal tissues;
[0297] FIG. 23 is a picture of the macroarray hybridization results showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 23. The STAR dsDNA clone representing SEQ. ID. NO. 23 was labeled with .sup.32P and hybridized to the macroarray. The hybridization results obtained confirm its upregulation in several malignant ovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F 1). Significant expression of this sequence was also evident in the breast cancer cell lines, MDA (A5) and MCF7 (B-C 5) and prostate cancer cell line, LNCap (G-H 6);
[0298] FIG. 24 is a picture of the macroarray hybridization results showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 24. The STAR dsDNA clone representing SEQ. ID. NO. 24 was labeled with .sup.32P and hybridized to the macroarray. The hybridization results obtained confirm its upregulation in several of the malignant ovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F 1). Significant expression of this sequence was also evident in the breast cancer cell line, MCF7 (B-C 5);
[0299] FIG. 25 is a picture of the macroarray hybridization results showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 25. The STAR dsDNA clone representing SEQ. ID. NO. 25 was labeled with .sup.32P and hybridized to the macroarray. The hybridization results obtained confirm its upregulation in a majority of malignant ovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F 1). Significant expression of this sequence was also evident in the prostate cancer cell line, LNCap (G-H 6);
[0300] FIG. 26 is a picture of the macroarray hybridization results showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 26. The STAR dsDNA clone representing SEQ. ID. NO. 26 was labeled with .sup.32P and hybridized to the macroarray. The hybridization results obtained confirm its upregulation in a majority of malignant ovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F 1). Significant expression of this sequence was also evident in the breast cancer cell lines, MDA (A5) and MCF7 (B-C 5), prostate cancer cell line, LNCap (G-H 6) and one normal tissue, testicle (F10). Weaker expression similar to that of the LMPs was seen in some normal tissues as well;
[0301] FIG. 27 is a picture of the macroarray hybridization results showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 27. The STAR dsDNA clone representing SEQ. ID. NO. 27 was labeled with .sup.32P and hybridized to the macroarray. The hybridization results obtained confirm its upregulation in a majority of malignant ovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F 1). Significant expression of this sequence was also evident in the breast cancer cell lines, MDA (A5) and MCF7 (B-C 5), prostate cancer cell line, LNCap (G-H 6). Weaker expression similar to that of the LMPs was seen in seven (adrenal (A7), placenta (F7), lung (A8), esophagus (C8), colon (D8), ovary (E8) and testicle (F10)) of the 30 normal tissues as well;
[0302] FIG. 28 is a picture of the macroarray hybridization results showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 28. The STAR dsDNA clone representing SEQ. ID. NO. 28 was labeled with .sup.32P and hybridized to the macroarray. The hybridization results obtained confirm its upregulation in a majority of malignant ovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F 1). Significant expression of this sequence was also evident in the breast cancer cell lines, MDA (A5) and MCF7 (B-C 5). Weaker expression similar to that of LMPs was seen for all other tissues;
[0303] FIG. 29 is a picture of the macroarray hybridization results showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 29. The STAR dsDNA clone representing SEQ. ID. NO. 29 was labeled with .sup.32P and hybridized to the macroarray. The hybridization results obtained confirm its upregulation in a majority of malignant ovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F 1). Significant expression of this sequence was also evident in the breast cancer cell line, MCF7 (B-C 5) and three (breast (B7), esophagus (C8) and fallopian tube (F9)) of the 30 normal tissues;
[0304] FIG. 30 is a picture of the macroarray hybridization results showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 30. The STAR dsDNA clone representing SEQ. ID. NO. 30 was labeled with .sup.32P and hybridized to the macroarray. The hybridization results obtained confirm its upregulation in a majority of malignant ovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F 1). Significant expression of this sequence was also evident in the breast cancer cell line, MCF7 (B-C 5), prostate cancer samples (D-H 6). Weaker expression similar to that of LMPs was seen in only very few normal tissues;
[0305] FIG. 31 is a picture of the macroarray hybridization results showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 31. The STAR dsDNA clone representing SEQ. ID. NO. 31 was labeled with .sup.32P and hybridized to the macroarray. The hybridization results obtained confirm its upregulation in a majority of malignant ovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F 1). Significant expression of this sequence was also evident in the breast cancer cell line, MCF7 (B-C 5), prostate cancer samples (D-H 6). Weaker expression similar to that of LMPs was seen in only very few normal tissues;
[0306] FIG. 32 is a picture of RT-PCR data showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 32. For this gene, the macroarray data was not available. A primer pair, OGS 1077 (GCGTCCGGGCCTGTCTTCAACCT; SEQ. ID. NO. 153) and OGS 1078 (GCCCCACCCTCTACCCCACCACTA; SEQ. ID. NO. 154) for SEQ. ID. NO. 32 was used to perform RT-PCR on normal ovarian tissue, and benign and different stages/grades of ovarian cancer. As indicated by the expected PCR amplicon product, compared to normal (Lane 1) and benign (Lanes 2-3), increased expression of SEQ. ID. NO. 32 mRNA was evident in LMPs (Lanes 4-7), clear cell carcinoma (Lanes 8-9), late stage endometrioid (Lane 12) and malignant serous (Lanes 15-17). These results confirm the upregulation of the gene expression for SEQ. ID. NO. 32 in malignant ovarian cancer;
[0307] FIG. 33 is a picture of the macroarray hybridization results showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 33. The STAR dsDNA clone representing SEQ. ID. NO. 33 was labeled with .sup.32P and hybridized to the macroarray. The hybridization results obtained confirm its upregulation in a majority of malignant ovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F 1). Significant expression of this sequence was also evident in the prostate cancer samples (B-F 6). Weaker expression was seen in many normal tissues and strong expression was seen trachea (D7), colon (D8), small intestine (D9), thymus (H8) and spleen (G9). These results confirm the upregulation of the gene expression for SEQ. ID. NO. 33 in malignant ovarian cancer;
[0308] FIG. 34 is a picture of the macroarray hybridization results showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 34. The STAR dsDNA clone representing SEQ. ID. NO. 34 was labeled with .sup.32P and hybridized to the macroarray. The hybridization results obtained confirm its upregulation in a majority of malignant ovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F 1). Significant expression of this sequence was also evident in the prostate cancer samples (B-F 6). Weaker expression was seen in many normal tissues and strong expression was seen trachea (D7), colon (D8), small intestine (D9), thymus (H8) and spleen (G9). These results confirm the upregulation of the gene expression for SEQ. ID. NO. 34 in malignant ovarian cancer;
[0309] FIG. 35 is a picture of RT-PCR data showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 35. For this gene, the macroarray data was not available. A primer pair, OGS 1141 (GAGATCCTGATCAAGGTGCAGG; SEQ. ID. NO. 155) and OGS 1142 (TGCACGCTCACAGCAGTCAGG; SEQ. ID. NO. 156) for SEQ. ID. NO. 35 was used to perform RT-PCR on LMP samples, different stages/grades of ovarian cancer and normal human tissue samples. As indicated by the expected PCR amplicon product (indicated as AB-0201), increased expression of SEQ. ID. NO. 35 mRNA was evident in some ovarian cancer lanes (lanes 10, 11, 14, 18, 28 and 29) and the mRNA was not expressed in LMP samples. Expression was observed in only one normal tissue sample, ileum (lane 27). Equal amounts of template cDNA used in each PCR reaction was confirmed by reamplifying GAPDH with a specific primer pair, OGS 315 (TGAAGGTCGGAGTCAACGGATTTGGT; SEQ. ID. NO. 167) and OGS 316 (CATGTGGGCCATGAGGTCCACCAC; SEQ. ID. NO. 168) for this housekeeping gene. These results confirm the upregulation of the gene expression for SEQ. ID. NO. 35 in malignant ovarian cancer;
[0310] FIG. 36 is a picture of the macroarray hybridization results showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 36. The STAR dsDNA clone representing SEQ. ID. NO. 36 was labeled with .sup.32P and hybridized to the macroarray. The hybridization results obtained confirm its upregulation in a few of the malignant ovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F 1). No expression was seen in other cancer types nor in normal human tissues. These results confirm the upregulation of the gene expression for SEQ. ID. NO. 36 in malignant ovarian cancer;
[0311] FIG. 37 is a picture of the macroarray hybridization results showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 37. The STAR dsDNA clone representing SEQ. ID. NO. 37 was labeled with .sup.32P and hybridized to the macroarray. The hybridization results obtained confirm its upregulation in a majority of malignant ovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F 1). Weak expression of this sequence was also evident in the prostate cancer samples (B-F 6). Weaker expression was seen in some normal tissues. These results confirm the upregulation of the gene expression for SEQ. ID. NO. 37 in malignant ovarian cancer;
[0312] FIG. 38 is a picture of RT-PCR data showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 38. For this gene, the macroarray data was not available. A primer pair, OGS 1202 (AACATGACTAAGATGCCCAACC; SEQ. ID. NO. 157) and OGS 1203 (AATCTCCTTCACCTCCACTACTG; SEQ. ID. NO. 158) for SEQ. ID. NO. 38 was used to perform RT-PCR on LMP samples, different stages/grades of ovarian cancer and normal human tissue samples. As indicated by the expected PCR amplicon product (indicated as AB-0332), increased expression of SEQ. ID. NO. 38 mRNA was evident in approximately half of the ovarian cancer lanes and weaker expression was seen in LMP samples. Expression was observed in many normal tissue samples. Equal amounts of template cDNA used in each PCR reaction was confirmed by reamplifying GAPDH with a specific primer pair, OGS 315 (TGAAGGTCGGAGTCAACGGATTTGGT; SEQ. ID. NO. 167) and OGS 316 (CATGTGGGCCATGAGGTCCACCAC; SEQ. ID. NO. 168) for this housekeeping gene. These results confirm the upregulation of the gene expression for SEQ. ID. NO. 38 in malignant ovarian cancer;
[0313] FIG. 39 is a picture of the macroarray hybridization results showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 39. The STAR dsDNA clone representing SEQ. ID. NO. 39 was labeled with .sup.32P and hybridized to the macroarray. The hybridization results obtained confirm its upregulation in a majority of malignant ovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F 1). Strong expression was also observed in breast cancer samples (A-C 5) and weak expression in prostate cancer samples (A-H 6). Weaker expression was seen in a few normal tissues with strong expression in testes (F 10). These results confirm the upregulation of the gene expression for SEQ. ID. NO. 39 in malignant ovarian cancer;
[0314] FIG. 40 is a picture of the macroarray hybridization results showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 40. The STAR dsDNA clone representing SEQ. ID. NO. 40 was labeled with .sup.32P and hybridized to the macroarray. The hybridization results obtained confirm its upregulation in a majority of malignant ovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F 1). Weak expression was seen in a few normal tissues with strong expression in kidney (F 8). These results confirm the upregulation of the gene expression for SEQ. ID. NO. 40 in malignant ovarian cancer;
[0315] FIG. 41 is a picture of RT-PCR data showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 41. For this gene, the macroarray data was not available. A primer pair, OGS 1212 (AAGCATAGCCATAGGTGATTGG; SEQ. ID. NO. 159) and OGS 1213 (ACAGGTATCAGACAAGGGAGCAG; SEQ. ID. NO. 160) for SEQ. ID. NO. 41 was used to perform RT-PCR on LMP samples, different stages/grades of ovarian cancer and normal human tissue samples. As indicated by the expected PCR amplicon product (indicated as AB-0532), increased expression of SEQ. ID. NO. 41 mRNA was evident in a large majority of the ovarian cancer lanes and weaker expression was seen in LMP samples. Expression was observed in a few normal tissue samples such as kidney, thymus and spleen (lanes 14, 16 and 23, respectively). Equal amounts of template cDNA used in each PCR reaction was confirmed by reamplifying GAPDH with a specific primer pair, OGS 315 (TGAAGGTCGGAGTCAACGGATTTGGT; SEQ. ID. NO. 167) and OGS 316 (CATGTGGGCCATGAGGTCCACCAC; SEQ. ID. NO. 168) for this housekeeping gene. These results confirm the upregulation of the gene expression for SEQ. ID. NO. 41 in malignant ovarian cancer;
[0316] FIG. 42 is a picture of the macroarray hybridization results showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 42. The STAR dsDNA clone representing SEQ. ID. NO. 42 was labeled with .sup.32P and hybridized to the macroarray. The hybridization results obtained showed its expression in both malignant ovarian cancer samples (A-F 2 and A-G 3-4) and LMP samples (A-F 1). Weak expression was also observed in breast cancer samples (A-C 5). Weak expression was seen in a few normal tissues with moderate expression in placenta (F 7). These results confirm the expression for SEQ. ID. NO. 42 in malignant ovarian cancer;
[0317] FIG. 43 is a picture of the macroarray hybridization results showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 43. The STAR dsDNA clone representing SEQ. ID. NO. 43 was labeled with .sup.32P and hybridized to the macroarray. The hybridization results obtained confirm its upregulation in a majority of malignant ovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F 1). Strong expression was also observed in breast cancer samples (A-C 5) and weak expression in prostate cancer samples (A-H 6). Weaker expression was seen in normal tissues with strong expression in testes (F 10). These results confirm the upregulation of the gene expression for SEQ. ID. NO. 43 in malignant ovarian cancer;
[0318] FIG. 44 is a picture of RT-PCR data showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 44. For this gene, the macroarray data was not available. A primer pair, OGS 1171 (TTACGACCTATTTCTCCGTGG; SEQ. ID. NO. 161) and OGS 1172 (AATGCAATAATTGGCCACTGC; SEQ. ID. NO. 162) for SEQ. ID. NO. 44 was used to perform RT-PCR on LMP samples, different stages/grades of ovarian cancer and normal human tissue samples. As indicated by the expected PCR amplicon product (indicated as AB-0795), increased expression of SEQ. ID. NO. 44 mRNA was evident in a large majority of the ovarian cancer lanes and weaker expression was seen in LMP samples. Expression was observed in several normal tissue samples such as aorta, skeletal muscle, small intestine and spleen (lanes 7, 17, 20 and 23, respectively). Equal amounts of template cDNA used in each PCR reaction was confirmed by reamplifying GAPDH with a specific primer pair, OGS 315 (TGAAGGTCGGAGTCAACGGATTTGGT; SEQ. ID. NO. 167) and OGS 316 (CATGTGGGCCATGAGGTCCACCAC; SEQ. ID. NO. 168) for this housekeeping gene. These results confirm the upregulation of the gene expression for SEQ. ID. NO. 44 in malignant ovarian cancer;
[0319] FIG. 45 is a picture of RT-PCR data showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 45. For this gene, the macroarray data was not available. A primer pair, OGS 1175 (ACACATCAAACTGCTTATCCAGG; SEQ. ID. NO. 163) and OGS 1176 (ACTGATGTGAAAATGCACATCC; SEQ. ID. NO. 164) for SEQ. ID. NO. 45 was used to perform RT-PCR on LMP samples, different stages/grades of ovarian cancer and normal human tissue samples. As indicated by the expected PCR amplicon product (indicated as AB-0846), increased expression of SEQ. ID. NO. 45 mRNA was evident in half of the ovarian cancer lanes and weaker expression was seen in LMP samples. Expression was observed in only a few normal tissue samples such as kidney, fallopian tube and testes (lanes 14, 22 and 30, respectively). Equal amounts of template cDNA used in each PCR reaction was confirmed by reamplifying GAPDH with a specific primer pair, OGS 315 (TGAAGGTCGGAGTCAACGGATTTGGT; SEQ. ID. NO. 167) and OGS 316 (CATGTGGGCCATGAGGTCCACCAC; SEQ. ID. NO. 168) for this housekeeping gene. These results confirm the upregulation of the gene expression for SEQ. ID. NO. 45 in malignant ovarian cancer;
[0320] FIG. 46 is a picture of the macroarray hybridization results showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 46. The STAR dsDNA clone representing SEQ. ID. NO. 46 was labeled with .sup.32P and hybridized to the macroarray. The hybridization results obtained confirm its upregulation in a majority of malignant ovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F 1). Weak expression was also observed in prostate cancer samples (A-H 6). Weaker expression was seen in a few normal tissues with moderate expression in breast (B 7) and ovary (E 8). These results confirm the upregulation of the gene expression for SEQ. ID. NO. 46 in malignant ovarian cancer;
[0321] FIG. 47 is a picture of the macroarray hybridization results showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 47. The STAR dsDNA clone representing SEQ. ID. NO. 47 was labeled with .sup.32P and hybridized to the macroarray. The hybridization results obtained confirm its upregulation in a majority of malignant ovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F 1). Significant expression of this sequence was also evident in the prostate cancer samples (B-F 6). Weaker expression was seen in many normal tissues and strong expression was seen trachea (D7), colon (D8), small intestine (D9), thymus (H8) and spleen (G9). These results confirm the upregulation of the gene expression for SEQ. ID. NO. 47 in malignant ovarian cancer;
[0322] FIG. 48 is a picture of RT-PCR data showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 48. For this gene, the macroarray data was not available. A primer pair, OGS 1282 (ATGGCTCATACAGCACTCAGG; SEQ. ID. NO. 165) and OGS 1283 (GAACTGTCACTCCGGAAAGCCT; SEQ. ID. NO. 166) for SEQ. ID. NO. 48 was used to perform RT-PCR on LMP samples, different stages/grades of ovarian cancer and normal human tissue samples. As indicated by the expected PCR amplicon product (indicated as AB-1120), increased expression of SEQ. ID. NO. 48 mRNA was evident in a majority of the ovarian cancer lanes and weaker expression was seen in LMP samples. Expression was evident in virtually all normal tissues. Equal amounts of template cDNA used in each PCR reaction was confirmed by reamplifying GAPDH with a specific primer pair, OGS 315 (TGAAGGTCGGAGTCAACGGATTTGGT; SEQ. ID. NO. 167) and OGS 316 (CATGTGGGCCATGAGGTCCACCAC; SEQ. ID. NO. 168) for this housekeeping gene. These results confirm the upregulation of the gene expression for SEQ. ID. NO. 48 in malignant ovarian cancer;
[0323] FIG. 49 is a picture of the macroarray hybridization results showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 49. The STAR dsDNA clone representing SEQ. ID. NO. 49 was labeled with .sup.32P and hybridized to the macroarray. The hybridization results obtained confirm its upregulation in a majority of malignant ovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F 1). Strong expression was also observed in breast cancer samples (A-C 5) and weak expression in prostate cancer samples (A-H 6). Weaker expression was seen in normal tissues. These results confirm the upregulation of the gene expression for SEQ. ID. NO. 49 in malignant ovarian cancer;
[0324] FIG. 50 is a picture of the macroarray hybridization results showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 50. The STAR dsDNA clone representing SEQ. ID. NO. 50 was labeled with .sup.32P and hybridized to the macroarray. The hybridization results obtained confirm its upregulation in a majority of malignant ovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F 1). Significant expression of this sequence was also evident in the seven (adrenal (A7), breast (B7), trachea (D7), placenta (F7), lung (A8), kidney (F8) and fallopian tube (F9)) of the 30 normal tissues;
[0325] FIG. 51 is a picture showing an example of STAR subtraction for the ovarian cancer samples. The housekeeping genes, GAPDH (Panel A) and .beta.-actin (Panel B) were nicely subtracted for both LMP minus Malignant (SL133 to SL137) and Malignant minus LMP (SL123 to SL127) whereas, a known differentially expressed upregulated gene, CCNE1 (Panel C) in malignant ovarian tumors was not subtracted in Malignant minus LMP STAR libraries but instead, enriched (Lanes SL123 to SL127 compared to Lanes 6 to 10);
[0326] FIG. 52 is a picture showing the effect of shRNAs on the expression of endogenous genes encoded by SEQ.ID Nos. 1 and 3 in transfected TOV-21G cells. Two shRNAs per SEQ.ID. were transfected in TOV-21G ovarian cancer cell lines and monitored by RT-PCR using gene-specific primers. In each case, both shRNAs attenuated the expression of the genes;
[0327] FIG. 53 is a picture showing the effect of SEQ.ID.-specific shRNAs on the proliferation of TOV-21G cells. Decreased proliferation is indicative of a gene that, when attenuated, is required for normal growth of the cancer cells. The cells were stably transfected with two separate shRNA expression vectors and the proliferation of the cells was measured in an MTT assay. The positive control plasmid expresses a shRNA that has homology to no known gene in humans;
[0328] FIG. 54 is a picture showing SEQ.ID.-specific shRNAs on the survival of TOV-21G cells. Less staining is indicative of a gene that, when attenuated, is required for survival of the cancer cells in this assay. The cells were transiently transfected with two separate shRNA expression vectors and the remaining colonies were stained with crystal violet and photographed. The positive control plasmid expresses a shRNA that has homology to no known gene in humans;
[0329] FIGS. 55A and 55B are pictures of RT-PCR data showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 01, 09, 12, 15, 17, 19, 20 and 24. To further demonstrate that the STAR SEQ. ID. NOs. selected after macroarray analysis were upregulated in malignant ovarian cancer samples compared to LMPs and normal ovarian samples, semi-quantitative RT-PCR was performed for 25 cycles using HotStarTaq polymerase according to the supplier instructions (Qiagen). Furthermore, these results serve to demonstrate the utility of these sequences as potential diagnostic, prognostic or theranostic markers for ovarian cancer. For SEQ. ID. NOs. 01, 09, 12, 15, 17, 19, 20 and 24, a specific primer pair for each was used. The differential expression results obtained for each SEQ. ID. NO. tested are shown in FIGS. 55A and 55B. As indicated by the expected PCR amplicon product for each SEQ. ID. NO., there is a clear tendency towards increased expression of the mRNAs corresponding to SEQ. ID. NOs. 01, 09, 12, 15, 17, 19, 20 and 24 in clear cell carcinoma (Lanes 8-9), late stage endometrioid (Lane 12) and different stages of malignant serous (Lanes 15-17) compared to normal (Lane 1), benign (Lanes 2-3) and LMPs (Lanes 4-7) ovarian samples. These results confirm the upregulation of the gene expression for SEQ. ID. NOs. 01, 09, 12, 15, 17, 19, 20 and 24 in the different stages of malignant ovarian cancer as was observed using the macroarrays;
[0330] FIG. 56 is a picture of the macroarray hybridization results showing the differential expression data for STAR selected ovarian cancer-related human SEQ. ID. NO. 169. The STAR dsDNA clone representing SEQ. ID. NO. 169 was labeled with .sup.32P and hybridized to the macroarray. The hybridization results obtained confirm its upregulation in malignant ovarian cancer samples (A-F 2 and A-G 3-4) compared to LMP samples (A-F 1). Weaker expression was seen in some normal tissues and strong expression was seen liver (E7) and aorta (G7). These results confirm the upregulation of the gene expression for SEQ. ID. NO. 169 in malignant ovarian cancer;
[0331] FIG. 57 is a picture of RT-PCR data showing the differential expression data for the STAR selected ovarian cancer-related human SEQ. ID. NO. 1 in RNA samples derived from the NCI-60 panel of cancer cell lines. A primer pair, OGS 1136 (GCTTAAAAGAGTCCTCCTGTGGC; SEQ. ID. NO. 171) and OGS 1044 (TGGACATTGTTCTTAAAGTGTGG; SEQ. ID. NO. 172) for SEQ. ID. NO. 1 was used to perform RT-PCR. As indicated by the expected PCR amplicon, increased expression of SEQ. ID. NO. 1 mRNA was evident in ovarian, renal, lung, colon, breast cancers and weaker expression was seen in melanoma samples;
[0332] FIG. 58 is a picture of RT-PCR data showing the differential expression data for the STAR selected ovarian cancer-related human SEQ. ID. NO. 2 in RNA samples derived from the NCI-60 panel of cancer cell lines. A primer pair, OGS 1250 (AGGTTTTATGGCCACCGTCAG; SEQ. ID. NO. 173) and OGS 1251 (ATCCTATACCGCTCGGTTATGC; SEQ. ID. NO. 174) for SEQ. ID. NO. 2 was used to perform RT-PCR. As indicated by the expected PCR amplicon, increased expression of SEQ. ID. NO. 2 mRNA was evident in all nine cancer types but weaker expression was seen in melanoma and leukemia samples;
[0333] FIG. 59 is a picture of RT-PCR data showing the differential expression data for the STAR selected ovarian cancer-related human SEQ. ID. NO. 3 in RNA samples derived from the NCI-60 panel of cancer cell lines. A primer pair, OGS 1049 (GGGCGGCGGCTCTTTCCTCCTC; SEQ. ID. NO. 175) and OGS 1050 (GCTAGCGGCCCCATACTCG; SEQ. ID. NO. 176) for SEQ. ID. NO. 3 was used to perform RT-PCR. As indicated by the expected PCR amplicon, increased expression of SEQ. ID. NO. 3 mRNA was evident in eight cancer types and absent in the leukemia samples;
[0334] FIG. 60 is a picture of RT-PCR data showing the differential expression data for the STAR selected ovarian cancer-related human SEQ. ID. NO. 4 in RNA samples derived from the NCI-60 panel of cancer cell lines. A primer pair, OGS 1051 (ACACTGGATGCCCTGAATGACACA; SEQ. ID. NO. 177) and OGS 1052 (GCTTTGGCCCTTTTTGCTAA; SEQ. ID. NO. 178) for SEQ. ID. NO. 4 was used to perform RT-PCR. As indicated by the expected PCR amplicon, increased expression of SEQ. ID. NO. 4 mRNA was evident in melanoma, ovarian, CNS, and lung cancers and weakly expressed in the leukemia samples;
[0335] FIG. 61 is a picture of RT-PCR data showing the differential expression data for the STAR selected ovarian cancer-related human SEQ. ID. NO. 5 in RNA samples derived from the NCI-60 panel of cancer cell lines. A primer pair, OGS 1252 (CCCACTTCTGTCTTACTGCATC; SEQ. ID. NO. 179) and OGS 1253 (CATAGTACTCCAGGGCTTATTC; SEQ. ID. NO. 180) for SEQ. ID. NO. 4 was used to perform RT-PCR. As indicated by the expected PCR amplicon, increased expression of SEQ. ID. NO. 5 mRNA was evident all cancer types;
[0336] FIG. 62 is a picture of RT-PCR data showing the differential expression data for the STAR selected ovarian cancer-related human SEQ. ID. NO. 6 in RNA samples derived from the NCI-60 panel of cancer cell lines. A primer pair, OGS 1083 (AACGATTGCCCGGATTGATGACA; SEQ. ID. NO. 181) and OGS 1084 (TACTTGAGGCTGGGGTGGGAGATG; SEQ. ID. NO. 182) for SEQ. ID. NO. 6 was used to perform RT-PCR. As indicated by the expected PCR amplicon, increased expression of SEQ. ID. NO. 6 mRNA was evident all cancer types;
[0337] FIG. 63 is a picture of RT-PCR data showing the differential expression data for the STAR selected ovarian cancer-related human SEQ. ID. NO. 7 in RNA samples derived from the NCI-60 panel of cancer cell lines. A primer pair, OGS 1053 (CACTACGCCAGGCACCCCCAAAAC; SEQ. ID. NO. 183) and OGS 1054 (CGAGGCGCACGGCAGTCT; SEQ. ID. NO. 184) for SEQ. ID. NO. 7 was used to perform RT-PCR. As indicated by the expected PCR amplicon, increased expression of SEQ. ID. NO. 7 mRNA was evident only in ovarian cancer samples;
[0338] FIG. 64 is a picture of RT-PCR data showing the differential expression data for the STAR selected ovarian cancer-related human SEQ. ID. NO. 8 in RNA samples derived from the NCI-60 panel of cancer cell lines. A primer pair, OGS 1037 (ATCCGTTGCTGCAGCTCGTTCCTC; SEQ. ID. NO. 185) and OGS 1038 (ACCCTGCTGACCTTCTTCCATTCC; SEQ. ID. NO. 186) for SEQ. ID. NO. 8 was used to perform RT-PCR. As indicated by the expected PCR amplicon, increased expression of SEQ. ID. NO. 8 mRNA was evident in all cancer types;
[0339] FIG. 65 is a picture of RT-PCR data showing the differential expression data for the STAR selected ovarian cancer-related human SEQ. ID. NO. 9 in RNA samples derived from the NCI-60 panel of cancer cell lines. A primer pair, OGS 1045 (TCGGAGGAGGGCTGGCTGGTGTTT; SEQ. ID. NO. 187) and OGS 1046 (CTTGGGCGTCTTGGAGCGGTTCTG; SEQ. ID. NO. 188) for SEQ. ID. NO. 9 was used to perform RT-PCR. As indicated by the expected PCR amplicon, (lower band on the gel; the top band is an artifact of the PCR reaction) increased expression of SEQ. ID. NO. 9 mRNA was evident in ovarian, lung, colon, breast cancer, and melanoma and weakly expressed in leukemia and CNS cancer;
[0340] FIG. 66 is a picture of RT-PCR data showing the differential expression data for the STAR selected ovarian cancer-related human SEQ. ID. NO. 10 in RNA samples derived from the NCI-60 panel of cancer cell lines. A primer pair, OGS 1240 (AGAGCCTATTGAAGATGAACAG; SEQ. ID. NO. 189) and OGS 1241 (TGATTGCCCCGGATCCTCTTAGG; SEQ. ID. NO. 190) for SEQ. ID. NO. 10 was used to perform RT-PCR. As indicated by the expected PCR amplicon, increased expression of SEQ. ID. NO. 10 mRNA was evident in all cancer types;
[0341] FIG. 67 is a picture of RT-PCR data showing the differential expression data for the STAR selected ovarian cancer-related human SEQ. ID. NO. 11 in RNA samples derived from the NCI-60 panel of cancer cell lines. A primer pair, OGS 1304 (GGACAAATACGACGACGAGG; SEQ. ID. NO. 191) and OGS 1305 (GGTTTCTTGGGTAGTGGGC; SEQ. ID. NO. 192) for SEQ. ID. NO. 11 was used to perform RT-PCR. As indicated by the expected PCR amplicon, increased expression of SEQ. ID. NO. 11 mRNA was evident in all cancer types;
[0342] FIG. 68 is a picture of RT-PCR data showing the differential expression data for the STAR selected ovarian cancer-related human SEQ. ID. NO. 12 in RNA samples derived from the NCI-60 panel of cancer cell lines. A primer pair, OGS 1039 (CCCCGGAGAAGGAAGAGCAGTA; SEQ. ID. NO. 193) and OGS 1040 (CGAAAGCCGGCAGTTAGTTATTGA; SEQ. ID. NO. 194) for SEQ. ID. NO. 12 was used to perform RT-PCR. As indicated by the expected PCR amplicon, increased expression of SEQ. ID. NO. 12 mRNA was evident in all cancer types but weakly in CNS cancer and leukemia;
[0343] FIG. 69 is a picture of RT-PCR data showing the differential expression data for the STAR selected ovarian cancer-related human SEQ. ID. NO. 13 in RNA samples derived from the NCI-60 panel of cancer cell lines. A primer pair, OGS 1095 (GGCGGGCAACGAATTCCAGGTGTC; SEQ. ID. NO. 195) and OGS 1096 (TCAGAGGTTCGTCGCATTTGTCCA; SEQ. ID. NO. 196) for SEQ. ID. NO. 13 was used to perform RT-PCR. As indicated by the expected PCR amplicon, increased expression of SEQ. ID. NO. 13 mRNA was evident in all cancer types;
[0344] FIG. 70 is a picture of RT-PCR data showing the differential expression data for the STAR selected ovarian cancer-related human SEQ. ID. NO. 15 in RNA samples derived from the NCI-60 panel of cancer cell lines. A primer pair, OGS 1284 (CAACAGTCATGATGTGTGGATG; SEQ. ID. NO. 197) and OGS 1285 (ACTGCACCTTGTCCGTGTTGAC; SEQ. ID. NO. 198) for SEQ. ID. NO. 15 was used to perform RT-PCR. As indicated by the expected PCR amplicon, increased expression of SEQ. ID. NO. 15 mRNA was evident in ovarian, prostate, lung, colon, and breast cancer;
[0345] FIG. 71 is a picture of RT-PCR data showing the differential expression data for the STAR selected ovarian cancer-related human SEQ. ID. NO. 16 in RNA samples derived from the NCI-60 panel of cancer cell lines. A primer pair, OGS 1063 (CCGGCTGGCTGCTTTGTTTA; SEQ. ID. NO. 199) and OGS 1064 (ATGATCAGCAGGTTCGTTGGTAGG; SEQ. ID. NO. 200) for SEQ. ID. NO. 16 was used to perform RT-PCR. As indicated by the expected PCR amplicon, increased expression of SEQ. ID. NO. 16 mRNA was evident in ovarian, lung, colon, and breast cancer;
[0346] FIG. 72 is a picture of RT-PCR data showing the differential expression data for the STAR selected ovarian cancer-related human SEQ. ID. NO. 17 in RNA samples derived from the NCI-60 panel of cancer cell lines. A primer pair, OGS 1031 (ATGCCGGAAGTGAATGTGG; SEQ. ID. NO. 201) and OGS 1032 (GGTGACTCCGCCTTTTGAT; SEQ. ID. NO. 202) for SEQ. ID. NO. 17 was used to perform RT-PCR. As indicated by the expected PCR amplicon, increased expression of SEQ. ID. NO. 17 mRNA was evident in ovarian, renal, lung, colon, and breast cancer but weakly in CNS cancer;
[0347] FIG. 73 is a picture of RT-PCR data showing the differential expression data for the STAR selected ovarian cancer-related human SEQ. ID. NO. 18 in RNA samples derived from the NCI-60 panel of cancer cell lines. A primer pair, OGS 1308 (ACATTCGCTTCTCCATCTGG; SEQ. ID. NO. 203) and OGS 1309 (TGTCACGGAAGGGAACCAGG; SEQ. ID. NO. 204) for SEQ. ID. NO. 18 was used to perform RT-PCR. As indicated by the expected PCR amplicon, increased expression of SEQ. ID. NO. 18 mRNA was evident in all cancer types;
[0348] FIG. 74 is a picture of RT-PCR data showing the differential expression data for the STAR selected ovarian cancer-related human SEQ. ID. NO. 19 in RNA samples derived from the NCI-60 panel of cancer cell lines. A primer pair, OGS 1069 (ACGCTGCCTCTGGGTCACTT; SEQ. ID. NO. 205) and OGS 1070 (TTGGCAAATCAATGGCTTGTAAT; SEQ. ID. NO. 206) for SEQ. ID. NO. 19 was used to perform RT-PCR. As indicated by the expected PCR amplicon, increased expression of SEQ. ID. NO. 19 mRNA was evident in all cancer types;
[0349] FIG. 75 is a picture of RT-PCR data showing the differential expression data for the STAR selected ovarian cancer-related human SEQ. ID. NO. 20 in RNA samples derived from the NCI-60 panel of cancer cell lines. A primer pair, OGS 1061 (ATGGCTTGGGTCATCAGGAC; SEQ. ID. NO. 207) and OGS 1062 (GTGTCACTGGGCGTAAGATACTG; SEQ. ID. NO. 208) for SEQ. ID. NO. 20 was used to perform RT-PCR. As indicated by the expected PCR amplicon, increased expression of SEQ. ID. NO. 20 mRNA was evident in all cancer types but weakly in breast and colon cancer;
[0350] FIG. 76 is a picture of RT-PCR data showing the differential expression data for the STAR selected ovarian cancer-related human SEQ. ID. NO. 21 in RNA samples derived from the NCI-60 panel of cancer cell lines. A primer pair, OGS 1097 (CACCAAATCAGCTGCTACTACTCC; SEQ. ID. NO. 209) and OGS 1098 (GATAAACCCCAAAGCAGAAAGATT; SEQ. ID. NO. 210) for SEQ. ID. NO. 21 was used to perform RT-PCR. As indicated by the expected PCR amplicon, increased expression of SEQ. ID. NO. 21 mRNA was evident in all cancer types but weakly in leukemia;
[0351] FIG. 77 is a picture of RT-PCR data showing the differential expression data for the STAR selected ovarian cancer-related human SEQ. ID. NO. 22 in RNA samples derived from the NCI-60 panel of cancer cell lines. A primer pair, OGS 1075 (CGAGATTCCGTGGGCGTAGG; SEQ. ID. NO. 211) and OGS 1076 (TGAGTGGGAGCTTCGTAGG; SEQ. ID. NO. 212) for SEQ. ID. NO. 22 was used to perform RT-PCR. As indicated by the expected PCR amplicon, increased expression of SEQ. ID. NO. 22 mRNA was evident in ovarian, lung, breast, and CNS cancer. Another larger transcript was weakly expressed in colon and renal cancer ion addition to melanoma;
[0352] FIG. 78 is a picture of RT-PCR data showing the differential expression data for the STAR selected ovarian cancer-related human SEQ. ID. NO. 23 in RNA samples derived from the NCI-60 panel of cancer cell lines. A primer pair, OGS 1232 (TCAGAGTGGACGTTGGATTAC; SEQ. ID. NO. 213) and OGS 1233 (TGCTTGAAATGTAGGAGAACA; SEQ. ID. NO. 214) for SEQ. ID. NO. 23 was used to perform RT-PCR. As indicated by the expected PCR amplicon, increased expression of SEQ. ID. NO. 23 mRNA was evident in all cancer types;
[0353] FIG. 79 is a picture of RT-PCR data showing the differential expression data for the STAR selected ovarian cancer-related human SEQ. ID. NO. 24 in RNA samples derived from the NCI-60 panel of cancer cell lines. A primer pair, OGS 1067 (GAGGGGCATCAATCACACCGAGAA; SEQ. ID. NO. 215) and OGS 1068 (CCCCACCGCCCACCCATTTAGG; SEQ. ID. NO. 216) for SEQ. ID. NO. 24 was used to perform RT-PCR. As indicated by the expected PCR amplicon, increased expression of SEQ. ID. NO. 24 mRNA was evident in ovarian, renal, lung, colon, breast cancer, and melanoma but weakly in CNS cancer and leukemia;
[0354] FIG. 80 is a picture of RT-PCR data showing the differential expression data for the STAR selected ovarian cancer-related human SEQ. ID. NO. 25 in RNA samples derived from the NCI-60 panel of cancer cell lines. A primer pair, OGS 1099 (GGGGGCACCAGAGGCAGTAA; SEQ. ID. NO. 217) and OGS 1100 (GGTTGTGGCGGGGGCAGTTGTG; SEQ. ID. NO. 218) for SEQ. ID. NO. 25 was used to perform RT-PCR. As indicated by the expected PCR amplicon, increased expression of SEQ. ID. NO. 25 mRNA was evident in all cancer types but weakly in leukemia;
[0355] FIG. 81 is a picture of RT-PCR data showing the differential expression data for the STAR selected ovarian cancer-related human SEQ. ID. NO. 26 in RNA samples derived from the NCI-60 panel of cancer cell lines. A primer pair, OGS 1246 (ACAGACTCCTGTACTGCAAACC; SEQ. ID. NO. 219) and OGS 1247 (TACCGGTTCGTCCTCTTCCTC; SEQ. ID. NO. 220) for SEQ. ID. NO. 26 was used to perform RT-PCR. As indicated by the expected PCR amplicon, increased expression of SEQ. ID. NO. 26 mRNA was evident in all cancer types;
[0356] FIG. 82 is a picture of RT-PCR data showing the differential expression data for the STAR selected ovarian cancer-related human SEQ. ID. NO. 27 in RNA samples derived from the NCI-60 panel of cancer cell lines. A primer pair, OGS 1093 (GAAGTTCCTCACGCCCTGCTATC; SEQ. ID. NO. 221) and OGS 1094 (CTGGCTGGTGACCTGCTTTGAGTA; SEQ. ID. NO. 222) for SEQ. ID. NO. 27 was used to perform RT-PCR. As indicated by the expected PCR amplicon, increased expression of SEQ. ID. NO. 27 mRNA was evident in all cancer types;
[0357] FIG. 83 is a picture of RT-PCR data showing the differential expression data for the STAR selected ovarian cancer-related human SEQ. ID. NO. 28 in RNA samples derived from the NCI-60 panel of cancer cell lines. A primer pair, OGS 1332 (TAGGCGCGCCTGACATACAGCAATGCCAGTT; SEQ. ID. NO. 223) and OGS 1333 (TAAGAATGCGGCCGCGCCACATCTTGAACACTTTGC; SEQ. ID. NO. 224) for SEQ. ID. NO. 28 was used to perform RT-PCR. As indicated by the expected PCR amplicon, increased expression of SEQ. ID. NO. 28 mRNA was evident in ovarian, prostate, and renal cancer but weakly in all other types;
[0358] FIG. 84 is a picture of RT-PCR data showing the differential expression data for the STAR selected ovarian cancer-related human SEQ. ID. NO. 29 in RNA samples derived from the NCI-60 panel of cancer cell lines. A primer pair, OGS 1101 (TGGGGAGGAGTTTGAGGAGCAGAC; SEQ. ID. NO. 225) and OGS 1102 (GTGGGACGGAGGGGGCAGTGAAG; SEQ. ID. NO. 226) for SEQ. ID. NO. 29 was used to perform RT-PCR. As indicated by the expected PCR amplicon, increased expression of SEQ. ID. NO. 29 mRNA was evident in ovarian, renal, lung, colon, and breast cancer but weakly in CNS cancer and melanoma;
[0359] FIG. 85 is a picture of RT-PCR data showing the differential expression data for the STAR selected ovarian cancer-related human SEQ. ID. NO. 30 in RNA samples derived from the NCI-60 panel of cancer cell lines. A primer pair, OGS 1300 (GCAACTATTCGGAGCGCGTG; SEQ. ID. NO. 227) and OGS 1301 (CCAGCAGCTTGTTGAGCTCC; SEQ. ID. NO. 228) for SEQ. ID. NO. 30 was used to perform RT-PCR. As indicated by the expected PCR amplicon, increased expression of SEQ. ID. NO. 30 mRNA was evident in all cancer types;
[0360] FIG. 86 is a picture of RT-PCR data showing the differential expression data for the STAR selected ovarian cancer-related human SEQ. ID. NO. 31 in RNA samples derived from the NCI-60 panel of cancer cell lines. A primer pair, OGS 1302 (GGAGGAGCTAAGCGTCATCGC; SEQ. ID. NO. 229) and OGS 1303 (TCGCTTCAGCGCGTAGACC; SEQ. ID. NO. 230) for SEQ. ID. NO. 31 was used to perform RT-PCR. As indicated by the expected PCR amplicon, increased expression of SEQ. ID. NO. 31 mRNA was evident in all cancer types;
[0361] FIG. 87 is a picture of RT-PCR data showing the differential expression data for the STAR selected ovarian cancer-related human SEQ. ID. NO. 32 in RNA samples derived from the NCI-60 panel of cancer cell lines. A primer pair, OGS 1077 (GCGTCCGGGCCTGTCTTCAACCT; SEQ. ID. NO. 153) and OGS 1078 (GCCCCACCCTCTACCCCACCACTA; SEQ. ID. NO. 154) for SEQ. ID. NO. 32 was used to perform RT-PCR. As indicated by the expected PCR amplicon, increased expression of SEQ. ID. NO. 32 mRNA was evident in ovarian cancer and melanoma but weaker expression was detectable in CNS, breast, colon, lung, and renal cancer;
[0362] FIG. 88 is a picture of RT-PCR data showing the differential expression data for the STAR selected ovarian cancer-related human SEQ. ID. NO. 33 in RNA samples derived from the NCI-60 panel of cancer cell lines. A primer pair, OGS 1292 (TATTAGTTGGGATGGTGGTAGCAC; SEQ. ID. NO. 231) and OGS 1294 (GAGAATTCGAGTCGACGATGAC; SEQ. ID. NO. 232) for SEQ. ID. NO. 33 was used to perform RT-PCR. As indicated by the expected PCR amplicon, increased expression of SEQ. ID. NO. 33 mRNA was evident only in ovarian cancer samples;
[0363] FIG. 89 is a picture of RT-PCR data showing the differential expression data for the STAR selected ovarian cancer-related human SEQ. ID. NO. 34 in RNA samples derived from the NCI-60 panel of cancer cell lines. A primer pair, OGS 1242 (GAAATTGTGTTGACGCAGTCTCC; SEQ. ID. NO. 233) and OGS 1243 (AGGCACACAACAGAGGCAGTTC; SEQ. ID. NO. 234) for SEQ. ID. NO. 34 was used to perform RT-PCR. As indicated by the expected PCR amplicon, increased expression of SEQ. ID. NO. 34 mRNA was evident only in ovarian cancer samples;
[0364] FIG. 90 is a picture of RT-PCR data showing the differential expression data for the STAR selected ovarian cancer-related human SEQ. ID. NO. 35 in RNA samples derived from the NCI-60 panel of cancer cell lines. A primer pair, OGS 1141 (GAGATCCTGATCAAGGTGCAGG; SEQ. ID. NO. 155) and OGS 1142 (TGCACGCTCACAGCAGTCAGG; SEQ. ID. NO. 156) for SEQ. ID. NO. 35 was used to perform RT-PCR. As indicated by the expected PCR amplicon, increased expression of SEQ. ID. NO. 35 mRNA was evident in ovarian, lung and breast cancer, but weakly in colon and CNS cancer;
[0365] FIG. 91 is a picture of RT-PCR data showing the differential expression data for the STAR selected ovarian cancer-related human SEQ. ID. NO. 36 in RNA samples derived from the NCI-60 panel of cancer cell lines. A primer pair, OGS 1280 (GTACATCAACCTCCTGCTGTCC; SEQ. ID. NO. 235) and OGS 1281 (GACATCTCCAAGTCCCAGCATG; SEQ. ID. NO. 236) for SEQ. ID. NO. 36 was used to perform RT-PCR. As indicated by the expected PCR amplicon, increased expression of SEQ. ID. NO. 36 mRNA was evident in all cancer types;
[0366] FIG. 92 is a picture of RT-PCR data showing the differential expression data for the STAR selected ovarian cancer-related human SEQ. ID. NO. 37 in RNA samples derived from the NCI-60 panel of cancer cell lines. A primer pair, OGS 1159 (AGTCTCTCACTGTGCCTTATGCC; SEQ. ID. NO. 237) and OGS 1160 (AGTCCTAAGAACTGTAAACG; SEQ. ID. NO. 238) for SEQ. ID. NO. 37 was used to perform RT-PCR. As indicated by the expected PCR amplicon, increased expression of SEQ. ID. NO. 37 mRNA was evident only in ovarian and renal cancer;
[0367] FIG. 93 is a picture of RT-PCR data showing the differential expression data for the STAR selected ovarian cancer-related human SEQ. ID. NO. 38 in RNA samples derived from the NCI-60 panel of cancer cell lines. A primer pair, OGS 1202 (AACATGACTAAGATGCCCAACC; SEQ. ID. NO. 157) and OGS 1203 (AATCTCCTTCACCTCCACTACTG; SEQ. ID. NO. 158) for SEQ. ID. NO. 38 was used to perform RT-PCR. As indicated by the expected PCR amplicon, increased expression of SEQ. ID. NO. 38 mRNA was evident in all cancer types;
[0368] FIG. 94 is a picture of RT-PCR data showing the differential expression data for the STAR selected ovarian cancer-related human SEQ. ID. NO. 39 in RNA samples derived from the NCI-60 panel of cancer cell lines. A primer pair, OGS 1310 (CATCTATACGTGGATTGAGGA; SEQ. ID. NO. 239) and OGS 1311 (ATAGGTACCAGGTATGAGCTG; SEQ. ID. NO. 240) for SEQ. ID. NO. 39 was used to perform RT-PCR. As indicated by the expected PCR amplicon, increased expression of SEQ. ID. NO. 39 mRNA was evident in all cancer types;
[0369] FIG. 95 is a picture of RT-PCR data showing the differential expression data for the STAR selected ovarian cancer-related human SEQ. ID. NO. 40 in RNA samples derived from the NCI-60 panel of cancer cell lines. A primer pair, OGS 1155 (TGTCCACATCATCATCGTCATCC; SEQ. ID. NO. 241) and OGS 1156 (TGTCACTGGTCGGTCGCTGAGG; SEQ. ID. NO. 242) for SEQ. ID. NO. 39 was used to perform RT-PCR. As indicated by the expected PCR amplicon, increased expression of SEQ. ID. NO. 39 mRNA was evident in all cancer types;
[0370] FIG. 96 is a picture of RT-PCR data showing the differential expression data for the STAR selected ovarian cancer-related human SEQ. ID. NO. 41 in RNA samples derived from the NCI-60 panel of cancer cell lines. A primer pair, OGS 1212 (AAGCATAGCCATAGGTGATTGG; SEQ. ID. NO. 159) and OGS 1213 (ACAGGTATCAGACAAGGGAGCAG; SEQ. ID. NO. 160) for SEQ. ID. NO. 41 was used to perform RT-PCR. As indicated by the expected PCR amplicon, increased expression of SEQ. ID. NO. 41 mRNA was evident only in ovarian and renal cancer and leukemia;
[0371] FIG. 97 is a picture of RT-PCR data showing the differential expression data for the STAR selected ovarian cancer-related human SEQ. ID. NO. 42 in RNA samples derived from the NCI-60 panel of cancer cell lines. A primer pair, OGS 1316 (CATGGGGCTTAAGATGTC; SEQ. ID. NO. 243) and OGS 1317 (GTCGATTTCTCCATCATCTG; SEQ. ID. NO. 244) for SEQ. ID. NO. 42 was used to perform RT-PCR. As indicated by the expected PCR amplicon, increased expression of SEQ. ID. NO. 42 mRNA was evident in all cancer types;
[0372] FIG. 98 is a picture of RT-PCR data showing the differential expression data for the STAR selected ovarian cancer-related human SEQ. ID. NO. 43 in RNA samples derived from the NCI-60 panel of cancer cell lines. A primer pair, OGS 1306 (AAGAGGCGCTCTACTAGCCG; SEQ. ID. NO. 245) and OGS 1307 (CTTTCCACATGGAACACAGG; SEQ. ID. NO. 246) for SEQ. ID. NO. 43 was used to perform RT-PCR. As indicated by the expected PCR amplicon, increased expression of SEQ. ID. NO. 43 mRNA was evident in all cancer types;
[0373] FIG. 99 is a picture of RT-PCR data showing the differential expression data for the STAR selected ovarian cancer-related human SEQ. ID. NO. 44 in RNA samples derived from the NCI-60 panel of cancer cell lines. A primer pair, OGS 1171 (TTACGACCTATTTCTCCGTGG; SEQ. ID. NO. 161) and OGS 1172 (AATGCAATAATTGGCCACTGC; SEQ. ID. NO. 162) for SEQ. ID. NO. 44 was used to perform RT-PCR. As indicated by the expected PCR amplicon, increased expression of SEQ. ID. NO. 44 mRNA was evident in all cancer types;
[0374] FIG. 100 is a picture of RT-PCR data showing the differential expression data for the STAR selected ovarian cancer-related human SEQ. ID. NO. 45 in RNA samples derived from the NCI-60 panel of cancer cell lines. A primer pair, OGS 1175 (ACACATCAAACTGCTTATCCAGG; SEQ. ID. NO. 163) and OGS 1176 (ACTGATGTGAAAATGCACATCC; SEQ. ID. NO. 164) for SEQ. ID. NO. 45 was used to perform RT-PCR. As indicated by the expected PCR amplicon, increased expression of SEQ. ID. NO. 45 mRNA was evident only in ovarian cancer samples;
[0375] FIG. 101 is a picture of RT-PCR data showing the differential expression data for the STAR selected ovarian cancer-related human SEQ. ID. NO. 46 in RNA samples derived from the NCI-60 panel of cancer cell lines. A primer pair, OGS 1286 (CATTTTCCTGGAATTTGATACAG; SEQ. ID. NO. 247) and OGS 1287 (GTAGAGAGTTTATTTGGGCCAAG; SEQ. ID. NO. 248) for SEQ. ID. NO. 46 was used to perform RT-PCR. As indicated by the expected PCR amplicon, increased expression of SEQ. ID. NO. 46 mRNA was evident in all cancer types;
[0376] FIG. 102 is a picture of RT-PCR data showing the differential expression data for the STAR selected ovarian cancer-related human SEQ. ID. NO. 47 in RNA samples derived from the NCI-60 panel of cancer cell lines. A primer pair, OGS 1244 (CATCTATGGTAACTACAATCG; SEQ. ID. NO. 249) and OGS 1245 (GTAGAAGTCACTGATCAGACAC; SEQ. ID. NO. 250) for SEQ. ID. NO. 47 was used to perform RT-PCR. As indicated by the expected PCR amplicon, increased expression of SEQ. ID. NO. 47 mRNA was evident only in ovarian cancer;
[0377] FIG. 103 is a picture of RT-PCR data showing the differential expression data for the STAR selected ovarian cancer-related human SEQ. ID. NO. 48 in RNA samples derived from the NCI-60 panel of cancer cell lines. A primer pair, OGS 1282 (ATGGCTCATACAGCACTCAGG; SEQ. ID. NO. 165) and OGS 1283 (GAACTGTCACTCCGGAAAGCCT; SEQ. ID. NO. 166) for SEQ. ID. NO. 48 was used to perform RT-PCR. As indicated by the expected PCR amplicon, increased expression of SEQ. ID. NO. 48 mRNA was evident in all cancer types;
[0378] FIG. 104 is a picture of RT-PCR data showing the differential expression data for the STAR selected ovarian cancer-related human SEQ. ID. NO. 50 in RNA samples derived from the NCI-60 panel of cancer cell lines. A primer pair, OGS 1035 (CTGCCTGCCAACCTTTCCATTTCT; SEQ. ID. NO. 251) and OGS 1036 (TGAGCAGCCACAGCAGCATTAGG; SEQ. ID. NO. 252) for SEQ. ID. NO. 50 was used to perform RT-PCR. As indicated by the expected PCR amplicon, increased expression of SEQ. ID. NO. 50 mRNA was evident in all cancer types but weak in CNS cancer and leukemia, and;
[0379] FIG. 105 is a picture of RT-PCR data showing the differential expression data for the STAR selected ovarian cancer-related human SEQ. ID. NO. 169 in RNA samples derived from the NCI-60 panel of cancer cell lines. A primer pair, OGS 1248 (CACCTGATCAGGTGGATAAGG; SEQ. ID. NO. 253) and OGS 1249 (TCCCAGGTAGAAGGTGGAATCC; SEQ. ID. NO. 254) for SEQ. ID. NO. 169 was used to perform RT-PCR. As indicated by the expected PCR amplicon, increased expression of SEQ. ID. NO. 169 mRNA was evident in ovarian, renal, and lung cancer but weak in CNS cancer.
DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS
[0380] The applicant employed a carefully planned strategy to identify and isolate genetic sequences involved in ovarian cancer. The process involved the following steps: 1) preparation of highly representative cDNA libraries using mRNA isolated from LMPs and malignant ovarian cancer samples of human origin; 2) isolation of sequences upregulated in the malignant ovarian cancer samples; 3) identification and characterization of upregulated sequences; 4) selection of upregulated sequences for tissue specificity; 5) determination of knock-down effects on ovarian cancer cell line proliferation and migration; and 6) determination of the expression pattern of each upregulated sequence in samples derived from nine different cancer types. The results discussed in this disclosure demonstrate the advantage of targeting ovarian cancer-related genes that are highly specific to this differentiated cell type compared to normal tissues and provide a more efficient screening method when studying the genetic basis of diseases and disorders. Polynucleotide and/or polypeptide sequences that are known but have not had a role assigned to them until the present disclosure have also been isolated and shown to have a critical role in ovarian cancer cell line proliferation and migration. Finally, novel polynucleotide and/or polypeptide sequences have been identified that play a role as well.
[0381] The present invention is illustrated in further details below in a non-limiting fashion.
A--Material and Methods
[0382] Commercially available reagents referred to in the present disclosure were used according to supplier's instructions unless otherwise indicated. Throughout the present disclosure certain starting materials were prepared as follows:
B--Preparation of LMP and Malignant Ovarian Cancer Cells
[0383] LMP and malignant ovarian tumor samples were selected based on histopathology to identify the respective stage and grade (Table B). LMP was chosen instead of normal ovarian tissue to avoid genes that associated with proliferation due to ovulation. Also very few cells would have been recovered and stromal cells would have been a major contaminant. LMP and serous (most common) ovarian tumors represent the extremes of tumorigenicity, differentiation and invasion. Once the sample were selected, total RNA was extracted with Trizol.TM. (InVitrogen, Grand Island, N.Y.) after the tissues were homogenized. The quality of the RNA was assessed using a 2100 Bioanalyzer (Agilent Technologies, Palo Alto, Calif.)
TABLE-US-00002 TABLE B shows the pathologies including grade and stage of the different ovarian cancer samples used on the macroarrays. MF Position Code on No. Pathologies Symbol Stage Grade Macroarray 15 Borderline serous B 1b B A1 16 Borderline serous B 2a B B1 17 Borderline/carcinoma B/CS 3c 1 F1 serous 18 Borderline serous B 3c B C1 19 Borderline serous B 1b B D1 20 Borderline serous B 1a B E1 42 Carcinoma serous of the CSS 3a 3 A4 surface 22 Carcinoma serous CS 1b 3 A2 30 Carcinoma serous CS 2c 3 E2 23 Carcinoma serous CS 3c 3 F2 25 Carcinoma serous CS 3c 3 B2 26 Carcinoma serous CS 3c 3 A3 27 Carcinoma serous CS 3c 3 C2 28 Carcinoma serous CS 3c 3 D2 43 Carcinoma serous CS 3c 3 B4 45 Carcinoma serous CS 3c 3 D4 49 Carcinoma serous CS 3c 2 F4 41 Carcinoma endo- CE 3b 3 G3 metrioide 40 Carcinoma endo- CE 3c 3 F3 metrioide 44 Carcinoma endo- CE 3c 3 C4 metrioide 39 Carcinoma endo- CE 3c 2 E3 metrioide 50 Carcinoma endo- CE 1c 1 G4 metrioide 46 Carcinoma endo- CE 1a 2 E4 metrioide 34 Clear cell carcinoma CCC 3c 2 B3 38 Clear cell carcinoma CCC 3c 3 D3 37 Clear cell carcinoma CCC 1c 2 C3
C--Method of Isolating Differentially Expressed mRNA
[0384] Key to the discovery of differentially expressed sequences unique to malignant ovarian cancer is the use of the applicant's patented STAR technology (Subtractive Transcription-based Amplification of mRNA; U.S. Pat. No. 5,712,127 Malek et al., 1998). Based on this procedure, mRNA isolated from malignant ovarian tumor sample is used to prepare "tester RNA", which is hybridized to complementary single-stranded "driver DNA" prepared from mRNA from LMP sample and only the un-hybridized "tester RNA" is recovered, and used to create cloned cDNA libraries, termed "subtracted libraries". Thus, the "subtracted libraries" are enriched for differentially expressed sequences inclusive of rare and novel mRNAs often missed by micro-array hybridization analysis. These rare and novel mRNA are thought to be representative of important gene targets for the development of better diagnostic and therapeutic strategies.
[0385] The clones contained in the enriched "subtracted libraries" are identified by DNA sequence analysis and their potential function assessed by acquiring information available in public databases (NCBI and GeneCard). The non-redundant clones are then used to prepare DNA micro-arrays, which are used to quantify their relative differential expression patterns by hybridization to fluorescent cDNA probes. Two classes of cDNA probes may be used, those which are generated from either RNA transcripts prepared from the same subtracted libraries (subtracted probes) or from mRNA isolated from different ovarian LMP and malignant samples (standard probes). The use of subtracted probes provides increased sensitivity for detecting the low abundance mRNA sequences that are preserved and enriched by STAR. Furthermore, the specificity of the differentially expressed sequences to malignant ovarian cancer is measured by hybridizing radio-labeled probes prepared from each selected sequence to macroarrays containing RNA from different LMP and malignant ovarian cancer samples and different normal human tissues.
[0386] A major challenge in gene expression profiling is the limited quantities of RNA available for molecular analysis. The amount of RNA isolated from many human specimens (needle aspiration, laser capture micro-dissection (LCM) samples and transfected cultured cells) is often insufficient for preparing: 1) conventional tester and driver materials for STAR; 2) standard cDNA probes for DNA micro-array analysis; 3) RNA macroarrays for testing the specificity of expression; 4) Northern blots and; 5) full-length cDNA clones for further biological validation and characterization etc. Thus, the applicant has developed a proprietary technology called RAMP (RNA Amplification Procedure) (U.S. patent application Ser. No. 11/000,958 published under No. US 2005/0153333A1 on Jul. 14, 2005 and entitled "Selective Terminal Tagging of Nucleic Acids"), which linearly amplifies the mRNA contained in total RNA samples yielding microgram quantities of amplified RNA sufficient for the various analytical applications. The RAMP RNA produced is largely full-length mRNA-like sequences as a result of the proprietary method for adding a terminal sequence tag to the 3'-ends of single-stranded cDNA molecules, for use in linear transcription amplification. Greater than 99.5% of the sequences amplified in RAMP reactions show <2-fold variability and thus, RAMP provides unbiased RNA samples in quantities sufficient to enable the discovery of the unique mRNA sequences involved in ovarian cancer.
D--Preparation of Human Malignant Ovarian Cancer Subtracted Library
[0387] Total RNA from five human ovarian LMP samples (MF-15, -16, -18, -19 and -20) (Table B) and five malignant ovarian cancer samples (MF-22, -25, -27, -28 and -30) (Table B) (CHUM, Montreal, QC) were prepared as described above. Following a slight modification of the teachings of Malek et al., 1998 (U.S. Pat. No. 5,712,127) i.e., preparation of the cDNA libraries on the paramagnetic beads as described below), 1 .mu.g of total RNA from each sample were used to prepare highly representative cDNA libraries on streptavidin-coated paramagnetic beads (InVitrogen, Grand Island, N.Y.) for preparing tester and driver materials. In each case, first-strand cDNA was synthesized using an oligo dT.sub.11 primer with 3' locking nucleotides (e.g., A, G or C), a 5'-biotin moiety and containing a Not I recognition site (OGS 364: SEQ. ID. NO. 90) Next, second-strand cDNA synthesis was performed according to the manufacturer's procedure for double-stranded cDNA synthesis (Invitrogen, Burlington, ON) and the resulting double-stranded cDNA ligated to linkers containing an Asc I recognition site (New England Biolabs, Pickering, ON). The double-stranded cDNAs were then digested with Asc I and Not I restriction enzymes (New England Biolabs, Pickering, ON), purified from the excess linkers using the cDNA fractionation column from Invitrogen (Burlington, ON) as specified by the manufacturer. Each sample was equally divided and ligated separately to specialized oligonucleotide promoter tags, TAG1 (OGS 594 and 595: SEQ. ID. NO: 91 and SEQ. ID. NO:92) and TAG2 (OGS458 and 459: SEQ. ID. NO:93 and SEQ. ID. NO:94) used for preparing tester and driver materials, respectively. Thereafter, each ligated cDNA was purified by capturing on the streptavidin beads as described by the supplier (InVitrogen, Grand Island, N.Y.), and transcribed in vitro with T7 RNA polymerase (Ambion, Austin, Tex.).
[0388] Next, in order to prepare 3'-represented tester and driver libraries, a 10-.mu.g aliquot of each of the in vitro synthesized RNA was converted to double-stranded cDNA by performing first-strand cDNA synthesis as described above followed by primer-directed (primer OGS 494 (SEQ. ID. NO:95) for TAG1 and primer OGS 302 (SEQ. ID. NO:96) for TAG2) second-strand DNA synthesis using Advantage-2 Taq polymerase (BD Biosciences Clontech, Mississauga, ON). The double-stranded cDNA was purified using Qiaquick columns and quantified at A.sub.260 nm. Thereafter, 6.times.1-.mu.g aliquots of each double-stranded cDNA was digested individually with one of the following 4-base recognition restriction enzymes Rsa 1, Sau3A1, Mse 1, Msp 1, HinPI 1 and Bsh 1236I (MBI Fermentas, Burlington, ON), yielding up to six possible 3'-fragments for each RNA species contained in the cDNA library. Following digestion, the restriction enzymes were inactivated with phenol and the set of six reactions pooled. The restriction enzymes sites were then blunted with T4 DNA polymerase and ligated to linkers containing an Asc 1 recognition site. Each linker-adapted pooled DNA sample was digested with Asc 1 and Not 1 restriction enzymes, desalted and ligated to specialized oligonucleotide promoter tags, TAG1 (OGS 594 and 595) for the original TAG1-derived materials to generate tester RNA and TAG2-related OGS 621 and 622 (SEQ. ID. NO:97 and SEQ. ID. NO:98) with only the promoter sequence for the original TAG2-derived materials for generating driver DNA. The promoter-ligated materials were purified using the streptavidin beads, which were then transcribed in vitro with either T7 RNA polymerase (Ambion, Austin, Tex.), purified and quantified at A.sub.260 nm. The resulting TAG1 3'-represented RNA was used directly as "tester RNA" whereas, the TAG2 3'-represented RNA was used to synthesize first-strand cDNA, which then served as single-stranded "driver DNA". Each "driver DNA" reaction was treated with RNase A and RNase H to remove the RNA, phenol extracted and purified before use. An equivalent amount of each driver RNA for the five LMP samples were pooled before synthesis of the single-stranded driver DNA.
The following 3'-represented libraries were prepared:
[0389] Tester 1 (MF-22)--human malignant ovarian cancer donor 1
[0390] Tester 2 (MF-25)--human malignant ovarian cancer donor 2
[0391] Tester 3 (MF-27)--human malignant ovarian cancer donor 3
[0392] Tester 4 (MF-28)--human malignant ovarian cancer donor 4
[0393] Tester 5 (MF-30)--human malignant ovarian cancer donor 5
[0394] Driver 1 (MF-15)--human ovarian LMP donor 1
[0395] Driver 2 (MF-16)--human ovarian LMP donor 2
[0396] Driver 3 (MF-18)--human ovarian LMP donor 3
[0397] Driver 4 (MF-19)--human ovarian LMP donor 4
[0398] Driver 5 (MF-20)--human ovarian LMP donor 5
[0399] Each tester RNA sample was subtracted following the teachings of U.S. Pat. No. 5,712,127 with the pooled driver DNA (MF-15, -16, -18, -19 and -20) in a ratio of 1:100 for 2-rounds following the teachings of Malek et al., 1998 (U.S. Pat. No. 5,712,127). Additionally, control reactions containing tester RNA and no driver DNA, and tester RNA plus driver DNA but no RNase H were prepared. The tester RNA remaining in each reaction after subtraction was converted to double-stranded DNA, and a volume of 5% removed and amplified in a standard PCR reaction for 30-cycles for analytical purposes. The remaining 95% of only the tester-driver plus RNase H subtracted samples after 2-rounds were amplified for 4-cycles in PCR, digested with Asc I and Not I restriction enzymes, and one half ligated into the pCATRMAN (SEQ. ID. NO:99) plasmid vector and the other half, into the p20 (SEQ. ID. NO:100) plasmid vector. The ligated materials were transformed into E. coli DH10B and individual clones contained in the pCATRMAN libraries were picked for further analysis (DNA sequencing and hybridization) whereas, clones contained in each p20 library were pooled for use as subtracted probes. Each 4-cycles amplified cloned subtracted library contained between 15,000 and 25,000 colonies. Additionally, in order to prepare subtracted cDNA probes, reciprocal subtraction for 2-rounds was performed using instead, the pooled driver RNA as "tester" and each of the malignant tester RNA as "driver". The materials remaining after subtraction for each were similarly amplified for 4-cycles in PCR, digested with Asc I and Not I restriction enzymes, and one half ligated into the p20 plasmid vector.
[0400] The following cloned subtracted libraries were prepared:
SL123--Tester 1 (MF-22) minus Pooled Driver (MF-15, -16, -18, -19 and -20) SL124--Tester 2 (MF-25) minus Pooled Driver (MF-15, -16, -18, -19 and -20) SL125--Tester 3 (MF-27) minus Pooled Driver (MF-15, -16, -18, -19 and -20) SL126--Tester 4 (MF-28) minus Pooled Driver (MF-15, -16, -18, -19 and -20) SL127--Tester 5 (MF-30) minus Pooled Driver (MF-15, -16, -18, -19 and -20) SL133--Pooled Driver (MF-15, -16, -18, -19 and -20) minus Tester 1 (MF-22) SL134--Pooled Driver (MF-15, -16, -18, -19 and -20) minus Tester 2 (MF-25) SL135--Pooled Driver (MF-15, -16, -18, -19 and -20) minus Tester 3 (MF-27) SL136--Pooled Driver (MF-15, -16, -18, -19 and -20) minus Tester 4 (MF-28) SL137--Pooled Driver (MF-15, -16, -18, -19 and -20) minus Tester 5 (MF-30)
[0401] A 5-.mu.L aliquot of the 30-cycles PCR amplified subtracted and non-subtracted materials were visualized on a 1.5% agarose gel containing ethidium bromide and then transferred to Hybond N+(Amersham Biosciences, Piscataway, N.J.) nylon membrane for Southern blot analysis. Using radiolabeled probes specific for GAPDH (glyceraldehyde-3-phosphate dehydrogenase; Accession #M32599.1) and .beta.-actin (Accession #X00351), which are typically non-differentially expressed house-keeping genes, it was evident that there was subtraction of both GAPDH and .beta.-actin (FIG. 51, Panels A and B). Yet, at the same time, a probe specific for CCNE1 (Accession #NM_001238, a gene known to be upregulated in malignant ovarian cancer, indicated that it was not subtracted (FIG. 51, Panel C). Based on these results, it was anticipated that the subtracted libraries would be enriched for differentially expressed upregulated sequences.
E--Sequence Identification and Annotation of Clones Contained in the Subtracted Libraries:
[0402] Approximately .about.5300 individual colonies contained in the pCATRMAN subtracted libraries (SL123 to SL127) described above were randomly picked using a Qbot (Genetix Inc., Boston, Mass.) into 60 .mu.L of autoclaved water. Then, 42 .mu.L of each was used in a 100-.mu.L standard PCR reaction containing oligonucleotide primers, OGS 1 and OGS 142 and amplified for 40-cycles (94.degree. C. for 10 minutes, 40.times. (94.degree. C. for 40 seconds, 55.degree. C. for 30 seconds and 72.degree. C. for 2 minutes) followed by 72.degree. C. for 7 minutes) in 96-wells microtitre plates using HotStart.TM. Taq polymerase (Qiagen, Mississauga, ON). The completed PCR reactions were desalted using the 96-well filter plates (Corning) and the amplicons recovered in 100 .mu.L 10 mM Tris (pH 8.0). A 5-.mu.L aliquot of each PCR reaction was visualized on a 1.5% agarose gel containing ethidium bromide and only those reactions containing a single amplified product were selected for DNA sequence analysis using standard DNA sequencing performed on an ABI 3100 instrument (Applied Biosystems, Foster City, Calif.). Each DNA sequence obtained was given a Sequence Identification Number and entered into a database for subsequent tracking and annotation.
[0403] Each sequence was selected for BLAST analysis of public databases (e.g. NCBI). Absent from these sequences were the standard housekeeping genes (GAPDH, actin, most ribosomal proteins etc.), which was a good indication that the subtracted library was depleted of at least the relatively abundant non-differentially expressed sequences.
[0404] Once sequencing and annotation of the selected clones were completed, the next step involved identifying those sequences that were actually upregulated in the malignant ovarian cancer samples compared to the LMP samples.
F--Hybridization Analysis for Identifying Upregulated Sequences
[0405] The PCR amplicons representing the annotated sequences from the pCATRMAN libraries described above were used to prepare DNA microarrays. The purified PCR amplicons contained in 70 .mu.L of the PCR reactions prepared in the previous section was lyophilized and each reconstituted in 20 .mu.L of spotting solution comprising 3.times.SSC and 0.1% sarkosyl. DNA micro-arrays of each amplicon in triplicate were then prepared using CMT-GAP2 slides (Corning, Corning, N.Y.) and the GMS 417 spotter (Affymetrix, Santa Clara, Calif.).
[0406] The DNA micro-arrays were then hybridized with either standard or subtracted cy3 and cy5 labelled cDNA probes as recommended by the supplier (Amersham Biosciences, Piscataway, N.J.). The standard cDNA probes were synthesized using RAMP amplified RNA prepared from the different human ovarian LMP and malignant samples. It is well known to the skilled artisan that standard cDNA probes only provide limited sensitivity of detection and consequently, low abundance sequences contained in the cDNA probes are usually missed. Thus, the hybridization analysis was also performed using cy3 and cy5 labelled subtracted cDNA probes prepared from in vitro transcribed RNA generated from subtracted libraries (SLP123 to SLP127 and SLP133 to SLP137) cloned into the p20 plasmid vector and represent the different tester and driver materials. These subtracted libraries may be enriched for low abundance sequences as a result of following the teachings of Malek et al., 1998 (U.S. Pat. No. 5,712,127), and therefore, may provide increased detection sensitivity.
[0407] All hybridization reactions were performed using the dye-swap procedure as recommended by the supplier (Amersham Biosciences, Piscataway, N.J.) and approximately 750 putatively differentially expressed upregulated (>2-fold) sequences were selected for further analysis.
G--Determining Malignant Ovarian Cancer Specificity of the Differentially Expressed Sequences Identified:
[0408] The differentially expressed sequences identified in Section F for the different human malignant ovarian cancer subtracted libraries (SL123 to SL127) were tested for specificity by hybridization to nylon membrane-based macroarrays. The macroarrays were prepared using RAMP amplified RNA from 6 LMP and 20 malignant human ovarian samples, and 30 normal human tissues (adrenal, liver, lung, ovary, skeletal muscle, heart, cervix, thyroid, breast, placenta, adrenal cortex, kidney, vena cava, fallopian tube, pancreas, testicle, jejunum, aorta, esophagus, prostate, stomach, spleen, ileum, trachea, brain, colon, thymus, small intestine, bladder and duodenum) purchased commercially (Ambion, Austin, Tex.). In addition, RAMP RNA prepared from breast cancer cell lines, MDA and MCF7, prostate cancer cell line, LNCap, and a normal and prostate cancer LCM microdissected sample. Because of the limited quantities of mRNA available for many of these samples, it was necessary to first amplify the mRNA using the RAMP methodology. Each amplified RNA sample was reconstituted to a final concentration of 250 ng/.mu.L in 3.times.SSC and 0.1% sarkosyl in a 96-well microtitre plate and 1 .mu.L spotted onto Hybond N+ nylon membranes using the specialized MULTI-PRINT.TM. apparatus (VP Scientific, San Diego, Calif.), air dried and UV-cross linked. Of the .about.750 different sequences selected from SL123 to SL127 for macroarray analysis, only 250 sequences were individually radiolabeled with .alpha.-.sup.32P-dCTP using the random priming procedure recommended by the supplier (Amersham, Piscataway, N.J.) and used as probes on the macroarrays thus far. Hybridization and washing steps were performed following standard procedures well known to those skilled in the art.
[0409] Occasionally, the results obtained from the macroarray methodology were inconclusive. For example, probing the membranes with certain STAR clones resulted in patterns where all the RNA samples appeared to express equal levels of the message or in patterns where there was no signal. This suggested that not all STAR clones were useful tools to verify the expression of their respective genes. To circumvent this problem, RT-PCR was used to determine the specificity of expression. Using the same RAMP RNA samples that were spotted on the macroarrays, 500 .mu.g of RNA was converted to single-stranded cDNA with Thermoscript RT (Invitrogen, Burlington, ON) as described by the manufacturer. The cDNA reaction was diluted so that 1/200 of the reaction was used for each PCR experiment. After trial PCR reactions with gene-specific primers designed against each SEQ. ID NOs. to be tested, the linear range of the reaction was determined and applied to all samples, PCR was conducted in 96-well plates using Hot-Start Taq Polymerase from Qiagen (Mississauga, ON) in a DNA Engine Tetrad from MJ Research. Half of the reaction mixture was loaded on a 1.2% agarose/ethidium bromide gel and the amplicons visualized with UV light.
[0410] Of the 250 sequences tested, approximately 55% were found to be upregulated in many of the malignant samples compared to the LMPs. However, many of these sequences were also readily detected in a majority of the different normal human tissues. Based on these results, those sequences that were detected in many of the other human tissues at significantly elevated levels were eliminated. Consequently, only 49 sequences, which appeared to be upregulated and highly malignant ovarian cancer-specific, were selected for biological validation studies. This subset of 49 sequences include some genes previously reported in the literature to be upregulated in ovarian cancer but without demonstration of their relative expression in normal tissues. The macroarray data for FOLR1 (SEQ. ID. NO. 50) is included to exemplify the hybridization pattern and specificity of a gene that is already known to be involved in the development of ovarian cancer.
[0411] FIGS. 1-49 and 51 show the macroarray hybridization signal patterns and RT-PCR amplification data for the malignant ovarian cancer and normal human tissues relative to LMPs for the 50 sequences isolated and selected for biological validation. Amongst the 50 selected sequences, 27 were associated with genes having functional annotation 15 were associated with genes with no functional annotation and 8 were novel sequences (genomic hits). The identification of gene products involved in regulating the development of ovarian cancer has thus led to the discovery of highly specific, including novel targets, for the development of new therapeutic strategies for ovarian cancer management. Representative sequences summarized in Table 2 are presented below and corresponding sequences are illustrated in Table 4.
[0412] The present invention thus relates in one aspect thereof to a method of representatively identifying a differentially expressed sequence involved in ovarian cancer. The sequence may be, for example, differentially expressed in a malignant ovarian cancer cell compared to a LMP ovarian cancer cell or normal ovarian cells. The sequence may be, for example, differentially expressed in a malignant ovarian cancer cell and a LMP ovarian cancer cell compared to a normal ovarian cell.
[0413] The method of the present invention may comprise the following steps or some of the following steps;
[0414] a) separately providing total messenger RNA from malignant and LMP ovarian cancer cells, and normal ovarian cells, the total messenger RNA may comprise, for example, at least one endogenously differentially expressed sequence,
[0415] b) generating (e.g., single copy) of a) single-stranded cDNA from each messenger RNA of malignant ovarian cancer cell and (e.g., randomly) tagging the 3'-end of the single-stranded cDNA with a RNA polymerase promoter sequence and a first sequence tag;
[0416] c) generating (e.g., single copy) of a) single-stranded cDNA from each messenger RNA of LMP ovarian cancer cells or normal ovarian cell and (e.g., randomly) tagging the 3'-end of the single-stranded cDNA with a RNA polymerase promoter sequence and a second sequence tag;
[0417] d) separately generating partially or completely double-stranded 5'-tagged-DNA from each of b) and c), the double-stranded 5'-tagged-DNA may thus comprise in a 5' to 3' direction, a double-stranded RNA polymerase promoter, a first or second sequence tag and an expressed nucleic acid sequence,
[0418] e) separately linearly amplifying a first and second tagged sense RNA from each of d) with a RNA polymerase enzyme (which may be selected based on the promoter used for tagging),
[0419] f) generating single-stranded complementary first or second tagged DNA from one of e),
[0420] g) hybridizing the single-stranded complementary first or second tagged DNA of f) with the other linearly amplified sense RNA of e),
[0421] h) recovering unhybridized RNA with the help of the first or second sequence tag (for example by PCR or hybridization), and;
[0422] i) identifying (determining) the nucleotide sequence of unhybridized RNA. The method may further comprise the step of comparatively determining the presence of the identified differentially expressed sequence in a cancer cell relative to a normal cell (e.g., a normal ovarian cell, a normal prostate cell, a normal breast cell etc.) or relative to a standard value.
[0423] The method may be used to preferentially identify a sequence which is upregulated in malignant ovarian cancer cell compared to a cell from a low malignancy potential ovarian cancer and/or compared to a normal cell.
[0424] In accordance with the present invention, a sequence may be further selected based on a reduced, lowered or substantially absent expression in a subset of other normal cell (e.g., a normal ovarian cell) or tissue, therefore representing a candidate sequence specifically involved in ovarian cancer.
[0425] The method may also further comprise a step of determining the complete sequence of the nucleotide sequence and may also comprise determining the coding sequence of the nucleotide sequence.
[0426] A sequence may also be selected for its specificity to other types of tumor cells, thus identifying a sequence having a more generalized involvement in the development of cancer. These types of sequence may therefore represent desirable candidates having a more universal utility in the treatment and/or detection of cancer.
[0427] The present invention also relates in a further aspect, to the isolated differentially expressed sequence (polynucleotide and polypeptide) identified by the method of the present invention.
SEQ. ID. NO:1:
[0428] The candidate STAR sequence for SEQ. ID. NO:1 maps to a genomic hit and est hits according to NCBI's nr and est databases (see Table 2). Although, the matching ests are clustered into a new Unigene identifier number, Hs.555871, the STAR sequence does not map to any of the known mRNA sequences listed in this cluster, which codes for guanine nucleotide binding protein (G protein), gamma transducing activity polypeptide 1 (GNGT1). We have demonstrated that this STAR clone sequence is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples and a majority of normal human tissues (FIG. 1), which have not been previously reported. Thus, it is believed that the gene comprising this STAR sequence or a related gene member as is outlined in the Unigene cluster may be required for ovarian cancer tumorigenesis.
SEQ. ID. NO:2:
[0429] The candidate protein encoded by the isolated SEQ. ID. NO:2 is associated with a previously identified gene that encodes a predicted polypeptide, interferon-induced protein 44-like (IFI44L) with an unknown function (see Table 2). We have demonstrated that expression of this gene is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples and a majority of normal human tissues (FIG. 2), which have not been previously reported. Thus, it is believed that expression of this gene may be required for or involved for ovarian cancer tumorigenesis.
SEQ. ID. NO:3:
[0430] The candidate protein encoded by the isolated SEQ. ID. NO:3 is associated with a previously identified gene that encodes a known polypeptide, HOX D1, which contains a homeobox DNA-binding domain. This gene is a member of the Antp homeobox family and is nuclear sequence-specific transcription factor that is previously known to be involved in differentiation and limb development (see Table 2). We have demonstrated that expression of this gene is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples and the normal human tissues (FIG. 3), which have not been previously reported. Thus, it is believed that the gene may be required for, or involved in ovarian cancer tumorigenesis as well.
SEQ. ID. NO:4:
[0431] The candidate protein encoded by the isolated SEQ. ID. NO:4 is associated with a previously identified gene that encodes a hypothetical polypeptide, LOC92196, similar to death-associated protein with an unknown function (see Table 2). We have demonstrated that expression of this gene is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples and a majority of normal human tissues (FIG. 4), which have not been previously reported. Thus, it is believed that expression of this gene may be required for, or involved in ovarian cancer tumorigenesis.
SEQ. ID. NO:5
[0432] The candidate protein encoded by the isolated SEQ. ID. NO:5 is associated with a previously identified gene that encodes a predicted polypeptide, interferon-induced protein with tetratricopeptide repeats 1 (IFIT1), with unknown function (see Table 2). We have demonstrated that expression of this gene is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples and a majority of normal human tissues (FIG. 5), which have not been previously reported. Thus, it is believed that expression of this gene may be required for, or involved in ovarian cancer tumorigenesis.
SEQ. ID. NO:6:
[0433] The candidate protein encoded by the isolated SEQ. ID. NO:6 is associated with a previously identified gene that encodes a known protein, glycine dehydrogenase (GLDC) (decarboxylating; glycine decarboxylase, glycine cleavage system protein P), which is a mitochondrial enzyme that catalyzes the degradation of glycine (see Table 2). We have demonstrated that expression of this gene is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples and a majority of normal human tissues (FIG. 6), which have not been previously reported. Thus, it is believed that expression of this gene may be required for, or involved in ovarian cancer tumorigenesis. The GLDC activity may be detected, for example, by measuring the degradation of glycine into urea.
SEQ. ID. NO:7:
[0434] The candidate protein encoded by the isolated SEQ. ID. NO:7 is associated with a previously identified gene that encodes a protein, dipeptidase 3 (DPEP3), which has membrane dipeptidase (proteolysis and peptidolysis) activity (see Table 2). We have demonstrated that expression of this gene is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples and a majority of normal human tissues (FIG. 7), which have not been previously reported. Thus, it is believed that expression of this gene may be required for, or involved in ovarian cancer tumorigenesis.
SEQ. ID. NO:8
[0435] The candidate protein encoded by the isolated SEQ. ID. NO:8 is associated with a previously identified gene that encodes a protein, neuromedin U (NMU), which is a neuropeptide with potent activity on smooth muscle (see Table 2). We have demonstrated that expression of this gene is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples and a majority of normal human tissues (FIG. 8), which have not been previously reported. Thus, it is believed that expression of the gene may be required for, or involved in ovarian cancer tumorigenesis.
SEQ. ID. NO:9
[0436] The candidate protein encoded by the isolated SEQ. ID. NO:9 is associated with a previously identified gene that encodes a protein, bone morphogenetic protein 7 (BMP7), which plays a role in calcium regulation and bone homeostasis (see Table 2). We have demonstrated that expression of this gene is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples and a majority of normal human tissues (FIG. 9), which have not been previously reported. Thus, it is believed that expression of the gene may be required for, or involved in ovarian cancer tumorigenesis.
SEQ. ID. NO:10
[0437] The candidate protein encoded by the isolated SEQ. ID. NO:10 is associated with a previously identified gene that encodes a protein, cyclin-dependent kinase inhibitor 3 (CDKN3) (CDK2-associated dual specificity phosphatase), which is expressed at the G1 to S transition of the cell cycle (see Table 2). We have demonstrated that expression of this gene is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples and a majority of normal human tissues (FIG. 10), which have not been previously reported. Thus, it is believed that expression of the gene may be required for, or involved in ovarian cancer tumorigenesis.
SEQ. ID. NO:11
[0438] The candidate protein encoded by the isolated SEQ. ID. NO:11 is associated with a previously identified gene that encodes a protein, CDC28 protein kinase regulatory subunit 1B (CKS1B), which has cyclin-dependent protein kinase activity in cell cycle regulation (see Table 2). We have demonstrated that expression of this gene is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples and a majority of normal human tissues (FIG. 11), which have not been previously reported. Thus, it is believed that expression of the gene may be required for, or involved in ovarian cancer tumorigenesis.
SEQ. ID. NO:12
[0439] The candidate protein encoded by the isolated SEQ. ID. NO:12 is associated with a previously identified gene that encodes a protein, preferentially expressed antigen in melanoma (PRAME), which has no known function (see Table 2). We have demonstrated that expression of this gene is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples and a majority of normal human tissues (FIG. 12), which have not been previously reported. Thus, it is believed that expression of the gene may be required for, or involved in ovarian cancer tumorigenesis.
SEQ. ID. NO:13
[0440] The candidate protein encoded by the isolated SEQ. ID. NO:13 is associated with a previously identified gene that encodes a protein, ISG15 ubiquitin-like modifier (ISG15), which is associated with ubiquitin-dependent protein catabolism (see Table 2). We have demonstrated that expression of this gene is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples and a majority of normal human tissues (FIG. 13), which have not been previously reported. Thus, it is believed that expression of the gene may be required for, or involved in ovarian cancer tumorigenesis.
SEQ. ID. NO:14
[0441] The candidate STAR sequence represented by the isolated SEQ. ID. NO:14 is associated with a previously identified partial gene sequence related to Accession #AI922121.1 (see Table 2), which codes for a yet unknown protein. We have demonstrated that this STAR clone sequence is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples and a majority of normal human tissues (FIG. 14), which have not been previously reported. Thus, it is believed that expression of the gene corresponding to this STAR sequence (and polynucleotide sequences comprising the STAR sequence) may be required for, or involved in ovarian cancer tumorigenesis.
SEQ. ID. NO:15
[0442] The candidate protein encoded by the isolated SEQ. ID. NO:15 is associated with a previously identified gene that encodes a hypothetical protein, FLJ33790, which has no known function (see Table 2). We have demonstrated that expression of this gene is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples and a majority of normal human tissues (FIG. 15), which have not been previously reported. Thus, it is believed that expression of the gene may be required for, or involved in ovarian cancer tumorigenesis.
SEQ. ID. NO:16
[0443] The STAR sequence represented by the isolated SEQ. ID. NO:16 maps to a previously identified est, BG213598 that is from a transcribed genomic locus contained in the Unigene cluster, Hs.334302, which encodes a yet unknown protein (see Table 2). We have demonstrated that this STAR clone sequence is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples and a majority of normal human tissues (FIG. 16), which have not been previously reported. Thus, it is believed that expression of the gene corresponding to this STAR sequence (and polynucleotides comprising this STAR sequence) or a related gene member as is outlined in the Unigene cluster may be required for, or involved in ovarian cancer tumorigenesis.
SEQ. ID. NO:17
[0444] The candidate protein encoded by the isolated SEQ. ID. NO:17 is associated with a previously identified gene that encodes a protein, V-set domain containing T cell activation inhibitor 1 (VTCN1), which has no known function (see Table 2). We have demonstrated that expression of this gene is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples and a majority of normal human tissues (FIG. 17), which have not been previously reported. Thus, it is believed that expression of the gene may be required for, or involved in ovarian cancer tumorigenesis.
SEQ. ID. NO:18
[0445] The candidate protein encoded by the isolated SEQ. ID. NO:18 is associated with a previously identified gene that encodes a protein, kinesin family member 20A (KIF20A), which is involved in cell division in and membrane traffic within the Golgi apparatus (see Table 2). We have demonstrated that expression of this gene is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples and a majority of normal human tissues (FIG. 18), which have not been previously reported. Thus, it is believed that expression of the gene may be required for, or involved in ovarian cancer tumorigenesis.
SEQ. ID. NO:19
[0446] The STAR sequence represented by the isolated SEQ. ID. NO:19 maps to a genomic hit, Accession #AY769439 and to a group of ests represented by Accession #AA744939. The ests are clustered into Unigene identifier, Hs.478368 representing the protein, potassium large conductance calcium-activated channel, subfamily M, beta member 2 (KCNMB2). However, the STAR sequence does not overlap with any of the mRNA sequences listed thus far in the Hs.478368 Unigene cluster (see Table 2). We have demonstrated that this STAR clone sequence is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples and a majority of normal human tissues (FIG. 19A), which have not been previously reported. In addition, performing RT-PCR using primers specific to either the STAR clone sequence for SEQ. ID. NO. 19 or the KCNMB2 sequence represented by Accession No. NM_005832, the amplification profiles were not the same across a number of ovarian samples tested (FIG. 19B). It was obvious that KCNMB2 was expressed in essentially all ovarian samples including the normal at similar levels whereas, PCR amplicons for SEQ. ID. NO. 19 was observed at higher levels in the malignant ovarian tumor samples compared to the LMPs and normal ovarian samples (FIG. 19B). Thus, it is believed that the expression of the gene corresponding to this STAR sequence (and polynucleotide sequences comprising the STAR sequence) or a related gene member may be required for, or involved in ovarian cancer tumorigenesis.
SEQ. ID. NO:20
[0447] The STAR sequence represented by the isolated SEQ. ID. NO:20 maps to a previously identified est, BU595315 belonging to a group of ests that is from a transcribed genomic locus contained in the Unigene cluster, Hs.603908, which encodes a yet unknown protein (see Table 2). We have demonstrated that this STAR clone sequence is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples and a majority of normal human tissues (FIG. 20), which have not been previously reported. Thus, it is believed that expression of the gene corresponding to this STAR sequence (and polynucleotide sequences comprising this STAR sequence) or a related gene member as is outlined in the Unigene cluster may be required for, or involved in ovarian cancer tumorigenesis.
SEQ. ID. NO:21
[0448] The candidate protein encoded by the isolated SEQ. ID. NO:21 is a previously identified gene that encodes a protein, chemokine (C-X-C motif) ligand 10 (CXCL10), which has chemokine activity (see Table 2). We have demonstrated that expression of this gene is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples and a majority of normal human tissues (FIG. 21), which have not been previously reported. Thus, it is believed that expression of the gene may be required for, or involved in ovarian cancer tumorigenesis.
SEQ. ID. NO:22
[0449] The STAR sequence represented by the isolated SEQ. ID. NO:22 maps to chromosome 14, and may represent a portion of an unknown gene sequence (see Table 2). We have demonstrated that this STAR clone sequence is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples and a majority of normal human tissues (FIG. 22), which have not been previously reported. Thus, it is believed that expression of the gene corresponding to this STAR sequence (and polynucleotides comprising this STAR sequence) may be required for, or involved in ovarian cancer tumorigenesis.
SEQ. ID. NO:23
[0450] The candidate protein encoded by the isolated SEQ. ID. NO:23 is a previously identified gene that encodes a protein, asparagine-linked glycosylation 8 homolog (yeast, alpha-1,3-glucosyltransferase) (ALG8), which catalyzes the addition of the second glucose residue to the lipid-linked oligosaccharide precursor for N-linked glycosylation of proteins (see Table 2). We have demonstrated that expression of this gene is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples and a majority of normal human tissues (FIG. 23), which have not been previously reported. Thus, it is believed that expression of the gene may be required for, or involved in ovarian cancer tumorigenesis.
SEQ. ID. NO:24
[0451] The candidate protein encoded by the isolated SEQ. ID. NO:24 is a previously identified gene that encodes a protein, kidney associated antigen 1 (KAAG1), which has no known function (see Table 2). We have demonstrated that expression of this gene is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples and a majority of normal human tissues (FIG. 24), which have not been previously reported. Thus, it is believed that expression of the gene may be required for, or involved in ovarian cancer tumorigenesis.
SEQ. ID. NO:25
[0452] The candidate protein encoded by the isolated SEQ. ID. NO:25 is a previously identified gene that encodes a protein, cyclin-dependent kinase inhibitor 2A (CDKN2A), which is involved in cell cycle control, G1/S Checkpoint (see Table 2). We have demonstrated that expression of this gene is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples and a majority of normal human tissues (FIG. 25), which have not been previously reported. Thus, it is believed that expression of the gene may be required for, or involved in ovarian cancer tumorigenesis.
SEQ. ID. NO:26
[0453] The candidate protein encoded by the isolated SEQ. ID. NO:26 is a previously identified gene that encodes a protein, microtubule-associated protein homolog (Xenopus laevis) (TPX2), which is involved in cell proliferation from the transition G1/S until the end of cytokinesis (see Table 2). We have demonstrated that expression of this gene is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples and a majority of normal human tissues (FIG. 26), which have not been previously reported. Thus, it is believed that expression of the gene may be required for, or involved in ovarian cancer tumorigenesis.
SEQ. ID. NO:27
[0454] The candidate protein encoded by the isolated SEQ. ID. NO:27 is a previously identified gene that encodes a protein, ubiquitin-conjugating enzyme E2C (UBE2C), which is required for the destruction of mitotic cyclins and for cell cycle progression (see Table 2). We have demonstrated that expression of this gene is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples and a majority of normal human tissues (FIG. 27), which have not been previously reported. Thus, it is believed that expression of the gene may be required for, or involved in ovarian cancer tumorigenesis.
SEQ. ID. NO:28
[0455] The STAR sequence represented by the isolated SEQ. ID. NO:28 maps to cDNA FLJ35538 f is, clone SPLEN2002463 of Unigene cluster, Hs.590469 and may represent a portion of an unknown gene sequence (see Table 2). We have demonstrated that this STAR clone sequence is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples and a majority of normal human tissues (FIG. 28), which have not been previously reported. Thus, it is believed that expression of the gene corresponding to this STAR sequence (and polynucleotides comprising this STAR sequence) or a related gene member as is outlined in the Unigene cluster may be required for, or involved in ovarian cancer tumorigenesis.
SEQ. ID. NO:29
[0456] The candidate protein encoded by the isolated SEQ. ID. NO:29 is a previously identified gene that encodes a protein, cellular retinoic acid binding protein 2 (CRABP2), whose function has not been precisely determined but this isoform is important in retinoic acid-mediated regulation of human skin growth and differentiation (see Table 2). We have demonstrated that expression of this gene is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples and a majority of normal human tissues (FIG. 29), which have not been previously reported. Thus, it is believed that expression of the gene may be required for, or involved in ovarian cancer tumorigenesis.
SEQ. ID. NO:30
[0457] The candidate protein encoded by the isolated SEQ. ID. NO:30 is a previously identified gene that encodes a protein, Histone 3, H2a (HIST3H2A), which is involved in nucleosome formation (see Table 2). We have demonstrated that expression of this gene is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples and a majority of normal human tissues (FIG. 30), which have not been previously reported. Thus, it is believed that expression of the gene may be required for, or involved in ovarian cancer tumorigenesis.
SEQ. ID. NO:31
[0458] The candidate protein encoded by the isolated SEQ. ID. NO:31 is a previously identified gene that encodes a protein, Histone 1, H4 h (HIST1H4H), which is involved in nucleosome formation (see Table 2). We have demonstrated that expression of this gene is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples and a majority of normal human tissues (FIG. 30), which have not been previously reported. Thus, it is believed that expression of the gene may be required for, or involved in ovarian cancer tumorigenesis.
SEQ. ID. NO:32
[0459] The candidate protein encoded by the isolated SEQ. ID. NO:32 is a previously identified gene that encodes a hypothetical protein, Homeo box D3 (HOXD3), which is a nuclear transcription factor involved in development and differentiation (see Table 2). We have demonstrated that expression of this gene is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples and a majority of normal human tissues (FIG. 32), which have not been previously reported. Thus, it is believed that expression of the gene may be required for ovarian cancer tumorigenesis.
SEQ. ID. NO:33
[0460] The candidate protein encoded by the isolated SEQ. ID. NO:33 is a previously identified gene that encodes a member of the immunoglobulin gene family, immunoglobulin constant gamma 1 (IGHG1), which probably plays a role in immune response and antigen binding (see Table 2). We have demonstrated that expression of this gene is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples and a majority of normal human tissues (FIG. 33), which have not been previously reported. The expression pattern of this gene is similar to two other genes disclosed here, SEQ. ID. NO. 34 and SEQ. ID. NO. 47, which also encode immunoglobulins. This type of clustered immunoglobulin expression in ovarian cancer has not been previously described. Thus, it is believed that expression of the gene may be required for ovarian cancer tumorigenesis.
SEQ. ID. NO:34
[0461] The candidate protein encoded by the isolated SEQ. ID. NO:34 is a previously identified gene that encodes a member of the immunoglobulin gene family, immunoglobulin kappa constant (IGKC), which probably plays a role in immune response and antigen binding (see Table 2). We have demonstrated that expression of this gene is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples and a majority of normal human tissues (FIG. 34), which have not been previously reported. The expression pattern of this gene is similar to two other genes disclosed here, SEQ. ID. NO. 33 and SEQ. ID. NO. 47, which also encode immunoglobulins. This type of clustered immunoglobulin expression in ovarian cancer has not been previously described. Thus, it is believed that expression of the gene may be required for ovarian cancer tumorigenesis.
SEQ. ID. NO:35
[0462] The candidate protein encoded by the isolated SEQ. ID. NO:35 is a gene located on chromosome 10 that encodes an open reading frame of unknown function. (see Table 2). The gene may encode a protein termed astroprincin that was found to be expressed in a critical region in DiGeorge syndrome. We have demonstrated that expression of this gene is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples and a majority of normal human tissues (FIG. 35), which have not been previously reported. Thus, it is believed that expression of the gene may be required for, or involved in ovarian cancer tumorigenesis.
SEQ. ID. NO:36
[0463] The candidate protein encoded by the isolated SEQ. ID. NO:36 is a previously identified gene that encodes a protein, histocompatibility (minor) 13 (HM13), which has no known function (see Table 2). We have demonstrated that expression of this gene is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples and a majority of normal human tissues (FIG. 36), which have not been previously reported. Thus, it is believed that expression of the gene may be required for, or involved in ovarian cancer tumorigenesis.
SEQ. ID. NO:37
[0464] The STAR sequence represented by the isolated SEQ. ID. NO:37 maps to chromosome 13, and may represent a portion of an unknown gene sequence (see Table 2). We have demonstrated that this STAR clone sequence is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples and a majority of normal human tissues (FIG. 37), which have not been previously reported. Thus, it is believed that expression of the gene corresponding to this STAR sequence (and polynucleotides comprising this STAR sequence) may be required for, or involved in ovarian cancer tumorigenesis.
SEQ. ID. NO:38
[0465] The candidate protein encoded by the isolated SEQ. ID. NO:38 is a previously identified gene that encodes a protein, frizzled-related protein (FRZB), which is associated with symptomatic osteoarthritis and may play a role in skeletal morphogenesis (see Table 2). We have demonstrated that expression of this gene is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples and a majority of normal human tissues (FIG. 38), which have not been previously reported. Thus, it is believed that expression of the gene may be required for, or involved in ovarian cancer tumorigenesis.
SEQ. ID. NO:39
[0466] The candidate protein encoded by the isolated SEQ. ID. NO:39 is a previously identified gene that encodes a protein, forkhead box M1 (FOXM1), which is a transcription factor that regulates genes involved in cell proliferation (see Table 2). We have demonstrated that expression of this gene is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples and a majority of normal human tissues (FIG. 39), which have not been previously reported. Thus, it is believed that expression of the gene may be required for, or involved in ovarian cancer tumorigenesis.
SEQ. ID. NO:40
[0467] The candidate protein encoded by the isolated SEQ. ID. NO:40 is a gene located on chromosome 20 that encodes an open reading frame of unknown function. (see Table 2). The gene is predicted to encode a membrane protein. We have demonstrated that expression of this gene is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples and a majority of normal human tissues (FIG. 40), which have not been previously reported. Thus, it is believed that expression of the gene may be required for, or involved in ovarian cancer tumorigenesis.
SEQ. ID. NO:41
[0468] The STAR sequence represented by the isolated SEQ. ID. NO:41 maps to chromosome 1, and may represent a portion of an unknown gene sequence (see Table 2). Weak homology has been found between SEQ. ID. NO. 41 and the envelop proteins present at the surface of human endogenous retroviruses. We have demonstrated that this STAR clone sequence is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples and a majority of normal human tissues (FIG. 41), which have not been previously reported. Thus, it is believed that expression of the gene corresponding to this STAR sequence (and polynucleotides comprising this STAR sequence) may be required for, or involved in ovarian cancer tumorigenesis.
SEQ. ID. NO:42
[0469] The candidate protein encoded by the isolated SEQ. ID. NO:42 is a gene located on chromosome 16 that encodes an open reading frame of unknown function. (see Table 2). The gene is predicted to encode a membrane protein. We have demonstrated that expression of this gene is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples and a majority of normal human tissues (FIG. 42), which have not been previously reported. Thus, it is believed that expression of the gene may be required for, or involved in ovarian cancer tumorigenesis.
SEQ. ID. NO:43
[0470] The candidate protein encoded by the isolated SEQ. ID. NO:43 is a previously identified gene that encodes a protein, Rac GTPase activating protein 1 (RACGAP1), which is a GTPase that interacts with Rho GTPases to control many cellular processes (see Table 2). These types of proteins are important effector molecules for the downstream signaling of Rho GTPases. We have demonstrated that expression of this gene is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples and a majority of normal human tissues (FIG. 43), which have not been previously reported. Thus, it is believed that expression of the gene may be required for, or involved in ovarian cancer tumorigenesis.
SEQ. ID. NO:44
[0471] The candidate protein encoded by the isolated SEQ. ID. NO:44 is a gene that encodes transmembrane protein 19 (TMEM19) that has no known function. (see Table 2). The gene is predicted to encode a membrane protein. We have demonstrated that expression of this gene is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples and a majority of normal human tissues (FIG. 44), which have not been previously reported. Thus, it is believed that expression of the gene may be required for, or involved in ovarian cancer tumorigenesis.
SEQ. ID. NO:45
[0472] The STAR sequence represented by the isolated SEQ. ID. NO:45 maps to chromosome 4, and may represent a portion of an unknown gene sequence (see Table 2). We have demonstrated that this STAR clone sequence is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples and a majority of normal human tissues (FIG. 45), which have not been previously reported. Thus, it is believed that expression of the gene corresponding to this STAR sequence (and polynucleotides comprising this STAR sequence) may be required for, or involved in ovarian cancer tumorigenesis.
SEQ. ID. NO:46
[0473] The STAR sequence represented by the isolated SEQ. ID. NO:46 maps to chromosome 1, and may represent a portion of an unknown gene sequence (see Table 2). We have demonstrated that this STAR clone sequence is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples and a majority of normal human tissues (FIG. 46), which have not been previously reported. Thus, it is believed that expression of the gene corresponding to this STAR sequence (and polynucleotides comprising this STAR sequence) may be required for, or involved in ovarian cancer tumorigenesis.
SEQ. ID. NO:47
[0474] The candidate protein encoded by the isolated SEQ. ID. NO:47 is a previously identified gene with the Unigene cluster, Hs.449585, and may represent a portion immunoglobulin lambda locus (IGLV@), which probably plays a role in immune response and antigen binding (see Table 2). We have demonstrated that expression of this gene is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples and a majority of normal human tissues (FIG. 47), which have not been previously reported. The expression pattern of this gene is similar to two other genes disclosed here, SEQ. ID. NO. 33 and SEQ. ID. NO. 34, which also encode immunoglobulins. This type of clustered immunoglobulin expression in ovarian cancer has not been previously described. Thus, it is believed that expression of the gene may be required for ovarian cancer tumorigenesis.
SEQ. ID. NO:48
[0475] The candidate protein encoded by the isolated SEQ. ID. NO:48 is a previously identified gene that encodes a protein, secretory carrier membrane protein 3 (SCAMP3), which functions as a cell surface carrier protein during vesicular transport (see Table 2). We have demonstrated that expression of this gene is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples but it is also expressed in a majority of normal human tissues (FIG. 48), which have not been previously reported. Thus, it is believed that expression of the gene may be required for, or involved in ovarian cancer tumorigenesis.
SEQ. ID. NO:49
[0476] The STAR sequence represented by the isolated SEQ. ID. NO:49 maps to chromosome 2, and may represent a portion of an unknown gene sequence (see Table 2). We have demonstrated that this STAR clone sequence is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples and a majority of normal human tissues (FIG. 49), which have not been previously reported. Thus, it is believed that expression of the gene corresponding to this STAR sequence (and polynucleotides comprising this STAR sequence) may be required for, or involved in ovarian cancer tumorigenesis.
SEQ. ID. NO:50
[0477] The candidate protein encoded by the isolated SEQ. ID. NO:50 is a previously identified gene that encodes a protein, Folate receptor 1 (adult) (FOLR1), with members of this gene family having a high affinity for folic acid and for several reduced folic acid derivatives, and mediate delivery of 5-methyltetrahydrofolate to the interior of cells (see Table 2). We have demonstrated that this gene is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples and a majority of normal human tissues (FIG. 50). The potential role of FOLR1 in ovarian cancer therapeutics has been previously documented (Leamon and Low, 2001 and Jhaveri et al., 2006, U.S. Pat. No. 7,030,236). By way of example of the FOLR1 gene target, similar genes described herein with upregulation in malignant ovarian tumors and limited or no expression in a majority of normal tissues may also serve as potential therapeutic targets for ovarian cancer.
SEQ. ID. NO:169
[0478] The candidate protein encoded by the isolated SEQ. ID. NO:169 is a previously identified gene that encodes a protein, ceruloplasmin (CP), that binds most of the copper in plasma and is involved in the peroxidation of Fe(II)transferrin. The deficiency of this metalloprotein, termed aceruloplasminemia, leads to iron accumulation and tissue damage, and is associated diabetes and neurologic diseases (see Table 2). We have demonstrated that this gene is markedly upregulated in malignant ovarian cancer samples compared to ovarian LMP samples and a majority of normal human tissues (FIG. 56) which have not been previously reported. Thus, it is believed that expression of the gene corresponding to this STAR sequence (and polynucleotides comprising this STAR sequence) may be required for, or involved in ovarian cancer tumorigenesis.
H--RNA Interference Studies
[0479] RNA interference is a recently discovered gene regulation mechanism that involves the sequence-specific decrease in a gene's expression by targeting the mRNA for degradation and although originally described in plants, it has been discovered across many animal kingdoms from protozoans and invertebrates to higher eukaryotes (reviewed in Agrawal et al., 2003). In physiological settings, the mechanism of RNA interference is triggered by the presence of double-stranded RNA molecules that are cleaved by an RNAse III-like protein active in cells, called Dicer, which releases the 21-23 bp siRNAs. The siRNA, in a homology-driven manner, complexes into a RNA-protein amalgamation termed RISC (RNA-induced silencing complex) in the presence of mRNA to cause degradation resulting in attenuation of that mRNA's expression (Agrawal et al., 2003).
[0480] Current approaches to studying the function of genes, such as gene knockout mice and dominant negatives, are often inefficient, and generally expensive, and time-consuming. RNA interference is proving to be a method of choice for the analysis of a large number of genes in a quick and relatively inexpensive manner. Although transfection of synthetic siRNAs is an efficient method, the effects are often transient at best (Hannon G. J., 2002). Delivery of plasmids expressing short hairpin RNAs by stable transfection has been successful in allowing for the analysis of RNA interference in longer-term studies (Brummelkamp et al., 2002; Elbashir et al., 2001).
I--Determination of Knockdown Effects on the Proliferation of Ovarian Cancer Cell Lines
[0481] In order to determine which ovarian cancer-specific genes participate in the proliferation of ovarian cancer cells, an assay was developed using stably transfected cell lines that contain attenuated (i.e., knocked down) levels of the specific gene being investigated. Two human ovarian cancer cell lines derived from chemotherapy-naive patients were utilized that have been previously characterized in terms of their morphology, tumorigenicity, and global expression profiles. In addition, these analyses revealed that these cell lines were excellent models for in vivo behavior of ovarian tumors in humans (Provencher et al., 2000 and Samouelian et al., 2004). These cell lines are designated TOV-21G and TOV-112D.
[0482] The design and subcloning of individual shRNA expression cassettes and the procedure utilized for the characterisation of each nucleotide sequence is described below. Selection of polynucleotides were chosen based on their upregulation in ovarian tumors and the selective nature of their expression in these tumors compared to other tissues as described above. The design of shRNA sequences was performed using web-based software that is freely available to those skilled in the art (Qiagen for example). These chosen sequences, usually 19-mers, were included in two complementary oligonucleotides that form the template for the shRNAs, i.e. the 19-nt sense sequence, a 9-nt linker region (loop), the 19-nt antisense sequence followed by a 5-6 poly-T tract for termination of the RNA polymerase III. Appropriate restriction sites were inserted at the ends of these oligonucleotides to facilitate proper positioning of the inserts so that the transcriptional start point is at a precise location downstream of the hU6 promoter. The plasmid utilized in all RNA interference studies, pSilencer 2.0 (SEQ. ID. NO. 101), was purchase from a commercial supplier (Ambion, Austin, Tex.). For each sequence selected, at least two different shRNA expression vectors were constructed to increase the chance of observing RNA interference.
[0483] TOV-21G or TOV-112D cells were seeded in 6-well plates in OSE (Samouelian et al., 2004) containing 10% fetal bovine serum at a density of 600 000 cells/well, allowed to plate overnight and transfected with 1 .mu.g of pSil-shRNA plasmid (FIG. 53, sh-1 and sh-2) using the Fugene 6 reagent (Roche, Laval, QC). After 16 h of incubation, fresh medium was added containing 2 .mu.g/ml puromycin (Sigma, St. Louis, Mo.) to select for stable transfectants. Control cells were transfected with a control pSil (sh-scr (SEQ. ID. NO. 102) that contains a scrambled shRNA sequence that displays homology to no known human gene. After approximately 4-5 days, pools and/or individual clones of cells were isolated and expanded for further analyses. The effectiveness of attenuation was verified in all shRNA cells lines. Total RNA was prepared by standard methods using Trizol.TM. reagent from cells grown in 6-well plates and expression of the target gene was determined by RT-PCR using gene-specific primers. First strand cDNA was generated using Thermoscript (Invitrogen, Burlington, ON) and semi-quantitative PCR was performed by standard methods (Qiagen, Mississauga, ON). 100% expression levels for a given gene was assigned to those found in the cell lines transfected with the control pSil plasmid (sh-scr). FIG. 52 shows representative results from the attenuation of two candidate genes, SEQ. ID. NO. 1 and SEQ. ID. NO. 3. When RT-PCR was performed using total RNA from the control cell lines (FIG. 52, pSil-scr), a single band of expected size was observed. When the total RNA from the cell line containing shRNAs to SEQ. ID. NO. 1 (0094) (sh-1: SEQ. ID. NO. 103 and sh-2: SEQ. ID. NO. 104) or SEQ. ID. NO. 3 (0671) (sh-1: SEQ. ID. NO. 107 and sh-2: SEQ. ID. NO. 108) was amplified under identical conditions, significant reduction in the levels of expression of these genes were observed. These results indicate that the shRNAs that were expressed in the TOV-21G stable transfectants were successful in attenuating the expression of their target genes. As a control for equal quantities of RNA in all reactions, the expression of glyceraldehyde-3-phosphate dehydrogenase (FIG. 52, GAPDH) was monitored and found to be expressed at equal levels in all samples used.
[0484] The proliferative ability of each shRNA-expressing cell line was determined and compared to cells expressing the scrambled shRNA (control). Cell number was determined spectrophotometrically by MTT assay at 570 nm (Mosmann, 1983). After selection of stably shRNA expressing pools and expansion of the lines, 5 000 cells/well of each cell lines was plated in 48-well plates in triplicate and incubated for 4 days under standard growth conditions. Representative data from 2 experiments .+-.SEM is displayed and experiments were typically repeated at least three times to confirm the results observed. FIG. 53 shows representative results that were obtained when the proliferation assay was applied to stable TOV-21G cells lines. The cell number after 4 days in the control cell line expressing the scrambled shRNA (FIG. 53, sh scr) was arbitrarily set to 100%. TOV-21G cell lines containing shRNA against SEQ. ID. NO. 1 (sh-1: SEQ. ID. NO. 103 and sh-2: SEQ. ID. NO. 104), SEQ. ID. NO. 3 (sh-1: SEQ. ID. NO. 107 and sh-2: SEQ. ID. NO. 108) and SEQ. ID. NO. 8 (0065) (sh-1: SEQ. ID. NO. 117 and sh-2: SEQ. ID. NO. 118) exhibited less than 50% proliferation for at least one shRNA compared to the control cell line (FIG. 53, sh-1 and sh-2 for each). The proliferation of TOV-21G cell lines containing shRNA against SEQ. ID. NO. 2 (0478) (sh-1: SEQ. ID. NO. 105 and sh-2: SEQ. ID. NO. 106) and SEQ. ID. NO. 7 (1096) (sh-1: SEQ. ID. NO. 115 and sh-2: SEQ. ID. NO. 116) was not affected to the same extent but significant inhibition of growth was still observed nevertheless. These results indicate that attenuation of these genes causes retardation in the growth of this ovarian cancer cell line. Several of these shRNA expression vectors were also transfected into the TOV-112D cell line and similar results were obtained (data not shown). This suggested that these genes are important for proliferation of ovarian cancer cells.
[0485] The gene encoding the folate receptor 1, SEQ. ID. NO. 50 (0967A) (FIG. 53, 0967A), which has been documented as being an important marker for ovarian cancer (Leamon and Low, 2001), was also attenuated in TOV-21G cells, and marked growth inhibition was observed in the presence of the shRNAs (sh-1: SEQ. ID. NO. 151 and sh-2: SEQ. ID. NO. 152). This gives credibility to the approach used to validate the genes presented in this patent and substantiated their functional importance in the proliferation of ovarian cancer cells.
[0486] Table 1 below lists all of the genes tested and the average growth inhibition (n=3-4) that was observed in TOV-21G cells. Differences of less than 20% (see Table 1, <20) compared to the control cell lines represent cells where statistically significant reduction in proliferation was measured within a range of 5-20%.
TABLE-US-00003 TABLE 1 List of genes tested in cell proliferation assay and results Average Growth Alethia's inhibition in Gene SEQ. ID. Gene TOV-21G cells NO. Code shRNA SEQ. ID. NO. (%) (n = 3-4) Control SEQ. ID. NO. 102 0 SEQ. ID. NO. 1 0094 SEQ. ID. NOs. 103 47.9 and 104 SEQ. ID. NO. 2 0478 SEQ. ID. NOs. 105 41.7 and 106 SEQ. ID. NO. 3 0671 SEQ. ID. NOs. 107 65.7 and 108 SEQ. ID. NO. 4 0851 SEQ. ID. NOs. 109 21.5 and 110 SEQ. ID. NO. 5 0713 SEQ. ID. NOs. 111 42.3 and 112 SEQ. ID. NO. 6 1064 SEQ. ID. NOs. 113 28.9 and 114 SEQ. ID. NO. 7 1096 SEQ. ID. NOs. 115 25.8 and 116 SEQ. ID. NO. 8 0065 SEQ. ID. NOs. 117 32.5 and 118 SEQ. ID. NO. 9 1313 SEQ. ID. NOs. 119 50.5 and 120 SEQ. ID. NO. 0059 SEQ. ID. NOs. 121 52.4 10 and 122 SEQ. ID. NO. 0239 SEQ. ID. NOs. 123 22.8 11 and 124 SEQ. ID. NO. 0291 SEQ. ID. NOs. 125 <20 12 and 126 SEQ. ID. NO. 0972 SEQ. ID. NOs. 127 <20 13 and 128 SEQ. ID. NO. 0875 SEQ. ID. NOs. 129 <20 14 and 130 SEQ. ID. NO. 0420 SEQ. ID. NOs. 131 <20 15 and 132 SEQ. ID. NO. 0125 SEQ. ID. NOs. 133 <20 16 and 134 SEQ. ID. NO. 0531 SEQ. ID. NOs. 135 0 17 and 136 SEQ. ID. NO. .sup. 0967B SEQ. ID. NOs. 137 0 18 and 138 SEQ. ID. NO. 0889 SEQ. ID. NOs. 139 <20 19 and 140 SEQ. ID. NO. 0313 SEQ. ID. NOs. 141 <20 20 and 142 SEQ. ID. NO. 1134 SEQ. ID. NOs. 143 <20 21 and 144 SEQ. ID. NO. 0488 SEQ. ID. NOs. 145 0 22 and 146 SEQ. ID. NO. 0216 SEQ. ID. NOs. 147 <20 23 and 148 SEQ. ID. NO. 0447 SEQ. ID. NOs. 149 0 24 and 150 SEQ. ID. NO. .sup. 0967A SEQ. ID. NOs. 151 47.4 50 and 152
J--a Method for Determining the Requirement for Specific Genes in the Survival of Ovarian Cancer Cells
[0487] As a means of complementing the growth inhibition data that was generated with the stable TOV-21G cell lines, a colony survival assay was used to determine the requirement of the selected genes in the survival of the cancer cells. The `colony formation assay` or `clonogenic assay` is a classical test to evaluate cell growth after treatment. The assay is widespread in oncological research areas where it is used to test the proliferating power of cancer cell lines after radiation and/or treatment with anticancer agents. It was expected that the results obtained when analyzing the genes that were functionally important in ovarian cancer would correlate between the growth inhibition study and the colony survival assay.
[0488] TOV-21G cells were seeded in 12-well plates at a density of 50 000 cells/well and transfected 24 h later with 1 .mu.g of pSil-shRNA vector, the same plasmids used in the previous assay. The next day, fresh medium was applied containing 2 .mu.g/ml puromycin and the selection of the cells was carried out for 3 days. The cells were washed and fresh medium without puromycin was added and growth continued for another 5 days. To visualize the remaining colonies, the cells were washed in PBS and fixed and stained simultaneously in 1% crystal violet/10% ethanol in PBS for 15 minutes at room temperature. Following extensive washing in PBS, the dried plates were scanned for photographic analysis.
[0489] As shown in FIG. 37 and as exemplified by SEQ. ID. NO. 1 (0094), SEQ. ID. NO. 3 (0671), and SEQ. ID. NO. 9 (1313), the amount of TOV-21G-derived colonies that survived correlated with the growth inhibition data. For example, the growth inhibition in the proliferation assay (FIG. 53) and cell death in the colony assay (FIG. 54) was greater in TOV-21G cells containing shRNA-2 compared to shRNA-1 for SEQ. ID. NO. 1 (0094) (0094-sh2 stronger than 0094-sh1) and SEQ. ID. NO. 3 (0671) (0671-sh2 stronger than 0671-sh1) whereas, for SEQ. ID. NO. 9 (1313), the 1313-sh1 was stronger than 1313-sh2. Similar convergence was observed with several other genes that were analyzed using these two assays (data not shown). Therefore, these results implied that a phenotypic manifestation in both assays was indicative of important genes that are functionally required in ovarian cancer cells and suggest that inhibition of the proteins they encode could be serve as important targets to develop new anticancer drugs.
K--A Method for Broadening the Scope of Intervention to Other Oncology Indications
[0490] One skilled in the art will recognize that the sequences described in this invention have utilities in not only ovarian cancer, but these applications can also be expanded to other oncology indications where the genes are expressed. To address this, a PCR-based method was adapted to determine the expression pattern of all sequences described above in cancer cell lines isolated from nine types of cancer. The cancer types represented by the cell lines are leukemia, central nervous system, breast, colon, lung, melanoma, ovarian, prostate, and renal cancer (see Table C). These RNA samples were obtained from the Developmental Therapeutics Program at the NCI/NIH. Using the same RAMP RNA samples that amplified from the total RNA samples obtained from the NCI, 500 .mu.g of RNA was converted to single-stranded cDNA with Thermoscript RT (Invitrogen, Burlington, ON) as described by the manufacturer. The cDNA reaction was diluted so that 1/200 of the reaction was used for each PCR experiment. After trial PCR reactions with gene-specific primers designed against each SEQ. ID NOs. to be tested, the linear range of the reaction was determined and applied to all samples, PCR was conducted in 96-well plates using Hot-Start Taq Polymerase from Qiagen (Mississauga, ON) in a DNA Engine Tetrad from MJ Research. Half of the reaction mixture was loaded on a 1.2% agarose/ethidium bromide gel and the amplicons visualized with UV light. To verify that equal quantities of RNA was used in each reaction, the level of RNA was monitored with GAPDH expression.
TABLE-US-00004 TABLE C List of cancer cell lines from the NCI-60 panel Cell line Cancer type K-562 leukemia MOLT-4 leukemia CCRF-CEM leukemia RPMI-8226 leukemia HL-60(TB) leukemia SR leukemia SF-268 CNS SF-295 CNS SF-539 CNS SNB-19 CNS SNB-75 CNS U251 CNS BT-549 breast HS 578T breast MCF7 breast NCI/ADR-RES breast MDA-MB-231 breast MDA-MB-435 breast T-47D breast COLO 205 colon HCC-2998 colon HCT-116 colon HCT-15 colon HT29 colon KM12 colon SW-620 colon A549/ATCC non-small cell lung EKVX non-small cell lung HOP-62 non-small cell lung HOP-92 non-small cell lung NCI-H322M non-small cell lung NCI-H226 non-small cell lung NCI-H23 non-small cell lung NCI-H460 non-small cell lung NCI-H522 non-small cell lung LOX IMVI melanoma M14 melanoma MALME-3M melanoma SK-MEL-2 melanoma SK-MEL-28 melanoma SK-MEL-5 melanoma UACC-257 melanoma UACC-62 melanoma IGROV-1 ovarian OVCAR-3 ovarian OVCAR-4 ovarian OVCAR-5 ovarian OVCAR-8 ovarian SK-OV-3 ovarian DU-145 prostate PC-3 prostate 786-O renal A498 renal ACHN renal CAKI-1 renal RXF-393 renal SN-12C renal TK-10 renal UO-31 renal
[0491] One of skill in the art will readily recognize that orthologues for all mammals maybe identified and verified using well-established techniques in the art, and that this disclosure is in no way limited to one mammal. The term "mammal(s)" for purposes of this disclosure refers to any animal classified as a mammal, including humans, domestic and farm animals, and zoo, sports, or pet animals, such as dogs, cats, cattle, horses, sheep, pigs, goats, rabbits, etc. Preferably, the mammal is human.
[0492] The sequences in the experiments discussed above are representative of the NSEQ being claimed and in no way limit the scope of the invention. The disclosure of the roles of the NSEQs in proliferation of ovarian cancer cells satisfies a need in the art to better understand ovarian cancer disease, providing new compositions that are useful for the diagnosis, prognosis, treatment, prevention and evaluation of therapies for ovarian cancer and other cancers where said genes are expressed as well.
[0493] The art of genetic manipulation, molecular biology and pharmaceutical target development have advanced considerably in the last two decades. It will be readily apparent to those skilled in the art that newly identified functions for genetic sequences and corresponding protein sequences allows those sequences, variants and derivatives to be used directly or indirectly in real world applications for the development of research tools, diagnostic tools, therapies and treatments for disorders or disease states in which the genetic sequences have been implicated.
[0494] Although the present invention has been described herein above by way of preferred embodiments thereof, it maybe modified, without departing from the spirit and nature of the subject invention as defined in the appended claims.
TABLE-US-00005 TABLE 2 Differentially expressed sequences found in malignant ovarian cancer. NCBI ORF Unigene Nucleotide #/Gene Positions/ Nucleotide Symbol/Gene Accession Polypeptide Sequence No. ID Number sequence No. Function SEQ ID NO. 1 STAR clone BX094904 Unknown Transcribed locus but possibly NM_021955 149-373 for guanine nucleotide belonging to for Hs.555871 binding protein (G cluster Hs.555871 encoding SEQ protein), gamma Hs.555871 ID NO.: 51 transducing activity polypeptide 1 SEQ ID NO. 2 Hs.389724/ NM_006820 242-1483 interferon-induced IFI44L/ encoding SEQ protein 44-like; 10964 ID NO.: 52 function unknown SEQ ID NO. 3 Hs.83465/ NM_024501 224-1210 homeobox D1; HOXD1/ encoding SEQ sequence-specific 3231 ID NO.: 53 transcription factor that is involved in differentiation and limb development SEQ ID NO. 4 Hs.59761/ NM_001017920 45-368 hypothetical protein LOC92196/ encoding SEQ LOC92196; 92196 ID NO.: 54 function unknown SEQ ID NO. 5 Hs.20315/ NM_001001887 93-1529 interferon-induced IFIT1/ encoding SEQ protein with 3434 ID NO.: 55 tetratricopeptide repeats 1; function unknown SEQ ID NO. 6 Hs.584238/ NM_000170 151-3213 glycine GLDC/ encoding SEQ dehydrogenase 2731 ID NO.: 56 (decarboxylating; glycine decarboxylase, glycine cleavage system protein P); mitochondrial glycine cleavage system catalyzes the degradation of glycine SEQ ID NO. 7 Hs.302028/ NM_022357 9-1550 dipeptidase 3; DPEP3/ encoding SEQ proteolysis and 64180 ID NO.: 57 peptidolysis SEQ ID NO. 8 Hs.418367/ NM_006681 106 . . . 630 neuromedin U NMU/ encoding SEQ (NMU); neuropeptide 10874 ID NO.: 58 signaling pathway, regulation of smooth muscle contraction SEQ ID NO. 9 Hs.473163/ NM_001719 123-1418 bone morphogenetic BMP7/ encoding SEQ protein 7; cell growth 655 ID NO.: 59 and/or maintenance, growth, skeletal development, cytokine activity, growth factor activity SEQ ID NO. 10 Hs.84113/ NM_005192 62-700 cyclin-dependent CDKN3/ encoding SEQ kinase inhibitor 3; a 1033 ID NO.: 60 cyclin-dependent kinase inhibitor, as well as, dephosphorylate CDK2 kinase which prevent the activation of CDK2 kinase SEQ ID NO. 11 Hs.374378/ NM_001826 10-249 CDC28 protein kinase CKS1B/ encoding SEQ regulatory subunit 1B; 1163 ID NO.: 61 cell cycle, cytokinesis, cyclin-dependent protein kinase activity SEQ ID NO. 12 Hs.30743/ NM_006115 250-1779 preferentially PRAME/ encoding SEQ expressed antigen in 23532 ID NO.: 62 melanoma; function unknown SEQ ID NO. 13 Hs.458485/ NM_005101 76-573 ISG15 ubiquitin-like ISG15/ encoding SEQ modifier; 9636 ID NO.: 63 protein binding SEQ ID NO. 14 STAR clone AI922121.1 Novel genomic hit SEQ ID NO. 15 Hs.292451/ NM_001039548 220-1311 hypothetical protein FLJ33790/ encoding SEQ LOC283212; 283212 ID NO.: 64 function unknown SEQ ID NO. 16 Hs.334302 BG213598 Transcribed locus; function unknown SEQ ID NO. 17 Hs.546434/ NM_024626 71-919 V-set domain VTCN1/ encoding SEQ containing T cell 79679 ID NO.: 65 activation inhibitor 1; function unknown SEQ ID NO. 18 Hs.73625/ NM_005733 28 . . . 2700 kinesin family KIF20A/ encoding SEQ member 20A; 10112 ID NO.: 66 kinesin family, interacts with guanosine triphosphate (GTP)- bound forms of RAB6A and RAB6B SEQ ID NO. 19 STAR clone AC117457 300-1007 novel genomic hit but a possibly NM_005832 encoding SEQ potassium large of it belonging for ID NO.: 67 conductance calcium- to cluster Hs.478368 activated channel, Hs.478368 subfamily M, beta according to member 2 for NCBI Hs.478368 SEQ ID NO. 20 Hs.603908 BU595315 Transcribed locus; function unknown SEQ ID NO. 21 Hs.632586/ NM_001565 67-363 chemokine (C-X-C CXCL10/ encoding SEQ motif) ligand 10; 3627 ID NO.: 68 chemokine SEQ ID NO. 22 STAR clone AL583809 Novel genomic hit SEQ ID NO. 23 Hs.503368/ NM_001007027 66-1469 asparagine-linked ALG8/ encoding SEQ glycosylation 8 79053 ID NO.: 69 homolog (S. cerevisiae, alpha-1,3- glucosyltransferase); catalyzes the addition of the second glucose residue to the lipid-linked oligosaccharide precursor for N-linked glycosylation of proteins SEQ ID NO. 24 Hs.591801/ NM_181337 738-992 kidney associated KAAG1 encoding SEQ antigen 1; fumction ID NO.: 70 unknown SEQ ID NO. 25 Hs.512599/ NM_000077 213-683 cyclin-dependent CDKN2A/ encoding SEQ kinase inhibitor 2A; 1029 ID NO.: 71 cell cycle G1 control SEQ ID NO. 26 Hs.244580/ NM_012112 699-2942 TPX2, microtubule- TPX2/ encoding SEQ associated, homolog 22974 ID NO.: 72 (Xenopus laevis); involve in cell proliferation SEQ ID NO. 27 Hs.93002/ NM_007019 81-620 ubiquitin-conjugating UBE2C/ encoding SEQ enzyme E2C; 11065 ID NO.: 73 required for the destruction of mitotic cyclins and for cell cycle progression SEQ ID NO. 28 Hs.590469 AK092857 cDNA FLJ35538 fis, clone SPLEN2002463; function unknown SEQ ID NO. 29 Hs.405662/ NM_001878 138-554 cellular retinoic acid CRABP2/ encoding SEQ binding protein 2; 1382 ID NO.: 74 function unknown but may be involved in human skin growth and differentiation SEQ ID NO. 30 Hs.26331/ NM_033445 43-435 histone 3, H2a; HIST3H2A/ encoding SEQ nucleosome formation 92815 ID NO.: 75 SEQ ID NO. 31 Hs.591790/ NM_003543 1-312 histone 1, H4h; HIST1H4H/ encoding SEQ nucleosome formation 8365 ID NO.: 76 SEQ ID NO. 32 Hs.93574/ NM_006898 177-1475 homeobox D3; may HOXD3/ encoding SEQ play a role in the 3232 ID NO.: 77 regulation of cell adhesion processes SEQ ID NO. 33 Hs.525641/ BC092518 61-1470 Immunoglobulin IGHG1/ encoding SEQ heavy constant 3500 ID NO.: 78 gamma 1; may play a role in immune response and antigen binding SEQ ID NO. 34 Hs.592988/ BC073793 10-717 Immunoglobulin IGKC/ encoding SEQ kappa constant; may 3514 ID NO.: 79 play a role in immune response and antigen binding SEQ ID NO. 35 Hs.66762 AY683003 55-2727 Chromosome 10 ORF encoding SEQ 38; unknown function ID NO.: 80 SEQ ID NO. 36 Hs.373741/ NM_178580 115-1299 Histocompatibility SPP/ encoding SEQ (minor) 13; unknown 81502 ID NO.: 81 function SEQ ID NO. 37 STAR clone AL157931 Novel genomic hit SEQ ID NO. 38 Hs.128453/ NM_001463 219-1196 Frizzled-related FRZB/ encoding SEQ protein; Wnt receptor 2487 ID NO.: 82 signaling pathway, development, skeletal, transmembrane receptor activity SEQ ID NO. 39 Hs.239/ NM_202003 266-2512 Forkhead box M1; FOXM1/ encoding SEQ transcriptional 2305 ID NO.: 83 regulation SEQ ID NO. 40 Hs.46627 NM_152864 89-715 Chromosome 20 ORF encoding SEQ 58; unknown function ID NO.: 84 SEQ ID NO. 41 STAR clone AK092936 Novel genomic hit SEQ ID NO. 42 Gene ID BC009078 552-746 Chromosome 16 ORF 404550 encoding SEQ 74; unknown function ID NO.: 85 SEQ ID NO. 43 Hs.645513/ NM_013277 225-2123 Rac GTPase RACGAP1/ encoding SEQ activating protein 1; 29127 ID NO.: 86 electron transport, intracellular signaling cascade; iron ion binding SEQ ID NO. 44 Hs.645522/ NM_018279 584-1594 Transmembrane TMEM19/ encoding SEQ protein 19; unknown 55266 ID NO.: 87 function SEQ ID NO. 45 STAR clone AC109350 Novel genomic hit SEQ ID NO. 46 STAR clone AC104837 Novel genomic hit SEQ ID NO. 47 STAR clone AC002060 Immunoglobulin lambda variable group @; may play a role in antigen binding SEQ ID NO. 48 Hs.200600/ NM_005698 254-1297 Secretory carrier SCAMP3/ encoding SEQ membrane protein 3; 10067 ID NO.: 88 post-Golgi transport, protein transport SEQ ID NO. 49 STAR clone AC068288 SEQ ID NO. 50 Hs.73769/ NM_000802 26-799 folate receptor 1 FOLR1/ encoding SEQ (adult); 2348 ID NO.: 89 mediate delivery of 5- methyltetrahydrofolate to the interior of cells SEQ ID NO. 169 Hs.558314/ NM_000096 251-3448 Ceruloplasmin; CP/ encoding SEQ secreted protein; 1356 ID NO.: 170 copper ion binding or transport
TABLE-US-00006 TABLE 3 List of additional sequences identification of plasmids, oligonucleotides and shRNA oligonucleotides Sequence Identification name Description SEQ. ID. NO. 90 OGS 364 Oligo dT.sub.11 + Not 1 + biotin SEQ. ID. NO. 91 OGS 594 Oligonucleotide promoter tag 1 SEQ. ID. NO. 92 OGS 595 Oligonucleotide promoter tag 1 SEQ. ID. NO. 93 OGS 458 Oligonucleotide promoter tag 2 SEQ. ID. NO. 94 OGS 459 Oligonucleotide promoter tag 2 SEQ. ID. NO. 95 OGS 494 Primer for second-strand synthesis from tag 1 SEQ. ID. NO. 96 OGS 302 Primer for second-strand synthesis from tag 2 SEQ. ID. NO. 97 OGS 621 Oligonucleotide promoter SEQ. ID. NO. 98 OGS 622 Oligonucleotide promoter SEQ. ID. NO. 99 pCATRMAN Vector for STAR SEQ. ID. NO. 100 p20 Vector for STAR SEQ. ID. NO: 101 pSilencer2.0 vector Vector for shRNA SEQ. ID. NO: 102 sh-scr Control shRNA (Ambion) SEQ. ID. NO: 103 sh-1 0094 shRNA sequence for SEQ. ID. NO. 1 SEQ. ID. NO: 104 sh-2 0094 shRNA sequence for SEQ. ID. NO. 1 SEQ. ID. NO: 105 sh-1 0478 shRNA sequence for SEQ. ID. NO. 2 SEQ. ID. NO: 106 sh-2 0478 shRNA sequence for SEQ ID NO. 2 SEQ. ID. NO: 107 sh-1 0671 shRNA sequence for SEQ. ID. NO. 3 SEQ. ID. NO: 108 sh-2 0671 shRNA sequence for SEQ. ID. NO. 3 SEQ. ID. NO: 109 sh-1 0851 shRNA sequence for SEQ. ID. NO. 4 SEQ. ID. NO: 110 sh-2 0851 shRNA sequence for SEQ ID NO. 4 SEQ. ID. NO: 111 sh-1 0713 shRNA sequence for SEQ. ID. NO. 5 SEQ. ID. NO: 112 sh-2 0713 shRNA sequence for SEQ. ID. NO. 5 SEQ. ID. NO: 113 sh-1 1064 shRNA sequence for SEQ. ID. NO. 5 SEQ. ID. NO: 114 sh-2 1064 shRNA sequence for SEQ ID NO. 6 SEQ. ID. NO: 115 sh-1 1096 shRNA sequence for SEQ. ID. NO. 7 SEQ. ID. NO: 116 sh-2 1096 shRNA sequence for SEQ. ID. NO. 7 SEQ. ID. NO: 117 sh-1 0065 shRNA sequence for SEQ. ID. NO. 8 SEQ. ID. NO: 118 sh-2 0065 shRNA sequence for SEQ ID NO. 8 SEQ. ID. NO: 119 sh-1 1313 shRNA sequence for SEQ. ID. NO. 9 SEQ. ID. NO: 120 sh-2 1313 shRNA sequence for SEQ ID NO. 9 SEQ. ID. NO: 121 sh-1 0059 shRNA sequence for SEQ. ID. NO. 10 SEQ. ID. NO: 122 sh-2 0059 shRNA sequence for SEQ ID NO. 10 SEQ. ID. NO: 123 sh-1 0239 shRNA sequence for SEQ. ID. NO. 11 SEQ. ID. NO: 124 sh-2 0239 shRNA sequence for SEQ ID NO. 11 SEQ. ID. NO: 125 sh-1 0291 shRNA sequence for SEQ. ID. NO. 12 SEQ. ID. NO: 126 sh-2 0291 shRNA sequence for SEQ ID NO. 12 SEQ. ID. NO: 127 sh-1 0972 shRNA sequence for SEQ. ID. NO. 13 SEQ. ID. NO: 128 sh-2 0972 shRNA sequence for SEQ ID NO. 13 SEQ. ID. NO: 129 sh-1 0875 shRNA sequence for SEQ. ID. NO. 14 SEQ. ID. NO: 130 sh-2 0875 shRNA sequence for SEQ ID NO. 14 SEQ. ID. NO: 131 sh-1 0420 shRNA sequence for SEQ. ID. NO. 15 SEQ. ID. NO: 132 sh-2 0420 shRNA sequence for SEQ ID NO. 15 SEQ. ID. NO: 133 sh-1 0125 shRNA sequence for SEQ. ID. NO. 16 SEQ. ID. NO: 134 sh-2 0125 shRNA sequence for SEQ ID NO. 16 SEQ. ID. NO: 135 sh-1 0531 shRNA sequence for SEQ. ID. NO. 17 SEQ. ID. NO: 136 sh-2 0531 shRNA sequence for SEQ ID NO. 17 SEQ. ID. NO: 137 sh-1 0967B shRNA sequence for SEQ. ID. NO. 18 SEQ. ID. NO: 138 sh-2 0967B shRNA sequence for SEQ ID NO. 18 SEQ. ID. NO: 139 sh-1 0889 shRNA sequence for SEQ. ID. NO. 19 SEQ. ID. NO: 140 sh-2 0889 shRNA sequence for SEQ ID NO. 19 SEQ. ID. NO: 141 sh-1 0313 shRNA sequence for SEQ. ID. NO. 20 SEQ. ID. NO: 142 sh-2 0313 shRNA sequence for SEQ ID NO. 20 SEQ. ID. NO: 143 sh-1 1134 shRNA sequence for SEQ. ID. NO. 21 SEQ. ID. NO: 144 sh-2 1134 shRNA sequence for SEQ ID NO. 21 SEQ. ID. NO: 145 sh-1 0488 shRNA sequence for SEQ. ID. NO. 22 SEQ. ID. NO: 146 sh-2 0488 shRNA sequence for SEQ ID NO. 22 SEQ. ID. NO: 147 sh-1 0216 shRNA sequence for SEQ. ID. NO. 23 SEQ. ID. NO: 148 sh-2 0216 shRNA sequence for SEQ ID NO. 23 SEQ. ID. NO: 149 sh-1 0447 shRNA sequence for SEQ. ID. NO. 24 SEQ. ID. NO: 150 sh-2 0447 shRNA sequence for SEQ ID NO. 24 SEQ. ID. NO: 151 sh-1 0967 shRNA sequence for SEQ. ID. NO. 50 SEQ. ID. NO: 152 sh-2 0967 shRNA sequence for SEQ ID NO. 50 SEQ. ID. NO: 153 OGS 1077 Forward primer for SEQ ID NO. 32 SEQ. ID. NO: 154 OGS 1078 Reverse primer for SEQ ID NO. 32 SEQ. ID. NO: 155 OGS 1141 Forward primer for SEQ ID NO. 35 SEQ. ID. NO: 156 OGS 1142 Reverse primer for SEQ ID NO. 35 SEQ. ID. NO: 157 OGS 1202 Forward primer for SEQ ID NO. 38 SEQ. ID. NO: 158 OGS 1203 Reverse primer for SEQ ID NO. 38 SEQ. ID. NO: 159 OGS 1212 Forward primer for SEQ ID NO. 41 SEQ. ID. NO: 160 OGS 1213 Reverse primer for SEQ ID NO. 41 SEQ. ID. NO: 161 OGS 1171 Forward primer for SEQ ID NO. 44 SEQ. ID. NO: 162 OGS 1172 Reverse primer for SEQ ID NO. 44 SEQ. ID. NO: 163 OGS 1175 Forward primer for SEQ ID NO. 45 SEQ. ID. NO: 164 OGS 1176 Reverse primer for SEQ ID NO. 45 SEQ. ID. NO: 165 OGS 1282 Forward primer for SEQ ID NO. 48 SEQ. ID. NO: 166 OGS 1283 Reverse primer for SEQ ID NO. 48 SEQ. ID. NO: 167 OGS 315 Forward primer for human GAPDH SEQ. ID. NO: 168 OGS 316 Reverse primer for human GAPDH SEQ. ID NO. 171 OGS 1136 Forward primer for SEQ ID NO. 1 SEQ. ID NO. 172 OGS 1044 Reverse primer for SEQ ID NO. 1 SEQ. ID NO. 173 OGS 1250 Forward primer for SEQ ID NO. 2 SEQ. ID NO. 174 OGS 1251 Reverse primer for SEQ ID NO. 2 SEQ. ID NO. 175 OGS 1049 Forward primer for SEQ ID NO. 3 SEQ. ID NO. 176 OGS 1050 Reverse primer for SEQ ID NO. 3 SEQ. ID NO. 177 OGS 1051 Forward primer for SEQ ID NO. 4 SEQ. ID NO. 178 OGS 1052 Reverse primer for SEQ ID NO. 4 SEQ. ID NO. 179 OGS 1252 Forward primer for SEQ ID NO. 5 SEQ. ID NO. 180 OGS 1253 Reverse primer for SEQ ID NO. 5 SEQ. ID NO. 181 OGS 1083 Forward primer for SEQ ID NO. 6 SEQ. ID NO. 182 OGS 1084 Reverse primer for SEQ ID NO. 6 SEQ. ID NO. 183 OGS 1053 Forward primer for SEQ ID NO. 7 SEQ. ID NO. 184 OGS 1054 Reverse primer for SEQ ID NO. 7 SEQ. ID NO. 185 OGS 1037 Forward primer for SEQ ID NO. 8 SEQ. ID NO. 186 OGS 1038 Reverse primer for SEQ ID NO. 8 SEQ. ID NO. 187 OGS 1045 Forward primer for SEQ ID NO. 9 SEQ. ID NO. 188 OGS 1046 Reverse primer for SEQ ID NO. 9 SEQ. ID NO. 189 OGS 1240 Forward primer for SEQ ID NO. 10 SEQ. ID NO. 190 OGS 1241 Reverse primer for SEQ ID NO. 10 SEQ. ID NO. 191 OGS 1304 Forward primer for SEQ ID NO. 11 SEQ. ID NO. 192 OGS 1305 Reverse primer for SEQ ID NO. 11 SEQ. ID NO. 193 OGS 1039 Forward primer for SEQ ID NO. 12 SEQ. ID NO. 194 OGS 1040 Reverse primer for SEQ ID NO. 12 SEQ. ID NO. 195 OGS 1095 Forward primer for SEQ ID NO. 13 SEQ. ID NO. 196 OGS 1096 Reverse primer for SEQ ID NO. 13 SEQ. ID NO. 197 OGS 1284 Forward primer for SEQ ID NO. 15 SEQ. ID NO. 198 OGS 1285 Reverse primer for SEQ ID NO. 15 SEQ. ID NO. 199 OGS 1063 Forward primer for SEQ ID NO. 16 SEQ. ID NO. 200 OGS 1064 Reverse primer for SEQ ID NO. 16 SEQ. ID NO. 201 OGS 1031 Forward primer for SEQ ID NO. 17 SEQ. ID NO. 202 OGS 1032 Reverse primer for SEQ ID NO. 17 SEQ. ID NO. 203 OGS 1308 Forward primer for SEQ ID NO. 18 SEQ. ID NO. 204 OGS 1309 Reverse primer for SEQ ID NO. 18 SEQ. ID NO. 205 OGS 1069 Forward primer for SEQ ID NO. 19 SEQ. ID NO. 206 OGS 1070 Reverse primer for SEQ ID NO. 19 SEQ. ID NO. 207 OGS 1061 Forward primer for SEQ ID NO. 20 SEQ. ID NO. 208 OGS 1062 Reverse primer for SEQ ID NO. 20 SEQ. ID NO. 209 OGS 1097 Forward primer for SEQ ID NO. 21 SEQ. ID NO. 210 OGS 1098 Reverse primer for SEQ ID NO. 21 SEQ. ID NO. 211 OGS 1075 Forward primer for SEQ ID NO. 22 SEQ. ID NO. 212 OGS 1076 Reverse primer for SEQ ID NO. 22 SEQ. ID NO. 213 OGS 1232 Forward primer for SEQ ID NO. 23 SEQ. ID NO. 214 OGS 1233 Reverse primer for SEQ ID NO. 23 SEQ. ID NO. 215 OGS 1067 Forward primer for SEQ ID NO. 24 SEQ. ID NO. 216 OGS 1068 Reverse primer for SEQ ID NO. 24 SEQ. ID NO. 217 OGS 1099 Forward primer for SEQ ID NO. 25 SEQ. ID NO. 218 OGS 1100 Reverse primer for SEQ ID NO. 25 SEQ. ID NO. 219 OGS 1246 Forward primer for SEQ ID NO. 26 SEQ. ID NO. 220 OGS 1247 Reverse primer for SEQ ID NO. 26 SEQ. ID NO. 221 OGS 1093 Forward primer for SEQ ID NO. 27 SEQ. ID NO. 222 OGS 1094 Reverse primer for SEQ ID NO. 27 SEQ. ID NO. 223 OGS 1332 Forward primer for SEQ ID NO. 28 SEQ. ID NO. 224 OGS 1333 Reverse primer for SEQ ID NO. 28 SEQ. ID NO. 225 OGS 1101 Forward primer for SEQ ID NO. 29 SEQ. ID NO. 226 OGS 1102 Reverse primer for SEQ ID NO. 29 SEQ. ID NO. 227 OGS 1300 Forward primer for SEQ ID NO. 30 SEQ. ID NO. 228 OGS 1301 Reverse primer for SEQ ID NO. 30 SEQ. ID NO. 229 OGS 1302 Forward primer for SEQ ID NO. 31 SEQ. ID NO. 230 OGS 1303 Reverse primer for SEQ ID NO. 31 SEQ. ID NO. 231 OGS 1292 Forward primer for SEQ ID NO. 33 SEQ. ID NO. 232 OGS 1294 Reverse primer for SEQ ID NO. 33 SEQ. ID NO. 233 OGS 1242 Forward primer for SEQ ID NO. 34 SEQ. ID NO. 234 OGS 1243 Reverse primer for SEQ ID NO. 34 SEQ. ID NO. 235 OGS 1280 Forward primer for SEQ ID NO. 36 SEQ. ID NO. 236 OGS 1281 Reverse primer for SEQ ID NO. 36 SEQ. ID NO. 237 OGS 1159 Forward primer for SEQ ID NO. 37 SEQ. ID NO. 238 OGS 1160 Reverse primer for SEQ ID NO. 37 SEQ. ID NO. 239 OGS 1310 Forward primer for SEQ ID NO. 39 SEQ. ID NO. 240 OGS 1311 Reverse primer for SEQ ID NO. 39 SEQ. ID NO. 241 OGS 1155 Forward primer for SEQ ID NO. 40 SEQ. ID NO. 242 OGS 1156 Reverse primer for SEQ ID NO. 40 SEQ. ID NO. 243 OGS 1316 Forward primer for SEQ ID NO. 42 SEQ. ID NO. 244 OGS 1317 Reverse primer for SEQ ID NO. 42 SEQ. ID NO. 245 OGS 1306 Forward primer for SEQ ID NO. 43 SEQ. ID NO. 246 OGS 1307 Reverse primer for SEQ ID NO. 43 SEQ. ID NO. 247 OGS 1286 Forward primer for SEQ ID NO. 46 SEQ. ID NO. 248 OGS 1287 Reverse primer for SEQ ID NO. 46 SEQ. ID NO. 249 OGS 1244 Forward primer for SEQ ID NO. 47 SEQ. ID NO. 250 OGS 1245 Reverse primer for SEQ ID NO. 47 SEQ. ID NO. 251 OGS 1035 Forward primer for SEQ ID NO. 50 SEQ. ID NO. 252 OGS 1036 Reverse primer for SEQ ID NO. 50 SEQ. ID NO. 253 OGS 1248 Forward primer for SEQ ID NO. 51 SEQ. ID NO. 254 OGS 1249 Reverse primer for SEQ ID NO. 51
TABLE-US-00007 TABLE 4 Nucleotide and amino acid sequences of the SEQ. ID NOs. Nucleotide Sequence (5'-3') ORFs SEQ.ID NO. 1 SEQ.ID NO. 51 STAR clone: MPVINIEDLTEKDKLKMEVDQLKKEV CTGGAAGCTGAAGAATCACCGGCTTCAGTGACATGGAACCCAGCGATTTGATTTTTGACGAGTATCG TLERMLVSKCCEEVRDYVEERSGEDP GGTGACTTTGAGGTGGTCAAGAAACCACACTTTAAGAACAATGTCCA LVKGIPEDKNPFKELKGGCVIS NM_021955: AATCATATTAGTGAAGATTAGGAAGAAGCTTTAAAATCCCAAGGCTAGTGTGCATTGCTAGAATTGT TAAGAGAGAGAGCTCATATGAAATTGGTTATCGTGGGATATTTAAAATAAAACAAAGAACAGTTTAC TTTCAGGCAAAAAGATGCCAGTAATCAATATTGAGGACCTGACAGAAAAGGACAAATTGAAGATGGA AGTTGACCAGCTCAAGAAAGAAGTGACACTGGAAAGAATGCTAGTTTCCAAATGTTGTGAAGAAGTA AGAGATTACGTTGAAGAACGATCTGGCGAGGATCCACTGGTAAAGGGCATCCCAGAGGACAAAAATC CCTTCAAGGAGCTCAAAGGAGGCTGTGTGATTTCATAATACAAACAAAAAGAAAAAAAATTAAACAA ATTCTTGGAAATATCTCAAATGTTAATAACAATATGAATTTTTCTCATGCATACTATTACTACTAAG CATGTACGTGAATTTTTAAATTTATAGATGTAAACTTTTAATAAAAATTGGGGTGTGGTAACCCATC ATTCTATGTTTTTCTTAACATAGCTGGCACAGGGTTTAACACATAATTGCCAATAAATATTGCTTAA AGTTCTTTAAAAAGAACTATGTTTT SEQ.ID NO. 2 SEQ.ID NO. 52 GCACGAGGAAGCCACAGATCTCTTAAGAACTTTCTGTCTCCAAACCGTGGCTGCTCGATAAATCAGA MVERCSRQGCTITMAYIDYNMIVAFM CAGAACAGTTAATCCTCAATTTAAGCCTGATCTAACCCCTAGAAACAGATATAGAACAATGGAAGTG LGNYINLRESSTEPNDSLWFSLQKKN ACAACAAGATTGACATGGAATGATGAAAATCATCTGCGCAACTGCTTGGAAATGTTTCTTTGAGTCT DTTEIETLLLNTAPKIIDEQLVCRLS TCTCTATAAGTCTAGTGTTCATGGAGGTAGCATTGAAGATATGGTTGAAAGATGCAGCCGTCAGGGA KTDIFIICRDNKIYLDKMITRNLKLR TGTACTATAACAATGGCTTACATTGATTACAATATGATTGTAGCCTTTATGCTTGGAAATTATATTA FYGHRQYLECEVERVEGIKDNLDDIK ATTTACGTGAAAGTTCTACAGAGCCAAATGATTCCCTATGGTTTTCACTTCAAAAGAAAAATGACAC RIIKAREHRNRLLADIRDYRPYADLV CACTGAAATAGAAACTTTACTCTTAAATACAGCACCAAAAATTATTGATGAGCAACTGGTGTGTCGT SEIRILLVGPVGSGKSSFFNSVKSIF TTATCGAAAACGGATATTTTCATTATATGTCGAGATAATAAAATTTATCTAGATAAAATGATAACAA HGHVTGQAVVGSDTTSITERYRIYSV GAAACTTGAAACTAAGGTTTTATGGCCACCGTCAGTATTTGGAATGTGAAGTTTTTCGAGTTGAAGG KDGKNGKSLPFMLCDTMGLDGAEGAG AATTAAGGATAACCTAGACGACATAAAGAGGATAATTAAAGCCAGAGAGCACAGAAATAGGCTTCTA LCMDDIPHILKGCMPDRYQFNSRKPI GCAGACATCAGAGACTATAGGCCCTATGCAGACTTGGTTTCAGAAATTCGTATTCTTTTGGTGGGTC TPEHSTFITSPSLKDRIHCVAYVLDI CAGTTGGGTCTGGAAAGTCCAGTTTTTTCAATTCAGTCAAGTCTATTTTTCATGGCCATGTGACTGG NSIDNLYSKMLAKVKQVHKEVLNCGI CCAAGCCGTAGTGGGGTCTGATACCACCAGCATAACCGAGCGGTATAGGATATATTCTGTTAAAGAT AYVALLTKVDDCSEVLQDNFLNMSRS GGAAAAAATGGAAAATCTCTGCCATTTATGTTGTGTGACACTATGGGGCTAGATGGGGCAGAAGGAG MTSQSRVMNVHKMLGIPISNILMVGN CAGGACTGTGCATGGATGACATTCCCCACATCTTAAAAGGTTGTATGCCAGACAGATATCAGTTTAA YASDLELDPMKDILILSALRQMLRAA TTCCCGTAAACCAATTACACCTGAGCATTCTACTTTTATCACCTCTCCATCTCTGAAGGACAGGATT DDFLEDLPLEETGAIERALQPCI CACTGTGTGGCTTATGTCTTAGACATCAACTCTATTGACAATCTCTACTCTAAAATGTTGGCAAAAG TGAAGCAAGTTCACAAAGAAGTATTAAACTGTGGTATAGCATATGTGGCCTTGCTTACTAAAGTGGA TGATTGCAGTGAGGTTCTTCAAGACAACTTTTTAAACATGAGTAGATCTATGACTTCTCAAAGCCGG GTCATGAATGTCCATAAAATGCTAGGCATTCCTATTTCCAATATTTTGATGGTTGGAAATTATGCTT CAGATTTGGAACTGGACCCCATGAAGGATATTCTCATCCTCTCTGCACTGAGGCAGATGCTGCGGGC TGCAGATGATTTTTTAGAAGATTTGCCTCTTGAGGAAACTGGTGCAATTGAGAGAGCGTTACAGCCC TGCATTTGAGATAAGTTGCCTTGATTCTGACATTTGGCCCAGCCTGTACTGGTGTGCCGCAATGAGA GTCAATCTCTATTGACAGCCTGCTTCAGATTTTGCTTTTGTTCGTTTTGCCTTCTGTCCTTGGAACA GTCATATCTCAAGTTCAAAGGCCAAAACCTGAGAAGCGGTGGGCTAAGATAGGTCCTACTGCAAACC ACCCCTCCATATTTCCGTACCATTTACAATTCAGTTTCTGTGACATCTTTTTAAACCACTGGAGGAA AAATGAGATATTCTCTAATTTATTCTTCTATAACACTCTATATAGAGCTATGTGAGTACTAATCACA TTGAATAATAGTTATAAAATTATTGTATAGACATCTGCTTCTTAAACAGATTGTGAGTTCTTTGAGA AACAGCGTGGATTTTACTTATCTGTGTATTCACAGAGCTTAGCACAGTGCCTGGTAATGAGCAAGCA TACTTGCCATTACTTTTCCTTCCCACTCTCTCCAACATCACATTCACTTTAAATTTTTCTGTATATA GAAAGGAAAACTAGCCTGGGCAACATGATGAAACCCCATCTCCACTGC SEQ.ID NO. 3 SEQ.ID NO. 53 GCCGAGCGGAGAGGCCGCCCATTGGCCGGCCAGCGCCACGTGGCCGCCCCCGCCGGTATATTAGGCC MSSYLEYVSCSSSGGVGGDVLSLAPK ACTATTTACCTCCGGCTCACTCGCCATGGGTTGGAGAGGGCAGCTCGGGTAGAGAGGGCTGGCGGAG FCRSDARPVALQPAFPLGNGDGAFVS CGGCGCAGACGGCGGCAGTCCTGCTCAGCCTCTGCCCGGCTCCGTACTCCGGCCCCGGCCTGCGCCC CLPLAAARPSPSPPAAPARPSVPPPA TCAGAAAGGTGGGGCCCGAACCATGAGCTCCTACCTGGAGTACGTGTCATGCAGCAGCAGCGGCGGG APQYAQCTLEGAYEPGAAPAAAAGGA GTCGGCGGCGACGTGCTCAGCTTGGCACCCAAGTTCTGCCGCTCCGACGCCCGGCCCGTGGCTCTGC DYGFLGSGPAYDFPGVLGRAADDGGS AGCCCGCCTTCCCTCTGGGCAACGGCGACGGCGCCTTCGTCAGCTGTCTGCCCCTGGCCGCCGCCCG HVHYATSAVFSGGGSFLLSGQVDYAA ACCCTCGCCTTCGCCCCCGGCCGCCCCCGCGCGGCCGTCCGTACCGCCTCCGGCCGCGCCCCAGTAC FGEPGPFPACLKASADGHPGAFQTAS GCGCAGTGCACCCTGGAGGGGGCCTACGAACCTGGTGCCGCACCTGCCGCGGCAGCTGGGGGCGCGG PAPGTYPKSVSPASGLPAAFSTFEWM ACTACGGCTTCCTGGGGTCCGGGCCGGCGTACGACTTCCCGGGCGTGCTGGGGCGGGCGGCCGACGA KVKRNASKKGKLAEYGAASPSSAIRT CGGCGGGTCTCACGTCCACTACGCCACCTCGGCCGTCTTCTCGGGCGGCGGCTCTTTCCTCCTCAGC NFSTKQLTELEKEFHFNKYLTRARRI GGCCAGGTGGATTACGCGGCCTTCGGCGAACCCGGCCCTTTTCCGGCTTGTCTCAAAGCGTCAGCCG EIANCLHLNDTQVKIWFQNRRMKQKK ACGGCCACCCTGGTGCTTTCCAGACCGCATCCCCGGCCCCAGGCACCTACCCCAAGTCCGTCTCTCC REREGLLATAIPVAPLQLPLSGTTPT CGCCTCCGGCCTCCCTGCCGCCTTCAGCACGTTCGAGTGGATGAAAGTGAAGAGGAATGCCTCTAAG KFIKNPGSPSQSQEPS AAAGGTAAACTCGCCGAGTATGGGGCCGCTAGCCCCTCCAGCGCGATCCGCACGAATTTCAGCACCA AGCAACTGACAGAACTGGAAAAAGAGTTTCATTTCAATAAGTACTTAACTCGAGCCCGGCGCATCGA GATAGCCAACTGCTTGCACCTGAATGACACGCAAGTCAAAATCTGGTTCCAGAACCGCAGGATGAAA CAGAAGAAAAGGGAACGAGAAGGGCTTCTGGCCACGGCCATTCCTGTGGCTCCCCTCCAACTTCCCC TCTCTGGAACAACCCCCACTAAGTTTATCAAGAACCCCGGCAGCCCTTCTCAGTCCCAAGAGCCTTC GTGAGGCCGGTACTTGGGGCCGAAAAACTGTGGCCTGCAGAAGTCCCAGGCGACCCCCATCCCTATC TAGACTTAGGAGCTCAGTTTGGGATGGAGGTGGGAGAACAAAAATGAATAGGGATTTCACTTGGGAA ATGAAGTACTTTAGTTGGCTTCCGAGTTCCAGACTATATGTCCAGATATTAATTGACTGTCTTGTAA GCCACTTGTTTGGTTATGATTTGTGTCTTATCAGGGAAAAGGTGCCCAGCTGCCAGCCCAGCTCCGC TGCTATCTTTGCCTCACTTAGTCATGTGCAATTCGCGTTGCAGAGTGGCAGACCATTAGTTGCTGAG TTCTGTCAGCACTCTGATGTGCTCAGAAGAGCACCTGCCCAAAGTTTTTCTGGTTTTAATTTAAAGG ACAAGGCTACATATATTCAGCTTTTTGAGATGACCAAAGCTAGTTAGGGTCTCCTTGATGTAGCTAA GCTGCTTCAGTGATCTTCACATTTGCACTCCAGTTTTTTTTTCTTTAAAAAAGCGGTTTCTACCTCT CTATGTGCCTGAGTGATGATACAATCGCTGTTTAGTTACTAGATGAACAAATCCACAGAATGGGTAA AGAGTAGAATCTGAACTATATCTTGACAAATATTATTCAAACTTGAATGTAAATATATACAGTATGT ATATTTTTTAAAAAGATTTGCTTGCAATGACCTTATAAGTGACATTTAATGTCATAGCATGTAAAGG GTTTTTTTTGTAATAAAAATTATAGAATCTGCAAAAAAAAAAAAAAAA SEQ.ID NO. 4 SEQ.ID NO. 54 CAGCCTCCAGAGCACCAGCACTGGCACTGGCACTGGCACACGCTATGGCAAATGAAGTGCAAGACCT MANEVQDLLSPRKGGHPPAVKAGGMR GCTCTCCCCTCGGAAAGGGGGACATCCTCCTGCAGTAAAAGCTGGAGGAATGAGAATTTCCAAAAAA ISKKQEIGTLERHTKKTGFEKTSAIA CAAGAAATTGGCACCTTGGAAAGACATACCAAAAAAACAGGATTCGAGAAAACAAGTGCCATTGCAA NVAKIQTLDALNDTLEKLNYKFPATV ATGTTGCCAAAATACAGACACTGGATGCCCTGAATGACACACTGGAGAAGCTCAACTATAAATTTCC HMAHQKPTPALEKVVPLKRIYIIQQP AGCAACAGTGCACATGGCACATCAAAAACCCACACCTGCTCTGGAAAAGGTTGTTCCACTGAAAAGG RKC ATCTACATTATTCAGCAGCCTCGAAAATGTTAAGCCTGGATTTAAAACACAGCCGTCTGGCCAGCTG CCTCGAATATCTGACAGCTTAGCAAAAAGGGCCAAAGCTTTCCATAGGCGTGCTGCACTTGCTTGGT AAATTAAACAGCTTTTGTATCTTCCCCTTTGACTTTAGGTAATAAAGCATCCAAACTTGTAAAAAAA AAA SEQ.ID NO. 5 SEQ.ID NO. 55 GTAACTGAAAATCCACAAGACAGAATAGCCAGATCTCAGAGGAGCCTGGCTAAGCAAAACCCTGCAG MSTNGDDHQVKDSLEQLRCHFTWELS AACGGCTGCCTAATTTACAGCAACCATGAGTACAAATGGTGATGATCATCAGGTCAAGGATAGTCTG IDDDEMPDLENRVLDQIEFLDTKYSV GAGCAATTGAGATGTCACTTTACATGGGAGTTATCCATTGATGACGATGAAATGCCTGATTTAGAAA GIHNLLAYVKHLKGQNEEALKSLKEA ACAGAGTCTTGGATCAGATTGAATTCCTAGACACCAAATACAGTGTGGGAATACACAACCTACTAGC ENLMQEEHDNQANVRSLVTWGNFAWM CTATGTGAAACACCTGAAAGGCCAGAATGAGGAAGCCCTGAAGAGCTTAAAAGAAGCTGAAAACTTA YYHMGRLAEAQTYLDKVENICKKLSN ATGCAGGAAGAACATGACAACCAAGCAAATGTGAGGAGTCTGGTGACCTGGGGCAACTTTGCCTGGA PFRYRMECPEIDCEEGWALLKCGGKN TGTATTACCACATGGGCAGACTGGCAGAAGCCCAGACTTACCTGGACAAGGTGGAGAACATTTGCAA YERAKACFEKVLEVDPENPESSAGYA GAAGCTTTCAAATCCCTTCCGCTATAGAATGGAGTGTCCAGAAATAGACTGTGAGGAAGGATGGGCC ISAYRLDGFKLATKNHKPFSLLPLRQ TTGCTGAAGTGTGGAGGAAAGAATTATGAACGGGCCAAGGCCTGCTTTGAAAAGGTGCTTGAAGTGG AVRLNPDNGYIKVLLALKLQDEGQEA ACCCTGAAAACCCTGAATCCAGCGCTGGGTATGCGATCTCTGCCTATCGCCTGGATGGCTTTAAATT EGEKYIEEALANMSSQTYVFRYAAKF AGCCACAAAAAATCACAAGCCATTTTCTTTGCTTCCCCTAAGGCAGGCTGTCCGCTTAAATCCAGAC YRRKGSVDKALELLKKALQETPTSVL AATGGATATATTAAGGTTCTCCTTGCCCTGAAGCTTCAGGATGAAGGACAGGAAGCTGAAGGAGAAA LHHQIGLCYKAQMIQIKEATKGQPRG AGTACATTGAAGAAGCTCTAGCCAACATGTCCTCACAGACCTATGTCTTTCGATATGCAGCCAAGTT QNREKLDKMIRSAIFHFESAVEKKPT TTACCGAAGAAAAGGCTCTGTGGATAAAGCTCTTGAGTTATTAAAAAAGGCCTTGCAGGAAACACCC FEVAHLDLARMYIEAGNHRKAEENFQ ACTTCTGTCTTACTGCATCACCAGATAGGGCTTTGCTACAAGGCACAAATGATCCAAATCAAGGAGG KLLCMKPVVEETMQDIHFHYGRFQEF CTACAAAAGGGCAGCCTAGAGGGCAGAACAGAGAAAAGCTAGACAAAATGATAAGATCAGCCATATT QKKSDVNAIIHYLKAIKIEQASLTRD TCATTTTGAATCTGCAGTGGAAAAAAAGCCCACATTTGAGGTGGCTCATCTAGACCTGGCAAGAATG KSINSLKKLVLRKLRRKALDLESLSL TATATAGAAGCAGGCAATCACAGAAAAGCTGAAGAGAATTTTCAAAAATTGTTATGCATGAAACCAG LGFVYKLEGNMNEALEYYERALRLAA TGGTAGAAGAAACAATGCAAGACATACATTTCCACTATGGTCGGTTTCAGGAATTTCAAAAGAAATC DFENSVRQGP TGACGTCAATGCAATTATCCATTATTTAAAAGCTATAAAAATAGAACAGGCATCATTAACAAGGGAT AAAAGTATCAATTCTTTGAAGAAATTGGTTTTAAGGAAACTTCGGAGAAAGGCATTAGATCTGGAAA GCTTGAGCCTCCTTGGGTTCGTCTACAAATTGGAAGGAAATATGAATGAAGCCCTGGAGTACTATGA GCGGGCCCTGAGACTGGCTGCTGACTTTGAGAACTCTGTGAGACAAGGTCCTTAGGCACCCAGATAT CAGCCACTTTCACATTTCATTTCATTTTATGCTAACATTTACTAATCATCTTTTCTGCTTACTGTTT TCAGAAACATTATAATTCACTGTAATGATGTAATTCTTGAATAATAAATCTGACAAAAAAAAAAAAA AAAAAAAAAAAAAAA SEQ.ID NO. 6 SEQ.ID NO. 56 CCCGCGAGCGTCCATCCATCTGTCCGGCCGACTGTCCAGCGAAAGGGGCTCCAGGCCGGGCGCACGT MQSCARAWGLRLGRGVGGGRRLAGGS CGACCCGGGGGACCGAGGCCAGGAGAGGGGCCAAGAGCGCGGCTGACCCTTGCGGGCCGGGGCAGGG GPCWAPRSRDSSSGGGDSAAAGASRL GACGGTGGCCGCGGCCATGCAGTCCTGTGCCAGGGCGTGGGGGCTGCGCCTGGGCCGCGGGGTCGGG LERLLPRHDDFARRHIGPGDKDQREM GGCGGCCGCCGCCTGGCTGGGGGATCGGGGCCGTGCTGGGCGCCGCGGAGCCGGGACAGCAGCAGTG LQTLGLASIDELIEKTVPANIRLKRP GCGGCGGGGACAGCGCCGCGGCTGGGGCCTCGCGCCTCCTGGAGCGCCTTCTGCCCAGACACGACGA LKMEDPVCENEILATLHAISSKNQIW CTTCGCTCGGAGGCACATCGGCCCTGGGGACAAAGACCAGAGAGAGATGCTGCAGACCTTGGGGCTG RSYIGMGYYNCSVPQTILRNLLENSG GCGAGCATTGATGAATTGATCGAGAAGACGGTCCCTGCCAACATCCGTTTGAAAAGACCCTTGAAAA WITQYTPYQPEVSQGRLESLLNYQTM TGGAAGACCCTGTTTGTGAAAATGAAATCCTTGCAACTCTGCATGCCATTTCAAGCAAAAACCAGAT VCDITGLDMANASLLDEGTAAAEALQ CTGGAGATCGTATATTGGCATGGGCTATTATAACTGCTCAGTGCCACAGACGATTTTGCGGAACTTA LCYRHNKRRKFLVDPRCHPQTIAVVQ CTGGAGAACTCAGGATGGATCACCCAGTATACTCCATACCAGCCTGAGGTGTCTCAGGGGAGGCTGG TRAKYTGVLTELKLPCEMDFSGKDVS AGAGTTTACTCAACTACCAGACCATGGTGTGTGACATCACAGGCCTGGACATGGCCAATGCATCCCT GVLFQYPDTEGKVEDFTELVERAHQS GCTGGATGAGGGGACTGCAGCCGCAGAGGCACTGCAGCTGTGCTACAGACACAACAAGAGGAGGAAA GSLACCATDLLALCILRPPGEFGVDI TTTCTCGTTGATCCCCGTTGCCACCCACAGACAATAGCTGTTGTCCAGACTCGAGCCAAATATACTG ALGSSQRFGVPLGYGGPHAAFFAVRE GAGTCCTCACTGAGCTGAAGTTACCCTGTGAAATGGACTTCAGTGGAAAAGATGTCAGTGGAGTGTT SLVRMMPGRMVGVTRDATGKEVYRLA GTTCCAGTACCCAGACACGGAGGGGAAGGTGGAAGACTTTACGGAACTCGTGGAGAGAGCTCATCAG LQTREQHIRRDKATSNICTAQALLAN AGTGGGAGCCTGGCCTGCTGTGCTACTGACCTTTTAGCTTTGTGCATCTTGAGGCCACCTGGAGAAT MAAMFRIYHGSHGLEHIARRVHNATL TTGGGGTAGACATCGCCCTGGGCAGCTCCCAGAGATTTGGAGTGCCACTGGGCTATGGGGGACCCCA ILSEGLKRAGHQLQHDLFFDTLKIHC TGCAGCATTTTTTGCTGTCCGAGAAAGCTTGGTGAGAATGATGCCTGGAAGAATGGTGGGGGTAACA GCSVKEVLGRAAQRQINFRLFEDGTL AGAGATGCCACTGGGAAAGAAGTGTATCGTCTTGCTCTTCAAACCAGGGAGCAACACATTCGGAGAG GISLDETVNEKDLDDLLWIFGCESSA ACAAGGCTACCAGCAACATCTGTACAGCTCAGGCCCTCTTGGCGAATATGGCTGCCATGTTTCGAAT ELVAESMGEECRGIPGSVFKRTSPFL CTACCATGGTTCCCATGGGCTGGAGCATATTGCTAGGAGGGTACATAATGCCACTTTGATTTTGTCA THQVFNSYHSETNIVRYMKKLENKDI GAAGGTCTCAAGCGAGCAGGGCATCAACTCCAGCATGACCTGTTCTTTGATACCTTGAAGATTCATT SLVHSMIPLGSCTMKLNSSSELAPIT GTGGCTGCTCAGTGAAGGAGGTCTTGGGCAGGGCGGCTCAGCGGCAGATCAATTTTCGGCTTTTTGA WKEFANIHPFVPLDQAQGYQQLFREL GGATGGCACACTTGGTATTTCTCTTGATGAAACAGTCAATGAAAAAGATCTGGACGATTTGTTGTGG EKDLCELTGYDQVCFQPNSGAQGEYA ATCTTTGGTTGTGAGTCATCTGCAGAACTGGTTGCTGAAAGCATGGGAGAGGAGTGCAGAGGTATTC GLATIRAYLNQKGEGHRTVCLIPKSA CAGGGTCTGTGTTCAAGAGGACCAGCCCGTTCCTCACCCATCAAGTGTTCAACAGCTACCACTCTGA HGTNPASAHMAGMKIQPVEVDKYGNI AACAAACATTGTCCGGTACATGAAGAAACTGGAAAATAAAGACATTTCCCTTGTTCACAGCATGATT DAVHLKAMVDKHKENLAAIMITYPST CCACTGGGATCCTGCACCATGAAACTGAACAGTTCGTCTGAACTCGCACCTATCACATGGAAAGAAT NGVFEENISDVCDLIHQHGGQVYLDG TTGCAAACATCCACCCCTTTGTGCCTCTGGATCAAGCTCAAGGATATCAGCAGCTTTTCCGAGAGCT ANMNAQVGICRPGDFGSDVSHLNLHK TGAGAAGGATTTGTGTGAACTCACAGGTTATGACCAGGTCTGTTTCCAGCCAAACAGCGGAGCCCAG TFCIPHGGGGPGMGPIGVKKHLAPFL GGAGAATATGCTGGACTGGCCACTATCCGAGCCTACTTAAACCAGAAAGGAGAGGGGCACAGAACGG PNHPVISLKRNEDACPVGTVSAAPWG TTTGCCTCATTCCGAAATCAGCACATGGGACCAACCCAGCAAGTGCCCACATGGCAGGCATGAAGAT SSSILPISWAYIKMMGGKGLKQATET TCAGCCTGTGGAGGTGGATAAATATGGGAATATCGATGCAGTTCACCTCAAGGCCATGGTGGATAAG AlLNANYMAKRLETHYRILFRGARGY CACAAGGAGAACCTAGCAGCTATCATGATTACATACCCATCCACCAATGGGGTGTTTGAAGAGAACA VGHEFILDTRPFKKSANIEAVDVAKR TCAGTGACGTGTGTGACCTCATCCATCAACATGGAGGACAGGTCTACCTAGACGGGGCAAATATGAA LQDYGFHAPTMSWPVAGTLMVEPTES
TGCTCAGGTGGGAATCTGTCGCCCTGGAGACTTCGGGTCTGATGTCTCGCACCTAAATCTTCACAAG EDKAELDRFCDAMISIRQEIADIEEG ACCTTCTGCATTCCCCACGGAGGAGGTGGTCCTGGCATGGGGCCCATCGGAGTGAAGAAACATCTCG RIDPRVNPLKMSPHSLTCVTSSHWDR CCCCGTTTTTGCCCAATCATCCCGTCATTTCACTAAAGCGGAATGAGGATGCCTGTCCTGTGGGAAC PYSREVAAFPLPFMKPENKFWPTIAR CGTCAGTGCGGCCCCATGGGGCTCCAGTTCCATCTTGCCCATTTCCTGGGCTTATATCAAGATGATG IDDIYGDQHLVCTCPPMEVYESPFSE GGAGGCAAGGGTCTTAAACAAGCCACGGAAACTGCGATATTAAATGCCAACTACATGGCCAAGCGAT QKRASS TAGAAACACACTACAGAATTCTTTTCAGGGGTGCAAGAGGTTATGTGGGTCATGAATTTATTTTGGA CACGAGACCCTTCAAAAAGTCTGCAAATATTGAGGCTGTGGATGTGGCCAAGAGACTCCAGGATTAT GGATTTCACGCCCCTACCATGTCCTGGCCTGTGGCAGGGACCCTCATGGTGGAGCCCACTGAGTCGG AGGACAAGGCAGAGCTGGACAGATTCTGTGATGCCATGATCAGCATTCGGCAGGAAATTGCTGACAT TGAGGAGGGCCGCATCGACCCCAGGGTCAATCCGCTGAAGATGTCTCCACACTCCCTGACCTGCGTT ACATCTTCCCACTGGGACCGGCCTTATTCCAGAGAGGTGGCAGCATTCCCACTCCCCTTCATGAAAC CAGAGAACAAATTCTGGCCAACGATTGCCCGGATTGATGACATATATGGAGATCAGCACCTGGTTTG TACCTGCCCACCCATGGAAGTTTATGAGTCTCCATTTTCTGAACAAAAGAGGGCGTCTTCTTAGTCC TCTCTCCCTAAGTTTAAAGGACTGATTTGATGCCTCTCCCCAGAGCATTTGATAAGCAAGAAAGATT TCATCTCCCACCCCAGCCTCAAGTAGGAGTTTTATATACTGTGTATATCTCTGTAATCTCTGTCAAG GTAAATGTAAATACAGTAGCTGGAGGGAGTCGAAGCTGATGGTTGGAAGACGGATTTGCTTTGGTAT TCTGCTTCCACATGTGCCAGTTGCCTGGATTGGGAGCCATTTTGTGTTTTGCGTAGAAAGTTTTAGG AACTTTAACTTTTAATGTGGCAAGTTTGCAGATGTCATAGAGGCTATCCTGGAGACTTAATAGACAT TTTTTTGTTCCAAAAGAGTCCATGTGGACTGTGCCATCTGTGGGAAATCCCAGGGCAAATGTTTACA TTTTGTATACCCTGAAGAACTCTTTTTCCTCTAATATGCCTAATCTGTAATCACATTTCTGAGTGTT TTCCTCTTTTTCTGTGTGAGGTTTTTTTTTTTTTTAATCTGCATTTATTAGTATTCTAATAAAAGCA TTTTGATCGGAAAAAAAAAAAAAAAAAAAAA SEQ.ID NO. 7 SEQ.ID NO. 57 GGGTCGTCATGATCCGGACCCCATTGTCGGCCTCTGCCCATCGCCTGCTCCTCCCAGGCTCCCGCGG MIRTPLSASAHRLLLPGSRGRPPRNM CCGACCCCCGCGCAACATGCAGCCCACGGGCCGCGAGGGTTCCCGCGCGCTCAGCCGGCGGTATCTG QPTGREGSRALSRRYLRRLLLLLLLL CGGCGTCTGCTGCTCCTGCTACTGCTGCTGCTGCTGCGGCAGCCCGTAACCCGCGCGGAGACCACGC LLRQPVTRAETTPGAPRALSTLGSPS CGGGCGCCCCCAGAGCCCTCTCCACGCTGGGCTCCCCCAGCCTCTTCACCACGCCGGGTGTCCCCAG LFTTPGVPSALTTPGLTTPGTPKTLD CGCCCTCACTACCCCAGGCCTCACTACGCCAGGCACCCCCAAAACCCTGGACCTTCGGGGTCGCGCG LRGRAQALMRSFPLVDGHNDLPQVLR CAGGCCCTGATGCGGAGTTTCCCACTCGTGGACGGCCACAATGACCTGCCCCAGGTCCTGAGACAGC QRYKNVLQDVNLRNFSHGQTSLDRLR GTTACAAGAATGTGCTTCAGGATGTTAACCTGCGAAATTTCAGCCATGGTCAGACCAGCCTGGACAG DGLVGAQFWSASVSCQSQDQTAVRLA GCTTAGAGACGGCCTCGTGGGTGCCCAGTTCTGGTCAGCCTCCGTCTCATGCCAGTCCCAGGACCAG LEQIDLIHRMCASYSELELVTSAEGL ACTGCCGTGCGCCTCGCCCTGGAGCAGATTGACCTCATTCACCGCATGTGTGCCTCCTACTCTGAAC NSSQKLACLIGVEGGHSLDSSLSVLR TCGAGCTTGTGACCTCAGCTGAAGGTCTGAACAGCTCTCAAAAGCTGGCCTGCCTCATTGGCGTGGA SFYVLGVRYLTLTFTCSTPWAESSTK GGGTGGTCACTCACTGGACAGCAGCCTCTCTGTGCTGCGCAGTTTCTATGTGCTGGGGGTGCGCTAC FRHHMYTNVSGLTSFGEKVVEELNRL CTGACACTTACCTTCACCTGCAGTACACCATGGGCAGAGAGTTCCACCAAGTTCAGACACCACATGT GMMIDLSYASDTLIRRVLEVSQAPVI ACACCAACGTCAGCGGATTGACAAGCTTTGGTGAGAAAGTAGTAGAGGAGTTGAACCGCCTGGGCAT FSHSAARAVCDNLLNVPDDILQLLKK GATGATAGATTTGTCCTATGCATCGGACACCTTGATAAGAAGGGTCCTGGAAGTGTCTCAGGCTCCT NGGIVMVTLSMGVLQCNLLANVSTVA GTGATCTTCTCCCACTCAGCTGCCAGAGCTGTGTGTGACAATTTGTTGAATGTTCCCGATGATATCC DHFDHIRAVIGSEFIGIGGNYDGTGR TGCAGCTTCTGAAGAAGAACGGTGGCATCGTGATGGTGACACTGTCCATGGGGGTGCTGCAGTGCAA FPQGLEDVSTYPVLIEELLSRSWSEE CCTGCTTGCTAACGTGTCCACTGTGGCAGATCACTTTGACCACATCAGGGCAGTCATTGGATCTGAG ELQGVLRGNLLRVFRQVEKVREESRA TTCATCGGGATTGGTGGAAATTATGACGGGACTGGCCGGTTCCCTCAGGGGCTGGAGGATGTGTCCA QSPVEAEFPYGQLSTSCHSHLVPQNG CATACCCAGTCCTGATAGAGGAGTTGCTGAGTCGTAGCTGGAGCGAGGAAGAGCTTCAAGGTGTCCT HQATHLEVTKQPTNRVPWRSSNASPY TCGTGGAAACCTGCTGCGGGTCTTCAGACAAGTGGAAAAGGTGAGAGAGGAGAGCAGGGCGCAGAGC LVPGLVAAATIPTFTQWLC CCCGTGGAGGCTGAGTTTCCATATGGGCAACTGAGCACATCCTGCCACTCCCACCTCGTGCCTCAGA ATGGACACCAGGCTACTCATCTGGAGGTGACCAAGCAGCCAACCAATCGGGTCCCCTGGAGGTCCTC AAATGCCTCCCCATACCTTGTTCCAGGCCTTGTGGCTGCTGCCACCATCCCAACCTTCACCCAGTGG CTCTGCTGACACAGTCGGTCCCCGCAGAGGTCACTGTGGCAAAGCCTCACAAAGCCCCCTCTCCTAG TTCATTCACAAGCATATGCTGAGAATAAACATGTTACACATGGAAAAAAAAAAAAAAAAAAA SEQ.ID NO. 8 SEQ.ID NO. 58 AGTCCTGCGTCCGGGCCCCGAGGCGCAGCAGGGCACCAGGTGGAGCACCAGCTACGCGTGGCGCAGC MLRTESCRPRSPAGQVAAASPLLLLL GCAGCGTCCCTAGCACCGAGCCTCCCGCAGCCGCCGAGATGCTGCGAACAGAGAGCTGCCGCCCCAG LLLAWCAGACRGAPILPQGLQPEQQL GTCGCCCGCCGGACAGGTGGCCGCGGCGTCCCCGCTCCTGCTGCTGCTGCTGCTGCTCGCCTGGTGC QLWNEIDDTCSSFLSIDSQPQASNAL GCGGGCGCCTGCCGAGGTGCTCCAATATTACCTCAAGGATTACAGCCTGAACAACAGCTACAGTTGT EELCFMIMGMLPKPQEQDEKDNTKRF GGAATGAGATAGATGATACTTGTTCGTCTTTTCTGTCCATTGATTCTCAGCCTCAGGCATCCAACGC LFHYSKTQKLGKSNVVSSVVHPLLQL ACTGGAGGAGCTTTGCTTTATGATTATGGGAATGCTACCAAAGCCTCAGGAACAAGATGAAAAAGAT VPHLHERRMKRFRVDEEFQSPFASQS AATACTAAAAGGTTCTTATTTCATTATTCGAAGACACAGAAGTTGGGCAAGTCAAATGTTGTGTCGT RGYFLFRPRNGRRSAGFI CAGTTGTGCATCCGTTGCTGCAGCTCGTTCCTCACCTGCATGAGAGAAGAATGAAGAGATTCAGAGT GGACGAAGAATTCCAAAGTCCCTTTGCAAGTCAAAGTCGAGGATATTTTTTATTCAGGCCACGGAAT GGAAGAAGGTCAGCAGGGTTCATTTAAAATGGATGCCAGCTAATTTTCCACAGAGCAATGCTATGGA ATACAAAATGTACTGACATTTTGTTTTCTTCTGAAAAAAATCCTTGCTAAATGTACTCTGTTGAAAA TCCCTGTGTTGTCAATGTTCTCAGTTGTAACAATGTTGTAAATGTTCAATTTGTTGAAAATTAAAAA ATCTAAAAATAAA SEQ.ID NO. 9 SEQ.ID NO. 59 GGGCGCAGCGGGGCCCGTCTGCAGCAAGTGACCGACGGCCGGGACGGCCGCCTGCCCCCTCTGCCAC MHVRSLRAAAPHSFVALWAPLFLLRS CTGGGGCGGTGCGGGCCCGGAGCCCGGAGCCCGGGTAGCGCGTAGAGCCGGCGCGATGCACGTGCGC ALADFSLDNEVHSSFIHRRLRSQERR TCACTGCGAGCTGCGGCGCCGCACAGCTTCGTGGCGCTCTGGGCACCCCTGTTCCTGCTGCGCTCCG EMQREILSILGLPHRPRPHLQGKHNS CCCTGGCCGACTTCAGCCTGGACAACGAGGTGCACTCGAGCTTCATCCACCGGCGCCTCCGCAGCCA APMFMLDLYNAMAVEEGGGPGGQGFS GGAGCGGCGGGAGATGCAGCGCGAGATCCTCTCCATTTTGGGCTTGCCCCACCGCCCGCGCCCGCAC YPYKAVFSTQGPPLASLQDSHFLTDA CTCCAGGGCAAGCACAACTCGGCACCCATGTTCATGCTGGACCTGTACAACGCCATGGCGGTGGAGG DMVMSFVNLVEHDKEFFHPRYHHREF AGGGCGGCGGGCCCGGCGGCCAGGGCTTCTCCTACCCCTACAAGGCCGTCTTCAGTACCCAGGGCCC RFDLSKIPEGEAVTAAEFRIYKDYIR CCCTCTGGCCAGCCTGCAAGATAGCCATTTCCTCACCGACGCCGACATGGTCATGAGCTTCGTCAAC ERFDNETFRISVYQVLQEHLGRESDL CTCGTGGAACATGACAAGGAATTCTTCCACCCACGCTACCACCATCGAGAGTTCCGGTTTGATCTTT FLLDSRTLWASEEGWLVFDITATSNH CCAAGATCCCAGAAGGGGAAGCTGTCACGGCAGCCGAATTCCGGATCTACAAGGACTACATCCGGGA WVVNPRHNLGLQLSVETLDGQSINPK ACGCTTCGACAATGAGACGTTCCGGATCAGCGTTTATCAGGTGCTCCAGGAGCACTTGGGCAGGGAA LAGLIGRHGPQNKQPFMVAFFKATEV TCGGATCTCTTCCTGCTCGACAGCCGTACCCTCTGGGCCTCGGAGGAGGGCTGGCTGGTGTTTGACA HFRSIRSTGSKQRSQNRSKTPKNQEA TCACAGCCACCAGCAACCACTGGGTGGTCAATCCGCGGCACAACCTGGGCCTGCAGCTCTCGGTGGA LRMANVAENSSSDQRQACKKHELYVS GACGCTGGATGGGCAGAGCATCAACCCCAAGTTGGCGGGCCTGATTGGGCGGCACGGGCCCCAGAAC FRDLGWQDWIIAPEGYAAYYCEGECA AAGCAGCCCTTCATGGTGGCTTTCTTCAAGGCCACGGAGGTCCACTTCCGCAGCATCCGGTCCACGG FPLNSYMNATNHAIVQTLVHFINPET GGAGCAAACAGCGCAGCCAGAACCGCTCCAAGACGCCCAAGAACCAGGAAGCCCTGCGGATGGCCAA VPKPCCAPTQLNAISVLYFDDSSNVI CGTGGCAGAGAACAGCAGCAGCGACCAGAGGCAGGCCTGTAAGAAGCACGAGCTGTATGTCAGCTTC LKKYRNMVVRACGCH CGAGACCTGGGCTGGCAGGACTGGATCATCGCGCCTGAAGGCTACGCCGCCTACTACTGTGAGGGGG AGTGTGCCTTCCCTCTGAACTCCTACATGAACGCCACCAACCACGCCATCGTGCAGACGCTGGTCCA CTTCATCAACCCGGAAACGGTGCCCAAGCCCTGCTGTGCGCCCACGCAGCTCAATGCCATCTCCGTC CTCTACTTCGATGACAGCTCCAACGTCATCCTGAAGAAATACAGAAACATGGTGGTCCGGGCCTGTG GCTGCCACTAGCTCCTCCGAGAATTCAGACCCTTTGGGGCCAAGTTTTTCTGGATCCTCCATTGCTC GCCTTGGCCAGGAACCAGCAGACCAACTGCCTTTTGTGAGACCTTCCCCTCCCTATCCCCAACTTTA AAGGTGTGAGAGTATTAGGAAACATGAGCAGCATATGGCTTTTGATCAGTTTTTCAGTGGCAGCATC CAATGAACAAGATCCTACAAGCTGTGCAGGCAAAACCTAGCAGGAAAAAAAAACAACGCATAAAGAA AAATGGCCGGGCCAGGTCATTGGCTGGGAAGTCTCAGCCATGCACGGACTCGTTTCCAGAGGTAATT ATGAGCGCCTACCAGCCAGGCCACCCAGCCGTGGGAGGAAGGGGGCGTGGCAAGGGGTGGGCACATT GGTGTCTGTGCGAAAGGAAAATTGACCCGGAAGTTCCTGTAATAAATGTCACAATAAAACGAATGAA TG SEQ.ID NO. 10 SEQ.ID NO. 60 CCGGTGAGTCGCCGGCGCTGCAGAGGGAGGCGGCACTGGTCTCGACGTGGGGCGGCCAGCGATGAAG MKPPSSIQTSEFDSSDEEPIEDEQTP CCGCCCAGTTCAATACAAACAAGTGAGTTTGACTCATCAGATGAAGAGCCTATTGAAGATGAACAGA IHISWLSLSRVNCSQFLGLCALPGCK CTCCAATTCATATATCATGGCTATCTTTGTCACGAGTGAATTGTTCTCAGTTTCTCGGTTTATGTGC FKDVRRNVQKDTEELKSCGIQDIFVF TCTTCCAGGTTGTAAATTTAAAGATGTTAGAAGAAATGTCCAAAAAGATACAGAAGAACTAAAGAGC CTRGELSKYRVPNLLDLYQQCGIITH TGTGGTATACAAGACATATTTGTTTTCTGCACCAGAGGGGAACTGTCAAAATATAGAGTCCCAAACC HHPIADGGTPDIASCCEIMEELTTCL TTCTGGATCTCTACCAGCAATGTGGAATTATCACCCATCATCATCCAATCGCAGATGGAGGGACTCC KNYRKTLIHCYGGLGRSCLVAACLLL TGACATAGCCAGCTGCTGTGAAATAATGGAAGAGCTTACAACCTGCCTTAAAAATTACCGAAAAACC YLSDTISPEQAIDSLRDLRGSGAIQT TTAATACACTGCTATGGAGGACTTGGGAGATCTTGTCTTGTAGCTGCTTGTCTCCTACTATACCTGT IKQYNYLHEFRDKLAAHLSSRDSQSR CTGACACAATATCACCAGAGCAAGCCATAGACAGCCTGCGAGACCTAAGAGGATCCGGGGCAATACA SVSR GACCATCAAGCAATACAATTATCTTCATGAGTTTCGGGACAAATTAGCTGCACATCTATCATCAAGA GATTCACAATCAAGATCTGTATCAAGATAAAGGAATTCAAATAGCATATATATGACCATGTCTGAAA TGTCAGTTCTCTAGCATAATTTGTATTGAAATGAAACCACCAGTGTTATCAACTTGAATGTAAATGT ACATGTGCAGATATTCCTAAAGTTTTATTGAC SEQ.ID NO. 11 SEQ.ID NO. 61 AGAGCGATCATGTCGCACAAACAAATTTACTATTCGGACAAATACGACGACGAGGAGTTTGAGTATC MSHKQIYYSDKYDDEEFEYRHVMLPK GACATGTCATGCTGCCCAAGGACATAGCCAAGCTGGTCCCTAAAACCCATCTGATGTCTGAATCTGA DIAKLVPKTHLMSESEWRNLGVQQSQ ATGGAGGAATCTTGGCGTTCAGCAGAGTCAGGGATGGGTCCATTATATGATCCATGAACCAGAACCT GWVHYMIHEPEPHILLFRRPLPKKPK CACATCTTGCTGTTCCGGCGCCCACTACCCAAGAAACCAAAGAAATGAAGCTGGCAAGCTACTTTTC K AGCCTCAAGCTTTACACAGCTGTCCTTACTTCCTAACATCTTTCTGATAACATTATTATGTTGCCTT CTTGTTTCTCACTTTGATATTTAAAAGATGTTCAATACACTGTTTGAATGTGCTGGTAACTGCTTTG CTTCTTGAGTAGAGCCACCACCACCATAGCCCAGCCAGATGAGTGCTCTGTGGACCCACAGCCTAAG CTGAGTGTGACCCCAGAAGCCACGATGTGCTCTGTATCCAGAACACACTTGGCAGATGGAGGAAGCA TCTGAGTTTGAGACCATGGCTGTTACAGGGATCATGTAAACTTGCTGTTTTTGTTTTTTCTGCCGGG TGTTGTATGTGTGGTGACTTGCGGATTTATGTTTCAGTGTACTGGAAACTTTCCATTTTATTCAAGA AATCTGTTCATGTTAAAAGCCTTGATTAAAGAGGAAGTTTTTATAAT SEQ.ID NO. 12 SEQ.ID NO. 62 CGAGTTCCGGCGAGGCTTCAGGGTACAGCTCCCCCGCAGCCAGAAGCCGGGCCTGCAGCGCCTCAGC MERRRLWGSIQSRYISMSVWTSPRRL ACCGCTCCGGGACACCCCACCCGCTTCCCAGGCGTGACCTGTCAACAGCAACTTCGCGGTGTGGTGA VELAGQSLLKDEALAIAALELLPREL ACTCTCTGAGGAAAAACCATTTTGATTATTACTCTCAGACGTGCGTGGCAACAAGTGACTGAGACCT FPPLFMAAFDGRHSQTLKAMVQAWPF AGAAATCCAAGCGTTGGAGGTCCTGAGGCCAGCCTAAGTCGCTTCAAAATGGAACGAAGGCGTTTGT TCLPLGVLMKGQHLHLETFKAVLDGL GGGGTTCCATTCAGAGCCGATACATCAGCATGAGTGTGTGGACAAGCCCACGGAGACTTGTGGAGCT DVLLAQEVRPRRWKLQVLDLRKNSHQ GGCAGGGCAGAGCCTGCTGAAGGATGAGGCCCTGGCCATTGCCGCCCTGGAGTTGCTGCCCAGGGAG DFWTVWSGNRASLYSFPEPEAAQPMT CTCTTCCCGCCACTCTTCATGGCAGCCTTTGACGGGAGACACAGCCAGACCCTGAAGGCAATGGTGC KKRKVDGLSTEAEQPFIPVEVLVDLF AGGCCTGGCCCTTCACCTGCCTCCCTCTGGGAGTGCTGATGAAGGGACAACATCTTCACCTGGAGAC LKEGACDELFSYLIEKVKRKKNVLRL CTTCAAAGCTGTGCTTGATGGACTTGATGTGCTCCTTGCCCAGGAGGTTCGCCCCAGGAGGTGGAAA CCKKLKIFAMPMQDIKMILKMVQLDS CTTCAAGTGCTGGATTTACGGAAGAACTCTCATCAGGACTTCTGGACTGTATGGTCTGGAAACAGGG IEDLEVTCTWKLPTLAKFSPYLGQMI CCAGTCTGTACTCATTTCCAGAGCCAGAAGCAGCTCAGCCCATGACAAAGAAGCGAAAAGTAGATGG NLRRLLLSHIHASSYISPEKEEQYIA TTTGAGCACAGAGGCAGAGCAGCCCTTCATTCCAGTAGAGGTGCTCGTAGACCTGTTCCTCAAGGAA QFTSQFLSLQCLQALYVDSLFFLRGR GGTGCCTGTGATGAATTGTTCTCCTACCTCATTGAGAAAGTGAAGCGAAAGAAAAATGTACTACGCC LDQLLRHVMNPLETLSITNCRLSEGD TGTGCTGTAAGAAGCTGAAGATTTTTGCAATGCCCATGCAGGATATCAAGATGATCCTGAAAATGGT VMHLSQSPSVSQLSVLSLSGVMLTDV GCAGCTGGACTCTATTGAAGATTTGGAAGTGACTTGTACCTGGAAGCTACCCACCTTGGCGAAATTT SPEPLQALLERASATLQDLVFDECGI TCTCCTTACCTGGGCCAGATGATTAATCTGCGTAGACTCCTCCTCTCCCACATCCATGCATCTTCCT TDDQLLALLPSLSHCSQLTTLSFYGN ACATTTCCCCGGAGAAGGAAGAGCAGTATATCGCCCAGTTCACCTCTCAGTTCCTCAGTCTGCAGTG SISISALQSLLQHLIGLSNLTHVLYP CCTGCAGGCTCTCTATGTGGACTCTTTATTTTTCCTTAGAGGCCGCCTGGATCAGTTGCTCAGGCAC VPLESYEDIHGTLHLERLAYLHARLR GTGATGAACCCCTTGGAAACCCTCTCAATAACTAACTGCCGGCTTTCGGAAGGGGATGTGATGCATC ELLCELGRPSMVWLSANPCPHCGDRT TGTCCCAGAGTCCCAGCGTCAGTCAGCTAAGTGTCCTGAGTCTAAGTGGGGTCATGCTGACCGATGT FYDPEPILCPCFMPN AAGTCCCGAGCCCCTCCAAGCTCTGCTGGAGAGAGCCTCTGCCACCCTCCAGGACCTGGTCTTTGAT GAGTGTGGGATCACGGATGATCAGCTCCTTGCCCTCCTGCCTTCCCTGAGCCACTGCTCCCAGCTTA CAACCTTAAGCTTCTACGGGAATTCCATCTCCATATCTGCCTTGCAGAGTCTCCTGCAGCACCTCAT CGGGCTGAGCAATCTGACCCACGTGCTGTATCCTGTCCCCCTGGAGAGTTATGAGGACATCCATGGT ACCCTCCACCTGGAGAGGCTTGCCTATCTGCATGCCAGGCTCAGGGAGTTGCTGTGTGAGTTGGGGC GGCCCAGCATGGTCTGGCTTAGTGCCAACCCCTGTCCTCACTGTGGGGACAGAACCTTCTATGACCC GGAGCCCATCCTGTGCCCCTGTTTCATGCCTAACTAGCTGGGTGCACATATCAAATGCTTCATTCTG CATACTTGGACACTAAAGCCAGGATGTGCATGCATCTTGAAGCAACAAAGCAGCCACAGTTTCAGAC AAATGTTCAGTGTGAGTGAGGAAAACATGTTCAGTGAGGAAAAAACATTCAGACAAATGTTCAGTGA GGAAAAAAAGGGGAAGTTGGGGATAGGCAGATGTTGACTTGAGGAGTTAATGTGATCTTTGGGGAGA TACATCTTATAGAGTTAGAAATAGAATCTGAATTTCTAAAGGGAGATTCTGGCTTGGGAAGTACATG TAGGAGTTAATCCCTGTGTAGACTGTTGTAAAGAAACTGTTGAAAATAAAGAGAAGCAATGTGAAGC AAAAAAAAAAAAAAAAAA SEQ.ID NO. 13 SEQ.ID NO. 63 CGGCTGAGAGGCAGCGAACTCATCTTTGCCAGTACAGGAGCTTGTGCCGTGGCCCACAGCCCACAGC MGWDLTVKMLAGNEFQVSLSSSMSVS CCACAGCCATGGGCTGGGACCTGACGGTGAAGATGCTGGCGGGCAACGAATTCCAGGTGTCCCTGAG ELKAQITQKIGVHAFQQRLAVHPSGV CAGCTCCATGTCGGTGTCAGAGCTGAAGGCGCAGATCACCCAGAAGATTGGCGTGCACGCCTTCCAG ALQDRVPLASQGLGPGSTVLLVVDKC CAGCGTCTGGCTGTCCACCCGAGCGGTGTGGCGCTGCAGGACAGGGTCCCCCTTGCCAGCCAGGGCC DEPLSILVRNNKGRSSTYEVRLTQTV TGGGCCCTGGCAGCACGGTCCTGCTGGTGGTGGACAAATGCGACGAACCTCTGAGCATCCTGGTGAG AHLKQQVSGLEGVQDDLFWLTFEGKP GAATAACAAGGGCCGCAGCAGCACCTACGAGGTCCGGCTGACGCAGACCGTGGCCCACCTGAAGCAG
LEDQLPLGEYGLKPLSTVFMNLRLRG CAAGTGAGCGGGCTGGAGGGTGTGCAGGACGACCTGTTCTGGCTGACCTTCGAGGGGAAGCCCCTGG GGTEPGGRS AGGACCAGCTCCCGCTGGGGGAGTACGGCCTCAAGCCCCTGAGCACCGTGTTCATGAATCTGCGCCT GCGGGGAGGCGGCACAGAGCCTGGCGGGCGGAGCTAAGGGCCTCCACCAGCATCCGAGCAGGATCAA GGGCCGGAAATAAAGGCTGTTGTAAGAGAAT SEQ.ID NO. 14 STAR clone: TGCCCACTTGGCCCCTCCTTCCAAGGTGTACTTTACTTCCTTTCATTCCTGCTCTAATACTGTTTAG TACATTTTCACTCCTGCTCTAAAACTTGCCTCAGTCTCTCACTGTGCCTTATGCCCCTCAGCTGAAT TCTTTCTTCTGAGCAGGCAGGAATTGAGGTTGCTGCAGACGTGTATGCATTTGCCACCAGTAACATA CTTTGGTGCCACATGACTAGGATATGTTCTCTAGTGCTAACATGTTCGTTTACAGTTCTTAGGACTC CCTGATA SEQ.ID NO. 15 SEQ.ID NO. 64 GGCCGCCTGCGCGCCGCCAACAGCCTAGCGCTGCGCCGCGTGGCCGCCGCCTTCTCGCTGGCCCCGC MRWVRHDAPARRGQLRRLLEHVRLPL TGGCCGAGCGCTGCGGCCGCGTCCTGCGTCAGGCCTTCGCCGAGGTGGCGCGCCACGCCGACTTCCT LAPAYFLEKVEADELLQACGECRPLL GGAGCTGGCGCCTGACGAGGTGGTGGCGCTGCTGGCGGACCCCGCGCTGGGCGTGGCGCGCGAGGAG LEARACFILGREAGALRTRPRRFMDL GCCGTGTTTGAAGCGGCCATGCGCTGGGTGCGCCACGACGCGCCGGCCCGCCGCGGCCAGCTGCGAC AEVIVVIGGCDRKGLLKLPFADAYHP GCCTGCTGGAGCACGTGCGCCTGCCGCTACTGGCGCCCGCTTACTTCCTGGAGAAGGTGGAGGCGGA ESQRWTPLPSLPGYTRSEFAACALRN CGAGCTGCTGCAGGCCTGCGGCGAGTGCCGCCCGCTGCTGCTCGAGGCTCGCGCCTGCTTCATCCTG DVYVSGGHINSHDVWMFSSHLHTWIK GGCCGCGAGGCCGGTGCGCTGCGGACCCGGCCGCGGAGATTCATGGACCTAGCTGAAGTGATCGTGG VASLHKGRWRHKMAVVQGQLFAVGGF TCATCGGCGGTTGCGACCGCAAAGGTCTCCTGAAGCTGCCCTTCGCCGATGCCTACCATCCAGAGAG DGLRRLHSVERYDPFSNTWAAAAPLP CCAGCGGTGGACCCCACTGCCCAGCCTGCCCGGCTACACTCGCTCAGAATTCGCCGCCTGTGCTCTC EAVSSAAVASCAGKLFVIGGARQGGV CGCAATGACGTCTACGTCTCCGGAGGCCACATCAACAGTCATGATGTGTGGATGTTTAGCTCCCATC NTDKVQCFDPKEDRWSLRSPAPFSQR TGCACACCTGGATCAAGGTAGCCTCTCTGCACAAGGGCAGGTGGAGGCACAAGATGGCAGTTGTGCA CLEAVSLEDTIYVMGGLMSKIFTYDP GGGGCAGCTGTTCGCGGTGGGTGGCTTCGACGGCCTGAGGCGCCTGCACAGCGTGGAGCGCTACGAC GTDVWGEAAVLPSPVESCGVTVCDGK CCCTTCTCCAACACCTGGGCGGCCGCCGCGCCCCTCCCGGAGGCCGTGAGCTCGGCGGCGGTGGCGT VHILGGRDDRGESTDKVFTFDPSSGQ CCTGCGCGGGCAAGCTCTTCGTGATTGGGGGCGCCAGGCAGGGCGGCGTCAACACGGACAAGGTGCA VEVQPSLQRCTSSHGCVTIIQSLGR GTGCTTTGACCCCAAGGAGGACCGGTGGAGCCTGCGGTCACCAGCACCCTTCTCACAGCGGTGTCTC GAGGCTGTCTCCCTTGAGGACACCATCTATGTCATGGGGGGTCTCATGAGCAAAATCTTCACCTATG ATCCAGGCACAGATGTGTGGGGGGAGGCAGCTGTCCTCCCCAGCCCTGTGGAAAGCTGTGGAGTCAC TGTGTGTGACGGGAAGGTCCACATCCTTGGCGGGCGGGATGATCGCGGAGAAAGCACCGATAAGGTC TTCACCTTTGACCCCAGCAGTGGGCAGGTGGAGGTCCAGCCATCCCTGCAGCGCTGCACCAGCTCCC ACGGCTGTGTCACCATCATCCAGAGCTTGGGCAGGTGATTCAGATTTGGACAGCCTGAGCCAGGAGG CGGAGAGGCAGGCGGAGCTCAGATGCACACTCTGCTCCCTCATGGCACCTCCACGCAAACAGCCCTT AACTTAATGGTCCCTTTTCTTGTATAAATAAAATCTTGTTGGGTCTGTGTTCCAGCTGCAGTC TGCCCTGCCTGGAGATGGAATGTCTAAAAAAAAAAAAAAAA SEQ.ID NO. 16 STAR clone: TTTCTAGCAGCCTGGGCAATGGCGGGCGCCCCTCCCCCAGCCTCGCTGCTGCCTTGCAGTTTGATCT CAGACTGCTGTGCTAGCAATCAGCAAGACTCCGTGGGCGTAGGACCCTCCGAGCCAGGTTGCAAGAA AGCTCAAGTAGCCTATGGAGAGGATGCAAGGCTTCCAGCTGATGCCCTCAGCCAGGCTCAGTAGCAG CCAGAACTAGCCTACCAACGAACCTGCTGATCATGTGCATAAGCCACCTTGAACGTCGATCCTCCTG CCTGGTGGAGCCATCCCAGCTGATGCCACATGAAGCAGACACAAGCTGTCCCTACTAAGCTCTGCTC AAGTTGGATATTCATGAGTGAAATAAATGACTGTTACTAA SEQ.ID NO. 17 SEQ.ID NO. 65 GAGTCACCAAGGAAGGCAGCGGCAGCTCCACTCAGCCAGTACCCAGATACGCTGGGAACCTTCCCCA MASLGQILFWSIISIIIILAGAIALI GCCATGGCTTCCCTGGGGCAGATCCTCTTCTGGAGCATAATTAGCATCATCATTATTCTGGCTGGAG IGFGISGRHSITVTTVASAGNIGEDG CAATTGCACTCATCATTGGCTTTGGTATTTCAGGGAGACACTCCATCACAGTCACTACTGTCGCCTC IQSCTFEPDIKLSDIVIQWLKEGVLG AGCTGGGAACATTGGGGAGGATGGAATCCAGAGCTGCACTTTTGAACCTGACATCAAACTTTCTGAT LVHEFKEGKDELSEQDEMFRGRTAVF ATCGTGATACAATGGCTGAAGGAAGGTGTTTTAGGCTTGGTCCATGAGTTCAAAGAAGGCAAAGATG ADQVIVGNASLRLKNVQLTDAGTYKC AGCTGTCGGAGCAGGATGAAATGTTCAGAGGCCGGACAGCAGTGTTTGCTGATCAAGTGATAGTTGG YIITSKGKGNANLEYKTGAFSMPEVN CAATGCCTCTTTGCGGCTGAAAAACGTGCAACTCACAGATGCTGGCACCTACAAATGTTATATCATC VDYNASSETLRCEAPRWFPQPTVVWA ACTTCTAAAGGCAAGGGGAATGCTAACCTTGAGTATAAAACTGGAGCCTTCAGCATGCCGGAAGTGA SQVDQGANFSEVSNTSFELNSENVTM ATGTGGACTATAATGCCAGCTCAGAGACCTTGCGGTGTGAGGCTCCCCGATGGTTCCCCCAGCCCAC KVVSVLYNVTINNTYSCMIENDIAKA AGTGGTCTGGGCATCCCAAGTTGACCAGGGAGCCAACTTCTCGGAAGTCTCCAATACCAGCTTTGAG TGDIKVTESEIKRRSHLQLLNSKASL CTGAACTCTGAGAATGTGACCATGAAGGTTGTGTCTGTGCTCTACAATGTTACGATCAACAACACAT CVSSFFAISWALLPLSPYLMLK ACTCCTGTATGATTGAAAATGACATTGCCAAAGCAACAGGGGATATCAAAGTGACAGAATCGGAGAT CAAAAGGCGGAGTCACCTACAGCTGCTAAACTCAAAGGCTTCTCTGTGTGTCTCTTCTTTCTTTGCC ATCAGCTGGGCACTTCTGCCTCTCAGCCCTTACCTGATGCTAAAATAATGTGCCTCGGCCACAAAAA AGCATGCAAAGTCATTGTTACAACAGGGATCTACAGAACTATTTCACCACCAGATATGACCTAGTTT TATATTTCTGGGAGGAAATGAATTCATATCTAGAAGTCTGGAGTGAGCAAACAAGAGCAAGAAACAA AAAGAAGCCAAAAGCAGAAGGCTCCAATATGAACAAGATAAATCTATCTTCAAAGACATATTAGAAG TTGGGAAAATAATTCATGTGAACTAGAGTCAACTGTGTCAGGGCTAAGAAACCCTGGTTTTGAGTAG AAAAGGGCCTGGAAAGAGGGGAGCCAACAAATCTGTCTGCTTCCTCACATTAGTCATTGGCAAATAA GCATTCTGTCTCTTTGGCTGCTGCCTCAGCACAGAGAGCCAGAACTCTATCGGGCACCAGGATAACA TCTCTCAGTGAACAGAGTTGACAAGGCCTATGGGAAATGCCTGATGGGATTATCTTCAGCTTGTTGA GCTTCTAAGTTTCTTTCCCTTCATTCTACCCTGCAAGCCAAGTTCTGTAAGAGAAATGCCTGAGTTC TAGCTCAGGTTTTCTTACTCTGAATTTAGATCTCCAGACCCTGCCTGGCCACAATTCAAATTAAGGC AACAAACATATACCTTCCATGAAGCACACACAGACTTTTGAAAGCAAGGACAATGACTGCTTGAATT GAGGCCTTGAGGAATGAAGCTTTGAAGGAAAAGAATACTTTGTTTCCAGCCCCCTTCCCACACTCTT CATGTGTTAACCACTGCCTTCCTGGACCTTGGAGCCACGGTGACTGTATTACATGTTGTTATAGAAA ACTGATTTTAGAGTTCTGATCGTTCAAGAGAATGATTAAATATACATTTCCTAAAAAAAAAAAAAAA AA SEQ.ID NO. 18 SEQ.ID NO. 66 TCTTCGGACCTAGGCTGCCCTGCCGTCATGTCGCAAGGGATCCTTTCTCCGCCAGCGGGCTTGCTGT MSQGILSPPAGLLSDDDVVVSPMFES CCGATGACGATGTCGTAGTTTCTCCCATGTTTGAGTCCACAGCTGCAGATTTGGGGTCTGTGGTACG TAADLGSVVRKNLLSDCSVVSTSLED CAAGAACCTGCTATCAGACTGCTCTGTCGTCTCTACCTCCCTAGAGGACAAGCAGCAGGTTCCATCT KQQVPSEDSMEKVKVYLRVRPLLPSE GAGGACAGTATGGAGAAGGTGAAAGTATACTTGAGGGTTAGGCCCTTGTTACCTTCAGAGTTGGAAC LERQEDQGCVRIENVETLVLQAPKDS GACAGGAAGATCAGGGTTGTGTCCGTATTGAGAATGTGGAGACCCTTGTTCTACAAGCACCCAAGGA FALKSNERGIGQATHRFTFSQIFGPE CTCGTTTGCCCTGAAGAGCAATGAACGGGGAATTGGCCAAGCCACACACAGGTTCACCTTTTCCCAG VGQASFFNLTVKEMVKDVLKGQNWLI ATCTTTGGGCCAGAAGTGGGACAGGCATCCTTCTTCAACCTAACTGTGAAGGAGATGGTAAAGGATG YTYGVTNSGKTHTIQGTIKDGGILPR TACTCAAAGGGCAGAACTGGCTCATCTATACATATGGAGTCACTAACTCAGGGAAAACCCACACGAT SLALIFNSLQGQLHPTPDLKPLLSNE TCAAGGTACCATCAAGGATGGAGGGATTCTCCCCCGGTCCCTGGCGCTGATCTTCAATAGCCTCCAA VIWLDSKQIRQEEMKKLSLLNGGLQE GGCCAACTTCATCCAACACCTGATCTGAAGCCCTTGCTCTCCAATGAGGTAATCTGGCTAGACAGCA EELSTSLKRSVYIESRIGTSTSFDSG AGCAGATCCGACAGGAGGAAATGAAGAAGCTGTCCCTGCTAAATGGAGGCCTCCAAGAGGAGGAGCT IAGLSSISQCTSSSQLDETSHRWAQP GTCCACTTCCTTGAAGAGGAGTGTCTACATCGAAAGTCGGATAGGTACCAGCACCAGCTTCGACAGT DTAPLPVPANIRFSIWISFFEIYNEL GGCATTGCTGGGCTCTCTTCTATCAGTCAGTGTACCAGCAGTAGCCAGCTGGATGAAACAAGTCATC LYDLLEPPSQQRKRQTLRLCEDQNGN GATGGGCACAGCCAGACACTGCCCCACTACCTGTCCCGGCAAACATTCGCTTCTCCATCTGGATCTC PYVKDLNWIHVQDAEEAWKLLKVGRK ATTCTTTGAGATCTACAACGAACTGCTTTATGACCTATTAGAACCGCCTAGCCAACAGCGCAAGAGG NQSFASTHLNQNSSRSHSIFSIRILH CAGACTTTGCGGCTATGCGAGGATCAAAATGGCAATCCCTATGTGAAAGATCTCAACTGGATTCATG LQGEGDIVPKISELSLCDLAGSERCK TGCAAGATGCTGAGGAGGCCTGGAAGCTCCTAAAAGTGGGTCGTAAGAACCAGAGCTTTGCCAGCAC DQKSGERLKEAGNINTSLHTLGRCIA CCACCTCAACCAGAACTCCAGCCGCAGTCACAGCATCTTCTCAATCAGGATCCTACACCTTCAGGGG ALRQNQQNRSKQNLVPFRDSKLTRVF GAAGGAGATATAGTCCCCAAGATCAGCGAGCTGTCACTCTGTGATCTGGCTGGCTCAGAGCGCTGCA QGFFTGRGRSCMIVNVNPCASTYDET AAGATCAGAAGAGTGGTGAACGGTTGAAGGAAGCAGGAAACATTAACACCTCTCTACACACCCTGGG LHVAKFSAIASQLVHAPPMQLGFPSL CCGCTGTATTGCTGCCCTTCGTCAAAACCAGCAGAACCGGTCAAAGCAGAACCTGGTTCCCTTCCGT HSFIKEHSLQVSPSLEKGAKADTGLD GACAGCAAGTTGACTCGAGTGTTCCAAGGTTTCTTCACAGGCCGAGGCCGTTCCTGCATGATTGTCA DDIENEADISMYGKEELLQVVEAMKT ATGTGAATCCCTGTGCATCTACCTATGATGAAACTCTTCATGTGGCCAAGTTCTCAGCCATTGCTAG LLLKERQEKLQLEMHLRDEICNEMVE CCAGCTTGTGCATGCCCCACCTATGCAACTGGGATTCCCATCCCTGCACTCGTTCATCAAGGAACAT QMQQREQWCSEHLDTQKELLEEMYEE AGTCTTCAGGTATCCCCCAGCTTAGAGAAAGGGGCTAAGGCAGACACAGGCCTTGATGATGATATTG KLNILKESLTSFYQEEIQERDEKIEE AAAATGAAGCTGACATCTCCATGTATGGCAAAGAGGAGCTCCTACAAGTTGTGGAAGCCATGAAGAC LEALLQEARQQSVAHQQSGSELALRR ACTGCTTTTGAAGGAACGACAGGAAAAGCTACAGCTGGAGATGCATCTCCGAGATGAAATTTGCAAT SQRLAASASTQQLQEVKAKLQQCKAE GAGATGGTAGAACAGATGCAACAGCGGGAACAGTGGTGCAGTGAACATTTGGACACCCAAAAGGAAC LNSTTEELHKYQKMLEPPPSAKPFTI TATTGGAGGAAATGTATGAAGAAAAACTAAATATCCTCAAGGAGTCACTGACAAGTTTTTACCAAGA DVDKKLEEGQKNIRLLRTELQKLGES AGAGATTCAGGAGCGGGATGAAAAGATTGAAGAGCTAGAAGCTCTCTTGCAGGAAGCCAGACAACAG LQSAERACCHSTGAGKLRQALTTCDD TCAGTGGCCCATCAGCAATCAGGGTCTGAATTGGCCCTACGGCGGTCACAAAGGTTGGCAGCTTCTG ILIKQDQTLAELQNNMVLVKLDLRKK CCTCCACCCAGCAGCTTCAGGAGGTTAAAGCTAAATTACAGCAGTGCAAAGCAGAGCTAAACTCTAC AACIAEQYHTVLKLQGQVSAKKRLGT CACTGAAGAGTTGCATAAGTATCAGAAAATGTTAGAACCACCACCCTCAGCCAAGCCCTTCACCATT NQENQQPNQQPPGKKPFLRNLLPRTP GATGTGGACAAGAAGTTAGAAGAGGGCCAGAAGAATATAAGGCTGTTGCGGACAGAGCTTCAGAAAC TCQSSTDCSPYARILRSRRSPLLKSG TTGGTGAGTCTCTCCAATCAGCAGAGAGAGCTTGTTGCCACAGCACTGGGGCAGGAAAACTTCGTCA PFGKKY AGCCTTGACCACTTGTGATGACATCTTAATCAAACAGGACCAGACTCTGGCTGAACTGCAGAACAAC ATGGTGCTAGTGAAACTGGACCTTCGGAAGAAGGCAGCATGTATTGCTGAGCAGTATCATACTGTGT TGAAACTCCAAGGCCAGGTTTCTGCCAAAAAGCGCCTTGGTACCAACCAGGAAAATCAGCAACCAAA CCAACAACCACCAGGGAAGAAACCATTCCTTCGAAATTTACTTCCCCGAACACCAACCTGCCAAAGC TCAACAGACTGCAGCCCTTATGCCCGGATCCTACGCTCACGGCGTTCCCCTTTACTCAAATCTGGGC CTTTTGGCAAAAAGTACTAAGGCTGTGGGGAAAGAGAAGAGCAGTCATGGCCCTGAGGTGGGTCAGC TACTCTCCTGAAGAAATAGGTCTCTTTTATGCTTTACCATATATCAGGAATTATATCCAGGATGCAA TACTCAGACACTAGCTTTTTTCTCACTTTTGTATTATAACCACCTATGTAATCTCATGTTGTTGTTT TTTTTTATTTACTTATATGATTTCTATGCACACAAAAACAGTTATATTAAAGATATTAT TGTTCACATTTTTTATTGAAAAAAAAAAAAAA STAR clone (SEQ.ID NO. 19): SEQ.ID NO. 67 TCCTTGTTACGATGAAGAAACTAAATCTCAGGAAGAAAAAACTAAGTGAAGACNAAAGAAGGATTTG MFIWTSGRTSSSYRHDEKRNIYQKIR AACTGAGGTTTGTCAGACTCTCGGGACCATGCTGTTGAAACCACTAAACCACGCTGCCTCTGGGTCA DHDLLDKRKTVTALKAGEDRAILLGL CTTGGTAAACAGCATTTAACCATTAAGAAAGTCATTAATAAAATTCCTTGTGCTCTCCTTGAGATTA AMMVCSIMMYFLLGITLLRSYMQSVW CAAGCCATTGATTTGCCAA TEESQCTLLNASITETFNCSFSCGPD NM_005832: CWKLSQYPCLQVYVNLTSSGEKLLLY GCTGGGCACCGTTCTGTTTTCTTTCTTTTCTTAATCCTATCCAAGTATGCAGTACGCTCTTGGGTCG HTEETIKINQ TCTCATGAGACCCAGGGGCATGTTGGAAAGAACTGAGAGAAAGAGCAACAAAGCGGCGAGTGGTGTG KCSYIPKCGKNFEESMSLVNVVMENF AGAGGGCAGCACGCGCTGTGGGGCCCTTCCAGAGAAATGTACTGAAAAAGTCTACGCAATGTCTGGG RKYQHFSCYSDPEGNQKSVILTKLYS ATTTGCTAAACAATACCTGGAAAGCAGACAGGTCTTTTTGCCATTCCTCCAGGACATCCACCATAAG SNVLEHSLFWPTCMMAGGVAIVAMVK GAAAGGAGACCCTGGACCAACATTCTCTAAGATGTTTATATGGACCAGTGGCCGGACCTCTTCATCT LTQYLSLLCERIQRINR TATAGACATGATGAAAAAAGAAATATTTACCAGAAAATCAGGGACCATGACCTCCTGGACAAAAGGA AAACAGTCACAGCACTGAAGGCAGGAGAGGACCGAGCTATTCTCCTGGGACTGGCTATGATGGTGTG CTCCATCATGATGTATTTTCTGCTGGGAATCACACTCCTGCGCTCATACATGCAGAGCGTGTGGACC GAAGAGTCTCAATGCACCTTGCTGAATGCGTCCATCACGGAAACATTTAATTGCTCCTTCAGCTGTG GTCCAGACTGCTGGAAACTTTCTCAGTACCCCTGCCTCCAGGTGTACGTTAACCTGACTTCTTCCGG GGAAAAGCTCCTCCTCTACCACACAGAAGAGACAATAAAAATCAATCAGAAGTGCTCCTATATACCT AAATGTGGAAAAAATTTTGAAGAATCCATGTCCCTGGTGAATGTTGTCATGGAAAACTTCAGGAAGT ATCAACACTTCTCCTGCTATTCTGACCCAGAAGGAAACCAGAAGAGTGTTATCCTAACAAAACTCTA CAGTTCCAACGTGCTGTTCCATTCACTCTTCTGGCCAACCTGTATGATGGCTGGGGGTGTGGCAATT GTTGCCATGGTGAAACTTACACAGTACCTCTCCCTACTATGTGAGAGGATCCAACGGATCAATAGAT AAATGCAAAAATGGATAAAATAATTTTTGTTAAAGCTCAAATACTGTTTTCTTTCATTCTTCACCAA AGAACCTTAAGTTTGTAACGTGCAGTCTGTTATGAGTTCCCTAATATATTCTTATATGTAGAGCAAT AATGCAAAAGCTGTTCTATATGCAAACATGATGTCTTTATTATTCAGGAGAATAAATAACTGTTTTG TGTTGGTTGGTGGTTTTCATAATCTTATTTCTGTACTGGAACTAGTACTTTCTTCTCTCATTCCGCC AAAACAGGGCTCAGTTATTCATTTGCCAAGCTTCGTGGAGGAATGTAGGTGACATCAATGTGATAAA GTCTGTGTTCTGAGTTGTCAGATCTCTTGAAGACAATATTTTTCATCACTTATTGTTTACTAAAGCT ACAGCCAAAAATATTTTTTTTTCTTATTCTAAACTGAGCCCTATAGCAAGTGAAGGGACCAGATTTC CTAATTAAAGGAAGTTAGGTACTTTTCTTGTATTTTTTACCATATCACTGTAAAGAAGAGGGGAAAC CCAGCCAGCTACTTTTTTTCATCACTTTTTATTCATAACTTCAGATTTGTAAAACTAATTTCCAAAA TATAAGCTGTTTTCATTAGCCAGTTCTATAATATCTTCCTGTGATTTATGTAGAAAATGAACACACC CCTTTTCCATTTAAGACCCTGCTACTGTGTGAAGAGATGATACTTACAAGGAGTGTCATTACCTGTG AGCTGACTGAATGTTGGTAGGTGCTCCATTACAATCCAGGAAAGTCTGTGTTACTGATATTTGTGTG GAAATCTTTATTTCACTTCAATTTAACCATTAGATGGTAAAATTAAGATGCTACTTGTTGGTAAAAA TTGGTGGACTGGTTTCAATGGGTAAATGTGTTGTGGCAAATTAATGTGTTGGAATATTGCTCTTTGT GAATTTGTGCTTAAGTCAATGAATGTGTAGTATCTCCTTCTGACAAGCATTCCCTATTGGGATTTTA AAGCTATGTGCACAGAATATTAGTCTCTTCTACATGTTTTATTTTTCTATTTATAATTCCCTTTTTT GTTGTTATATTTTATACACAGAATAGATCTTTTTTCTAACACATATTTGAACTGAATAACAGACTTA AAGAAAGCCTTTGTTCACATTGCTATTTACTTTTGTGTTTGGGGGAAAATACGAGGGATTGATTTTA AATAAAAAACATTCCATCTTTCATTTAATATCAATATCAAAAGAAGAAGACAAACATCTATCTTTCT CATCTATATTTAAGTACCTTTTTGTAATGTAGTATCAAAGTTTTTTAGGTAATGCAAAATTTTACAA ATCATTTGTGGAATGAATGGTAAAACTAATCTGATGAAATGGAAAATTATTCTGCAATATTGTAATT CATAGTTTGACTTTTCATAAGCAAATAAATCCCTAGGA TGTAATCAGGACTTCAAATGTGTAATTAAATTTTTTTAAAAAAAATCTA SEQ.ID NO. 20 STAR clone: GAACACAGCTAAGCAGATGGCTTGGGTCATCAGGACGTCCATTACATCCAAAGGAAGACAGCCTGTG ACGTTTCAAAAGCAAAAGTCCCCTACCAGCCAGTGAAGCTACCTGATTTCTCAGTATCTTACGCCCA GTGACACGATCTACCCTCAAAACTTA SEQ.ID NO. 21 SEQ.ID NO. 68 GAGACATTCCTCAATTGCTTAGACATATTCTGAGCCTACAGCAGAGGAACCTCCAGTCTCAGCACCA MNQTAILICCLIFLTLSGIQGVPLSR TGAATCAAACTGCGATTCTGATTTGCTGCCTTATCTTTCTGACTCTAAGTGGCATTCAAGGAGTACC TVRCTCISISNQPVNPRSLEKLEIIP TCTCTCTAGAACCGTACGCTGTACCTGCATCAGCATTAGTAATCAACCTGTTAATCCAAGGTCTTTA
ASQFCPRVEIIATMKKKGEKRCLNPE GAAAAACTTGAAATTATTCCTGCAAGCCAATTTTGTCCACGTGTTGAGATCATTGCTACAATGAAAA SKAIKNLLKAVSKEMSKRSP AGAAGGGTGAGAAGAGATGTCTGAATCCAGAATCGAAGGCCATCAAGAATTTACTGAAAGCAGTTAG CAAGGAAATGTCTAAAAGATCTCCTTAAAACCAGAGGGGAGCAAAATCGATGCAGTGCTTCCAAGGA TGGACCACACAGAGGCTGCCTCTCCCATCACTTCCCTACATGGAGTATATGTCAAGCCATAATTGTT CTTAGTTTGCAGTTACACTAAAAGGTGACCAATGATGGTCACCAAATCAGCTGCTACTACTCCTGTA GGAAGGTTAATGTTCATCATCCTAAGCTATTCAGTAATAACTCTACCCTGGCACTATAATGTAAGCT CTACTGAGGTGCTATGTTCTTAGTGGATGTTCTGACCCTGCTTCAAATATTTCCCTCACCTTTCCCA TCTTCCAAGGGTACTAAGGAATCTTTCTGCTTTGGGGTTTATCAGAATTCTCAGAATCTCAAATAAC TAAAAGGTATGCAATCAAATCTGCTTTTTAAAGAATGCTCTTTACTTCATGGACTTCCACTGCCATC CTCCCAAGGGGCCCAAATTCTTTCAGTGGCTACCTACATACAATTCCAAACACATACAGGAAGGTAG AAATATCTGAAAATGTATGTGTAAGTATTCTTATTTAATGAAAGACTGTACAAAGTATAAGTCTTAG ATGTATATATTTCCTATATTGTTTTCAGTGTACATGGAATAACATGTAATTAAGTACTATGTATCAA TGAGTAACAGGAAAATTTTAAAAATACAGATAGATATATGCTCTGCATGTTACATAAGATAAATGTG CTGAATGGTTTTCAAATAAAAATGAGGTACTCTCCTGGAAATATTAAGAAAGACTATCTAAATGTTG AAAGATCAAAAGGTTAATAAAGTAATTATAACT SEQ.ID NO. 22 STAR clone: TTTGCAGGTTTGATCTCAGACTGCTGTGCTAGTAATCAGCGAGATTCCGTGGGCGTAGGAGCCTCCA AGCCAGGTCCTGAAGAAAATGAAGTTGATGTTTCAGTGAGACACCTGTATGCCAGAGAGTAAAAGGG ATTATTGTGGATTCCTGAGAATTTTCTACATATGAAATCATGTCATCTATGAACAGAGATGGGACTG TCTCGTTGGAGGAAAACAAGCTCAGGGCTCCCACTGATTCCACATTATGTTGCAAGCTCCTACGAAG CTCCCACTCA SEQ.ID NO. 23 SEQ.ID NO. 69 TTTCTCCGCATGCGCGGGATCCCGGATGTGGATCAAGTTGGTGGGAAGCGTGCGGTGCCGCAGCAAT MAALTIATGTGNWFSALALGVTLLKC GGCGGCGCTCACAATTGCCACGGGTACTGGCAATTGGTTTTCGGCTTTGGCGCTCGGGGTGACTCTT LLIPTYHSTDFEVHRNWLAITHSLPI CTCAAATGCCTTCTCATCCCCACATACCATTCCACAGATTTTGAAGTACACCGAAACTGGCTTGCTA SQWYYEATSEWTLDYPPFFAWFEYIL TCACTCACAGTTTGCCAATATCACAGTGGTATTATGAGGCAACTTCAGAGTGGACGTTGGATTACCC SHVAKYFDQEMLNVHNLNYSSSRTLL CCCTTTCTTTGCATGGTTTGAGTATATCCTGTCACATGTTGCCAAATATTTTGATCAAGAAATGCTG FQRFSVIFMDVLFVYAVRECCKCIDG AATGTCCATAATTTGAATTACTCCAGCTCAAGGACCTTACTTTTCCAGAGATTTTCCGTCATCTTTA KKVGKELTEKPKFILSVLLLWNFGLL TGGATGTACTCTTTGTGTATGCTGTCCGTGAGTGCTGTAAATGCATTGATGGAAAAAAAGTGGGTAA IVDHIHFQYNGFLFGLMLLSIARLFQ AGAACTTACAGAAAAGCCAAAATTTATTCTGTCGGTATTACTTCTGTGGAACTTCGGGTTATTAATT KRHMEGAFLFAVLLHFKHIYLYVAPA GTGGACCATATTCATTTTCAGTACAATGGCTTTTTATTTGGATTAATGCTACTCTCCATTGCACGAT YGVYLLRSYCFTANKPDGSIRWKSFS TATTTCAGAAAAGGCATATGGAAGGAGCATTTCTCTTTGCTGTTCTCCTACATTTCAAGCATATCTA FVRVISLGLVVFLVSALSLGPFLALN CCTCTATGTAGCACCAGCTTATGGTGTATATCTGCTGCGATCCTACTGTTTCACTGCAAATAAACCA QLPQVFSRLFPFKRGLCHAYWAPNFW GATGGGTCTATTCGATGGAAGAGTTTCAGCTTTGTTCGTGTTATTTCCCTGGGACTGGTTGTTTTCT ALYNALDKVLSVIGLKLKFLDPNNIP TAGTTTCTGCTCTTTCATTGGGTCCTTTCCTGGCCTTGAATCAGCTGCCTCAAGTCTTTTCCCGACT KASMTSGLVQQFQHTVLPSVTPLATL CTTTCCTTTCAAGAGGGGCCTCTGTCATGCATATTGGGCTCCAAACTTCTGGGCTTTGTACAATGCT ICTLIAILPSIFCLWFKPQGPRGFLR TTGGACAAAGTGCTGTCTGTCATCGGTTTGAAATTGAAATTTCTTGATCCCAACAATATTCCCAAGG CLTLCALSSFMFGWHVHEKAILLAIL CCTCAATGACAAGTGGTTTGGTTCAGCAGTTCCAACACACAGTCCTTCCCTCAGTGACTCCCTTGGC PMSLLSVGKAGDASIFLILTTTGHYS AACCCTCATCTGCACACTGATTGCCATATTGCCCTCTATTTTCTGTCTTTGGTTTAAACCCCAAGGG LFPLLFTAPELPIKILLMLLFTIYSI CCCAGAGGCTTTCTCCGATGTCTAACTCTTTGTGCCTTGAGCTCCTTTATGTTTGGGTGGCATGTTC SSLKTLFRRSFTLVAQAGVQWHDLS ATGAAAAAGCCATACTTCTAGCAATTCTCCCAATGAGCCTTTTGTCTGTGGGAAAAGCAGGAGACGC TTCGATTTTTCTGATTCTGACCACAACAGGACATTATTCCCTCTTTCCTCTGCTCTTCACTGCACCA GAACTTCCCATTAAAATCTTACTCATGTTACTATTCACCATATATAGTATTTCGTCACTGAAGACTT TATTCAGACGGAGTTTCACCCTTGTTGCCCAGGCTGGAGTGCAATGGCACGATCTCAGCTAACTGAA ACCTCCGCCTCCCAGAAAAGAAAAACCTCTTTTTAATTGGATGGAAACTTTCTACCTGCTTGGCCTG GGGCCTCTGGAAGTCTGCTGTGAATTTGTATTCCCTTTCACCTCCTGGAAGGTGAAGTACCCCTTCA TCCCTTTGTTACTAACCTCAGTGTATTGTGCAGTAGGCATCACATATGCTTGGTTCAAACTGTATGT TTCAGTATTGATTGACTCTGCTATTGGCAAGACAAAGAAACAATGAATAAAGGAACTGCTTAGATAT G SEQ.ID NO. 24 SEQ.ID NO. 70 CATTATGCTAACAGCATAAACATGCAGGGGGTGGGAGCAGGGTCACAAAAGTGAGTGTTGTCAATTC MDDDAAPRVEGVPVAVHKHALHDGLR TACTTGGAATGAAAGGTTGAAATAATTTAAACAGTACGGGAAATGCAGAGCAATTTTCTCCTCTGGT QVAGPGAAAAHLPRWPPPQLAASRRE GACAATATAGTGTCCAACACTTGGAAGTGATTTTTAAGAATGTTTATTTAAATTAAAAGGATGGATT APPLSQRPHRTQGAGSPPETNEKLTN TCCAAGGAAAAAAAATAAGGAAAAGGAAAGAAAAAACTGAACAGAAAACGCAAAAGTATCAGTTTGG PQVKEK TCACTAACCTTTGCAAGGATACCTTTTTATTTTCTTTAAGATTCCTGTTGTTTATACACAGATTTTA AGTTTACTCCTACTGCTGACCCAAGTGAAATTCCTTCTCCAGTCACAGTGTCAACCTCTACCCCCCA ACTGCAACGAGAGTTTTGAGGGGCATCAATCACACCGAGAAGTCACAGCCCCTCAACCACTGAGGTG TGGGGGGGTAGGGATCTGCATTTCTTCATATCAACCCCACACTATAGGGCACCTAAATGGGTGGGCG GTGGGGGAGACCGACTCACTTGAGTTTCTTGAAGGCTTCCTGGCCTCCAGCCACGTAATTGCCCCCG CTCTGGATCTGGTCTAGCTTCCGGATTCGGTGGCCAGTCCGCGGGGTGTAGATGTTCCTGACGGCCC CAAAGGGTGCCTGAACGCCGCCGGTCACCTCCTTCAGGAAGACTTCGAAGCTGGACACCTTCTTCTC ATGGATGACGACGCGGCGCCCCGCGTAGAAGGGGTCCCCGTTGCGGTACACAAGCACGCTCTTCACG ACGGGCTGAGACAGGTGGCTGGACCTGGCGCTGCTGCCGCTCATCTTCCCCGCTGGCCGCCGCCTCA GCTCGCTGCTTCGCGTCGGGAGGCACCTCCGCTGTCCCAGCGGCCTCACCGCACCCAGGGCGCGGGA TCGCCTCCTGAAACGAACGAGAAACTGACGAATCCACAGGTGAAAGAGAAGTAACGGCCGTGCGCCT AGGCGTCCACCCAGAGGAGACACTAGGAGCTTGCAGGACTCGGAGTAGACGCTCAAGTTTTTCACCG TGGCGTGCACAGCCAATCAGGACCCGCAGTGCGCGCACCACACCAGGTTCACCTGCTACGGGCAGAA TCAAGGTGGACAGCTTCTGAGCAGGAGCCGGAAACGCGCGGGGCCTTCAAACAGGCACGCCTAGTGA GGGCAGGAGAGAGGAGGACGCACACACACACACACACACAAATATGGTGAAACCCAATTTCTTACAT CATATCTGTGCTACCCTTTCCAAACAGCCTAATTTTTCTTTTCTCTCTTCTTGCACCTTTACCCCTC AATCTCCTGCTTCCTCCCAAATTAAAGCAATTAAGTTCCTGG SEQ.ID NO. 25 SEQ.ID NO. 71 CTCCTCCGAGCACTCGCTCACGGCGTCCCCTTGCCTGGAAAGATACCGCGGTCCCTCCAGAGGATTT MEPAAGSSMEPSADWLATAAARGRVE GAGGGACAGGGTCGGAGGGGGCTCTTCCGCCAGCACCGGAGGAAGAAAGAGGAGGGGCTGGCTGGTC EVRALLEAGALPNAPNSYGRRPIQVM ACCAGAGGGTGGGGCGGACCGCGTGCGCTCGGCGGCTGCGGAGAGGGGGAGAGCAGGCAGCGGGCGG MMGSARVAELLLLHGAEPNCADPATL CGGGGAGCAGCATGGAGCCGGCGGCGGGGAGCAGCATGGAGCCTTCGGCTGACTGGCTGGCCACGGC TRPVHDAAREGFLDTLVVLHRAGARL CGCGGCCCGGGGTCGGGTAGAGGAGGTGCGGGCGCTGCTGGAGGCGGGGGCGCTGCCCAACGCACCG DVRDAWGRLPVDLAEELGHRDVARYL AATAGTTACGGTCGGAGGCCGATCCAGGTCATGATGATGGGCAGCGCCCGAGTGGCGGAGCTGCTGC RAAAGGTRGS TGCTCCACGGCGCGGAGCCCAACTGCGCCGACCCCGCCACTCTCACCCGACCCGTGCACGACGCTGC NHARIDAAEGPSDIPD CCGGGAGGGCTTCCTGGACACGCTGGTGGTGCTGCACCGGGCCGGGGCGCGGCTGGACGTGCGCGAT GCCTGGGGCCGTCTGCCCGTGGACCTGGCTGAGGAGCTGGGCCATCGCGATGTCGCACGGTACCTGC GCGCGGCTGCGGGGGGCACCAGAGGCAGTAACCATGCCCGCATAGATGCCGCGGAAGGTCCCTCAGA CATCCCCGATTGAAAGAACCAGAGAGGCTCTGAGAAACCTCGGGAAACTTAGATCATCAGTCACCGA AGGTCCTACAGGGCCACAACTGCCCCCGCCACAACCCACCCCGCTTTCGTAGTTTTCATTTAGAAAA TAGAGCTTTTAAAAATGTCCTGCCTTTTAACGTAGATATATGCCTTCCCCCACTACCGTAAATGTCC ATTTATATCATTTTTTATATATTCTTATAAAAATGTAAAAAAGAAAAACACCGCTTCTGCCTTTTCA CTGTGTTGGAGTTTTCTGGAGTGAGCACTCACGCCCTAAGCGCACATTCATGTGGGCATTTCTTGCG AGCCTCGCAGCCTCCGGAAGCTGTCGACTTCATGACAAGCATTTTGTGAACTAGGGAAGCTCAGGGG GGTTACTGGCTTCTCTTGAGTCACACTGCTAGCAAATGGCAGAACCAAAGCTCAAATAAAAATAAAA TAATTTTCATTCATTCACTCAAAA SEQ.ID NO. 26 SEQ.ID NO. 72 AGTGGACTCACGCAGGCGCAGGAGACTACACTTCCCAGGAACTCCGGGCCGCGTTGTTCGCTGGTAC MSQVKSSYSYDAPSDFINFSSLDDEG CTCCTTCTGACTTCCGGTATTGCTGCGGTCTGTAGGGCCAATCGGGAGCCTGGAATTGCTTTCCCGG DTQNIDSWFEEKANLENKLLGKNGTG CGCTCTGATTGGTGCATTCGACTAGGCTGCCTGGGTTCAAAATTTCAACGATACTGAATGAGTCCCG GLFQGKTPLRKANLQQAIVTPLKPVD CGGCGGGTTGGCTCGCGCTTCGTTGTCAGATCTGAGGCGAGGCTAGGTGAGCCGTGGGAAGAAAAGA NTYYKEAEKENLVEQSIPSNACSSLE GGGAGCAGCTAGGGCGCGGGTCTCCCTCCTCCCGGAGTTTGGAACGGCTGAAGTTCACCTTCCAGCC VEAAISRKTPAQPQRRSLRLSAQKDL CCTAGCGCCGTTCGCGCCGCTAGGCCTGGCTTCTGAGGCGGTTGCGGTGCTCGGTCGCCGCCTAGGC EQKEKHHVKMKAKRCATPVIIDEILP GGGGCAGGGTGCGAGCAGGGGCTTCGGGCCACGCTTCTCTTGGCGACAGGATTTTGCTGTGAAGTCC SKKMKVSNNKKKPEEEGSAHQDTAEK GTCCGGGAAACGGAGGAAAAAAAGAGTTGCGGGAGGCTGTCGGCTAATAACGGTTCTTGATACATAT NASSPEKAKGRHTVPCMPPAKQKFLK TTGCCAGACTTCAAGATTTCAGAAAAGGGGTGAAAGAGAAGATTGCAACTTTGAGTCAGACCTGTAG STEEQELEKSMKMQQEVVEMRKKNEE GCCTGATAGACTGATTAAACCACAGAAGGTGACCTGCTGAGAAAAGTGGTACAAATACTGGGAAAAA FKKLALAGIGQPVKKSVSQVTKSVDF CCTGCTCTTCTGCGTTAAGTGGGAGACAATGTCACAAGTTAAAAGCTCTTATTCCTATGATGCCCCC HFRTDERIKQHPKNQEEYKEVNFTSE TCGGATTTCATCAATTTTTCATCCTTGGATGATGAAGGAGATACTCAAAACATAGATTCATGGTTTG LRKHPSSPARVTKGCTIVKPFNLSQG AGGAGAAGGCCAATTTGGAGAATAAGTTACTGGGGAAGAATGGAACTGGAGGGCTTTTTCAGGGCAA KKRTFDETVSTYVPLAQQVEDFHKRT AACTCCTTTGAGAAAGGCTAATCTTCAGCAAGCTATTGTCACACCTTTGAAACCAGTTGACAACACT PNRYHLRSKKDDINLLPSKSSVTKIC TACTACAAAGAGGCAGAAAAAGAAAATCTTGTGGAACAATCCATTCCGTCAAATGCTTGTTCTTCCC RDPQTPVLQTKHRARAVTCKSTAELE TGGAAGTTGAGGCAGCCATATCAAGAAAAACTCCAGCCCAGCCTCAGAGAAGATCTCTTAGGCTTTC AEELEKLQQYKFKARELDPRILEGGP TGCTCAGAAGGATTTGGAACAGAAAGAAAAGCATCATGTAAAAATGAAAGCCAAGAGATGTGCCACT ILPKKPPVKPPTEPIGFDLEIEKRIQ CCTGTAATCATCGATGAAATTCTACCCTCTAAGAAAATGAAAGTTTCTAACAACAAAAAGAAGCCAG ERESKKKTEDEHFEFHSRPCPTKILE AGGAAGAAGGCAGTGCTCATCAAGATACTGCTGAAAAGAATGCATCTTCCCCAGAGAAAGCCAAGGG DVVGVPEKKVLPITVPKSPAFALKNR TAGACATACTGTGCCTTGTATGCCACCTGCAAAGCAGAAGTTTCTAAAAAGTACTGAGGAGCAAGAG IRMPTKEDEEEDEPVVIKAQPVPHYG CTGGAGAAGAGTATGAAAATGCAGCAAGAGGTGGTGGAGATGCGGAAAAAGAATGAAGAATTCAAGA VPFKPQIPEARTVEICPFSFDSRDKE AACTTGCTCTGGCTGGAATAGGGCAACCTGTGAAGAAATCAGTGAGCCAGGTCACCAAATCAGTTGA RQLQKEKKIKELQKGEVPKFKALPLP CTTCCACTTCCGCACAGATGAGCGAATCAAACAACATCCTAAGAACCAGGAGGAATATAAGGAAGTG HFDTINLPEKKVKNVTQIEPFCLETD AACTTTACATCTGAACTACGAAAGCATCCTTCATCTCCTGCCCGAGTGACTAAGGGATGTACCATTG RRGALKAQTWKHQLEEELRQQKEAAC TTAAGCCTTTCAACCTGTCCCAAGGAAAGAAAAGAACATTTGATGAAACAGTTTCTACATATGTGCC FKARPNTVISQEPFVPKKEKKSVAEG CCTTGCACAGCAAGTTGAAGACTTCCATAAACGAACCCCTAACAGATATCATTTGAGGAGCAAGAAG LSGSLVQEPFQLATEKRAKERQELEK GATGATATTAACCTGTTACCCTCCAAATCTTCTGTGACCAAGATTTGCAGAGACCCACAGACTCCTG RMAEVEAQKAQQLEEARLQEEEQKKE TACTGCAAACCAAACACCGTGCACGGGCTGTGACCTGCAAAAGTACAGCAGAGCTGGAGGCTGAGGA ELARLRRELVHKANPIRKYQGLEIKS GCTCGAGAAATTGCAACAATACAAATTCAAAGCACGTGAACTTGATCCCAGAATACTTGAAGGTGGG SDQPLTVPVSPKFSTRFHC CCCATCTTGCCCAAGAAACCACCTGTGAAACCACCCACCGAGCCTATTGGCTTTGATTTGGAAATTG AGAAAAGAATCCAGGAGCGAGAATCAAAGAAGAAAACAGAGGATGAACACTTTGAATTTCATTCCAG ACCTTGCCCTACTAAGATTTTGGAAGATGTTGTGGGTGTTCCTGAAAAGAAGGTACTTCCAATCACC GTCCCCAAGTCACCAGCCTTTGCATTGAAGAACAGAATTCGAATGCCCACCAAAGAAGATGAGGAAG AGGACGAACCGGTAGTGATAAAAGCTCAACCTGTGCCACATTATGGGGTGCCTTTTAAGCCCCAAAT CCCAGAGGCAAGAACTGTGGAAATATGCCCTTTCTCGTTTGATTCTCGAGACAAAGAACGTCAGTTA CAGAAGGAGAAGAAAATAAAAGAACTGCAGAAAGGGGAGGTGCCCAAGTTCAAGGCACTTCCCTTGC CTCATTTTGACACCATTAACCTGCCAGAGAAGAAGGTAAAGAATGTGACCCAGATTGAACCTTTCTG CTTGGAGACTGACAGAAGAGGTGCTCTGAAGGCACAGACTTGGAAGCACCAGCTGGAAGAAGAACTG AGACAGCAGAAAGAAGCAGCTTGTTTCAAGGCTCGTCCAAACACCGTCATCTCTCAGGAGCCCTTTG TTCCCAAGAAAGAGAAGAAATCAGTTGCTGAGGGCCTTTCTGGTTCTCTAGTTCAGGAACCTTTTCA GCTGGCTACTGAGAAGAGAGCCAAAGAGCGGCAGGAGCTGGAGAAGAGAATGGCTGAGGTAGAAGCC CAGAAAGCCCAGCAGTTGGAGGAGGCCAGACTACAGGAGGAAGAGCAGAAAAAAGAGGAGCTGGCCA GGCTACGGAGAGAACTGGTGCATAAGGCAAATCCAATACGCAAGTACCAGGGTCTGGAGATAAAGTC AAGTGACCAGCCTCTGACTGTGCCTGTATCTCCCAAATTCTCCACTCGATTCCACTGCTAAACTCAG CTGTGAGCTGCGGATACCGCCCGGCAATGGGACCTGCTCTTAACCTCAAACCTAGGACCGTCTTGCT TTGTCATTGGGCATGGAGAGAACCCATTTCTCCAGACTTTTACCTACCCGTGCCTGAGAAAGCATAC TTGACAACTGTGGACTCCAGTTTTGTTGAGAATTGTTTTCTTACATTACTAAGGCTAATAATGAGAT GTAACTCATGAATGTCTCGATTAGACTCCATGTAGTTACTTCCTTTAAACCATCAGCCGGCCTTTTA TATGGGTCTTCACTCTGACTAGAATTTAGTCTCTGTGTCAGCACAGTGTAATCTCTATTGCTATTGC CCCTTACGACTCTCACCCTCTCCCCACTTTTTTTAAAAATTTTAACCAGAAAATAAAGATAGTTAAA TCCTAAGATAGAGATTAAGTCATGGTTTAAATGAGGAACAATCAGTAAATCAGATTCTGTCCTCTTC TCTGCATACCGTGAATTTATAGTTAAGGATCCCTTTGCTGTGAGGGTAGAAAACCTCACCAACTGCA CCAGTGAGGAAGAAGACTGCGTGGATTCATGGGGAGCCTCACAGCAGCCACGCAGCAGGCTCTGGGT GGGGCTGCCGTTAAGGCACGTTCTTTCCTTACTGGTGCTGATAACAACAGGGAACCGTGCAGTGTGC ATTTTAAGACCTGGCCTGGAATAAATACGTTTTGTCTTTCCCTCAAAAAAAAAAAAAAAAAAAAAAA SEQ.ID NO. 27 SEQ.ID NO. 73 AAACGCGGGCGGGCGGGCCCGCAGTCCTGCAGTTGCAGTCGTGTTCTCCGAGTTCCTGTCTCTCTGC MASQNRDPAATSVAAARKGAEPSGGA CAACGCCGCCCGGATGGCTTCCCAAAACCGCGACCCAGCCGCCACTAGCGTCGCCGCCGCCCGTAAA ARGPVGKRLQQELMTLMMSGDKGISA GGAGCTGAGCCGAGCGGGGGCGCCGCCCGGGGTCCGGTGGGCAAAAGGCTACAGCAGGAGCTGATGA FPESDNLFKWVGTIHGAAGTVYEDLR CCCTCATGATGTCTGGCGATAAAGGGATTTCTGCCTTCCCTGAATCAGACAACCTTTTCAAATGGGT YKLSLEFPSGYPYNAPTVKFLTPCYH AGGGACCATCCATGGAGCAGCTGGAACAGTATATGAAGACCTGAGGTATAAGCTCTCGCTAGAGTTC PNVDTQGNICLDILKEKWSALYDVRT CCCAGTGGCTACCCTTACAATGCGCCCACAGTGAAGTTCCTCACGCCCTGCTATCACCCCAACGTGG ILLSIQSLLGEPNIDSPLNTHAAELW ACACCCAGGGTAACATATGCCTGGACATCCTGAAGGAAAAGTGGTCTGCCCTGTATGATGTCAGGAC KNPTAFKKYLQETYSKQVTSQEP CATTCTGCTCTCCATCCAGAGCCTTCTAGGAGAACCCAACATTGATAGTCCCTTGAACACACATGCT GCCGAGCTCTGGAAAAACCCCACAGCTTTTAAGAAGTACCTGCAAGAAACCTACTCAAAGCAGGTCA CCAGCCAGGAGCCCTGACCCAGGCTGCCCAGCCTGTCCTTGTGTCGTCTTTTTAATTTTTCCTTAGA TGGTCTGTCCTTTTTGTGATTTCTGTATAGGACTCTTTATCTTGAGCTGTGGTATTTTTGTTTTGTT TTTGTCTTTTAAATTAAGCCTCGGTTGAGCCCTTGTATATTAAATAAATGCATTTTTGTCCTTTTTT AGACAAAAAAAAAAAAAAA SEQ.ID NO. 28 CAGCTAAATTTTAAAGGTGTTTTTGTAGAGATGAGGTTTCACTATATTGCCCAGGCTGGTCTCGAAC TCCTGGACTTAAGTGATCCTTCCTCTTTGGCCTCCCAAAGTGCTGGGATTACAGGCATGAGCCACTG CCCCAGCCAAGACTGTCTTTTCTCCATTGTATTGCGTTTGCTTCCTTGTCAAAGATCAGTTGACTAT ATTTGTGTGGGGCTATTTCTGGGCTCCCTATTTGTTTCCAGTGATTATGTCTATTTTTTCACCATTA CCACCCTATCTTAATTACTGTAGCTTTATAGTGAGTCTTAAAGTTGGGTAATATCAGTCTTCTGACC TTTTTCTCTTTCAATATTGTGCCAGCTATTCTGGGTCTTTTGCCTTTCCATGTAAACTTTAGAACCA GTTTGTCAGGATCCACAAAATACTTTGCTGGGTTTTGATTGGGATTGCATTGAATCCACAGGTCAAG TTGGCAAAAACTGACATACAGCAATGCCAGTTTATTGTTTTGTGATAGCCTTAATCCAGCTAGTTTC TTCACAGGATGATGTTGAAAATATGGGATGCTCATAATCCCTGAATATTTTTTATGTGGATAATTAA ACTTGTTCTGGGTGGATGGTTGGATAGCCAGAATAGTAATAACCTCTCTTCCAGCCACTCAAAGAAA ATGATATAAACGTAGGGTTGGTTTAATTGTTGAGAGGTCACGTTTTTTCCATTCTTGCTCTCAGGTA AGGAAAGAGCACTGTTGGTTCACGCATTCCTTTTTCCCTCATACACTTTGTTGGGCACTGATATGGT TTGGCTCTGTGTTCCCACCCAAATCTCATGTTGAATTGTGATCCTGAGTGTTGGAGGTGGGGCCTCG CGGGAGACGACTGGATCATGGGGGCGGATTTTCCCCTTGCTGTTCTCATGATAGTGAGTTCTCATGA GATCTGGTTGTTTAAAAGTGTATAGCACTTCCTGCTTCACTCTCTCCCACTCCACCATGTGAAGAAG
GTGCCTTTGCCCTTCCGCCACGACTGTGTTTCCTGAGGCCTCCCCAGCCATGCCTCCTGTACAGCCT GCGGAACTGTCAGTTAAACCTCTTTTCTTCATTAATTACCCACTCTCAGGTGGTTTTTTATGGCAGT GTGAGAACGGACTAATACAGAAAATTGGTACCAGAGAAGTGGGATATTGCTATAAAATACCTGAAAA TGTGGAAGTGACTTTGGAACTGGGTAATGGGCAGAGGTTGGAACAGTTTGGAGGGCTCAGAAGAAGA CAGGAAGATGAGGGAAAGTTTGCAGCTTCCTAGAGACTTGTTGAATGGTTGTGACCAAAGTGCTGAT AGTGATATGGACAGTGAAGTCCAGGCTGAGTTGGTCTCAGATGGGAGATGAGAATCTTATTCCGAAC TGGAGTGAAGGTCACTCTTGGCTGTGCTTTAGCAAAGAGAGTGGTGGCATTGTGCCCCTGCTCTAGA GATCTGTGAACTCTGAACTCGAGAGGGTATCTGGCAGAAAAAAATTTCTAAGCAGCAAAGTGTTCAA GATGTGGCCTGATTGCTTCTAAAAGCCTATGCTCATTTGCATGAACAAAGTGGAACTTATATTTAAA ACAGAAGCTGAGCTTTTATAAAAGTTTGGAGAATTTGCAGCCCAACCATGTGGTGAAAAAGAAAAAT CCATTTTCTGGGGAGGTATTCAAGGCTGCAGAAATTTGCATAAGAAGAGCCTCATGTTAACAGCCAA GAGAGTGAGGAAAATGCCTCTAGAGCATTTCAGAGACCTTCACAGCAGCTCCTCCCATCACAGGCAT GGAAGCCCAGGAGGAAGAAATGCTTTTGTGGGCCAGCCCAGGGCCCCACTGTTCTGTGCAGCCTTGG GACATGGTGCCCTGCATCCCAGCCACTCCAGCTCCAGCTGTGACTAAAAGGGGCCAAGGTACAGCTT GGGCTGCTGCTTCAGAGGGTGCAAGCCCCAAGCCTTGGTGGCTTCCATGTGGTGTTAGGCAGGTGTG CAGAAGAGTTGAGGTTTAGGAACCTCTACCTAGATTTCAGAGGATGTATGGAAATGCCCGGATGTCC AGGCAGAAGTTTGCTGCAGAGGCAGAGCCCTCATAGATAACCTCTGCGAGGGCAGTGTGGAGGGGAA ATGTGGGGTTGGAGCTATGAGAAGAGGGCCACCATCCACCAGACCCCAGAATTGTAGATCCACTGAC AGCTTGCACTATGCACCTGTAAAAGTTGCAGGCAGTTAATGCTAGCCTGTGAAAGCAGCTGTGGGGA CTATATGCAGAGCCACAGAGGCAGAGCTGCCCAGAGCCTTGGGAGCCCACTCCTTGTGTCAGTGTGG CCTGGATGTGAGACGTGGAGTCAAAGATCATTTTGGAGGTTTGAGATTTAATGACTGCCCTCCTGGA TTTTGGACTTGCATGGGGCCCATAGCCCCTTTGTTTTGGCTGATTTCTCCTATTTGGAATGGGAGCA TTTACCCAATGCCTGTATCCCCATTGTATCTTGGAGATAACTGACTTGTTTTTGATTTTACAGGCTC ACAGGAGGAAGGGACTTGGCTGGTCTCAGATGAGACTTGACTTGGACATTTGAGTTAATGCTGGAAT GAGTTAAGACTTTAGGGGGCTATTGGGAAGGCATGATTGTGTTTTGAAATGTGAGGACATGAGATTT GGGAGGGGCCAGGGTGGAATGATATGGTTTGGCTGTGTCCCCCCACCCAAATCTCATGTTGAATTGT GATCCTGAGTCTTGGAGGTAGAGCCTGGTGGGAGGTGATTGGATCATGGGGGCAGATTTCCCCCTTG CTGTTCTCATGACAGTGAGTTCTCATGAGATCTGGTTAAGTGTGTAGCACTTCCCCCTTTGCTTGCT CTCTCCCTCTGCCATGTGAAGAAGGTGCTTGCTTTCCCTTCGCCCTTCTGCCATGACTGTAAGTTTC TTGAGGCCTCGCAGCCATGCTTCCTGTACAGCCTGCAGAACTGTGAGTTAATTAAACCTCTTTTCTT CAT SEQ.ID NO. 29 SEQ.ID NO. 74 AGCTTTGGGGTTGTCCCTGGACTTGTCTTGGTTCCAGAACCTGACGACCCGGCGACGGCGACGTCTC MPNFSGNWKIIRSENFEELLKVLGVN TTTTGACTAAAAGACAGTGTCCAGTGCTCCAGCCTAGGAGTCTACGGGGACCGCCTCCCGCGCCGCC VMLRKIAVAAASKPAVEIKQEGDTFY ACCATGCCCAACTTCTCTGGCAACTGGAAAATCATCCGATCGGAAAACTTCGAGGAATTGCTCAAAG IKTSTTVRTTEINFKVGEEFEEQTVD TGCTGGGGGTGAATGTGATGCTGAGGAAGATTGCTGTGGCTGCAGCGTCCAAGCCAGCAGTGGAGAT GRPCKSLVKWESENKMVCEQKLLKGE CAAACAGGAGGGAGACACTTTCTACATCAAAACCTCCACCACCGTGCGCACCACAGAGATTAACTTC GPKTSWTRELTNDGELILTMTADDVV AAGGTTGGGGAGGAGTTTGAGGAGCAGACTGTGGATGGGAGGCCCTGTAAGAGCCTGGTGAAATGGG CTRVYVRE AGAGTGAGAATAAAATGGTCTGTGAGCAGAAGCTCCTGAAGGGAGAGGGCCCCAAGACCTCGTGGAC CAGAGAACTGACCAACGATGGGGAACTGATCCTGACCATGACGGCGGATGACGTTGTGTGCACCAGG GTCTACGTCCGAGAGTGAGTGGCCACAGGTAGAACCGCGGCCGAAGCCCACCACTGGCCATGCTCAC CGCCCTGCTTCACTGCCCCCTCCGTCCCACCCCCTCCTTCTAGGATAGCGCTCCCCTTACCCCAGTC ACTTCTGGGGGTCACTGGGATGCCTCTTGCAGGGTCTTGCTTTCTTTGACCTCTTCTCTCCTCCCCT ACACCAACAAAGAGGAATGGCTGCAAGAGCCCAGATCACCCATTCCGGGTTCACTCCCCGCCTCCCC AAGTCAGCAGTCCTAGCCCCAAACCAGCCCAGAGCAGGGTCTCTCTAAAGGGGACTTGAGGGCCTGA GCAGGAAAGACTGGCCCTCTAGCTTCTACCCTTTGTCCCTGTAGCCTATACAGTTTAGAATATTTAT TTGTTAATTTTATTAAAATGCTTTAAAAAAA SEQ.ID NO. 30 SEQ.ID NO. 75 CTCGCTTTTCGGTTGCCGTTGTCTTTTTTCCTTGACTCGGAAATGTCCGGTCGTGGTAAGCAGGGTG MSGRGKQGGKARAKAKSRSSRAGLQF GCAAGGCGCGCGCCAAGGCTAAGTCGCGCTCGTCGCGCGCGGGGCTGCAGTTCCCCGTGGGCCGCGT PVGRVHRLLRKGNYSERVGAGAPVYL GCACCGGTTGCTCCGCAAGGGCAACTATTCGGAGCGCGTGGGCGCCGGCGCCCCGGTCTATCTGGCC AAVLEYLTAEILELAGNAARDNKKTR GCGGTGCTCGAGTACTTGACTGCCGAGATCCTGGAGCTTGCCGGCAACGCGGCGCGCGACAACAAGA IIPRHLQLAIRNDEELNKLLGRVTIA AGACGCGCATCATCCCGCGCCACCTGCAGCTGGCCATCCGCAACGACGAGGAGCTCAACAAGCTGCT QGGVLPNIQAVLLPKKTESHHKAKGK GGGCCGCGTGACCATCGCGCAGGGTGGCGTCCTGCCCAACATCCAGGCCGTACTGCTGCCCAAGAAG ACGGAGAGCCACCACAAGGCCAAGGGCAAGTGAGGCCGCCCGCCGCCCCCGGGGCCCCTTTGATGGA CATAAAGGCTCTTTTCAGAGC CACCTA SEQ.ID NO. 31 SEQ.ID NO. 76 ATGTCTGGCCGTGGTAAAGGTGGAAAAGGTTTGGGTAAGGGAGGAGCTAAGCGTCATCGCAAGGTTT MSGRGKGGKGLGKGGAKRHRKVLRDN TGCGCGATAACATCCAGGGCATCACTAAGCCAGCTATCCGGCGCCTTGCTCGTCGCGGCGGTGTCAA IQGITKPAIRRLARRGGVKRISGLIY GCGAATTTCTGGCCTTATCTATGAGGAGACTCGTGGTGTTCTGAAGGTGTTCCTGGAGAACGTGATT EETRGVLKVFLENVIRDAVTYTEHAK CGTGACGCTGTCACTTACACAGAGCACGCCAAACGCAAGACCGTGACAGCAATGGATGTGGTCTACG RKTVTAMDVVYALKRQGRTLYGFGG CGCTGAAGCGACAGGGACGCACTCTTTACGGCTTCGGTGGCTAAGGCTCCTGCTTGCTGCACTCTTA TTTTCATTTTCAACCAAAGGCCCTTTTCAGGGCCGCCCA SEQ.ID NO. 32 SEQ.ID NO. 77 GCCTCCACAGATATCAAAAGAAACCTGAAGAGCCTACAAAAAAAAAAGAGATAAAGACAAAATTCAA MLFEQGQQALELPECTMQKAAYYENP GAAAACACACACATACATAATTGTGGTCACCTGGAGCCTGGGGGCCGGCCCAGCTCTCTCAGGATTC GLFGGYGYSKTTDTYGYSTPHQPYPP AGCAGACATTGGAGGTGGCAGTGAAGGATACAGTGGTAGTCAATGTTATTTGAGCAGGGTCAGCAGG PAAASSLDTDYPGSACSIQSSAPLRA CCCTGGAGCTTCCTGAGTGCACAATGCAGAAGGCTGCTTACTATGAAAACCCAGGACTGTTTGGAGG PAHKGAELNGSCMRPGTGNSQGGGGG CTATGGCTACAGCAAAACTACGGACACTTACGGCTACAGCACCCCCCACCAGCCCTACCCACCCCCT SQPPGLNSEQQPPQPPPPPPTLPPSS GCTGCTGCCAGCTCCCTGGACACTGACTATCCAGGTTCTGCCTGCTCCATCCAGAGCTCTGCCCCTC PTNPGGGVPAKKPKGGPNASSSSATI TGAGAGCCCCAGCCCACAAAGGAGCTGAACTCAATGGCAGCTGCATGCGGCCGGGCACTGGGAACAG SKQIFPWMKESRQNSKQKNSCATAGE CCAGGGTGGGGGTGGTGGCAGCCAGCCTCCTGGTCTGAACTCAGAGCAGCAGCCACCACAACCCCCT SCEDKSPPGPASKRVRTAYTSAQLVE CCTCCACCACCGACCCTGCCCCCATCTTCACCCACCAATCCTGGAGGTGGAGTGCCTGCCAAGAAGC LEKEFHFNRYLCRPRRVEMANLLNLT CCAAAGGTGGGCCCAATGCTTCTAGCTCCTCAGCCACCATCAGCAAGCAGATCTTCCCCTGGATGAA ERQIKIWFQNRRMKYKKDQKAKGILH AGAGTCTCGACAGAACTCCAAGCAGAAGAACAGCTGTGCCACTGCAGGAGAGAGCTGCGAGGACAAG SPASQSPERSPPLGGAAGHVAYSGQL AGCCCGCCAGGCCCAGCATCCAAGCGGGTACGCACGGCATACACGAGCGCGCAGCTGGTGGAATTGG PPVPGLAYDAPSPPAFAKSQPNMYGL AAAAGGAATTCCACTTCAACCGCTACTTGTGCCGGCCGCGCCGCGTGGAGATGGCCAACCTGCTGAA AAYTAPLSSCLPQQKRYAAPEFEPHP TCTCACGGAACGCCAGATCAAGATCTGGTTCCAGAACCGGCGCATGAAGTACAAGAAGGACCAGAAG MASNGGGFASANLQGSPVYVGGNFVE GCCAAGGGCATCCTGCACTCGCCGGCTAGCCAGTCCCCTGAGCGCAGCCCACCGCTCGGCGGCGCCG SMAPASGPVFNLGHLSHPSSASVDYS CTGGCCACGTGGCCTACTCCGGCCAGCTGCCGCCAGTGCCCGGCCTGGCCTACGACGCGCCCTCGCC CAAQIPGNHHHGPCDPHPTYTDLSAH GCCTGCTTTCGCCAAATCACAGCCCAATATGTACGGCCTGGCCGCCTACACGGCGCCACTCAGCAGC HSSQGRLPEAPKLTHL TGCCTGCCACAACAGAAGCGCTACGCAGCGCCGGAGTTCGAGCCCCATCCCATGGCGAGCAACGGCG GCGGCTTCGCCAGCGCCAACTTGCAGGGCAGCCCGGTGTACGTGGGCGGCAACTTCGTCGAGTCCAT GGCGCCCGCGTCCGGGCCTGTCTTCAACCTGGGCCACCTCTCGCACCCGTCGTCGGCCAGCGTGGAC TACAGTTGCGCCGCGCAGATTCCAGGCAACCACCACCATGGACCTTGCGACCCTCATCCCACCTACA CAGATCTCTCGGCCCACCACTCGTCTCAGGGACGACTGCCGGAGGCTCCCAAACTGACGCATCTGTA GCGGCCGCCGCCAGCCCGAACTCGCGGCAAAATTACCTCTCTTGCTGTAGTGGTGGGGTAGAGGGTG GGGCCCGCGGGGCAGTTCGGGAACCCCCTTCCCCGCTCTTGCCCTGCCGCCGCCTCCCGGGTCTCAG GCCTCCAGCGGCGGAGGCGCAGGCGACCGGGCCTCCCCTCCATGGGCGTCCTTTGGGTGACTCGCCA TAAATCAGCCGCAAGGATCCTTCCCTGTAAATTTGACAGTGCCACATACTGCGGACCAAGGGACTCC AATCTGGTAATGGTGTCCCAAAGGTAAGTCTGAGACCCATCAGCGGCGCGCCCTGCAGAGGGACCAG AGCTTGGAGAGTCTTGGGCCTGGCCCGCGTCTAGCTTAGTTTCAGAGACCTTAATTTATATTCTCCT TCCTGTGCCGTAAGGATTGCATCGGACTAAACTATCTGTATTTATTATTTGAAGCGAGTCATTTCGT TCCCTGATTATTTATCCTTGTCTGAATGTATTTATGTGTATATTTGTAGATTTATCCAGCCGAGCTT AGGAATTCGCTTCCAGGCCGTGGGGGCCACATTTCACCTCCTTAGTCCCCCTGGTCTGAACTAGTTG AGAGAGTAGTTTTGAACAGTCGTAACCGTGGCTGGTGTTTGTAGTTGACATAAAGGATTAAGACCGC AAATTGTCCTTCATGGGTAGAGTCAGGAAGCCCGGTGGCGTGGCACAACACACTTTGGTCATTTCTC AAAAACCACAGTCCTCACCACAGTTTATTGATTTCAAATTGTCTGGTACTATTGGAACAAATATTTA GAATAAAAAAATTTCCCAGTCAAAAAAAAAAAAAAAAAAAA SEQ.ID NO. 33 SEQ.ID NO. 78 CCAGCCCTGAGATTCCCAGGTGTTTCCATTCGGTGATCAGCACTGAACACAGAACTCACCATGGAGT MEFGLSWVFLVAILKGVQCEVQLVES TTGGACTGAGCTGGGTTTTCCTTGTTGCTATTTTAAAAGGTGTCCAGTGTGAAGTGCAGCTGGTGGA GGVVVQPGGSLRLSCAASGFTFDDYA GTCTGGGGGAGTCGTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACC MHWVRQAPGKGLEWVSLISWDGGSTY TTTGATGACTATGCCATGCACTGGGTCCGTCAAGCTCCGGGGAAGGGTCTGGAGTGGGTCTCCCTTA YADSVKGRFTISRDNSKNSLYLQMNS TTAGTTGGGATGGTGGTAGCACCTACTATGCAGACTCTGTGAAGGGTCGATTCACCATCTCCAGAGA LRAEDTALYYCATRGGYSTAGFDYWG CAATAGTAAAAATTCCTTGTATCTGCAAATGAACAGTCTGAGAGCTGAGGACACCGCCTTGTATTAC QGTLVTVSSASTKGPSVFPLAPSSKS TGTGCAACCCGGGGGGGTTATTCCACCGCCGGCTTTGACTACTGGGGCCAGGGAACCCTGGTCACCG TSGGTAALGCLVKDYFPEPVTVSWNS TCTCCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGG GALTSGVHTFPAVLQSSGLYSLSSVV GGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAAC TVPSSSLGTQTYICNVNHKPSNTKVD TCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCC KKVEPKSCDKTHTCPPCPAPELLGGP TCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCA SVFLFPPKPKDTLMISRTPEVTCVVV CAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGC DVSHEDPEVKFNWYVDGVEVHNAKTK CCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGG PREEQYNSTYRVVSVLTVLHQDWLNG ACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCC KEYKCKVSNKALPAPIEKTISKAKGQ TGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAG PREPQVYTLPPSRDELTKNQVSLTCL GAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATG VKGFYPSDIAVEWESNGQPENNYKTT GCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAA PPVLDSDGSFFLYSKLTVDKSRWQQG AGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAG NVFSCSVMHEALHNHYTQKSLSLSPG AACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGA K GCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTT CCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTG ATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAATGAGTGC GACGGCCGGCAAGCCCCCGCTCCCCGGGCTCTCGCGGTCGCACGAGGATGCTTGGCACGTACCCCGT GTACATACTTCCCGGGCGCCCAGCATGGAAATAAAGCACCCAGCGCTGCCCTGGGCCCCTGCGAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAA SEQ.ID NO. 34 SEQ.ID NO. 79 GAGGGAACCATGGAAACCCCAGCGCAGCTTCTCTTCCTCCTGCTACTCTGGCTCCCAGATATCACCG METPAQLLFLLLLWLPDITGEIVLTQ GAGAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGAGAAAGAGCCGCCCTCTC SPGTLSLSPGERAALSCRASQSVNSK ATGCAGGGCCAGTCAGAGTGTTAACAGCAAGTACTTAGCCTGGTACCAGCAGAAGCCTGGCCAGGCT YLAWYQQKPGQAPRLLMYAASIRATG CCCAGGCTCCTCATGTATGCTGCATCCATCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAGTG IPDRFSGSGSGTDFTLTISRLESEDF GGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAATCTGAGGACTTTGCACTGTATTTCTG ALYFCQQYGTSPLTFGGGTKVEIKRT TCAGCAATATGGTACTTCACCTCTCACTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGAACTGTG VAAPSVFIFPPSDEQLKSGTASVVCL GCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTG LNNFYPREAKVQWKVDNALQSGNSQE TGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCA SVTEQDSKDSTYSLSSTLTLSKADYE ATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGC KHKVYACEVTHQGLSSPVTKSFNRGE ACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGG C GCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAGAGGGAGAAGTGCCCCCACCT GCTCCTCAGTTCCAGCCTGACCCCCTCCCATCCTTTGGCCTCTGACCCTTTTTCCACAGGGGACCTA CCCCTATTGCGGTCCTCCAGCTCATCTTTCACCTCACCCCCCTCCTCCTCCTTGGCTTTAATTATGC TAATGTTGGAGGAGAATGAATAAATAAAGTGAATCTTTGCACCTAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA SEQ.ID NO. 35 SEQ.ID NO. 80 ACGCGGGGGGCCCGCTCTCGGCGAGCCCGAGCCGCCGCCGGCCCCGCGGCGGAGATGAGCAGGTCCG MSRSATLLLCLLGCHVWKAVTKTLRE CGACGCTGCTGCTGTGCCTGCTGGGCTGCCACGTCTGGAAGGCGGTGACCAAGACGCTGCGGGAGCC PGAGAQEVTLKVHISDASTHQPVADA CGGCGCCGGAGCCCAAGAGGTGACGTTAAAGGTGCACATCAGCGACGCCAGCACCCACCAGCCCGTA LIEIFTNQASIASGTSGTDGVAFIKF GCAGATGCGCTCATCGAGATCTTCACCAACCAGGCCTCCATAGCCTCTGGCACCTCGGGGACTGATG QYKLGSQLIVTASKHAYVPNSAPWKP GCGTCGCCTTTATCAAGTTCCAGTATAAGCTGGGCAGTCAGTTGATTGTCACCGCCTCGAAGCATGC IRLPVESSLSLGLLPERSATLMVYED CTACGTGCCAAACTCTGCCCCATGGAAGCCAATCCGGTTACCTGTATTTTCCTCTCTGAGCCTTGGC VVQIVSGFQGARPQPRVHFQRRALRL CTGCTTCCAGAACGCTCTGCCACTCTAATGGTATATGAAGATGTCGTCCAAATAGTATCAGGATTCC PENTSYSDLTAFLTAASSPSEVDSFP AAGGTGCCCGGCCACAGCCTCGCGTTCATTTCCAGAGAAGGGCTCTGAGGTTGCCTGAGAACACCAG YLRGLDGNGTGNSTRHDLTPVTAVSV CTACAGTGACCTGACCGCGTTTCTCACGGCCGCCAGCTCCCCTTCGGAGGTGGACAGTTTTCCTTAT HLLSSNGTPVLVDGPIYVTVPLATQS TTGCGAGGATTAGACGGAAATGGAACAGGAAACAGCACCAGGCATGACCTGACCCCAGTCACAGCCG SLRHNAYVAAWRFDQKLGTWLKSGLG TCAGCGTCCACTTGCTGAGCAGTAATGGAACGCCGGTGCTGGTGGATGGTCCCATCTATGTCACTGT LVHQEGSQLTWTYIAPQLGYWVAAMS GCCCCTGGCCACGCAGAGCAGCCTGAGGCACAATGCCTATGTCGCGGCGTGGCGGTTTGACCAGAAG PPIPGPVVTQDITTYHTVFLLAILGG CTGGGAACGTGGCTGAAGAGCGGTCTGGGTCTTGTGCACCAGGAAGGCAGCCAGCTGACGTGGACAT MAFILLVLLCLLLYYCRRKCLKPRQH ACATTGCCCCCCAGTTGGGGTACTGGGTGGCCGCCATGTCCCCTCCCATCCCAGGTCCCGTTGTAAC HRKLQLPAGLESSKRDQSTSMSHINL ACAGGACATTACCACGTATCACACGGTGTTTCTTTTGGCCATTTTAGGAGGAATGGCTTTCATACTT LFSRRASEFPGPLSVTSHGRPEAPGT TTGGTTTTGCTGTGTCTCCTTTTATATTATTGCAGGAGGAAGTGCTTGAAACCTCGTCAGCACCACA KELMSGVHLEMMSPGGEGDLHTPMLK GAAAACTGCAGCTCCCTGCAGGACTGGAGAGTTCCAAAAGAGACCAGTCCACGTCCATGTCACACAT LSYSTSQEFSSREELLSCKEEDKSQI TAACTTGCTGTTTTCACGCCGAGCGTCAGAATTCCCTGGCCCGCTGTCCGTCACCAGCCACGGCCGC SFDNLTPSGTLGKDYHKSVEVFPLKA CCCGAGGCCCCCGGCACGAAGGAACTGATGAGTGGAGTCCATTTGGAAATGATGTCTCCGGGCGGCG RKSMEREGYESSGNDDYRGSYNTVLS AAGGGGACCTGCACACCCCCATGCTCAAGCTCTCCTACAGCACCTCCCAGGAATTTAGCTCCCGGGA QPLFEKQDREGPASTGSKLTIQEHLY GGAGCTCCTCTCTTGCAAGGAAGAGGATAAAAGCCAGATCTCCTTTGATAACCTCACTCCAAGTGGG
PAPSSPEKEQLLDRRPTECMMSRSVD ACGCTGGGGAAAGACTACCATAAGTCAGTGGAGGTTTTTCCCTTAAAGGCAAGAAAATCTATGGAAA HLERPTSFPRPGQLICCSSVDQVNDS GAGAAGGCTACGAGTCCTCGGGCAATGATGACTACAGGGGTAGTTACAACACCGTGCTCTCACAGCC VYRKVLPALVIPAHYMKLPGDHSYVS TTTATTTGAAAAGCAGGACAGAGAAGGTCCAGCCTCCACGGGAAGCAAACTCACCATTCAGGAACAT QPLVVPADQQLEIERLQAELSNPHAG CTGTACCCCGCGCCTTCATCACCTGAGAAAGAACAGCTGCTGGACCGCAGACCCACTGAATGTATGA IFPHPSSQIQPQPLSSQAISQQHLQD TGTCGCGATCAGTAGATCACCTCGAGAGACCTACGTCCTTCCCACGGCCCGGCCAGTTAATCTGCTG AGTREWSPQNASMSESLSIPASLNDA CAGTTCTGTCGACCAGGTCAATGACAGCGTTTACAGGAAAGTACTGCCTGCCTTGGTCATCCCGGCT ALAQMNSEVQLLTEKALMELGGGKPL CATTATATGAAACTCCCCGGGGACCACTCCTATGTCAGCCAGCCCCTCGTCGTCCCGGCTGATCAGC PHPRAWFVSLDGRSNAHVRHSYIDLQ AGCTTGAGATAGAAAGACTACAGGCTGAGCTGTCCAATCCCCATGCCGGGATCTTCCCACACCCGTC RAGRNGSNDASLDSGVDMNEPKSARK CTCACAGATCCAGCCCCAGCCCCTGTCTTCCCAGGCCATCTCTCAGCAGCACCTGCAGGATGCGGGC GRGDALSLQQNYPPVQEHQQKEPRAP ACCCGGGAGTGGAGCCCTCAGAACGCATCCATGTCGGAGTCTCTCTCCATCCCAGCTTCCCTGAACG DSTAYTQLVYLDDVEQSGSECGTTVC ACGCGGCTTTGGCTCAGATGAACAGTGAGGTGCAGCTCCTGACTGAAAAGGCCCTGATGGAGCTTGG TPEDSALRCLLEGSSRRSGGQLPSLQ GGGTGGGAAGCCGCTTCCGCACCCCCGGGCGTGGTTCGTCTCCTTGGATGGCAGGTCCAACGCTCAC EETTRRTADAPSEPAASPHQRRSAHE GTTAGACATTCATACATTGATCTCCAAAGAGCTGGAAGGAACGGAAGTAATGATGCCAGTTTGGACT EEEDDDDDDQGEDKKSPWQKREERPL CTGGCGTAGATATGAATGAACCAAAATCAGCCCGGAAGGGAAGGGGAGATGCTTTGTCTCTGCAGCA MAFNIK GAACTACCCGCCCGTCCAAGAGCACCAGCAGAAAGAGCCTCGAGCCCCAGACAGCACGGCCTACACG CAGCTCGTGTACCTGGATGACGTGGAACAGAGTGGTAGCGAATGTGGGACCACGGTCTGTACCCCCG AGGACAGTGCCCTGCGATGCTTGTTGGAGGGGTCGAGTCGGAGAAGTGGTGGCCAGCTGCCCAGCCT GCAGGAGGAGACGACCAGACGGACTGCGGATGCCCCCTCGGAGCCAGCAGCCAGCCCCCACCAGAGA AGATCTGCCCACGAGGAAGAGGAAGACGATGATGATGATGACCAAGGAGAAGACAAGAAAAGCCCCT GGCAGAAACGGGAGGAGAGGCCCCTGATGGCGTTTAACATTAAATGAGCTATCGCAGACCCACCTGA CTGTGGAATATAAAATTGCCAAATATCCTTTCTCATGGAAGCGCGTACCCGTTCGTGGAGGAAACGG AACGGCAGCCCAGCCGTGGGACGGACGTGGACGTTTACTGCATTCCTGTTTGCCGTGTAAATGTTAG AAAGGAATTAAAGTTATTACTCGGAATAAAGGATGACTTTGGCGGATGTCGCCCCTGCAAGGAGGTG GCTGAAAGTGGTGTCCAGATGTCCTTCCGAGGACTCGGCGTATCCGCCACCAGGGACATTAAGAAAC CGCACGTGATGTCGCTATGCTCTAACGATCACCTCAGTTCTCCCTCGGATTCTGGGAACAGATGAAA CTTTTTGCATCGCTTGAGTCATTTTTATCACAATAATCCTACTGTGAAGCTGTCGTTGAGAACTTAG GTTGGCACGTAGCGTCTCAAGGTATGCGTTCTCTCAAAGGAAAGCTATGCATCGCTGCTTCTTTGTC TGATTTTGCTTAGATTTTGCTTTGGTTAGGTTGCGTTTTGGGGTTTGCCTTTTTTTGTTGTCGCTTA AATGCAATTTGGTTGTAAAGATTTGATTCCTTTGTGTTCATCTGTTCCGCTTCTCAGCGGTCCATCT CAGCGTCTCCCTTCAGGAACCGCTGAGTGTCCTCTCTTAACATCCAAGCCTTTTAATGAAATCGTAC TGAAATCTGTATCAGCTAAGAGTCCTCCAATCCTGGTCCCATTAACTCCAAGTGCCTTTTTGTCAGT GACAACAGACAGTCCCTCGCTTTTTGTTGTTGTTGGTTTTCTTAACCCCTTTAATGGAACTGCCTGG ATTTTATACAGTTATTAAAGGATGTCTCTTTTGCTTTAAACTGCATGCTGCCAAGTGCCATTTGGGG TCAGCATCCTCGTTTCAACACAGTGTGCTCTCTAGTTATCATGTGTAACGTGGGTTCTGTTTAGCGA AGATAGACTAGAGGACACGTTAGAGATGCCCTTCCCTGCTCCATCCCTGTGGCACCATTATGGTTTT TTGGCTGTTTGTATATACGGTTACGTATTAACTCTGGAATCCTATGGGCTCATCTTGCTCACCCAAT GTGGGAGTCTGGTTTGAGCAAGCGAGCTGAATGTGACTATTAAAAAAAATTTAAAAAAAAAAAAGAA AATCTTATGTACTATCCAAAAGTGCCAGAATGACTCTTCTGTGCATTCTTCTTAAAGAGCTGCTTGG TTATCCAAAAATGAAAATTCAAAATAAACTCTGAAAAAAAAAAAAAAAAAAAA SEQ.ID NO. 36 SEQ.ID NO. 81 CGTCACTTCCTGTTGCCTTAGGGGAACGTGGCTTTCCCTGCAGAGCCGGTGTCTCCGCCTGCGTCCC MDSALSDPHNGSAEAGGPTNSTTRPP TGCTGCAGCAACCGGAGCTGGAGTCGGATCCCGAACGCACCCTCGCCATGGACTCGGCCCTCAGCGA STPEGIALAYGSLLLMALLPIFFGAL TCCGCATAACGGCAGTGCCGAGGCAGGCGGCCCCACCAACAGCACTACGCGGCCGCCTTCCACGCCC RSVRCARGKNASDMPETITSRDAARF GAGGGCATCGCGCTGGCCTACGGCAGCCTCCTGCTCATGGCGCTGCTGCCCATCTTCTTCGGCGCCC PIIASCTLLGLYLFFKIFSQEYINLL TGCGCTCCGTACGCTGCGCCCGCGGCAAGAATGCTTCAGACATGCCTGAAACAATCACCAGCCGGGA LSMYFFVLGILALSHTISPFMNKFFP TGCCGCCCGCTTCCCCATCATCGCCAGCTGCACACTCTTGGGGCTCTACCTCTTTTTCAAAATATTC ASFPNRQYQLLFTQGSGENKEEIINY TCCCAGGAGTACATCAACCTCCTGCTGTCCATGTATTTCTTCGTGCTGGGAATCCTGGCCCTGTCCC EFDTKDLVCLGLSSIVGVWYLLRKHW ACACCATCAGCCCCTTCATGAATAAGTTTTTTCCAGCCAGCTTTCCAAATCGACAGTACCAGCTGCT IANNLFGLAFSLNGVELLHLNNVSTG CTTCACACAGGGTTCTGGGGAAAACAAGGAAGAGATCATCAATTATGAATTTGACACCAAGGACCTG CILLGGLFIYDVFWVFGTNVMVTVAK GTGTGCCTGGGCCTGAGCAGCATCGTTGGCGTCTGGTACCTGCTGAGGAAGCACTGGATTGCCAACA SFEAPIKLVFPQDLLEKGLEANNFAM ACCTTTTTGGCCTGGCCTTCTCCCTTAATGGAGTAGAGCTCCTGCACCTCAACAATGTCAGCACTGG LGLGDVVIPGIFIALLLRFDISLKKN CTGCATCCTGCTGGGCGGACTCTTCATCTACGATGTCTTCTGGGTATTTGGCACCAATGTGATGGTG THTYFYTSFAAYIFGLGLTIFIMHIF ACAGTGGCCAAGTCCTTCGAGGCACCAATAAAATTGGTGTTTCCCCAGGATCTGCTGGAGAAAGGCC KHAQPALLYLVPACIGFPVLVALAKG TCGAAGCAAACAACTTTGCCATGCTGGGACTTGGAGATGTCGTCATTCCAGGGATCTTCATTGCCTT EVTEMFSYESSAEILPHTPRLTHFPT GCTGCTGCGCTTTGACATCAGCTTGAAGAAGAATACCCACACCTACTTCTACACCAGCTTTGCAGCC VSGSPASLADSMQQKLAGPRRRRPQN TACATCTTCGGCCTGGGCCTTACCATCTTCATCATGCACATCTTCAAGCATGCTCAGCCTGCCCTCC PSAM TATACCTGGTCCCCGCCTGCATCGGTTTTCCTGTCCTGGTGGCGCTGGCCAAGGGAGAAGTGACAGA GATGTTCAGCTACGAGTCCTCGGCGGAAATCCTGCCTCATACCCCGAGGCTCACCCACTTCCCCACA GTCTCGGGCTCCCCAGCCAGCCTGGCCGACTCCATGCAGCAGAAGCTAGCTGGCCCTCGCCGCCGGC GCCCGCAGAATCCCAGCGCCATGTAATGCCCAGCGGGTGCCCACCTGCCCGCTTCCCCCTACTGCCC CGGGGCCCAAGTTATGAGGAGTCAAATCCTAAGGATCCAGCGGCAGTGACAGAATCCAAAGAGGGAA CAGAGGCATCAGCATCGAAGGGGCTGGAGAAGAAAGAGAAATGATGCAGCTGGTGCCCGAGCCTCTC AGGGCCAGACCAGACAGATGGGGGCTGGGCCCACACAGGCGTGCACCGGTAGAGGGCACAGGAGGCC AAGGGCAGCTCCAGGACAGGGCAGGGGGCAGCAGGATACCTCCAGCCAGGCCTCTGTGGCCTCTGTT TCCTTCTCCCTTTCTTGGCCCTCCTCTGCTCCTCCCCACACCCTGCAGGCAAAAGAAACCCCCAGCT TCCCCCCTCCCCGGGAGCCAGGTGGGAAAAGTGGGTGTGATTTTTAGATTTTGTATTGTGGACTGAT TTTGCCTCACATTAAAAACTCATCCCATGGCCAGGGCGGGCCACTGTGCTCCTGGAAAAAAAAAA SEQ.ID NO. 37 STAR clone: TGCCTCAGTCTCTCACTGTGCCTTATGCCCCTCAGCTGAATTCTTTCTTCTGAGCAGGCAGGAATTG AGGTTGCTGCAGACGTGTATGCATTTGCCACCAGTAACATACTTTGGTGCCACATGACTAGGATATG TTCTCTAGTGCTAACATGTTCGTTTACAGTTCTTAGGACTCCCTGATAGAAAAAAACACAAAAAAAA ACACAAAAAAACCCAACCA SEQ.ID NO. 38 SEQ.ID NO. 82 GTTGGGAAAGAGCAGCCTGGGCGGCAGGGGCGGTGGCTGGAGCTCGGTAAAGCTCGTGGGACCCCAT MVCGSPGGMLLLRAGLLALAALCLLR TGGGGGAATTTGATCCAAGGAAGCGGTGATTGCCGGGGGAGGAGAAGCTCCCAGATCCTTGTGTCCA VPGARAAACEPVRIPLCKSLPWNMTK CTTGCAGCGGGGGAGGCGGAGACGGCGGAGCGGGCCTTTTGGCGTCCACTGCGCGGCTGCACCCTGC MPNHLHHSTQANAILAIEQFEGLLGT CCCATCCTGCCGGGATCATGGTCTGCGGCAGCCCGGGAGGGATGCTGCTGCTGCGGGCCGGGCTGCT HCSPDLLFFLCAMYAPICTIDEQHEP TGCCCTGGCTGCTCTCTGCCTGCTCCGGGTGCCCGGGGCTCGGGCTGCAGCCTGTGAGCCCGTCCGC IKPCKSVCERARQGCEPILIKYRHSW ATCCCCCTGTGCAAGTCCCTGCCCTGGAACATGACTAAGATGCCCAACCACCTGCACCACAGCACTC PENLACEELPVYDRGVCISPEAIVTA AGGCCAACGCCATCCTGGCCATCGAGCAGTTCGAAGGTCTGCTGGGCACCCACTGCAGCCCCGATCT DGADFPMDSSNGNCRGASSERCKCKP GCTCTTCTTCCTCTGTGCCATGTACGCGCCCATCTGCACCATTGACTTCCAGCACGAGCCCATCAAG IRATQKTYFRNNYNYVIRAKVKEIKT CCCTGTAAGTCTGTGTGCGAGCGGGCCCGGCAGGGCTGTGAGCCCATACTCATCAAGTACCGCCACT KCHDVTAVVEVKEILKSSLVNIPRDT CGTGGCCGGAGAACCTGGCCTGCGAGGAGCTGCCAGTGTACGACAGGGGCGTGTGCATCTCTCCCGA VNLYTSSGCLCPPLNVNEEYIIMGYE GGCCATCGTTACTGCGGACGGAGCTGATTTTCCTATGGATTCTAGTAACGGAAACTGTAGAGGGGCA DEERSRLLLVEGSIAEKWKDRLGKKV AGCAGTGAACGCTGTAAATGTAAGCCTATTAGAGCTACACAGAAGACCTATTTCCGGAACAATTACA KRWDMKLRHLGLSKSDSSNSDSTQSQ ACTATGTCATTCGGGCTAAAGTTAAAGAGATAAAGACTAAGTGCCATGATGTGACTGCAGTAGTGGA KSGRNSNPRQARN GGTGAAGGAGATTCTAAAGTCCTCTCTGGTAAACATTCCACGGGACACTGTCAACCTCTATACCAGC TCTGGCTGCCTCTGCCCTCCACTTAATGTTAATGAGGAATATATCATCATGGGCTATGAAGATGAGG AACGTTCCAGATTACTCTTGGTGGAAGGCTCTATAGCTGAGAAGTGGAAGGATCGACTCGGTAAAAA AGTTAAGCGCTGGGATATGAAGCTTCGTCATCTTGGACTCAGTAAAAGTGATTCTAGCAATAGTGAT TCCACTCAGAGTCAGAAGTCTGGCAGGAACTCGAACCCCCGGCAAGCACGCAACTAAATCCCGAAAT ACAAAAAGTAACACAGTGGACTTCCTATTAAGACTTACTTGCATTGCTGGACTAGCAAAGGAAAATT GCACTATTGCACATCATATTCTATTGTTTACTATAAAAATCATGTGATAACTGATTATTACTTCTGT TTCTCTTTTGGTTTCTGCTTCTCTCTTCTCTCAACCCCTTTGTAATGGTTTGGGGGCAGACTCTTAA GTATATTGTGAGTTTTCTATTTCACTAATCATGAGAAAAACTGTTCTTTTGCAATAATAATAAATTA AACATGCTGTTACCAGAGCCTCTTTGCTGGAGTCTCCAGATGTTAATTTACTTTCTGCACCCCAATT GGGAATGCAATATTGGATGAAAAGAGAGGTTTCTGGTATTCACAGAAAGCTAGATATGCCTTAAAAC ATACTCTGCCGATCTAATTACAGCCTTATTTTTGTATGCCTTTTGGGCATTCTCCTCATGCTTAGAA AGTTCCAAATGTTTATAAAGGTAAAATGGCAGTTTGAAGTCAAATGTCACATAGGCAAAGCAATCAA GCACCAGGAAGTGTTTATGAGGAAACAACACCCAAGATGAATTATTTTTGAGACTGTCAGGAAGTAA AATAAATAGGAGCTTAAGAAAGAACATTTTGCCTGATTGAGAAGCACAACTGAAACCAGTAGCCGCT GGGGTGTTAATGGTAGCATTCTTCTTTTGGCAATACATTTGATTTGTTCATGAATATATTAATCAGC ATTAGAGAAATGAATTATAACTAGACATCTGCTGTTATCACCATAGTTTTGTTTAATTTGCTTCCTT TTAAATAAACCCATTGGTGAAAGTCCCAAAAAAAAAAAAAAAAAAAAA SEQ.ID NO. 39 SEQ,ID NO. 83 ACTGAAAGCTCCGGTGCCAGACCCCACCCCCGGCCCCGGCCCGGGACCCCCTCCCCTCCCGGGATCC MKTSPRRPLILKRRRLPLPVQNAPSE CCCGGGGTTCCCACCCCGCCCGCACCGCCGGGGACCCGGCCGGTCCGGCGCGAGCCCCCGTCCGGGG TSEEEPKRSPAQQESNQAEASKEVAE CCCTGGCTCGGCCCCCAGGTTGGAGGAGCCCGGAGCCCGCCTTCGGAGCTACGGCCTAACGGCGGCG SNSCKFPAGIKIINHPTMPNTQVVAI GCGACTGCAGTCTGGAGGGTCCACACTTGTGATTCTCAATGGAGAGTGAAAACGCAGATTCATAATG PNNANIHSIITALTAKGKESGSSGPN AAAACTAGCCCCCGTCGGCCACTGATTCTCAAAAGACGGAGGCTGCCCCTTCCTGTTCAAAATGCCC KFILISCGGAPTQPPGLRPQTQTSYD CAAGTGAAACATCAGAGGAGGAACCTAAGAGATCCCCTGCCCAACAGGAGTCTAATCAAGCAGAGGC AKRTEVTLETLGPKPAARDVNLPRPP CTCCAAGGAAGTGGCAGAGTCCAACTCTTGCAAGTTTCCAGCTGGGATCAAGATTATTAACCACCCC GALCEQKRETCADGEAAGCTINNSLS ACCATGCCCAACACGCAAGTAGTGGCCATCCCCAACAATGCTAATATTCACAGCATCATCACAGCAC NIQWLRKMSSDGLGSRSIKQEMEEKE TGACTGCCAAGGGAAAAGAGAGTGGCAGTAGTGGGCCCAACAAATTCATCCTCATCAGCTGTGGGGG NCHLEQRQVKVEEPSRPSASWQNSVS AGCCCCAACTCAGCCTCCAGGACTCCGGCCTCAAACCCAAACCAGCTATGATGCCAAAAGGACAGAA ERPPYSYMAMIQFAINSTERKRMTLK GTGACCCTGGAGACCTTGGGACCAAAACCTGCAGCTAGGGATGTGAATCTTCCTAGACCACCTGGAG DIYTWIEDHFPYFKHIAKPGWKNSIR CCCTTTGCGAGCAGAAACGGGAGACCTGTGCAGATGGTGAGGCAGCAGGCTGCACTATCAACAATAG HNLSLHDMFVRETSANGKVSFWTIHP CCTATCCAACATCCAGTGGCTTCGAAAGATGAGTTCTGATGGACTGGGCTCCCGCAGCATCAAGCAA SANRYLTLDQVFKQQKRPNPELRRNM GAGATGGAGGAAAAGGAGAATTGTCACCTGGAGCAGCGACAGGTTAAGGTTGAGGAGCCTTCGAGAC TIKTELPLGARRKMKPLLPRVSSYLV CATCAGCGTCCTGGCAGAACTCTGTGTCTGAGCGGCCACCCTACTCTTACATGGCCATGATACAATT PIQFPVNQSLVLQPSVKVPLPLAASL CGCCATCAACAGCACTGAGAGGAAGCGCATGACTTTGAAAGACATCTATACGTGGATTGAGGACCAC MSSELARHSKRVRIAPKVLLAEEGIA TTTCCCTACTTTAAGCACATTGCCAAGCCAGGCTGGAAGAACTCCATCCGCCACAACCTTTCCCTGC PLSSAGPGKEEKLLFGEGFSPLLPVQ ACGACATGTTTGTCCGGGAGACGTCTGCCAATGGCAAGGTCTCCTTCTGGACCATTCACCCCAGTGC TIKEEEIQPGEEMPHLARPIKVESPP CAACCGCTACTTGACATTGGACCAGGTGTTTAAGCAGCAGAAACGACCGAATCCAGAGCTCCGCCGG LEEWPSPAPSFKEESSHSWEDSSQSP AACATGACCATCAAAACCGAACTCCCCCTGGGCGCACGGCGGAAGATGAAGCCACTGCTACCACGGG TPRPKKSYSGLRSPTRCVSEMLVIQH TCAGCTCATACCTGGTACCTATCCAGTTCCCGGTGAACCAGTCACTGGTGTTGCAGCCCTCGGTGAA RERRERSRSRRKQHLLPPCVDEPELL GGTGCCATTGCCCCTGGCGGCTTCCCTCATGAGCTCAGAGCTTGCCCGCCATAGCAAGCGAGTCCGC FSEGPSTSRWAAELPFPADSSDPASQ ATTGCCCCCAAGGTGCTGCTAGCTGAGGAGGGGATAGCTCCTCTTTCTTCTGCAGGACCAGGGAAAG LSYSQEVGGPFKTPIKETLPISSTPS AGGAGAAACTCCTGTTTGGAGAAGGGTTTTCTCCTTTGCTTCCAGTTCAGACTATCAAGGAGGAAGA KSVLPRTPESWRLTPPAKVGGLDFSP AATCCAGCCTGGGGAGGAAATGCCACACTTAGCGAGACCCATCAAAGTGGAGAGCCCTCCCTTGGAA VQTSQGASDPLPDPLGLMDLSTTPLQ GAGTGGCCCTCCCCGGCCCCATCTTTCAAAGAGGAATCATCTCACTCCTGGGAGGATTCGTCCCAAT SAPPLESPQRLLSSEPLDLISVPFGN CTCCCACCCCAAGACCCAAGAAGTCCTACAGTGGGCTTAGGTCCCCAACCCGGTGTGTCTCGGAAAT SSPSDIDVPKPGSPEPQVSGLAANRS GCTTGTGATTCAACACAGGGAGAGGAGGGAGAGGAGCCGGTCTCGGAGGAAACAGCATCTACTGCCT LTEGLVLDTMNDSLSKILLDISFPGL CCCTGTGTGGATGAGCCGGAGCTGCTCTTCTCAGAGGGGCCCAGTACTTCCCGCTGGGCCGCAGAGC DEDPLGPDNINWSQFIPELQ TCCCGTTCCCAGCAGACTCCTCTGACCCTGCCTCCCAGCTCAGCTACTCCCAGGAAGTGGGAGGACC TTTTAAGACACCCATTAAGGAAACGCTGCCCATCTCCTCCACCCCGAGCAAATCTGTCCTCCCCAGA ACCCCTGAATCCTGGAGGCTCACGCCCCCAGCCAAAGTAGGGGGACTGGATTTCAGCCCAGTACAAA CCTCCCAGGGTGCCTCTGACCCCTTGCCTGACCCCCTGGGGCTGATGGATCTCAGCACCACTCCCTT GCAAAGTGCTCCCCCCCTTGAATCACCGCAAAGGCTCCTCAGTTCAGAACCCTTAGACCTCATCTCC GTCCCCTTTGGCAACTCTTCTCCCTCAGATATAGACGTCCCCAAGCCAGGCTCCCCGGAGCCACAGG TTTCTGGCCTTGCAGCCAATCGTTCTCTGACAGAAGGCCTGGTCCTGGACACAATGAATGACAGCCT CAGCAAGATCCTGCTGGACATCAGCTTTCCTGGCCTGGACGAGGACCCACTGGGCCCTGACAACATC AACTGGTCCCAGTTTATTCCTGAGCTACAGTAGAGCCCTGCCCTTGCCCCTGTGCTCAAGCTGTCCA CCATCCCGGGCACTCCAAGGCTCAGTGCACCCCAAGCCTCTGAGTGAGGACAGCAGGCAGGGACTGT TCTGCTCCTCATAGCTCCCTGCTGCCTGATTATGCAAAAGTAGCAGTCACACCCTAGCCACTGCTGG GACCTTGTGTTCCCCAAGAGTATCTGATTCCTCTGCTGTCCCTGCCAGGAGCTGAAGGGTGGGAACA ACAAAGGCAATGGTGAAAAGAGATTAGGAACCCCCCAGCCTGTTTCCATTCTCTGCCCAGCAGTCTC TTACCTTCCCTGATCTTTGCAGGGTGGTCCGTGTAAATAGTATAAATTCTCCAAATTATCCTCTAAT TATAAATGTAAGCTTATTTCCTTAGATCATTATCCAGAGACTGCCAGAAGGTGGGTAGGATGACCTG GGGTTTCAATTGACTTCTGTTCCTTGCTTTTAGTTTTGATAGAAGGGAAGACCTGCAGTGCACGGTT TCTTCCAGGCTGAGGTACCTGGATCTTGGGTTCTTCACTGCAGGGACCCAGACAAGTGGATCTGCTT GCCAGAGTCCTTTTTGCCCCTCCCTGCCACCTCCCCGTGTTTCCAAGTCAGCTTTCCTGCAAGAAGA AATCCTGGTTAAAAAAGTCTTTTGTATTGGGTCAGGAGTTGAATTTGGGGTGGGAGGATGGATGCAA CTGAAGCAGAGTGTGGGTGCCCAGATGTGCGCTATTAGATGTTTCTCTGATAATGTCCCCAATCATA CCAGGGAGACTGGCATTGACGAGAACTCAGGTGGAGGCTTGAGAAGGCCGAAAGGGCCCCTGACCTG CCTGGCTTCCTTAGCTTGCCCCTCAGCTTTGCAAAGAGCCACCCTAGGCCCCAGCTGACCGCATGGG TGTGAGCCAGCTTGAGAACACTAACTACTCAATAAAAGCGAAGGTGGACAAAAAAAAAAAAAAAAAA AAA SEQ.ID NO. 40 SEQ.ID NO. 84 GTCGAGGCTGCGGCGCGTGGGGAGCGGGCGGAGCGGGGGCGGGGGCCGAGCGCGGGGCACCCGGGGG MGSCSGRCALVVLCAFQLVAALERQV CCTCCTGTATAGGCGGGCACCATGGGCTCCTGCTCCGGCCGCTGCGCGCTCGTCGTCCTCTGCGCTT FDFLGYQWAPILANFVHIIIVILGLF TTCAGCTGGTCGCCGCCCTGGAGAGGCAGGTGTTTGACTTCCTGGGCTACCAGTGGGCGCCCATCCT GTIQYRLRYVMVYTLWAAVWVTWNVF GGCCAACTTTGTCCACATCATCATCGTCATCCTGGGACTCTTCGGCACCATCCAGTACCGGCTGCGC IICFYLEVGGLLKDSELLTFSLSRHR TATGTCATGGTGTACACGCTGTGGGCAGCCGTCTGGGTCACCTGGAACGTCTTCATCATCTGCTTCT SWWRERWPGCLHEEVPAVGLGAPHGQ ACCTGGAAGTCGGTGGCCTCTTAAAGGACAGCGAGCTACTGACCTTCAGCCTCTCCCGGCATCGCTC ALVSGAGCALEPSYVEALHSCLQILI CTGGTGGCGTGAGCGCTGGCCAGGCTGTCTGCATGAGGAGGTGCCAGCAGTGGGCCTCGGGGCCCCC ALLGFVCGCQVVSVFTDEEDSFDFIG
CATGGCCAGGCCCTGGTGTCAGGTGCTGGCTGTGCCCTGGAGCCCAGCTATGTGGAGGCCCTACACA GFDPFPLYHVNEKPSSLLSKQVYLPA GTTGCCTGCAGATCCTGATCGCGCTTCTGGGCTTTGTCTGTGGCTGCCAGGTGGTCAGCGTGTTTAC GGATGAAGAGGACAGCTTTGATTTCATTGGTGGATTTGATCCATTTCCTCTCTACCATGTCAATGAA AAGCCATCCAGTCTCTTGTCCAAGCAGGTGTACTTGCCTGCGTAAGTGAGGAAACAGCTGACCCTGC TCCTGTGGCCTCCAGCCTCAGCGACCGACCAGTGACAATGACAGGAGCTCCCAGGCCTTGGGACGCG CCCCCACCCAGCACCCCCCAGGCGGCCGGCAGCACCTGCCCTGGGTTCTAAGTACTGGACACCAGCC AGGGCGGCAGGGCAGTGCCACGGCTGGCTGCAGCGTCAAGAGAGTTTGTAATTTCCTTTCTCTTAAA AAAAAAAAAGAAAAGAAAACATACAAAAGAAAAGGCAAAACCCCACATGCCCACCTCCTCTGGCAAC ATGGGGGTCACAGCTCTGCCCCCAGGCTGTCGTCTCGTCGAGGAGCCCCTCCCTCAGGTGCCAACCT GGGGCTGCTGGACCCTCGGGCTGCAAGCACTGCTGCTGGGATGCAGCCTCCCCAGGAAGTCAATGTG AGGCCCGAGACCCCTCAAGCGGTGAGGGCCCCTGTTGAACATGGAGGGTTCCTAACCCCAAACTCGT GCCAGAAGAACCCCCACCCCACCCAGGAGCTGAGGCTGATGGAGCCCTAGGGTGGGGGCTGGGCTTG ACCAGGAACAGCAGAGCCAGGCCCCAAGGCATAGGGCAGGGCACATGGTGGTGACGAGCAGGCAGTA CTCTTGTAAAGGGGGCTCTTGGGCAAACAGTCCCAAAGGCTCCCCCAGGTATCATCAAGTTGGTAAA TAAACAGGAACATGGCCCAAAAAAAAAAAAAAAA SEQ.ID NO. 41 STAR clone: AAAAAATAAGTATATCTGTCNAGAATCNTATTTATGTGAGATGTGTCAATACTGGTCTTGCGTTATT TCGGCTACTTGAAAATAAGTTAAAAAAGATAGTGTTTGGTTCCAAAAAGGAAAAGTCAGCCTCTCCT GCNTGAGTGGGAGCTGCAACCTTTTAGAATTGATAATCACAAACCCCTCAGACCCAAAGTGGAATAA AGAAAAATATGTAACATTAGGCATTGATGGAAAAGGACTAGATCCTAGTGTAAGCATCCTAATAAAA GGAGAGGTTCACAA SEQ.ID NO. 42 SEQ.ID NO. 85 GCAGCCAGATCTGCTGGGACACCTTTCCCAAGGAAGAGCCCGTTGCACTGGGCTTTGAAGGATAAGC MCVSSSSSSHDEAPVLNDKHLDVPDI AGGAGCTTGTTACTCAGGCAGAGGAAGAAAGAGCATCCCAGGCGGGGGGAGCAGCATATGCAAAGGC IITPPTPTGMMLPRDLGSTVWLDETG ACGAAGGGGCCCCAGGAGCCTAGGGAGTCTGGGGAAGTGTGAGCACTTTGGAGAGTGGAGGCTGGAG SCPDDGEIDPEA CGCTGTGGAGAGTGGGGGCTGGTGGCCGGGAATGAAGCTGCAGCTGGCTGGGCCACATGGTAAAGGC TGACAACTGGACCCAGAGGCCAACTAGCCTATGATCAGCATTTCCCAAAATCTGTTTCCCGACTCAT GGTTCTGTGAGATGTGACAAGGGCTCCTTTTTCATTCCTGAGACGCCGGTTTTCATCTGTGATGCGG GGACAGCTGCGCTCCTTGCTGCGAGGCGTCAGGACCCAGGTGATAGTGAAGGGAGGGTGGCGCCCGC GGTTCCCGGCGGCCACTGATGCCTGTCTCTCTGTCGTGTGTACGTGCGTGTGTGCTCCACGCCTGGC TTCTCAGGCTTTCAAATGTGTGTCAGCAGCAGCAGCAGCAGCCACGACGAGGCCCCCGTCCTGAACG ACAAGCACCTGGACGTGCCCGACATCATCATCACGCCCCCCACCCCCACGGGCATGATGCTGCCGAG GGACTTGGGGAGCACAGTCTGGCTGGATGAGACAGGGTCGTGCCCAGATGATGGAGAAATCGACCCA GAAGCCTGAGGAGGTGTCCTGGGTTTGGCTGGCTGGCTCCTGCTCCAGCGGCCCGGCTTCAGGTGTC CGGGGGCGTGGCTGCCTGGAGCAGGTGTGCTGAATACCCTGGATGGGAACTGAGCGAACCCGGGCCT CCGCTCAGAGAGACGTGGCAGGACCAGCGAGGAATCCAGCCTGTCCACTTCCAGAACAGTGTTTCCC AGGCCCCGCTGAGTGGACCGGACCTCTGACACCTCCAGGTTCTTGCTGACTCCGGCCTGGTGAAAGG GAGCGCCATGGTCCTGGCTGTTGGGGTCCCAGGGAGAGGCTCTCTTCTGGACAAACACACCCTCCCA GCCCCCAGGGCTGTGCAAACACATGCCCCTCCCATAAGCACCAACAAGAACTTCTTGCAGGTGGAGT GGCTGTTTTTTATAAGTTGTTTTACAGATACGGAAACAGTCCAAAATGGGATTTATAATTTCTTTTT TGCATTATAAATAAAGATCCTCTGTAACAAAAAAAAAAAAAAAAAAAAAAAAAAA SEQ.ID NO. 43 SEQ.ID NO. 86 GCGAAGTGAAGGGTGGCCCAGGTGGGGCCAGGCTGACTGAATGTATCTCCTAGCTATGGACTAAATA MDTMMLNVRNLFEQLVRRVEILSEGN ATACATGGGGGGAAATAAACAAGTATTCATGAGGGTGAAAATGTGACCCAGCAGGAAAATTACAACT EVQFIQLAKDFEDFRKKWQRTDHELG ATTTTCAATTGACGTTGAATAGGATGAGTCATGGAATTTAAGTGATTTACTGAAGATTATACTACTG KYKDLLMKAETERSALDVKLKHARNQ GTAGATAGAAGAGCTAAAGAAAGATGGATACTATGATGCTGAATGTGCGGAATCTGTTTGAGCAGCT VDVEIKRRQRAEADCEKLERQIQLIR TGTGCGCCGGGTGGAGATTCTCAGTGAAGGAAATGAAGTCCAATTTATCCAGTTGGCGAAGGACTTT EMLMCDTSGSIQLSEEQKSALAFLNR GAGGATTTCCGTAAAAAGTGGCAGAGGACTGACCATGAGCTGGGGAAATACAAGGATCTTTTGATGA GQPSSSNAGNKRLSTIDESGSILSDI AAGCAGAGACTGAGCGAAGTGCTCTGGATGTTAAGCTGAAGCATGCACGTAATCAGGTGGATGTAGA SFDKTDESLDWDSSLVKTFKLKKREK GATCAAACGGAGACAGAGAGCTGAGGCTGACTGCGAAAAGCTGGAACGACAGATTCAGCTGATTCGA RRSTSRQFVDGPPGPVKKTRSIGSAV GAGATGCTCATGTGTGACACATCTGGCAGCATTCAACTAAGCGAGGAGCAAAAATCAGCTCTGGCTT DQGNESIVAKTTVTVPNDGGPIEAVS TTCTCAACAGAGGCCAACCATCCAGCAGCAATGCTGGGAACAAAAGACTATCAACCATTGATGAATC TIETVPYWTRSRRKTGTLQPWNSDST TGGTTCCATTTTATCAGATATCAGCTTTGACAAGACTGATGAATCACTGGATTGGGACTCTTCTTTG LNSRQLEPRTETDSVGTPQSNGGMRL GTGAAGACTTTCAAACTGAAGAAGAGAGAAAAGAGGCGCTCTACTAGCCGACAGTTTGTTGATGGTC HDEVSKTVIKPESCVPCGKRIKEGKL CCCCTGGACCTGTAAAGAAAACTCGTTCCATTGGCTCTGCAGTAGACCAGGGGAATGAATCCATAGT SLKCRDCRVVSHPECRDRCPLPCIPT TGCAAAAACTACAGTGACTGTTCCCAATGATGGCGGGCCCATCGAAGCTGTGTCCACTATTGAGACT LIGTPVKIGEGMLADFVSQTSPMIPS GTGCCATATTGGACCAGGAGCCGAAGGAAAACAGGTACTTTACAACCTTGGAACAGTGACTCCACCC IVVHCVNEIEQRGLTETGLYRISGCD TGAACAGCAGGCAGCTGGAGCCAAGAACTGAGACAGACAGTGTGGGCACGCCACAGAGTAATGGAGG RTVKELKEKFLRVKTVPLLSKVDDIH GATGCGCCTGCATGACTTTGTTTCTAAGACGGTTATTAAACCTGAATCCTGTGTTCCATGTGGAAAG AICSLLKDFLRNLKEPLLTFRLNRAF CGGATAAAATTTGGCAAATTATCTCTGAAGTGTCGAGACTGTCGTGTGGTCTCTCATCCAGAATGTC MEAAEITDEDNSIAAMYQAVGELPQA GGGACCGCTGTCCCCTTCCCTGCATTCCTACCCTGATAGGAACACCTGTCAAGATTGGAGAGGGAAT NRDTLAFLMIHLQRVAQSPHTKMDVA GCTGGCAGACTTTGTGTCCCAGACTTCTCCAATGATCCCCTCCATTGTTGTGCATTGTGTAAATGAG NLAKVFGPTIVAHAVPNPDPVTMLQD ATTGAGCAAAGAGGTCTGACTGAGACAGGCCTGTATAGGATCTCTGGCTGTGACCGCACAGTAAAAG IKRQPKVVERLLSLPLEYWSQFMMVE AGCTGAAAGAGAAATTCCTCAGAGTGAAAACTGTACCCCTCCTCAGCAAAGTGGATGATATCCATGC QENIDPLHVIENSNAFSTPQTPDIKV TATCTGTAGCCTTCTAAAAGACTTTCTTCGAAACCTCAAAGAACCTCTTCTGACCTTTCGCCTTAAC SLLGPVTTPEHQLLKTPSSSSLSQRV AGAGCCTTTATGGAAGCAGCAGAAATCACAGATGAAGACAACAGCATAGCTGCCATGTACCAAGCTG RSTLTKNTPRFGSKSKSATNLGRQGN TTGGTGAACTGCCCCAGGCCAACAGGGACACATTAGCTTTCCTCATGATTCACTTGCAGAGAGTGGC FFASPMLK TCAGAGTCCACATACTAAAATGGATGTTGCCAATCTGGCTAAAGTCTTTGGCCCTACAATAGTGGCC CATGCTGTGCCCAATCCAGACCCAGTGACAATGTTACAGGACATCAAGCGTCAACCCAAGGTGGTTG AGCGCCTGCTTTCCTTGCCTCTGGAGTATTGGAGTCAGTTCATGATGGTGGAGCAAGAGAACATTGA CCCCCTACATGTCATTGAAAACTCAAATGCCTTTTCAACACCACAGACACCAGATATTAAAGTGAGT TTACTGGGACCTGTGACCACTCCTGAACATCAGCTTCTCAAGACTCCTTCATCTAGTTCCCTGTCAC AGAGAGTCCGTTCCACCCTCACCAAGAACACTCCTAGATTTGGGAGCAAAAGCAAGTCTGCCACTAA CCTAGGACGACAAGGCAACTTTTTTGCTTCTCCAATGCTCAAGTGAAGTCACATCTGCCTGTTACTT CCCAGCATTGACTGACTATAAGAAAGGACACATCTGTACTCTGCTCTGCAGCCTCCTGTACTCATTA CTACTTTTAGCATTCTCCAGGCTTTTACTCAAGTTTAATTGTGCATGAGGGTTTTATTAAAACTATA TATATCTCCCCTTCCTTCTCCTCAAGTCACATAATATCAGCACTTTGTGCTGGTCATTGTTGGGAGC TTTTAGATGAGACATCTTTCCAGGGGTAGAAGGGTTAGTATGGAATTGGTTGTGATTCTTTTTGGGG AAGGGGGTTATTGTTCCTTTGGCTTAAAGCCAAATGCTGCTCATAGAATGATCTTTCTCTAGTTTCA TTTAGAACTGATTTCCGTGAGACAATGACAGAAACCCTACCTATCTGATAAGATTAGCTTGTCTCAG GGTGGGAAGTGGGAGGGCAGGGCAAAGAAAGGATTAGACCAGAGGATTTAGGATGCCTCCTTCTAAG AACCAGAAGTTCTCATTCCCCATTATGAACTGAGCTATAATATGGAGCTTTCATAAAAATGGGATGC ATTGAGGACAGAACTAGTGATGGGAGTATGCGTAGCTTTGATTTGGATGATTAGGTCTTTAATAGTG TTGAGTGGCACAACCTTGTAAATGTGAAAGTACAACTCGTATTTATCTCTGATGTGCCGCTGGCTGA ACTTTGGGTTCATTTGGGGTCAAAGCCAGTTTTTCTTTTAAAATTGAATTCATTCTGATGCTTGGCC CCCATACCCCCAACCTTGTCCAGTGGAGCCCAACTTCTAAAGGTCAATATATCATCCTTTGGCATCC CAACTAACAATAAAGAGTAGGCTATAAGGGAAGATTGTCAATATTTTGTGGTAAGAAAAGCTACAGT CATTTTTTCTTTGCACTTTGGATGCTGAAATTTTTCCCATGGAACATAGCCACATCTAGATAGATGT GAGCTTTTTCTTCTGTTAAAATTATTCTTAATGTCTGTAAAAACGATTTTCTTCTGTAGAATGTTTG ACTTCGTATTGACCCTTATCTGTAAAACACCTATTTGGGATAATATTTGGAAAAAAAGTAAATAGCT TTTTCAAAATGAAAAAAAAAA SEQ.ID NO. 44 SEQ.ID NO. 87 AGGCGCTAGAGGCGGGGGCGCCGGGAGGCGCGGGCTTTGCTCCTGGGGTCTCGGCCTTGGCCGGCTG MTDLNDNICKRYIKMITNIVILSLII GACCTGACCCTAGGGCGGCTTGCGCAGCTGTCGGGACGTGACTGCGTTCAGCCGCGTCGGGCGTGCT CISLAFWIISMTASTYYGNLRPISPW TCCCAGACTTGCCCAAGTTCGGGTGCCCTAGCTGCCCCTTTGCAGCCGCTGGCCTACCCGGCCCGCG RWLFSVVVPVLIVSNGLKKKSLDHSG GGTGAGAAGGTTGCGACGGGAGGTGGGTGGAACTCGCCAGCGCCGGGACCGCGGATTGGCTGCCTCG ALGGLVVGFILTIANFSFFTSLLMFF GCTTTCTCTTTTCCCCGTGGGCTCCGGCGTGAGGCGCTGAAGCGGCCGGCAGCCGGCGACCGGCCCT LSSSKLTKWKGEVKKRLDSEYKEGGQ CACCGTCCGCCGGGTTGCGCTCTGCTTTTGCGGTGAGGCGTTGACCACGCCCATATGAATTGGAGCT RNWVQVFCNGAVPTELALLYMIENGP CTCCGCCAGTAGGAGTTTCCGGAAGGAGTTTGAATTTTTGTGATTTTTATGCTTGTTTGGTCGGTGG GEIPVDFSKQYSASWMCLSLLAALAC AATATGTTGGGATTTATGTTTGCCTCTGAACAAGTGTCTTGCTCACATCGTAAATGACTTTCTCTCC SAGDTWASEVGPVLSKSSPRLITTWE GAAACGCTAAATATTCTTTCCCGCAGGAGCTCATATCCTTATTTTCCATGACAGATCTTAACGACAA KVPVGTNGGVTVVGLVSSLLGGTFVG TATATGCAAAAGATATATAAAGATGATAACTAATATAGTTATACTGAGCCTGATCATTTGCATTTCG IAYFLTQLIFVNDLDISAPQWPIIAF TTAGCTTTCTGGATTATATCAATGACTGCAAGCACCTATTATGGTAACTTACGACCTATTTCTCCGT GGLAGLLGSIVDSYLGATMQYTGLDE GGCGTTGGCTGTTTTCTGTTGTTGTTCCTGTTCTGATCGTCTCTAATGGCCTTAAAAAGAAAAGTCT STGMVVNSPTNKARHIAGKPILDNNA AGATCACAGTGGGGCTCTAGGAGGGCTAGTCGTTGGATTTATCCTAACCATTGCAAATTTCAGCTTT VNLFSSVLIALLLPTAAWGFWPRG TTTACCTCTTTGCTGATGTTTTTCTTGTCTTCTTCGAAACTCACTAAATGGAAGGGAGAAGTGAAGA AGCGTCTAGATTCAGAATATAAGGAAGGTGGGCAAAGGAATTGGGTTCAGGTGTTCTGTAATGGAGC TGTACCCACAGAACTGGCCCTGCTGTACATGATAGAAAATGGCCCCGGGGAAATCCCAGTCGATTTT TCCAAGCAGTACTCCGCTTCCTGGATGTGTTTGTCTCTCTTGGCTGCACTGGCCTGCTCTGCTGGAG ACACATGGGCTTCAGAAGTTGGCCCAGTTCTGAGTAAAAGTTCTCCAAGACTGATAACAACCTGGGA GAAAGTTCCAGTTGGTACCAATGGAGGAGTTACAGTGGTGGGCCTTGTCTCCAGTCTCCTTGGTGGT ACCTTTGTGGGCATTGCATACTTCCTCACACAGCTGATTTTTGTGAATGATTTAGACATTTCTGCCC CGCAGTGGCCAATTATTGCATTTGGTGGTTTAGCTGGATTACTAGGATCAATTGTGGACTCATACTT AGGGGCTACAATGCAGTATACTGGGTTGGATGAAAGCACTGGCATGGTGGTCAACAGCCCAACAAAT AAGGCAAGGCACATAGCAGGGAAACCCATTCTTGATAACAACGCAGTGAATCTGTTTTCTTCTGTTC TTATTGCCCTCTTGCTCCCAACTGCTGCTTGGGGTTTTTGGCCCAGGGGGTGAACTTTATTTCATTT CCACAGGTTGAAACTGGTGAGTCCAGCTAAATTTGCAATTCCAACTTTCATCCTAAGAATAATAACT GTAATGGCAAAGCGGAAATGCCAGTTCCTCCTGTATTCCATTGAGATGGGATTTCACATTTTCCTCT CATCAACTCCCCTGTAATAGCTAGCGTCTTTCTAGTGAAAGAGAAGAATTCCTAGAACTTATGCATT TTTTTCCTGCTGAATGGAAGTCTTGAGCAATGAAGCTATATTGTCCCTACATATTACTATATATTGA ACTGAAAGTTCTTACATAATCAATGTCAAGTTTTGTCTTATTTTGTTTTGTTTGTTTAAACCAGTGT AGGAAATAAAAGTGATGATATTTAAAATAGTTCTCAGTTGAAGCAGAGAAATGCCACTGTGCTAGTT GCCCAAATGTTGTATCTATTTTAAATAGTTTAAGCTGATGTGTATGGGAGCCTAAACAAGTGTAGTA TCCTGAACTTCTCCCATTAATTGCTATTCACAATTGGGAAAAGTGTGGAGATTGGTTCCTAGTGAGT TTTGTGGCCTACTCCACATTTGTTCTTCCTTCCTCAGGGTTAGTGATGAAAAAAAGTAAATATCTTT TTCATATGTCCATTAGAATGTATGAAAAAAATCATTTTAACTAAAAGCAAAAGAATTTTATCTTATA TCTAAAAAATATATAACTTACTATATGTTTCAGTTGCTCTCTGAACAAAAATTATCTTCAATTTAAT ATGTGGAATGTGTTTTCTAGCTTTCTTTGAATTATGTATGGCAACCTGGTTTAGCACTGGCATCCTG AACAGTTAAGAGTCACTGGGAAATTATTGTATTTCTTTATAAATTTACTGTCATATCAATTGCTGGA AAATGCTATGATTTTTCTATTATTACCTTCTAAGTTGTATTCTCTCTTACACTGTAGCCTCAACTAA GGCAATTCTGCTATGTTTGTTCTTCACTATGATTTACTGTGTGCCAAAGGAGTTTTGACAGGGTACA GAGTATTTTACTAAAAGTATTTTTAAATGTTTCTCATGTGATTTCTGTACCTTCTTCCTCCTGCCCC TTTTGCTTTTTTAAAGAAACTGGGGAAGGATTTATGAATACACCACCACCAGAGTGGATAATGCTTA GAATTCTTTATTGGTGGCCCTACTATGGTGATGATCTAGAACTGACTTACTTCAGGACAGAAGAAAA AACAATCACACCCTTAACCTTTAAGCCAGTTAGATCAGGGGGTTGCAACAATTGGGTTAAACTTTGG GTATACATTGGAAGCACCAGGGCATGTTTGCTTTTTTTGTTTATGTGTTTGTTTTTTGAGACAGAGT CTCACACTGTGGCCCAGGCTGGACTCCAGCACAGTGGCATGATCTCAGCTCCGCCTCCTGGGTTCAC GTGATTCTCATGCCTCAGCCTCCCAAGTAGCTGGGATCACAGGCGTGCACCATCACGCCCGGCTAAT TTTTGTATTTTCAGTAGAGACAGGGTTTCGCCACGTTGGCTAGGCTGGTCTCGAACTCCTGACCTCA AGTGATCTGCCCATCTCAGCCTCCCAAAGATCTATTACAAGATGTGAGCCACTGTGCCCAGCCACCA GGGCATGTTTTTAAAAAAGTACTGATGTCTGGGTTTCACACTGCAAAATTCTGATTTATCTGATCTA AGGTACAGCCTGGATATTGAGACTTTTTAAAGCTCTGACTGTACATTGAATCATCATGTAAGGAGTT TTTAAAACATTGTTGCCAGGGCCCCTTTCTAGACCAAGTTAGTCAGAATGTTGGACAATGAGGCCCA TGCATGGGTATTTTTACAAAGCTCTCTGGGAGATTCTAATGCTTAACCAAATTGAGAAGCACTGAAT AAGAATATCCTGGGCCGGGCGCACTGGCTCATGCCTGTAATCCCAGCATTTTGGAAGGCCGAGGCGG GTGGATCACTTGAGGTCAGGAGTTCGAGACCAGCCTGGCCAACATGGTGAAACACCGTCTCTACTAA AAATACAAAAAATTAGGTGTGGTGGTGCGTGCCTGTATTCCCAGCCACTCAGGAGGCTGAGGCAGGA GAATCGCTGGAACCTGGGATGTGGAGGTTGCAGTGAGCCAAGATTGCACCACTGTACTCCAGCCTGG GCAACAGAGGGAGACTCCATCTAGACTCCATCTCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAGAATATTCTAAGCACTAGAACTACATAAGAATGTCCTAAAGCACTGTATCTAAGCACTTGA AAAGAATGGGACTTTTCGGTTTTAGGGAGATAACTATTAGCAACCACACAATATGTTATCTTTATGG ATGAATAACTTCTGGTAATGACACAGTGTCTTACAGCTACATCATTTATAAAATCATGTGTCAGTTT TCACACAGCCTGCACATCGTTCTGACATGCCCTTTTTTTCCCTGGAGATTTATCCTCATGACATACA AGGGGACAAAAATATTTATTGGGACTGTCTTTGAATTTAGTAGAATCACTGTATCATTAACAGTTTG GGGAAGTACTGCTTTGCAGTCCTTTATTTGAAAACTTAGGTCTAGCTGTGTTTTGCATCAAAATTTT TGAGCTATTCAAAAACTAATAGGATCTGTGTAAAATATTTCACTCAAAACTACTAAAAAAAAGTCTG GGATGGCAGCTCATTATCAAATATACTCCTATTTTTGTGGTGATTTATGAACATCCCCACTAAGTAT AACTAAAGATCATAAAGAGCCTCAGATCAAGTTTGGTCAGGTTTTGTCACCAAGCTTTGTAAATAAA CTGGTTTTCATAGCTTTTTGGAGATGAGAATTGAGGATAAGAAATTGTGTCTCTGTCCTTTTTTTTT TTTTTTGTTAAGTCTTACATGTATTTTACTGTAACATCTTTTGAATTGGATATTTAACTAATTCAAC ATATTTTTCCTCTTTGCAGAATGGGCAGTTCATGTTAAAATCACTTTTCATGGAAAGAGCTCTATGT AACAGCATAATAAAACTGCCTACCTAGCAGCATAAA SEQ.ID NO. 45 STAR clone: CNGGACACATCAAACTGCTTATCCAGGNACCACTAGAAGTGAATCTCTTCTTGAGTATTCCATACTG CTGCCCCTGCTATTCACTTGGGGTCCCAGTCAGTTGTTACTATATATTTGTCATCTATTGTGAGAGT CGTGATATCACCTTCCACATCAGTGATACTGAGAAGGAACAAATCTGCCAAAGATGCTTCACAGTTA GTTGTTACCTTTTTAAGAAGACTGTGCTTGAAAATTATGGTAAAACACATTTAGAAGAAGGATGTGC ATTTTCACATCAGTCTATGAAGTATAACTTGACATTTAAATTAAAATGCTGTTCTTCAAAATCGA SEQ.ID NO. 46 STAR clone: GTTCCCGACTAGCTGCCCNTGCACATTATCTTCATTTTCCTGGAATTTGATACAGAGAGCAATTTAT AGCCNATTGATAGCTTATGCTGTTTCAATGTAAATTCGTGGTAAATAACTTAGGAACTGCCTCTTCT TTTTCTTTGAAAACCTACTTATAACTGTTGCTAATAAGAATGTGTATTGTTCAGGACAACTTGTCTC CATACAGTTGGGTTGTAACCCTCATGCTTGGCCCAAATAAACTCTCTACTTATATCAGTA SEQ.ID NO. 47 STAR clone: CTAGGGGTCCTGACGGTTCTCTGGCTCCAAGTCTGGCCCCTCAACCTCCCTGGTCATCAGTGGGCTC CAGGCTGAGGATGAGGCTGATTACTACTGTGCAGCATGGGATGACAGCCTGAAAGGTCCTGCGTTCG GAGGAGGCACCCACCTGACCGTCCTCGGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCACC CTCCTCTGAGGAGCTTCAAGCCAACAAGGCCACACTGGTGTGTCTCGTAAGTGACTTCTACCCGGGA GCCGTGACAGTGGCCTGGAAGGCAGATGGCAGCCCCGTCAAGGTGGGAGTGGAGACCACCAAACCCT CCAAACAAAGCAACAACAAGTATGCGGCCAGCAGCTACCTGAGCCTGACGCCCGAGCAGTGGAAGTC CCACAGAAGCTACAGCTGCCGGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTGCA GAATGCTCTTAGGCCCCCGACCCTCACCCCACCCACAGGGGCCTGGAGCTGCAGGTTCCCAGGGGAG GGGTCTCTGCCCCCATCCCAAGTCATCCAGCCCTTCTCAATAAATATCCTCATCGTCAACGA SEQ.ID NO. 48 SEQ.ID NO. 88 GGTAGTTGGTTGTGGGCACTGGGTTAGAGGTATCACGTGGGGGCACTTTCGTCTTAGCTTTTGGACA MAQSRDGGNPFAEPSELDNPFQDPAV AGACGCAGGCGCAACCCACGGCTGCTGCGGGGATCCTTGTGGCCCTTCCGGTCGGTGGAACCAATCC IQHRPSRQYATLDVYNPFETREPPPA GTGCACAGAGAAGCGGGGCGAACTGAGGCGAGTGAAGTGGACTCTGAGGGCTACCGCTACCGCCACT YEPPAPAPLPPPSAPSLQPSRKLSPT GCTGCGGCAGGGGCGTGGAGGGCAGAGGGCCGCGGAGGCCGCAGTTGCAAACATGGCTCAGAGCAGA EPKNYGSYSTQASAAAATAELLKKQE GACGGCGGAAACCCGTTCGCCGAGCCCAGCGAGCTTGACAACCCCTTTCAGGACCCAGCTGTGATCC ELNRKAEELDRRERELQHAALGGTAT AGCACCGACCCAGCCGGCAGTATGCCACGCTTGACGTCTACAACCCTTTTGAGACCCGGGAGCCACC RQNNWPPLPSFCPVQPCFFQDISMEI ACCAGCCTATGAGCCTCCAGCCCCTGCCCCATTGCCTCCACCCTCAGCTCCCTCCTTGCAGCCCTCG
PQEFQKTVSTMYYLWMCSTLALLLNF AGAAAGCTCAGCCCCACAGAACCTAAGAACTATGGCTCATACAGCACTCAGGCCTCAGCTGCAGCAG LACLASFCVETNNGAGFGLSILWVLL CCACAGCTGAGCTGCTGAAGAAACAGGAGGAGCTCAACCGGAAGGCAGAGGAGTTGGACCGAAGGGA FTPCSFVCWYRPMYKAFRSDSSFNFF GCGAGAGCTGCAGCATGCTGCCCTGGGGGGCACAGCTACTCGACAGAACAATTGGCCCCCTCTACCT VFFFIFFVQDVLFVLQAIGIPGWGFS TCTTTTTGTCCAGTTCAGCCCTGCTTTTTCCAGGACATCTCCATGGAGATCCCCCAAGAATTTCAGA GWISALVVPKGNTAVSVLMLLVALLF AGACTGTATCCACCATGTACTACCTCTGGATGTGCAGCACGCTGGCTCTTCTCCTGAACTTCCTCGC TGIAVLGIVMLKRIHSLYRRTGASFQ CTGCCTGGCCAGCTTCTGTGTGGAAACCAACAATGGCGCAGGCTTTGGGCTTTCTATCCTCTGGGTC KAQQEFAAGVFSNPAVRTAAANAAAG CTCCTTTTCACTCCCTGCTCCTTTGTCTGCTGGTACCGCCCCATGTATAAGGCTTTCCGGAGTGACA AAENAFRAP GTTCATTCAATTTCTTCGTTTTCTTCTTCATTTTCTTCGTCCAGGATGTGCTCTTTGTCCTCCAGGC CATTGGTATCCCAGGTTGGGGATTCAGTGGCTGGATCTCTGCTCTGGTGGTGCCGAAGGGCAACACA GCAGTATCCGTGCTCATGCTGCTGGTCGCCCTGCTCTTCACTGGCATTGCTGTGCTAGGAATTGTCA TGCTGAAACGGATCCACTCCTTATACCGCCGCACAGGTGCCAGCTTTCAGAAGGCCCAGCAAGAATT TGCTGCTGGTGTCTTCTCCAACCCTGCGGTGCGAACCGCAGCTGCCAATGCAGCCGCTGGGGCTGCT GAAAATGCCTTCCGGGCCCCGTGACCCCTGACTGGGATGCCCTGGCCCTGCTACTTGAGGGAGCTGA CTTAGCTCCCGTCCCTAAGGTCTCTGGGACTTGGAGAGACATCACTAACTGATGGCTCCTCCGTAGT GCTCCCAATCCTATGGCCATGACTGCTGAACCTGACAGGCGTGTGGGGAGTTCACTGTGACCTAGTC CCCCCATCAGGCCACACTGCTGCCACCTCTCACACGCCCCAACCCAGCTTCCCTCTGCTGTGCCACG GCTGTTGCTTCGGTTATTTAAATAAAAAGAAAGTGGAACTGGAACTGACAAAAAAAAAAAAAAAAAA AAAAAA SEQ.ID NO. 49 STAR clone: CTGCAAGAACTANTCATTCNAGGTCACCAGANAGGAGCCCTGACCCNTCGCTGCCCAGCCTGTCCTT GTGTCGTCTTTTTACGGGAGACGACTGGATCATGGGGGCGGATTTTCCCCTTGCTGTTCTCATGATA GTGAGTTCTCATGAGATCTGGTTGTTTAAAAGTGTATAGCACTTCCTGCTTCACTCTCTCCCACTCC ACCATGTGAAGAAGGTGCCTTTGCCCTTCCGCCACGACTGTGTTTCCTGAGGCCTCCCCAGCCATGC TTCCTGTACAGCCTGCAGAACTGTGAGTTAATTAAACCTCTTTTCTTCATAAAGAACA SEQ.ID NO. 50 SEQ.ID NO. 89 TCAAGATTAAACGACAAGGACAGACATGGCTCAGCGGATGACAACACAGCTGCTGCTCCTTCTAGTG MAQRMTTQLLLLLVWVAVVGEAQTRI TGGGTGGCTGTAGTAGGGGAGGCTCAGACAAGGATTGCATGGGCCAGGACTGAGCTTCTCAATGTCT AWARTELLNVCMNAKHHKEKPGPEDK GCATGAACGCCAAGCACCACAAGGAAAAGCCAGGCCCCGAGGACAAGTTGCATGAGCAGTGTCGACC LHEQCRPWRKNACCSTNTSQEAHKDV CTGGAGGAAGAATGCCTGCTGTTCTACCAACACCAGCCAGGAAGCCCATAAGGATGTTTCCTACCTA SYLYRFNWNHCGEMAPACKRHFIQDT TATAGATTCAACTGGAACCACTGTGGAGAGATGGCACCTGCCTGCAAACGGCATTTCATCCAGGACA CLYECSPNLGPWIQQVDQSWRKERVL CCTGCCTCTACGAGTGCTCCCCCAACTTGGGGCCCTGGATCCAGCAGGTGGATCAGAGCTGGCGCAA NVPLCKEDCEQWWEDCRTSYTCKSNW AGAGCGGGTACTGAACGTGCCCCTGTGCAAAGAGGACTGTGAGCAATGGTGGGAAGATTGTCGCACC HKGWNWTSGFNKCAVGAACQPFHFYF TCCTACACCTGCAAGAGCAACTGGCACAAGGGCTGGAACTGGACTTCAGGGTTTAACAAGTGCGCAG PTPTVLCNEIWTHSYKVSNYSRGSGR TGGGAGCTGCCTGCCAACCTTTCCATTTCTACTTCCCCACACCCACTGTTCTGTGCAATGAAATCTG CIQMWFDPAQGNPNEEVARFYAAAMS GACTCACTCCTACAAGGTCAGCAACTACAGCCGAGGGAGTGGCCGCTGCATCCAGATGTGGTTCGAC GAGPWAAWPFLLSLALMLLWLLS CCAGCCCAGGGCAACCCCAATGAGGAGGTGGCGAGGTTCTATGCTGCAGCCATGAGTGGGGCTGGGC CCTGGGCAGCCTGGCCTTTCCTGCTTAGCCTGGCCCTAATGCTGCTGTGGCTGCTCAGCTGACCTCC TTTTACCTTCTGATACCTGGAAATCCCTGCCCTGTTCAGCCCCACAGCTCCCAACTATTTGGTTCCT GCTCCATGGTCGGGCCTCTGACAGCCACTTTGAATAAACCAGACACCGCACATGTGTCTTGAGAATT ATTTGG SEQ.ID NO. 90 biotin-actgtactAACCCTGCGGCCGCTTTTTTTTTTTTTTTTTTTTV SEQ.ID NO. 91 GGAATTCTAATACGACTCACTATAGGGAGACGAAGACAGTAGACAGG SEQ.ID NO. 92 CGCGCCTGTCTACTGTCTTCGTCTCCCTATAGTGAGTCGTATTAGAATTC SEQ.ID NO. 93 GGAATTCTAATACGACTCACTATAGGGAGAGCCTGCACCAACAGTTAACAGG SEQ.ID NO. 94 CGCGCCTGTTAACTGTTGGTGCAGGCTCTCCCTATAGTGAGTCGTATTAGAATTC SEQ.ID NO. 95 GGGAGACGAAGACAGTAGA SEQ.ID NO. 96 GCCTGCACCAACAGTTAACA SEQ.ID NO. 97 GGAATTCTAATACGACTCACTATAGGGA SEQ.ID NO. 98 CGCGTCCCTATAGTGAGTCGTATTAGAATTC SEQ.ID NO. 99 TTTTCCCAGTCACGACGTTGTAAAACGACGGCCAGTGAATTCTAATACGACTCACTATAGGGAGATG GAGAAAAAAATCACTGGACGCGTGGCGCGCCATTAATTAATGCGGCCGCTAGCTCGAGTGATAATAA GCGGATGAATGGCTGCAGGCATGCAAGCTTGGCGTAATCATGGTCATAGCTGTTTCCTGTGTGAAAT TGTTATCCGCTCACAATTCCACACAACATACGAGCCGGAAGCATAAAGTGTAAAGCCTGGGGTGCCT AATGAGTGAGCTAACTCACATTAATTGCGTTGCGCTCACTGCCCGCTTTCCAGTCGGGAAACCTGTC GTGCCAGCTGCATTAATGAATCGGCCAACGCGCGGGGAGAGGCGGTTTGCGTATTGGGCGCTCTTCC GCTTCCTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGCTGCGGCGAGCGGTATCAGCTCACTCAA AGGCGGTAATACGGTTATCCACAGAATCAGGGGATAACGCAGGAAAGAACATGTGAGCAAAAGGCCA GCAAAAGGCCAGGAACCGTAAAAAGGCCGCGTTGCTGGCGTTTTTCCATAGGCTCCGCCCCCCTGAC GAGCATCACAAAAATCGACGCTCAAGTCAGAGGTGGCGAAACCCGACAGGACTATAAAGATACCAGG CGTTTCCCCCTGGAAGCTCCCTCGTGCGCTCTCCTGTTCCGACCCTGCCGCTTACCGGATACCTGTC CGCCTTTCTCCCTTCGGGAAGCGTGGCGCTTTCTCAATGCTCACGCTGTAGGTATCTCAGTTCGGTG TAGGTCGTTCGCTCCAAGCTGGGCTGTGTGCACGAACCCCCCGTTCAGCCCGACCGCTGCGCCTTAT CCGGTAACTATCGTCTTGAGTCCAACCCGGTAAGACACGACTTATCGCCACTGGCAGCAGCCACTGG TAACAGGATTAGCAGAGCGAGGTATGTAGGCGGTGCTACAGAGTTCTTGAAGTGGTGGCCTAACTAC GGCTACACTAGAAGGACAGTATTTGGTATCTGCGCTCTGCTGAAGCCAGTTACCTTCGGAAAAAGAG TTGGTAGCTCTTGATCCGGCAAACAAACCACCGCTGGTAGCGGTGGTTTTTTTGTTTGCAAGCAGCA GATTACGCGCAGAAAAAAAGGATCTCAAGAAGATCCTTTGATCTTTTCTACGGGGTCTGACGCTCAG TGGAACGAAAACTCACGTTAAGGGATTTTGGTCATGAGATTATCAAAAAGGATCTTCACCTAGATCC TTTTAAATTAAAAATGAAGTTTTAAATCAATCTAAAGTATATATGAGTAAACTTGGTCTGACAGTTA CCAATGCTTAATCAGTGAGGCACCTATCTCAGCGATCTGTCTATTTCGTTCATCCATAGTTGCCTGA CTCCCCGTCGTGTAGATAACTACGATACGGGAGGGCTTACCATCTGGCCCCAGTGCTGCAATGATAC CGCGAGACCCACGCTCACCGGCTCCAGATTTATCAGCAATAAACCAGCCAGCCGGAAGGGCCGAGCG CAGAAGTGGTCCTGCAACTTTATCCGCCTCCATCCAGTCTATTAATTGTTGCCGGGAAGCTAGAGTA AGTAGTTCGCCAGTTAATAGTTTGCGCAACGTTGTTGCCATTGCTACAGGCATCGTGGTGTCACGCT CGTCGTTTGGTATGGCTTCATTCAGCTCCGGTTCCCAACGATCAAGGCGAGTTACATGATCCCCCAT GTTGTGCAAAAAAGCGGTTAGCTCCTTCGGTCCTCCGATCGTTGTCAGAAGTAAGTTGGCCGCAGTG TTATCACTCATGGTTATGGCAGCACTGCATAATTCTCTTACTGTCATGCCATCCGTAAGATGCTTTT CTGTGACTGGTGAGTACTCAACCAAGTCATTCTGAGAATAGTGTATGCGGCGACCGAGTTGCTCTTG CCCGGCGTCAATACGGGATAATACCGCGCCACATAGCAGAACTTTAAAAGTGCTCATCATTGGAAAA CGTTCTTCGGGGCGAAAACTCTCAAGGATCTTACCGCTGTTGAGATCCAGTTCGATGTAACCCACTC GTGCACCCAACTGATCTTCAGCATCTTTTACTTTCACCAGCGTTTCTGGGTGAGCAAAAACAGGAAG GCAAAATGCCGCAAAAAAGGGAATAAGGGCGACACGGAAATGTTGAATACTCATACTCTTCCTTTTT CAATATTATTGAAGCATTTATCAGGGTTATTGTCTCATGAGCGGATACATATTTGAATGTATTTAGA AAAATAAACAAATAGGGGTTCCGCGCACATTTCCCCGAAAAGTGCCACCTGACGTCTAAGAAACCAT TATTATCATGACATTAACCTATAAAAATAGGCGTATCACGAGGCCCTTTCGTCTCGCGCGTTTCGGT GATGACGGTGAAAACCTCTGACACATGCAGCTCCCGGAGACGGTCACAGCTTGTCTGTAAGCGGATG CCGGGAGCAGACAAGCCCGTCAGGGCGCGTCAGCGGGTGTTGGCGGGTGTCGGGGCTGGCTTAACTA TGCGGCATCAGAGCAGATTGTACTGAGAGTGCACCATATGCGGTGTGAAATACCGCACAGATGCGTA AGGAGAAAATACCGCATCAGGCGCCATTCGCCATTCAGGCTGCGCAACTGTTGGGAAGGGCGATCGG TGCGGGCCTCTTCGCTATTACGCCAGCTGGCGAAAGGGGGATGTGCTGCAAGGCGATTAAGTTGGGT AACGCCAGGG SEQ.ID NO. 100 TTTTCCCAGTCACGACGTTGTAAAACGACGGCCAGTGAATTCAATTAACCCTCACTAAAGGGAGACT TGTTCCAAATGTGTTAGGcgCGCCGCATGCGTCGACGGATCCTGAGAACTTCAGGCTCCTGGGCAAC GTGCTGGTTATTGTGCTGTCTCATCATTTTGGCAAAGAATTCACTCCTCAGGTGCAGGCTGCCTATC AGAAGGTGGTGGCTGGTGTGGCCAATGCCCTGGCTCACAAATACCACTGAGATCTTTTTCCCTCTGC CAAAAATTATGGGGACATCATGAAGCCCCTTGAGCATCTGACTTCTGGCTAATAAAGGAAATTTATT TTCATTGCAAAAAAAAAAAGCGGCCGCTCTTCTATAGTGTCACCTAAATGGCCCAGCGGCCGAGCTT GGCGTAATCATGGTCATAGCTGTTTCCTGTGTGAAATTGTTATCCGCTCACAATTCCACACAACATA CGAGCCGGAAGCATAAAGTGTAAAGCCTGGGGTGCCTAATGAGTGAGCTAACTCACATTAATTGCGT TGCGCTCACTGCCCGCTTTCCAGTCGGGAAACCTGTCGTGCCAGCTGCATTAATGAATCGGCCAACG CGCGGGGAGAGGCGGTTTGCGTATTGGGCGCTCTTCCGCTTCCTCGCTCACTGACTCGCTGCGCTCG GTCGTTCGGCTGCGGCGAGCGGTATCAGCTCACTCAAAGGCGGTAATACGGTTATCCACAGAATCAG GGGATAACGCAGGAAAGAACATGTGAGCAAAAGGCCAGCAAAAGGCCAGGAACCGTAAAAAGGCCGC GTTGCTGGCGTTTTTCCATAGGCTCCGCCCCCCTGACGAGCATCACAAAAATCGACGCTCAAGTCAG AGGTGGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGGAAGCTCCCTCGTGCGCT CTCCTGTTCCGACCCTGCCGCTTACCGGATACCTGTCCGCCTTTCTCCCTTCGGGAAGCGTGGCGCT TTCTCAAAGCTCACGCTGTAGGTATCTCAGTTCGGTGTAGGTCGTTCGCTCCAAGCTGGGCTGTGTG CACGAACCCCCCGTTCAGCCCGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACCCGG TAAGACACGACTTATCGCCACTGGCAGCAGCCACTGGTAACAGGATTAGCAGAGCGAGGTATGTAGG CGGTGCTACAGAGTTCTTGAAGTGGTGGCCTAACTACGGCTACACTAGAAGAACAGTATTTGGTATC TGCGCTCTGCTGAAGCCAGTTACCTTCGGAAAAAGAGTTGGTAGCTCTTGATCCGGCAAACAAACCA CCGCTGGTAGCGGTGGTTTTTTTGTTTGCAAGCAGCAGATTACGCGCAGAAAAAAAGGATCTCAAGA AGATCCTTTGATCTTTTCTACGGGGTCTGACGCTCAGTGGAACGAAAACTCACGTTAAGGGATTTTG GTCATGAGATTATCAAAAAGGATCTTCACCTAGATCCTTTTAAATTAAAAATGAAGTTTTAAATCAA TCTAAAGTATATATGAGTAAACTTGGTCTGACAGTTACCAATGCTTAATCAGTGAGGCACCTATCTC AGCGATCTGTCTATTTCGTTCATCCATAGTTGCCTGACTCCCCGTCGTGTAGATAACTACGATACGG GAGGGCTTACCATCTGGCCCCAGTGCTGCAATGATACCGCGAGACCCACGCTCACCGGCTCCAGATT TATCAGCAATAAACCAGCCAGCCGGAAGGGCCGAGCGCAGAAGTGGTCCTGCAACTTTATCCGCCTC CATCCAGTCTATTAATTGTTGCCGGGAAGCTAGAGTAAGTAGTTCGCCAGTTAATAGTTTGCGCAAC GTTGTTGCCATTGCTACAGGCATCGTGGTGTCACGCTCGTCGTTTGGTATGGCTTCATTCAGCTCCG GTTCCCAACGATCAAGGCGAGTTACATGATCCCCCATGTTGTGCAAAAAAGCGGTTAGCTCCTTCGG TCCTCCGATCGTTGTCAGAAGTAAGTTGGCCGCAGTGTTATCACTCATGGTTATGGCAGCACTGCAT AATTCTCTTACTGTCATGCCATCCGTAAGATGCTTTTCTGTGACTGGTGAGTACTCAACCAAGTCAT TCTGAGAATAGTGTATGCGGCGACCGAGTTGCTCTTGCCCGGCGTCAATACGGGATAATACCGCGCC ACATAGCAGAACTTTAAAAGTGCTCATCATTGGAAAACGTTCTTCGGGGCGAAAACTCTCAAGGATC TTACCGCTGTTGAGATCCAGTTCGATGTAACCCACTCGTGCACCCAACTGATCTTCAGCATCTTTTA CTTTCACCAGCGTTTCTGGGTGAGCAAAAACAGGAAGGCAAAATGCCGCAAAAAAGGGAATAAGGGC GACACGGAAATGTTGAATACTCATACTCTTCCTTTTTCAATATTATTGAAGCATTTATCAGGGTTAT TGTCTCATGAGCGGATACATATTTGAATGTATTTAGAAAAATAAACAAATAGGGGTTCCGCGCACAT TTCCCCGAAAAGTGCCACCTGACGTCTAAGAAACCATTATTATCATGACATTAACCTATAAAAATAG GCGTATCACGAGGCCCTTTCGTCTCGCGCGTTTCGGTGATGACGGTGAAAACCTCTGACACATGCAG CTCCCGGAGACGGTCACAGCTTGTCTGTAAGCGGATGCCGGGAGCAGACAAGCCCGTCAGGGCGCGT CAGCGGGTGTTGGCGGGTGTCGGGGCTGGCTTAACTATGCGGCATCAGAGCAGATTGTACTGAGAGT GCACCATATGCGGTGTGAAATACCGCACAGATGCGTAAGGAGAAAATACCGCATCAGGCGCCATTCG CCATTCAGGCTGCGCAACTGTTGGGAAGGGCGATCGGTGCGGGCCTCTTCGCTATTACGCCAGCTGG CGAAAGGGGGATGTGCTGCAAGGCGATTAAGTTGGGTAACGCCAGGG SEQ.ID NO. 101 TCGCGCGTTTCGGTGATGACGGTGAAAACCTCTGACACATGCAGCTCCCGGAGACGGTCACAGCTTG TCTGTAAGCGGATGCCGGGAGCAGACAAGCCCGTCAGGGCGCGTCAGCGGGTGTTGGCGGGTGTCGG GGCTGGCTTAACTATGCGGCATCAGAGCAGATTGTACTGAGAGTGCACCATATGCGGTGTGAAATAC CGCACAGATGCGTAAGGAGAAAATACCGCATCAGGCGCCATTCGCCATTCAGGCTGCGCAACTGTTG GGAAGGGCGATCGGTGCGGGCCTCTTCGCTATTACGCCAGCTGGCGAAAGGGGGATGTGCTGCAAGG CGATTAAGTTGGGTAACGCCAGGGTTTTCCCAGTCACGACGTTGTAAAACGACGGCCAGTGCCAAGC TTTTCCAAAAAACTACCGTTGTTATAGGTGTCTCTTGAACACCTATAACAACGGTAGTGGATCCCGC GTCCTTTCCACAAGATATATAAACCCAAGAAATCGAAATACTTTCAAGTTACGGTAAGCATATGATA GTCCATTTTAAAACATAATTTTAAAACTGCAAACTACCCAAGAAATTATTACTTTCTACGTCACGTA TTTTGTACTAATATCTTTGTGTTTACAGTCAAATTAATTCTAATTATCTCTCTAACAGCCTTGTATC GTATATGCAAATATGAAGGAATCATGGGAAATAGGCCCTCTTCCTGCCCGACCTTGGCGCGCGCTCG GCGCGCGGTCACGCTCCGTCACGTGGTGCGTTTTGCCTGCGCGTCTTTCCACTGGGGAATTCATGCT TCTCCTCCCTTTAGTGAGGGTAATTCTCTCTCTCTCCCTATAGTGAGTCGTATTAATTCCTTCTCTT CTATAGTGTCACCTAAATCGTTGCAATTCGTAATCATGTCATAGCTGTTTCCTGTGTGAAATTGTTA TCCGCTCACAATTCCACACAACATACGAGCCGGAAGCATAAAGTGTAAAGCCTGGGGTGCCTAATGA GTGAGCTAACTCACATTAATTGCGTTGCGCTCACTGCCCGCTTTCCAGTCGGGAAACCTGTCGTGCC AGCTGCATTAATGAATCGGCCAACGCGCGGGGAGAGGCGGTTTGCGTATTGGGCGCTCTTCCGCTTC CTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGCTGCGGCGAGCGGTATCAGCTCACTCAAAGGCG GTAATACGGTTATCCACAGAATCAGGGGATAACGCAGGAAAGAACATGTGAGCAAAAGGCCAGCAAA AGGCCAGGAACCGTAAAAAGGCCGCGTTGCTGGCGTTTTTCCATAGGCTCCGCCCCCCTGACGAGCA TCACAAAAATCGACGCTCAAGTCAGAGGTGGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTT CCCCCTGGAAGCTCCCTCGTGCGCTCTCCTGTTCCGACCCTGCCGCTTACCGGATACCTGTCCGCCT TTCTCCCTTCGGGAAGCGTGGCGCTTTCTCATAGCTCACGCTGTAGGTATCTCAGTTCGGTGTAGGT CGTTCGCTCCAAGCTGGGCTGTGTGCACGAACCCCCCGTTCAGCCCGACCGCTGCGCCTTATCCGGT AACTATCGTCTTGAGTCCAACCCGGTAAGACACGACTTATCGCCACTGGCAGCAGCCACTGGTAACA GGATTAGCAGAGCGAGGTATGTAGGCGGTGCTACAGAGTTCTTGAAGTGGTGGCCTAACTACGGCTA CACTAGAAGAACAGTATTTGGTATCTGCGCTCTGCTGAAGCCAGTTACCTTCGGAAAAAGAGTTGGT AGCTCTTGATCCGGCAAAAAAACCACCGCTGGTAGCGGTGGTTTTTTTGTTTGCAAGCAGCAGATTA CGCGCAGAAAAAAAGGATCTCAAGAAGATCCTTTGATCTTTTCTACGGGGTCTGACGCTCAGTGGAA CGAAAACTCACGTTAAGGGATTTTGGTCATGAGATTATCAAAAAGGATCTTCACCTAGATCCTTTTA AATTAAAAATGAAGTTTTAAATCAATCTAAAGTATATATGAGTAAACTTGGTCTGACAGTTACCAAT GCTTAATCAGTGAGGCACCTATCTCAGCGATCTGTCTATTTCGTTCATCCATAGTTGCCTGACTCCC CGTCGTGTAGATAACTACGATACGGGAGGGCTTACCATCTGGCCCCAGTGCTGCAATGATACCGCGA GACCCACGCTCACCGGCTCCAGATTTATCAGCAATAAACCAGCCAGCCGGAAGGGCCGAGCGCAGAA GTGGTCCTGCAACTTTATCCGCCTCCATCCAGTCTATTAATTGTTGCCGGGAAGCTAGAGTAAGTAG TTCGCCAGTTAATAGTTTGCGCAACGTTGTTGCCATTGCTACAGGCATCGTGGTGTCACGCTCGTCG TTTGGTATGGCTTCATTCAGCTCCGGTTCCCAACGATCAAGGCGAGTTACATGATCCCCCATGTTGT GCAAAAAAGCGGTTAGCTCCTTCGGTCCTCCGATCGTTGTCAGAAGTAAGTTGGCCGCAGTGTTATC ACTCATGGTTATGGCAGCACTGCATAATTCTCTTACTGTCATGCCATCCGTAAGATGCTTTTCTGTG ACTGGTGAGTACTCAACCAAGTCATTCTGAGAATAGTGTATGCGGCGACCGAGTTGCTCTTGCCCGG CGTCAATACGGGATAATACCGCGCCACATAGCAGAACTTTAAAAGTGCTCATCATTGGAAAACGTTC TTCGGGGCGAAAACTCTCAAGGATCTTACCGCTGTTGAGATCCAGTTCGATGTAACCCACTCGTGCA CCCAACTGATCTTCAGCATCTTTTACTTTCACCAGCGTTTCTGGGTGAGCAAAAACAGGAAGGCAAA ATGCCGCAAAAAAGGGAATAAGGGCGACACGGAAATGTTGAATACTCATACTCTTCCTTTTTCAATA TTATTGAAGCATTTATCAGGGTTATTGTCTCATGAGCGGATACATATTTGAATGTATTTAGAAAAAT AAACAAATAGGGGTTCCGCGCACATTTCCCCGAAAAGTGCCACCTATTGGTGTGGAAAGTCCCCAGG CTCCCCAGCAGGCAGAAGTATGCAAAGCATGCATCTCAATTAGTCAGCAACCAGGTGTGGAAAGTCC CCAGGCTCCCCAGCAGGCAGAAGTATGCAAAGCATGCATCTCAATTAGTCAGCAACCATAGTCCCGC CCCTAACTCCGCCCATCCCGCCCCTAACTCCGCCCAGTTCCGCCCATTCTCCGCCCCATGGCTGACT AATTTTTTTTATTTATGCAGAGGCCGAGGCCGCCTCGGCCTCTGAGCTATTCCAGAAGTAGTGAGGA GGCTTTTTTGGAGGCCTAGGCTTTTGCAAAAAGCTAGCTTGCATGCCTGCAGGTCGGCCGCCACGAC CGGTGCCGCCACCATCCCCTGACCCACGCCCCTGACCCCTCACAAGGAGACGACCTTCCATGACCGA GTACAAGCCCACGGTGCGCCTCGCCACCCGCGACGACGTCCCCCGGGCCGTACGCACCCTCGCCGCC GCGTTCGCCGACTACCCCGCCACGCGCCACACCGTCGACCCGGACCGCCACATCGAGCGGGTCACCG AGCTGCAAGAACTCTTCCTCACGCGCGTCGGGCTCGACATCGGCAAGGTGTGGGTCGCGGACGACGG CGCCGCGGTGGCGGTCTGGACCACGCCGGAGAGCGTCGAAGCGGGGGCGGTGTTCGCCGAGATCGGC CCGCGCATGGCCGAGTTGAGCGGTTCCCGGCTGGCCGCGCAGCAACAGATGGAAGGCCTCCTGGCGC CGCACCGGCCCAAGGAGCCCGCGTGGTTCCTGGCCACCGTCGGCGTCTCGCCCGACCACCAGGGCAA GGGTCTGGGCAGCGCCGTCGTGCTCCCCGGAGTGGAGGCGGCCGAGCGCGCCGGGGTGCCCGCCTTC CTGGAGACCTCCGCGCCCCGCAACCTCCCCTTCTACGAGCGGCTCGGCTTCACCGTCACCGCCGACG TCGAGGTGCCCGAAGGACCGCGCACCTGGTGCATGACCCGCAAGCCCGGTGCCTGACGCCCGCCCCA CGACCCGCAGCGCCCGACCGAAAGGAGCGCACGACCCCATGGCTCCGACCGAAGCCACCCGGGGCGG CCCCGCCGACCCCGCACCCGCCCCCGAGGCCCACCGACTCTAGAGGATCATAATCAGCCATACCACA TTTGTAGAGGTTTTACTTGCTTTAAAAAACCTCCCACACCTCCCCCTGAACCTGAAACATAAAATGA ATGCAATTGTTGTTGTTAACTTGTTTATTGCAGCTTATAATGGTTACAAATAAAGCAATAGCATCAC AAATTTCACAAATAAAGCATTTTTTTCACTGCAATCTAAGAAACCATTATTATCATGACATTAACCT ATAAAAATAGGCGTATCACGAGGCCCTTTCGTC SEQ.ID NO. 102 Sequence information not disclosed by Ambion
SEQ.ID NO. 103 GTCAAGAAACCACACTTTA SEQ.ID NO. 104 GTGACATGGAACCCAGCGA SEQ.ID NO. 105 ACCGTGGCTGCTCGATAAA SEQ.ID NO. 106 GCCAGAGAGCACAGAAATA SEQ.ID NO. 107 GAGGAATGCCTCTAAGAAA SEQ.ID NO. 108 GGGAACGAGAAGGGCTTCT SEQ.ID NO. 109 AGCTGGAGGAATGAGAATT SEQ.ID NO. 110 AGGGCCAAAGCTTTCCATA SEQ.ID NO. 111 GGCAGGCTGTCCGCTTAAA SEQ.ID NO. 112 GGTCCTTAGGCACCCAGAT SEQ.ID NO. 113 GCGGAGCCCAGGGAGAATA SEQ.ID NO. 114 GCCCGGATTGATGACATAT SEQ.ID NO. 115 GTGGAGGCTGAGTTTCCAT SEQ.ID NO. 116 GGATGTTAACCTGCGAAAT SEQ.ID NO. 117 GGTCAGCAGGGTTCATTTA SEQ.ID NO. 118 GCCTCAGGAACAAGATGAA SEQ.ID NO. 119 GCGCGAGATCCTCTCCATT SEQ.ID NO. 120 GCGCCAGAGGAGCGGGAAG SEQ.ID NO. 121 GCCGCCCAGTTCAATACAA SEQ.ID NO. 122 GAGCTTACAACCTGCCTTA SEQ.ID NO. 123 GGCGCCCACTACCCAAGAA SEQ.ID NO. 124 GAGTCAGGGATGGGTCCAT SEQ.ID NO. 125 GGGCCAGTCTGTACTCATT SEQ.ID NO. 126 GGGAATTCCATCTCCATAT SEQ.ID NO. 127 GGCGCAGATCACCCAGAAG SEQ.ID NO. 128 GAGCATCCTGGTGAGGAAT SEQ.ID NO. 129 GGTGCCACATGACTAGGAT SEQ.ID NO. 130 GCTGCAGACGTGTATGCAT SEQ.ID NO. 131 GCGGAGGCACTGGGCTTAT SEQ.ID NO. 132 GCCCGCTTACTTCCTGGAG SEQ.ID NO. 133 GCTCTGCTCAAGTTGGATA SEQ.ID NO. 134 GCTGCTGCCTTGCAGTTTG SEQ.ID NO. 135 GCCCTTACCTGATGCTAAA SEQ.ID NO. 136 GGCACCTACAAATGTTATA SEQ.ID NO. 137 GAGGCCTGGAAGCTCCTAA SEQ.ID NO. 138 GCAGCTTCAGGAGGTTAAA SEQ.ID NO. 139 GCCGGACCTCTTCATCTTA SEQ.ID NO. 140 GCGTCCATCACGGAAACAT SEQ.ID NO. 141 GTCATCAGGACGTCCATTA SEQ.ID NO. 142 GACACGATCTACCCTCAAA SEQ.ID NO. 143 GGGCCATAGGGAAGCTTGA SEQ.ID NO. 144 GCCCACGTGTTGAGATCAA SEQ.ID NO. 145 GCTCCCACTGATTCCACAT SEQ.ID NO. 146 GCCAGAGAGTAAAAGGGAT SEQ.ID NO. 147 GGCATATGGAAGGAGCATT SEQ.ID NO. 148 GTGGTTTGGTTCAGCAGTT SEQ.ID NO. 149 GGCCTCCAGCCACGTAATT SEQ.ID NO. 150 GGCGCTGCTGCCGCTCATC SEQ.ID NO. 151 GGGCTGGAACTGGACTTCA SEQ.ID NO. 152 GCCCATAAGGATGTTTCCT SEQ.ID NO. 153 GCGTCCGGGCCTGTCTTCAACCT SEQ.ID NO. 154 GCCCCACCCTCTACCCCACCACTA SEQ.ID NO. 155 GAGATCCTGATCAAGGTGCAGG SEQ.ID NO. 156 TGCACGCTCACAGCAGTCAGG SEQ.ID NO. 157 AACATGACTAAGATGCCCAACC SEQ.ID NO. 158 AATCTCCTTCACCTCCACTACTG SEQ.ID NO. 159 AAGCATAGCCATAGGTGATTGG SEQ.ID NO. 160 ACAGGTATCAGACAAGGGAGCAG SEQ.ID NO. 161 TTACGACCTATTTCTCCGTGG SEQ.ID NO. 162 AATGCAATAATTGGCCACTGC SEQ.ID NO. 163 ACACATCAAACTGCTTATCCAGG SEQ.ID NO. 164 ACTGATGTGAAAATGCACATCC SEQ.ID NO. 165 ATGGCTCATACAGCACTCAGG SEQ.ID NO. 166 GAACTGTCACTCCGGAAAGCCT SEQ.ID NO. 167 TGAAGGTCGGAGTCAACGGATTTGGT SEQ.ID NO. 168 CATGTGGGCCATGAGGTCCACCAC SEQ.ID NO. 169 SEQ.ID NO. 170 ccctaatgcctccaacaataactgttgactttttattttcagtcagagaagcctggcaaccaagaac MKILILGIFLFLCSTPAWAKEKHYYI tgtttttttggtggtttacgagaacttaactgaattggaaaatatttgctttaatgaaacaatttac GIIETTWDYASDHGEKKLISVDTEHS tcttgtgcaacactaaattgtgtcaatcaagcaaataaggaagaaagtcttatttataaaattgcct NIYLQNGPDRIGRLYKKALYLQYTDE gctcctgattttacttcatttcttctcaggctccaagaaggggaaaaaaatgaagattttgatactt TFRTTIEKPVWLGFLGPIIKAETGDK ggtatttttctgtttttatgtagtaccccagcctgggcgaaagaaaagcattattacattggaatta VYVHLKNLASRPYTFHSHGITYYKEH ttgaaacgacttgggattatgcctctgaccatggggaaaagaaacttatttctgttgacacggaaca EGAIYPDNTTDFQRADDKVYPGEQYT ttccaatatctatcttcaaaatggcccagatagaattgggagactatataagaaggccctttatctt YMLLATEEQSPGEGDGNCVTRIYHSH cagtacacagatgaaacctttaggacaactatagaaaaaccggtctggcttgggtttttaggcccta IDAPKDIASGLIGPLIICKKDSLDKE ttatcaaagctgaaactggagataaagtttatgtacacttaaaaaaccttgcctctaggccctacac KEKHIDREFVVMFSVVDENFSWYLED ctttcattcacatggaataacttactataaggaacatgagggggccatctaccctgataacaccaca NIKTYCSEPEKVDKDNEDFQESNRMY gattttcaaagagcagatgacaaagtatatccaggagagcagtatacatacatgttgcttgccactg SVNGYTFGSLPGLSMCAEDRVKWYLF aagaacaaagtcctggggaaggagatggcaattgtgtgactaggatttaccattcccacattgatgc GMGNEVDVHAAFFHGQALTNKNYRID tccaaaagatattgcctcaggactcatcggacctttaataatctgtaaaaaagattctctagataaa TINLFPATLFDAYMVAQNPGEWMLSC gaaaaagaaaaacatattgaccgagaatttgtggtgatgttttctgtggtggatgaaaatttcagct QNLNHLKAGLQAFFQVQECNKSSSKD ggtacctagaagacaacattaaaacctactgctcagaaccagagaaagttgacaaagacaacgaaga NIRGKHVRHYYIAAEEIIWNYAPSGI cttccaggagagtaacagaatgtattctgtgaatggatacacttttggaagtctcccaggactctcc DIFTKENLTAPGSDSAVFFEQGTTRI atgtgtgctgaagacagagtaaaatggtacctttttggtatgggtaatgaagttgatgtgcacgcag GGSYKKLVYREYTDASFTNRKERGPE ctttctttcacgggcaagcactgactaacaagaactaccgtattgacacaatcaacctctttcctgc EEHLGILGPVIWAEVGDTIRVTFHNK taccctgtttgatgcttatatggtggcccagaaccctggagaatggatgctcagctgtcagaatcta GAYPLSIEPIGVRFNKNNEGTYYSPN aaccatctgaaagccggtttgcaagcctttttccaggtccaggagtgtaacaagtcttcatcaaagg YNPQSRSVPPSASHVAPTETFTYEWT ataatatccgtgggaagcatgttagacactactacattgccgctgaggaaatcatctggaactatgc VPKEVGPTNADPVCLAKMYYSAVDPT tccctctggtatagacatcttcactaaagaaaacttaacagcacctggaagtgactcagcggtgttt KDIFTGLIGPMKICKKGSLHANGRQK tttgaacaaggtaccacaagaattggaggctcttataaaaagctggtttatcgtgagtacacagatg DVDKEFYLFPTVFDENESLLLEDNIR cctccttcacaaatcgaaaggagagaggccctgaagaagagcatcttggcatcctgggtcctgtcat MFTTAPDQVDKEDEDFQESNKMHSMN ttgggcagaggtgggagacaccatcagagtaaccttccataacaaaggagcatatcccctcagtatt GFMYGNQPGLTMCKGDSVVWYLFSAG gagccgattggggtgagattcaataagaacaacgagggcacatactattccccaaattacaaccccc
NEADVHGIYFSGNTYLWRGERRDTAN agagcagaagtgtgcctccttcagcctcccatgtggcacccacagaaacattcacctatgaatggac LFPQTSLTLHMWPDTEGTFNVECLTT tgtccccaaagaagtaggacccactaatgcagatcctgtgtgtctagctaagatgtattattctgct DHYTGGMKQKYTVNQCRRQSEDSTFY gtggatcccactaaagatatattcactgggcttattgggccaatgaaaatatgcaagaaaggaagtt LGERTYYIAAVEVEWDYSPQREWEKE tacatgcaaatgggagacagaaagatgtagacaaggaattctatttgtttcctacagtatttgatga LHHLQEQNVSNAFLDKGEFYIGSKYK gaatgagagtttactcctggaagataatattagaatgtttacaactgcacctgatcaggtggataag KVVYRQYTDSTFRVPVERKAEEEHLG gaagatgaagactttcaggaatctaataaaatgcactccatgaatggattcatgtatgggaatcagc ILGPQLHADVGDKVKIIFKNMATRPY cgggtctcactatgtgcaaaggagattcggtcgtgtggtacttattcagcgccggaaatgaggccga SIHAHGVQTESSTVTPTLPGETLTYV tgtacatggaatatacttttcaggaaacacatatctgtggagaggagaacggagagacacagcaaac WKIPERSGAGTEDSACIPWAYYSTVD ctcttccctcaaacaagtcttacgctccacatgtggcctgacacagaggggacttttaatgttgaat QVKDLYSGLIGPLIVCRRPYLKVFNP gccttacaactgatcattacacaggcggcatgaagcaaaaatatactgtgaaccaatgcaggcggca RRKLEFALLFLVFDENESWYLDDNIK gtctgaggattccaccttctacctgggagagaggacatactatatcgcagcagtggaggtggaatgg TYSDHPEKVNKDDEEFIESNKMHAIN gattattccccacaaagggagtgggaaaaggagctgcatcatttacaagagcagaatgtttcaaatg GRMFGNLQGLTMHVGDEVNWYLMGMG catttttagataagggagagttttacataggctcaaagtacaagaaagttgtgtatcggcagtatac NEIDLHTVHFHGHSFQYKHRGVYSSD tgatagcacattccgtgttccagtggagagaaaagctgaagaagaacatctgggaattctaggtcca VFDIFPGTYQTLEMFPRTPGIWLLHC caacttcatgcagatgttggagacaaagtcaaaattatctttaaaaacatggccacaaggccctact HVTDHIHAGMETTYTVLQNEDTKSG caatacatgcccatggggtacaaacagagagttctacagttactccaacattaccaggtgaaactct cacttacgtatggaaaatcccagaaagatctggagctggaacagaggattctgcttgtattccatgg gcttattattcaactgtggatcaagttaaggacctctacagtggattaattggccccctgattgttt gtcgaagaccttacttgaaagtattcaatcccagaaggaaactggaatttgcccttctgtttctagt ttttgatgagaatgaatcttggtacttagatgacaacatcaaaacatactctgatcaccccgagaaa gtaaacaaagatgatgaggaattcatagaaagcaataaaatgcatgctattaatggaagaatgtttg gaaacctacaaggcctcacaatgcacgtgggagatgaagtcaactggtatctgatgggaatgggcaa tgaaatagacttacacactgtacattttcacggccatagcttccaatacaagcacaggggagtttat agttctgatgtctttgacattttccctggaacataccaaaccctagaaatgtttccaagaacacctg gaatttggttactccactgccatgtgaccgaccacattcatgctggaatggaaaccacttacaccgt tctacaaaatgaagacaccaaatctggctgaatgaaataaattggtgataagtggaaaaaagagaaa aaccaatgattcataacaatgtatgtgaaagtgtaaaatagaatgttactttggaatgactataaac attaaaagaagactggaagcatacaactttgtacatttgtgggggaaaactattaattttttgcaaa tggaaagatcaacagactatataatgatacatgactgacacttgtacactaggtaataaaactgatt catacagtctaatgatatcaccgctgttagggttttataaaactgcatttaaaaaaagatctatgac cagatattctcctgggtgctcctcaaaggaacactattaaggttcattgaaatgttttcaatcattg ccttcccattgatccttctaacatgctgttgacatcacacctaatattcagagggaatgggcaaggt atgagggaaggaaataaaaaataaaataaataaaatagaatgacacaaatttgagttttgtgaaccc ctgaacagatggtcttaaggacgttatctggaactggagaaaagcagagttgagagacaattctata gattaaatcctggtaaggacaaacattgccattagaagaaaagcttcaaaatagacctgtggcagat gtcacatgagtagaatttctgcccagccttaactgcattcagaggataatatcaatgaactaaactt gaactaaaaattttttaaacaaaaagttataaatgaagacacatggttgtgaatacaatgatgtatt tctttattttcacatacactctagctaaaagagcaagagtacacatcaacaaaaatggaaacaaggc tttggctgaaaaaaacatgcatttgacaaatcatgttaatagctagacaagaagaaagttagctttg taaacttctacttcatttgattcagagaaacagagcatgagttttcttaaaagtaacaagaaaa SEQ.ID NO. 171 GCTTAAAAGAGTCCTCCTGTGGC SEQ.ID NO. 172 TGGACATTGTTCTTAAAGTGTGG SEQ.ID NO. 173 AGGTTTTATGGCCACCGTCAG SEQ.ID NO. 174 ATCCTATACCGCTCGGTTATGC SEQ.ID NO. 175 GGGCGGCGGCTCTTTCCTCCTC SEQ.ID NO. 176 GCTAGCGGCCCCATACTCG SEQ.ID NO. 177 ACACTGGATGCCCTGAATGACACA SEQ.ID NO. 178 GCTTTGGCCCTTTTTGCTAA SEQ.ID NO. 179 CCCACTTCTGTCTTACTGCATC SEQ.ID NO. 180 CATAGTACTCCAGGGCTTATTC SEQ.ID NO. 181 AACGATTGCCCGGATTGATGACA SEQ.ID NO. 182 TACTTGAGGCTGGGGTGGGAGATG SEQ.ID NO. 183 CACTACGCCAGGCACCCCCAAA SEQ.ID NO. 184 CGAGGCGCACGGCAGTCT SEQ.ID NO. 185 ATCCGTTGCTGCAGCTCGTTCCTC SEQ.ID NO. 186 ACCCTGCTGACCTTCTTCCATTCC SEQ.ID NO. 187 TCGGAGGAGGGCTGGCTGGTGTTT SEQ.ID NO. 188 CTTGGGCGTCTTGGAGCGGTTCTG SEQ.ID NO. 189 AGAGCCTATTGAAGATGAACAG SEQ.ID NO. 190 TGATTGCCCCGGATCCTCTTAGG SEQ.ID NO. 191 GGACAAATACGACGACGAGG SEQ.ID NO. 192 GGTTTCTTGGGTAGTGGGC SEQ.ID NO. 193 CCCCGGAGAAGGAAGAGCAGTA SEQ.ID NO. 194 CGAAAGCCGGCAGTTAGTTATTGA SEQ.ID NO. 195 GGCGGGCAACGAATTCCAGGTGTC SEQ.ID NO. 196 TCAGAGGTTCGTCGCATTTGTCCA SEQ.ID NO. 197 CAACAGTCATGATGTGTGGATG SEQ.ID NO. 198 ACTGCACCTTGTCCGTGTTGAC SEQ.ID NO. 199 CCGGCTGGCTGCTTTGTTTA SEQ.ID NO. 200 ATGATCAGCAGGTTCGTTGGTAGG SEQ.ID NO. 201 ATGCCGGAAGTGAATGTGG SEQ.ID NO. 202 GGTGACTCCGCCTTTTGAT SEQ.ID NO. 203 ACATTCGCTTCTCCATCTGG SEQ.ID NO. 204 TGTCACGGAAGGGAACCAGG SEQ.ID NO. 205 ACGCTGCCTCTGGGTCACTT SEQ.ID NO. 206 TTGGCAAATCAATGGCTTGTAAT SEQ.ID NO. 207 ATGGCTTGGGTCATCAGGAC SEQ.ID NO. 208 GTGTCACTGGGCGTAAGATACTG SEQ.ID NO. 209 CACCAAATCAGCTGCTACTACTCC SEQ.ID NO. 210 GATAAACCCCAAAGCAGAAAGATT SEQ.ID NO. 211 CGAGATTCCGTGGGCGTAGG SEQ.ID NO. 212 TGAGTGGGAGCTTCGTAGG SEQ.ID NO. 213 TCAGAGTGGACGTTGGATTAC SEQ.ID NO. 214 TGCTTGAAATGTAGGAGAACA SEQ.ID NO. 215 GAGGGGCATCAATCACACCGAGAA SEQ.ID NO. 216 CCCCACCGCCCACCCATTTAGG SEQ.ID NO. 217 GGGGGCACCAGAGGCAGTAA SEQ.ID NO. 218 GGTTGTGGCGGGGGCAGTTGTG SEQ.ID NO. 219 ACAGACTCCTGTACTGCAAACC SEQ.ID NO. 220 TACCGGTTCGTCCTCTTCCTC SEQ.ID NO. 221 GAAGTTCCTCACGCCCTGCTATC SEQ.ID NO. 222 CTGGCTGGTGACCTGCTTTGAGTA SEQ.ID NO. 223 TAGGCGCGCCTGACATACAGCAATGCCAGTT SEQ.ID NO. 224 TAAGAATGCGGCCGCGCCACATCTTGAACACTTTGC SEQ.ID NO. 225 TGGGGAGGAGTTTGAGGAGCAGAC SEQ.ID NO. 226 GTGGGACGGAGGGGGCAGTGAAG SEQ.ID NO. 227 GCAACTATTCGGAGCGCGTG SEQ.ID NO. 228 CCAGCAGCTTGTTGAGCTCC SEQ.ID NO. 229 GGAGGAGCTAAGCGTCATCGC SEQ.ID NO. 230 TCGCTTCAGCGCGTAGACC SEQ.ID NO. 231 TATTAGTTGGGATGGTGGTAGCAC SEQ.ID NO. 232 GAGAATTCGAGTCGACGATGAC SEQ.ID NO. 233 GAAATTGTGTTGACGCAGTCTCC SEQ.ID NO. 234 AGGCACACAACAGAGGCAGTTC SEQ.ID NO. 235 GTACATCAACCTCCTGCTGTCC
SEQ.ID NO. 236 GACATCTCCAAGTCCCAGCATG SEQ.ID NO. 237 AGTCTCTCACTGTGCCTTATGCC SEQ.ID NO. 238 AGTCCTAAGAACTGTAAACG SEQ.ID NO. 239 CATCTATACGTGGATTGAGGA SEQ.ID NO. 240 ATAGGTACCAGGTATGAGCTG SEQ.ID NO. 241 TGTCCACATCATCATCGTCATCC SEQ.ID NO. 242 TGTCACTGGTCGGTCGCTGAGG SEQ.ID NO. 243 CATGGGGCTTAAGATGTC SEQ.ID NO. 244 GTCGATTTCTCCATCATCTG SEQ.ID NO. 245 AAGAGGCGCTCTACTAGCCG SEQ.ID NO. 246 CTTTCCACATGGAACACAGG SEQ.ID NO. 247 CATTTTCCTGGAATTTGATACAG SEQ.ID NO. 248 GTAGAGAGTTTATTTGGGCCAAG SEQ.ID NO. 249 CATCTATGGTAACTACAATCG SEQ.ID NO. 250 GTAGAAGTCACTGATCAGACAC SEQ.ID NO. 251 CTGCCTGCCAACCTTTCCATTTCT SEQ.ID NO. 252 TGAGCAGCCACAGCAGCATTAGG SEQ.ID NO. 253 CACCTGATCAGGTGGATAAGG SEQ.ID NO. 254 TCCCAGGTAGAAGGTGGAATCC
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Sequence CWU
1
1
2541114DNAHomo sapiens 1ctggaagctg aagaatcacc ggcttcagtg acatggaacc
cagcgatttg atttttgacg 60agtatcgggt gactttgagg tggtcaagaa accacacttt
aagaacaatg tcca 11422058DNAHomo sapiens 2gcacgaggaa gccacagatc
tcttaagaac tttctgtctc caaaccgtgg ctgctcgata 60aatcagacag aacagttaat
cctcaattta agcctgatct aacccctaga aacagatata 120gaacaatgga agtgacaaca
agattgacat ggaatgatga aaatcatctg cgcaactgct 180tggaaatgtt tctttgagtc
ttctctataa gtctagtgtt catggaggta gcattgaaga 240tatggttgaa agatgcagcc
gtcagggatg tactataaca atggcttaca ttgattacaa 300tatgattgta gcctttatgc
ttggaaatta tattaattta cgtgaaagtt ctacagagcc 360aaatgattcc ctatggtttt
cacttcaaaa gaaaaatgac accactgaaa tagaaacttt 420actcttaaat acagcaccaa
aaattattga tgagcaactg gtgtgtcgtt tatcgaaaac 480ggatattttc attatatgtc
gagataataa aatttatcta gataaaatga taacaagaaa 540cttgaaacta aggttttatg
gccaccgtca gtatttggaa tgtgaagttt ttcgagttga 600aggaattaag gataacctag
acgacataaa gaggataatt aaagccagag agcacagaaa 660taggcttcta gcagacatca
gagactatag gccctatgca gacttggttt cagaaattcg 720tattcttttg gtgggtccag
ttgggtctgg aaagtccagt tttttcaatt cagtcaagtc 780tatttttcat ggccatgtga
ctggccaagc cgtagtgggg tctgatacca ccagcataac 840cgagcggtat aggatatatt
ctgttaaaga tggaaaaaat ggaaaatctc tgccatttat 900gttgtgtgac actatggggc
tagatggggc agaaggagca ggactgtgca tggatgacat 960tccccacatc ttaaaaggtt
gtatgccaga cagatatcag tttaattccc gtaaaccaat 1020tacacctgag cattctactt
ttatcacctc tccatctctg aaggacagga ttcactgtgt 1080ggcttatgtc ttagacatca
actctattga caatctctac tctaaaatgt tggcaaaagt 1140gaagcaagtt cacaaagaag
tattaaactg tggtatagca tatgtggcct tgcttactaa 1200agtggatgat tgcagtgagg
ttcttcaaga caacttttta aacatgagta gatctatgac 1260ttctcaaagc cgggtcatga
atgtccataa aatgctaggc attcctattt ccaatatttt 1320gatggttgga aattatgctt
cagatttgga actggacccc atgaaggata ttctcatcct 1380ctctgcactg aggcagatgc
tgcgggctgc agatgatttt ttagaagatt tgcctcttga 1440ggaaactggt gcaattgaga
gagcgttaca gccctgcatt tgagataagt tgccttgatt 1500ctgacatttg gcccagcctg
tactggtgtg ccgcaatgag agtcaatctc tattgacagc 1560ctgcttcaga ttttgctttt
gttcgttttg ccttctgtcc ttggaacagt catatctcaa 1620gttcaaaggc caaaacctga
gaagcggtgg gctaagatag gtcctactgc aaaccacccc 1680tccatatttc cgtaccattt
acaattcagt ttctgtgaca tctttttaaa ccactggagg 1740aaaaatgaga tattctctaa
tttattcttc tataacactc tatatagagc tatgtgagta 1800ctaatcacat tgaataatag
ttataaaatt attgtataga catctgcttc ttaaacagat 1860tgtgagttct ttgagaaaca
gcgtggattt tacttatctg tgtattcaca gagcttagca 1920cagtgcctgg taatgagcaa
gcatacttgc cattactttt ccttcccact ctctccaaca 1980tcacattcac tttaaatttt
tctgtatata gaaaggaaaa ctagcctggg caacatgatg 2040aaaccccatc tccactgc
205831991DNAHomo sapiens
3gccgagcgga gaggccgccc attggccggc cagcgccacg tggccgcccc cgccggtata
60ttaggccact atttacctcc ggctcactcg ccatgggttg gagagggcag ctcgggtaga
120gagggctggc ggagcggcgc agacggcggc agtcctgctc agcctctgcc cggctccgta
180ctccggcccc ggcctgcgcc ctcagaaagg tggggcccga accatgagct cctacctgga
240gtacgtgtca tgcagcagca gcggcggggt cggcggcgac gtgctcagct tggcacccaa
300gttctgccgc tccgacgccc ggcccgtggc tctgcagccc gccttccctc tgggcaacgg
360cgacggcgcc ttcgtcagct gtctgcccct ggccgccgcc cgaccctcgc cttcgccccc
420ggccgccccc gcgcggccgt ccgtaccgcc tccggccgcg ccccagtacg cgcagtgcac
480cctggagggg gcctacgaac ctggtgccgc acctgccgcg gcagctgggg gcgcggacta
540cggcttcctg gggtccgggc cggcgtacga cttcccgggc gtgctggggc gggcggccga
600cgacggcggg tctcacgtcc actacgccac ctcggccgtc ttctcgggcg gcggctcttt
660cctcctcagc ggccaggtgg attacgcggc cttcggcgaa cccggccctt ttccggcttg
720tctcaaagcg tcagccgacg gccaccctgg tgctttccag accgcatccc cggccccagg
780cacctacccc aagtccgtct ctcccgcctc cggcctccct gccgccttca gcacgttcga
840gtggatgaaa gtgaagagga atgcctctaa gaaaggtaaa ctcgccgagt atggggccgc
900tagcccctcc agcgcgatcc gcacgaattt cagcaccaag caactgacag aactggaaaa
960agagtttcat ttcaataagt acttaactcg agcccggcgc atcgagatag ccaactgctt
1020gcacctgaat gacacgcaag tcaaaatctg gttccagaac cgcaggatga aacagaagaa
1080aagggaacga gaagggcttc tggccacggc cattcctgtg gctcccctcc aacttcccct
1140ctctggaaca acccccacta agtttatcaa gaaccccggc agcccttctc agtcccaaga
1200gccttcgtga ggccggtact tggggccgaa aaactgtggc ctgcagaagt cccaggcgac
1260ccccatccct atctagactt aggagctcag tttgggatgg aggtgggaga acaaaaatga
1320atagggattt cacttgggaa atgaagtact ttagttggct tccgagttcc agactatatg
1380tccagatatt aattgactgt cttgtaagcc acttgtttgg ttatgatttg tgtcttatca
1440gggaaaaggt gcccagctgc cagcccagct ccgctgctat ctttgcctca cttagtcatg
1500tgcaattcgc gttgcagagt ggcagaccat tagttgctga gttctgtcag cactctgatg
1560tgctcagaag agcacctgcc caaagttttt ctggttttaa tttaaaggac aaggctacat
1620atattcagct ttttgagatg accaaagcta gttagggtct ccttgatgta gctaagctgc
1680ttcagtgatc ttcacatttg cactccagtt tttttttctt taaaaaagcg gtttctacct
1740ctctatgtgc ctgagtgatg atacaatcgc tgtttagtta ctagatgaac aaatccacag
1800aatgggtaaa gagtagaatc tgaactatat cttgacaaat attattcaaa cttgaatgta
1860aatatataca gtatgtatat tttttaaaaa gatttgcttg caatgacctt ataagtgaca
1920tttaatgtca tagcatgtaa agggtttttt ttgtaataaa aattatagaa tctgcaaaaa
1980aaaaaaaaaa a
19914539DNAHomo sapiens 4cagcctccag agcaccagca ctggcactgg cactggcaca
cgctatggca aatgaagtgc 60aagacctgct ctcccctcgg aaagggggac atcctcctgc
agtaaaagct ggaggaatga 120gaatttccaa aaaacaagaa attggcacct tggaaagaca
taccaaaaaa acaggattcg 180agaaaacaag tgccattgca aatgttgcca aaatacagac
actggatgcc ctgaatgaca 240cactggagaa gctcaactat aaatttccag caacagtgca
catggcacat caaaaaccca 300cacctgctct ggaaaaggtt gttccactga aaaggatcta
cattattcag cagcctcgaa 360aatgttaagc ctggatttaa aacacagccg tctggccagc
tgcctcgaat atctgacagc 420ttagcaaaaa gggccaaagc tttccatagg cgtgctgcac
ttgcttggta aattaaacag 480cttttgtatc ttcccctttg actttaggta ataaagcatc
caaacttgta aaaaaaaaa 53951690DNAHomo sapiens 5gtaactgaaa atccacaaga
cagaatagcc agatctcaga ggagcctggc taagcaaaac 60cctgcagaac ggctgcctaa
tttacagcaa ccatgagtac aaatggtgat gatcatcagg 120tcaaggatag tctggagcaa
ttgagatgtc actttacatg ggagttatcc attgatgacg 180atgaaatgcc tgatttagaa
aacagagtct tggatcagat tgaattccta gacaccaaat 240acagtgtggg aatacacaac
ctactagcct atgtgaaaca cctgaaaggc cagaatgagg 300aagccctgaa gagcttaaaa
gaagctgaaa acttaatgca ggaagaacat gacaaccaag 360caaatgtgag gagtctggtg
acctggggca actttgcctg gatgtattac cacatgggca 420gactggcaga agcccagact
tacctggaca aggtggagaa catttgcaag aagctttcaa 480atcccttccg ctatagaatg
gagtgtccag aaatagactg tgaggaagga tgggccttgc 540tgaagtgtgg aggaaagaat
tatgaacggg ccaaggcctg ctttgaaaag gtgcttgaag 600tggaccctga aaaccctgaa
tccagcgctg ggtatgcgat ctctgcctat cgcctggatg 660gctttaaatt agccacaaaa
aatcacaagc cattttcttt gcttccccta aggcaggctg 720tccgcttaaa tccagacaat
ggatatatta aggttctcct tgccctgaag cttcaggatg 780aaggacagga agctgaagga
gaaaagtaca ttgaagaagc tctagccaac atgtcctcac 840agacctatgt ctttcgatat
gcagccaagt tttaccgaag aaaaggctct gtggataaag 900ctcttgagtt attaaaaaag
gccttgcagg aaacacccac ttctgtctta ctgcatcacc 960agatagggct ttgctacaag
gcacaaatga tccaaatcaa ggaggctaca aaagggcagc 1020ctagagggca gaacagagaa
aagctagaca aaatgataag atcagccata tttcattttg 1080aatctgcagt ggaaaaaaag
cccacatttg aggtggctca tctagacctg gcaagaatgt 1140atatagaagc aggcaatcac
agaaaagctg aagagaattt tcaaaaattg ttatgcatga 1200aaccagtggt agaagaaaca
atgcaagaca tacatttcca ctatggtcgg tttcaggaat 1260ttcaaaagaa atctgacgtc
aatgcaatta tccattattt aaaagctata aaaatagaac 1320aggcatcatt aacaagggat
aaaagtatca attctttgaa gaaattggtt ttaaggaaac 1380ttcggagaaa ggcattagat
ctggaaagct tgagcctcct tgggttcgtc tacaaattgg 1440aaggaaatat gaatgaagcc
ctggagtact atgagcgggc cctgagactg gctgctgact 1500ttgagaactc tgtgagacaa
ggtccttagg cacccagata tcagccactt tcacatttca 1560tttcatttta tgctaacatt
tactaatcat cttttctgct tactgttttc agaaacatta 1620taattcactg taatgatgta
attcttgaat aataaatctg acaaaaaaaa aaaaaaaaaa 1680aaaaaaaaaa
169063783DNAHomo sapiens
6cccgcgagcg tccatccatc tgtccggccg actgtccagc gaaaggggct ccaggccggg
60cgcacgtcga cccgggggac cgaggccagg agaggggcca agagcgcggc tgacccttgc
120gggccggggc aggggacggt ggccgcggcc atgcagtcct gtgccagggc gtgggggctg
180cgcctgggcc gcggggtcgg gggcggccgc cgcctggctg ggggatcggg gccgtgctgg
240gcgccgcgga gccgggacag cagcagtggc ggcggggaca gcgccgcggc tggggcctcg
300cgcctcctgg agcgccttct gcccagacac gacgacttcg ctcggaggca catcggccct
360ggggacaaag accagagaga gatgctgcag accttggggc tggcgagcat tgatgaattg
420atcgagaaga cggtccctgc caacatccgt ttgaaaagac ccttgaaaat ggaagaccct
480gtttgtgaaa atgaaatcct tgcaactctg catgccattt caagcaaaaa ccagatctgg
540agatcgtata ttggcatggg ctattataac tgctcagtgc cacagacgat tttgcggaac
600ttactggaga actcaggatg gatcacccag tatactccat accagcctga ggtgtctcag
660gggaggctgg agagtttact caactaccag accatggtgt gtgacatcac aggcctggac
720atggccaatg catccctgct ggatgagggg actgcagccg cagaggcact gcagctgtgc
780tacagacaca acaagaggag gaaatttctc gttgatcccc gttgccaccc acagacaata
840gctgttgtcc agactcgagc caaatatact ggagtcctca ctgagctgaa gttaccctgt
900gaaatggact tcagtggaaa agatgtcagt ggagtgttgt tccagtaccc agacacggag
960gggaaggtgg aagactttac ggaactcgtg gagagagctc atcagagtgg gagcctggcc
1020tgctgtgcta ctgacctttt agctttgtgc atcttgaggc cacctggaga atttggggta
1080gacatcgccc tgggcagctc ccagagattt ggagtgccac tgggctatgg gggaccccat
1140gcagcatttt ttgctgtccg agaaagcttg gtgagaatga tgcctggaag aatggtgggg
1200gtaacaagag atgccactgg gaaagaagtg tatcgtcttg ctcttcaaac cagggagcaa
1260cacattcgga gagacaaggc taccagcaac atctgtacag ctcaggccct cttggcgaat
1320atggctgcca tgtttcgaat ctaccatggt tcccatgggc tggagcatat tgctaggagg
1380gtacataatg ccactttgat tttgtcagaa ggtctcaagc gagcagggca tcaactccag
1440catgacctgt tctttgatac cttgaagatt cattgtggct gctcagtgaa ggaggtcttg
1500ggcagggcgg ctcagcggca gatcaatttt cggctttttg aggatggcac acttggtatt
1560tctcttgatg aaacagtcaa tgaaaaagat ctggacgatt tgttgtggat ctttggttgt
1620gagtcatctg cagaactggt tgctgaaagc atgggagagg agtgcagagg tattccaggg
1680tctgtgttca agaggaccag cccgttcctc acccatcaag tgttcaacag ctaccactct
1740gaaacaaaca ttgtccggta catgaagaaa ctggaaaata aagacatttc ccttgttcac
1800agcatgattc cactgggatc ctgcaccatg aaactgaaca gttcgtctga actcgcacct
1860atcacatgga aagaatttgc aaacatccac ccctttgtgc ctctggatca agctcaagga
1920tatcagcagc ttttccgaga gcttgagaag gatttgtgtg aactcacagg ttatgaccag
1980gtctgtttcc agccaaacag cggagcccag ggagaatatg ctggactggc cactatccga
2040gcctacttaa accagaaagg agaggggcac agaacggttt gcctcattcc gaaatcagca
2100catgggacca acccagcaag tgcccacatg gcaggcatga agattcagcc tgtggaggtg
2160gataaatatg ggaatatcga tgcagttcac ctcaaggcca tggtggataa gcacaaggag
2220aacctagcag ctatcatgat tacataccca tccaccaatg gggtgtttga agagaacatc
2280agtgacgtgt gtgacctcat ccatcaacat ggaggacagg tctacctaga cggggcaaat
2340atgaatgctc aggtgggaat ctgtcgccct ggagacttcg ggtctgatgt ctcgcaccta
2400aatcttcaca agaccttctg cattccccac ggaggaggtg gtcctggcat ggggcccatc
2460ggagtgaaga aacatctcgc cccgtttttg cccaatcatc ccgtcatttc actaaagcgg
2520aatgaggatg cctgtcctgt gggaaccgtc agtgcggccc catggggctc cagttccatc
2580ttgcccattt cctgggctta tatcaagatg atgggaggca agggtcttaa acaagccacg
2640gaaactgcga tattaaatgc caactacatg gccaagcgat tagaaacaca ctacagaatt
2700cttttcaggg gtgcaagagg ttatgtgggt catgaattta ttttggacac gagacccttc
2760aaaaagtctg caaatattga ggctgtggat gtggccaaga gactccagga ttatggattt
2820cacgccccta ccatgtcctg gcctgtggca gggaccctca tggtggagcc cactgagtcg
2880gaggacaagg cagagctgga cagattctgt gatgccatga tcagcattcg gcaggaaatt
2940gctgacattg aggagggccg catcgacccc agggtcaatc cgctgaagat gtctccacac
3000tccctgacct gcgttacatc ttcccactgg gaccggcctt attccagaga ggtggcagca
3060ttcccactcc ccttcatgaa accagagaac aaattctggc caacgattgc ccggattgat
3120gacatatatg gagatcagca cctggtttgt acctgcccac ccatggaagt ttatgagtct
3180ccattttctg aacaaaagag ggcgtcttct tagtcctctc tccctaagtt taaaggactg
3240atttgatgcc tctccccaga gcatttgata agcaagaaag atttcatctc ccaccccagc
3300ctcaagtagg agttttatat actgtgtata tctctgtaat ctctgtcaag gtaaatgtaa
3360atacagtagc tggagggagt cgaagctgat ggttggaaga cggatttgct ttggtattct
3420gcttccacat gtgccagttg cctggattgg gagccatttt gtgttttgcg tagaaagttt
3480taggaacttt aacttttaat gtggcaagtt tgcagatgtc atagaggcta tcctggagac
3540ttaatagaca tttttttgtt ccaaaagagt ccatgtggac tgtgccatct gtgggaaatc
3600ccagggcaaa tgtttacatt ttgtataccc tgaagaactc tttttcctct aatatgccta
3660atctgtaatc acatttctga gtgttttcct ctttttctgt gtgaggtttt tttttttttt
3720aatctgcatt tattagtatt ctaataaaag cattttgatc ggaaaaaaaa aaaaaaaaaa
3780aaa
378371670DNAHomo sapiens 7gggtcgtcat gatccggacc ccattgtcgg cctctgccca
tcgcctgctc ctcccaggct 60cccgcggccg acccccgcgc aacatgcagc ccacgggccg
cgagggttcc cgcgcgctca 120gccggcggta tctgcggcgt ctgctgctcc tgctactgct
gctgctgctg cggcagcccg 180taacccgcgc ggagaccacg ccgggcgccc ccagagccct
ctccacgctg ggctccccca 240gcctcttcac cacgccgggt gtccccagcg ccctcactac
cccaggcctc actacgccag 300gcacccccaa aaccctggac cttcggggtc gcgcgcaggc
cctgatgcgg agtttcccac 360tcgtggacgg ccacaatgac ctgccccagg tcctgagaca
gcgttacaag aatgtgcttc 420aggatgttaa cctgcgaaat ttcagccatg gtcagaccag
cctggacagg cttagagacg 480gcctcgtggg tgcccagttc tggtcagcct ccgtctcatg
ccagtcccag gaccagactg 540ccgtgcgcct cgccctggag cagattgacc tcattcaccg
catgtgtgcc tcctactctg 600aactcgagct tgtgacctca gctgaaggtc tgaacagctc
tcaaaagctg gcctgcctca 660ttggcgtgga gggtggtcac tcactggaca gcagcctctc
tgtgctgcgc agtttctatg 720tgctgggggt gcgctacctg acacttacct tcacctgcag
tacaccatgg gcagagagtt 780ccaccaagtt cagacaccac atgtacacca acgtcagcgg
attgacaagc tttggtgaga 840aagtagtaga ggagttgaac cgcctgggca tgatgataga
tttgtcctat gcatcggaca 900ccttgataag aagggtcctg gaagtgtctc aggctcctgt
gatcttctcc cactcagctg 960ccagagctgt gtgtgacaat ttgttgaatg ttcccgatga
tatcctgcag cttctgaaga 1020agaacggtgg catcgtgatg gtgacactgt ccatgggggt
gctgcagtgc aacctgcttg 1080ctaacgtgtc cactgtggca gatcactttg accacatcag
ggcagtcatt ggatctgagt 1140tcatcgggat tggtggaaat tatgacggga ctggccggtt
ccctcagggg ctggaggatg 1200tgtccacata cccagtcctg atagaggagt tgctgagtcg
tagctggagc gaggaagagc 1260ttcaaggtgt ccttcgtgga aacctgctgc gggtcttcag
acaagtggaa aaggtgagag 1320aggagagcag ggcgcagagc cccgtggagg ctgagtttcc
atatgggcaa ctgagcacat 1380cctgccactc ccacctcgtg cctcagaatg gacaccaggc
tactcatctg gaggtgacca 1440agcagccaac caatcgggtc ccctggaggt cctcaaatgc
ctccccatac cttgttccag 1500gccttgtggc tgctgccacc atcccaacct tcacccagtg
gctctgctga cacagtcggt 1560ccccgcagag gtcactgtgg caaagcctca caaagccccc
tctcctagtt cattcacaag 1620catatgctga gaataaacat gttacacatg gaaaaaaaaa
aaaaaaaaaa 16708817DNAHomo sapiens 8agtcctgcgt ccgggccccg
aggcgcagca gggcaccagg tggagcacca gctacgcgtg 60gcgcagcgca gcgtccctag
caccgagcct cccgcagccg ccgagatgct gcgaacagag 120agctgccgcc ccaggtcgcc
cgccggacag gtggccgcgg cgtccccgct cctgctgctg 180ctgctgctgc tcgcctggtg
cgcgggcgcc tgccgaggtg ctccaatatt acctcaagga 240ttacagcctg aacaacagct
acagttgtgg aatgagatag atgatacttg ttcgtctttt 300ctgtccattg attctcagcc
tcaggcatcc aacgcactgg aggagctttg ctttatgatt 360atgggaatgc taccaaagcc
tcaggaacaa gatgaaaaag ataatactaa aaggttctta 420tttcattatt cgaagacaca
gaagttgggc aagtcaaatg ttgtgtcgtc agttgtgcat 480ccgttgctgc agctcgttcc
tcacctgcat gagagaagaa tgaagagatt cagagtggac 540gaagaattcc aaagtccctt
tgcaagtcaa agtcgaggat attttttatt caggccacgg 600aatggaagaa ggtcagcagg
gttcatttaa aatggatgcc agctaatttt ccacagagca 660atgctatgga atacaaaatg
tactgacatt ttgttttctt ctgaaaaaaa tccttgctaa 720atgtactctg ttgaaaatcc
ctgtgttgtc aatgttctca gttgtaacaa tgttgtaaat 780gttcaatttg ttgaaaatta
aaaaatctaa aaataaa 81791878DNAHomo sapiens
9gggcgcagcg gggcccgtct gcagcaagtg accgacggcc gggacggccg cctgccccct
60ctgccacctg gggcggtgcg ggcccggagc ccggagcccg ggtagcgcgt agagccggcg
120cgatgcacgt gcgctcactg cgagctgcgg cgccgcacag cttcgtggcg ctctgggcac
180ccctgttcct gctgcgctcc gccctggccg acttcagcct ggacaacgag gtgcactcga
240gcttcatcca ccggcgcctc cgcagccagg agcggcggga gatgcagcgc gagatcctct
300ccattttggg cttgccccac cgcccgcgcc cgcacctcca gggcaagcac aactcggcac
360ccatgttcat gctggacctg tacaacgcca tggcggtgga ggagggcggc gggcccggcg
420gccagggctt ctcctacccc tacaaggccg tcttcagtac ccagggcccc cctctggcca
480gcctgcaaga tagccatttc ctcaccgacg ccgacatggt catgagcttc gtcaacctcg
540tggaacatga caaggaattc ttccacccac gctaccacca tcgagagttc cggtttgatc
600tttccaagat cccagaaggg gaagctgtca cggcagccga attccggatc tacaaggact
660acatccggga acgcttcgac aatgagacgt tccggatcag cgtttatcag gtgctccagg
720agcacttggg cagggaatcg gatctcttcc tgctcgacag ccgtaccctc tgggcctcgg
780aggagggctg gctggtgttt gacatcacag ccaccagcaa ccactgggtg gtcaatccgc
840ggcacaacct gggcctgcag ctctcggtgg agacgctgga tgggcagagc atcaacccca
900agttggcggg cctgattggg cggcacgggc cccagaacaa gcagcccttc atggtggctt
960tcttcaaggc cacggaggtc cacttccgca gcatccggtc cacggggagc aaacagcgca
1020gccagaaccg ctccaagacg cccaagaacc aggaagccct gcggatggcc aacgtggcag
1080agaacagcag cagcgaccag aggcaggcct gtaagaagca cgagctgtat gtcagcttcc
1140gagacctggg ctggcaggac tggatcatcg cgcctgaagg ctacgccgcc tactactgtg
1200agggggagtg tgccttccct ctgaactcct acatgaacgc caccaaccac gccatcgtgc
1260agacgctggt ccacttcatc aacccggaaa cggtgcccaa gccctgctgt gcgcccacgc
1320agctcaatgc catctccgtc ctctacttcg atgacagctc caacgtcatc ctgaagaaat
1380acagaaacat ggtggtccgg gcctgtggct gccactagct cctccgagaa ttcagaccct
1440ttggggccaa gtttttctgg atcctccatt gctcgccttg gccaggaacc agcagaccaa
1500ctgccttttg tgagaccttc ccctccctat ccccaacttt aaaggtgtga gagtattagg
1560aaacatgagc agcatatggc ttttgatcag tttttcagtg gcagcatcca atgaacaaga
1620tcctacaagc tgtgcaggca aaacctagca ggaaaaaaaa acaacgcata aagaaaaatg
1680gccgggccag gtcattggct gggaagtctc agccatgcac ggactcgttt ccagaggtaa
1740ttatgagcgc ctaccagcca ggccacccag ccgtgggagg aagggggcgt ggcaaggggt
1800gggcacattg gtgtctgtgc gaaaggaaaa ttgacccgga agttcctgta ataaatgtca
1860caataaaacg aatgaatg
187810836DNAHomo sapiens 10ccggtgagtc gccggcgctg cagagggagg cggcactggt
ctcgacgtgg ggcggccagc 60gatgaagccg cccagttcaa tacaaacaag tgagtttgac
tcatcagatg aagagcctat 120tgaagatgaa cagactccaa ttcatatatc atggctatct
ttgtcacgag tgaattgttc 180tcagtttctc ggtttatgtg ctcttccagg ttgtaaattt
aaagatgtta gaagaaatgt 240ccaaaaagat acagaagaac taaagagctg tggtatacaa
gacatatttg ttttctgcac 300cagaggggaa ctgtcaaaat atagagtccc aaaccttctg
gatctctacc agcaatgtgg 360aattatcacc catcatcatc caatcgcaga tggagggact
cctgacatag ccagctgctg 420tgaaataatg gaagagctta caacctgcct taaaaattac
cgaaaaacct taatacactg 480ctatggagga cttgggagat cttgtcttgt agctgcttgt
ctcctactat acctgtctga 540cacaatatca ccagagcaag ccatagacag cctgcgagac
ctaagaggat ccggggcaat 600acagaccatc aagcaataca attatcttca tgagtttcgg
gacaaattag ctgcacatct 660atcatcaaga gattcacaat caagatctgt atcaagataa
aggaattcaa atagcatata 720tatgaccatg tctgaaatgt cagttctcta gcataatttg
tattgaaatg aaaccaccag 780tgttatcaac ttgaatgtaa atgtacatgt gcagatattc
ctaaagtttt attgac 83611717DNAHomo sapiens 11agagcgatca tgtcgcacaa
acaaatttac tattcggaca aatacgacga cgaggagttt 60gagtatcgac atgtcatgct
gcccaaggac atagccaagc tggtccctaa aacccatctg 120atgtctgaat ctgaatggag
gaatcttggc gttcagcaga gtcagggatg ggtccattat 180atgatccatg aaccagaacc
tcacatcttg ctgttccggc gcccactacc caagaaacca 240aagaaatgaa gctggcaagc
tacttttcag cctcaagctt tacacagctg tccttacttc 300ctaacatctt tctgataaca
ttattatgtt gccttcttgt ttctcacttt gatatttaaa 360agatgttcaa tacactgttt
gaatgtgctg gtaactgctt tgcttcttga gtagagccac 420caccaccata gcccagccag
atgagtgctc tgtggaccca cagcctaagc tgagtgtgac 480cccagaagcc acgatgtgct
ctgtatccag aacacacttg gcagatggag gaagcatctg 540agtttgagac catggctgtt
acagggatca tgtaaacttg ctgtttttgt tttttctgcc 600gggtgttgta tgtgtggtga
cttgcggatt tatgtttcag tgtactggaa actttccatt 660ttattcaaga aatctgttca
tgttaaaagc cttgattaaa gaggaagttt ttataat 717122162DNAHomo Sapiens
12cgagttccgg cgaggcttca gggtacagct cccccgcagc cagaagccgg gcctgcagcg
60cctcagcacc gctccgggac accccacccg cttcccaggc gtgacctgtc aacagcaact
120tcgcggtgtg gtgaactctc tgaggaaaaa ccattttgat tattactctc agacgtgcgt
180ggcaacaagt gactgagacc tagaaatcca agcgttggag gtcctgaggc cagcctaagt
240cgcttcaaaa tggaacgaag gcgtttgtgg ggttccattc agagccgata catcagcatg
300agtgtgtgga caagcccacg gagacttgtg gagctggcag ggcagagcct gctgaaggat
360gaggccctgg ccattgccgc cctggagttg ctgcccaggg agctcttccc gccactcttc
420atggcagcct ttgacgggag acacagccag accctgaagg caatggtgca ggcctggccc
480ttcacctgcc tccctctggg agtgctgatg aagggacaac atcttcacct ggagaccttc
540aaagctgtgc ttgatggact tgatgtgctc cttgcccagg aggttcgccc caggaggtgg
600aaacttcaag tgctggattt acggaagaac tctcatcagg acttctggac tgtatggtct
660ggaaacaggg ccagtctgta ctcatttcca gagccagaag cagctcagcc catgacaaag
720aagcgaaaag tagatggttt gagcacagag gcagagcagc ccttcattcc agtagaggtg
780ctcgtagacc tgttcctcaa ggaaggtgcc tgtgatgaat tgttctccta cctcattgag
840aaagtgaagc gaaagaaaaa tgtactacgc ctgtgctgta agaagctgaa gatttttgca
900atgcccatgc aggatatcaa gatgatcctg aaaatggtgc agctggactc tattgaagat
960ttggaagtga cttgtacctg gaagctaccc accttggcga aattttctcc ttacctgggc
1020cagatgatta atctgcgtag actcctcctc tcccacatcc atgcatcttc ctacatttcc
1080ccggagaagg aagagcagta tatcgcccag ttcacctctc agttcctcag tctgcagtgc
1140ctgcaggctc tctatgtgga ctctttattt ttccttagag gccgcctgga tcagttgctc
1200aggcacgtga tgaacccctt ggaaaccctc tcaataacta actgccggct ttcggaaggg
1260gatgtgatgc atctgtccca gagtcccagc gtcagtcagc taagtgtcct gagtctaagt
1320ggggtcatgc tgaccgatgt aagtcccgag cccctccaag ctctgctgga gagagcctct
1380gccaccctcc aggacctggt ctttgatgag tgtgggatca cggatgatca gctccttgcc
1440ctcctgcctt ccctgagcca ctgctcccag cttacaacct taagcttcta cgggaattcc
1500atctccatat ctgccttgca gagtctcctg cagcacctca tcgggctgag caatctgacc
1560cacgtgctgt atcctgtccc cctggagagt tatgaggaca tccatggtac cctccacctg
1620gagaggcttg cctatctgca tgccaggctc agggagttgc tgtgtgagtt ggggcggccc
1680agcatggtct ggcttagtgc caacccctgt cctcactgtg gggacagaac cttctatgac
1740ccggagccca tcctgtgccc ctgtttcatg cctaactagc tgggtgcaca tatcaaatgc
1800ttcattctgc atacttggac actaaagcca ggatgtgcat gcatcttgaa gcaacaaagc
1860agccacagtt tcagacaaat gttcagtgtg agtgaggaaa acatgttcag tgaggaaaaa
1920acattcagac aaatgttcag tgaggaaaaa aaggggaagt tggggatagg cagatgttga
1980cttgaggagt taatgtgatc tttggggaga tacatcttat agagttagaa atagaatctg
2040aatttctaaa gggagattct ggcttgggaa gtacatgtag gagttaatcc ctgtgtagac
2100tgttgtaaag aaactgttga aaataaagag aagcaatgtg aagcaaaaaa aaaaaaaaaa
2160aa
216213634DNAHomo sapiens 13cggctgagag gcagcgaact catctttgcc agtacaggag
cttgtgccgt ggcccacagc 60ccacagccca cagccatggg ctgggacctg acggtgaaga
tgctggcggg caacgaattc 120caggtgtccc tgagcagctc catgtcggtg tcagagctga
aggcgcagat cacccagaag 180attggcgtgc acgccttcca gcagcgtctg gctgtccacc
cgagcggtgt ggcgctgcag 240gacagggtcc cccttgccag ccagggcctg ggccctggca
gcacggtcct gctggtggtg 300gacaaatgcg acgaacctct gagcatcctg gtgaggaata
acaagggccg cagcagcacc 360tacgaggtcc ggctgacgca gaccgtggcc cacctgaagc
agcaagtgag cgggctggag 420ggtgtgcagg acgacctgtt ctggctgacc ttcgagggga
agcccctgga ggaccagctc 480ccgctggggg agtacggcct caagcccctg agcaccgtgt
tcatgaatct gcgcctgcgg 540ggaggcggca cagagcctgg cgggcggagc taagggcctc
caccagcatc cgagcaggat 600caagggccgg aaataaaggc tgttgtaaga gaat
63414275DNAHomo sapiens 14tgcccacttg gcccctcctt
ccaaggtgta ctttacttcc tttcattcct gctctaatac 60tgtttagtac attttcactc
ctgctctaaa acttgcctca gtctctcact gtgccttatg 120cccctcagct gaattctttc
ttctgagcag gcaggaattg aggttgctgc agacgtgtat 180gcatttgcca ccagtaacat
actttggtgc cacatgacta ggatatgttc tctagtgcta 240acatgttcgt ttacagttct
taggactccc tgata 275151511DNAHomo sapiens
15ggccgcctgc gcgccgccaa cagcctagcg ctgcgccgcg tggccgccgc cttctcgctg
60gccccgctgg ccgagcgctg cggccgcgtc ctgcgtcagg ccttcgccga ggtggcgcgc
120cacgccgact tcctggagct ggcgcctgac gaggtggtgg cgctgctggc ggaccccgcg
180ctgggcgtgg cgcgcgagga ggccgtgttt gaagcggcca tgcgctgggt gcgccacgac
240gcgccggccc gccgcggcca gctgcgacgc ctgctggagc acgtgcgcct gccgctactg
300gcgcccgctt acttcctgga gaaggtggag gcggacgagc tgctgcaggc ctgcggcgag
360tgccgcccgc tgctgctcga ggctcgcgcc tgcttcatcc tgggccgcga ggccggtgcg
420ctgcggaccc ggccgcggag attcatggac ctagctgaag tgatcgtggt catcggcggt
480tgcgaccgca aaggtctcct gaagctgccc ttcgccgatg cctaccatcc agagagccag
540cggtggaccc cactgcccag cctgcccggc tacactcgct cagaattcgc cgcctgtgct
600ctccgcaatg acgtctacgt ctccggaggc cacatcaaca gtcatgatgt gtggatgttt
660agctcccatc tgcacacctg gatcaaggta gcctctctgc acaagggcag gtggaggcac
720aagatggcag ttgtgcaggg gcagctgttc gcggtgggtg gcttcgacgg cctgaggcgc
780ctgcacagcg tggagcgcta cgaccccttc tccaacacct gggcggccgc cgcgcccctc
840ccggaggccg tgagctcggc ggcggtggcg tcctgcgcgg gcaagctctt cgtgattggg
900ggcgccaggc agggcggcgt caacacggac aaggtgcagt gctttgaccc caaggaggac
960cggtggagcc tgcggtcacc agcacccttc tcacagcggt gtctcgaggc tgtctccctt
1020gaggacacca tctatgtcat ggggggtctc atgagcaaaa tcttcaccta tgatccaggc
1080acagatgtgt ggggggaggc agctgtcctc cccagccctg tggaaagctg tggagtcact
1140gtgtgtgacg ggaaggtcca catccttggc gggcgggatg atcgcggaga aagcaccgat
1200aaggtcttca cctttgaccc cagcagtggg caggtggagg tccagccatc cctgcagcgc
1260tgcaccagct cccacggctg tgtcaccatc atccagagct tgggcaggtg attcagattt
1320ggacagcctg agccaggagg cggagaggca ggcggagctc agatgcacac tctgctccct
1380catggcacct ccacgcaaac agcccttaac ttaatggtcc cttttcttgt ataaataaaa
1440tcttgttggg tctgtgttcc agctgcagtc tgccctgcct ggagatggaa tgtctaaaaa
1500aaaaaaaaaa a
151116375DNAHomo sapiens 16tttctagcag cctgggcaat ggcgggcgcc cctcccccag
cctcgctgct gccttgcagt 60ttgatctcag actgctgtgc tagcaatcag caagactccg
tgggcgtagg accctccgag 120ccaggttgca agaaagctca agtagcctat ggagaggatg
caaggcttcc agctgatgcc 180ctcagccagg ctcagtagca gccagaacta gcctaccaac
gaacctgctg atcatgtgca 240taagccacct tgaacgtcga tcctcctgcc tggtggagcc
atcccagctg atgccacatg 300aagcagacac aagctgtccc tactaagctc tgctcaagtt
ggatattcat gagtgaaata 360aatgactgtt actaa
375171811DNAHomo sapiens 17gagtcaccaa ggaaggcagc
ggcagctcca ctcagccagt acccagatac gctgggaacc 60ttccccagcc atggcttccc
tggggcagat cctcttctgg agcataatta gcatcatcat 120tattctggct ggagcaattg
cactcatcat tggctttggt atttcaggga gacactccat 180cacagtcact actgtcgcct
cagctgggaa cattggggag gatggaatcc agagctgcac 240ttttgaacct gacatcaaac
tttctgatat cgtgatacaa tggctgaagg aaggtgtttt 300aggcttggtc catgagttca
aagaaggcaa agatgagctg tcggagcagg atgaaatgtt 360cagaggccgg acagcagtgt
ttgctgatca agtgatagtt ggcaatgcct ctttgcggct 420gaaaaacgtg caactcacag
atgctggcac ctacaaatgt tatatcatca cttctaaagg 480caaggggaat gctaaccttg
agtataaaac tggagccttc agcatgccgg aagtgaatgt 540ggactataat gccagctcag
agaccttgcg gtgtgaggct ccccgatggt tcccccagcc 600cacagtggtc tgggcatccc
aagttgacca gggagccaac ttctcggaag tctccaatac 660cagctttgag ctgaactctg
agaatgtgac catgaaggtt gtgtctgtgc tctacaatgt 720tacgatcaac aacacatact
cctgtatgat tgaaaatgac attgccaaag caacagggga 780tatcaaagtg acagaatcgg
agatcaaaag gcggagtcac ctacagctgc taaactcaaa 840ggcttctctg tgtgtctctt
ctttctttgc catcagctgg gcacttctgc ctctcagccc 900ttacctgatg ctaaaataat
gtgcctcggc cacaaaaaag catgcaaagt cattgttaca 960acagggatct acagaactat
ttcaccacca gatatgacct agttttatat ttctgggagg 1020aaatgaattc atatctagaa
gtctggagtg agcaaacaag agcaagaaac aaaaagaagc 1080caaaagcaga aggctccaat
atgaacaaga taaatctatc ttcaaagaca tattagaagt 1140tgggaaaata attcatgtga
actagagtca actgtgtcag ggctaagaaa ccctggtttt 1200gagtagaaaa gggcctggaa
agaggggagc caacaaatct gtctgcttcc tcacattagt 1260cattggcaaa taagcattct
gtctctttgg ctgctgcctc agcacagaga gccagaactc 1320tatcgggcac caggataaca
tctctcagtg aacagagttg acaaggccta tgggaaatgc 1380ctgatgggat tatcttcagc
ttgttgagct tctaagtttc tttcccttca ttctaccctg 1440caagccaagt tctgtaagag
aaatgcctga gttctagctc aggttttctt actctgaatt 1500tagatctcca gaccctgcct
ggccacaatt caaattaagg caacaaacat ataccttcca 1560tgaagcacac acagactttt
gaaagcaagg acaatgactg cttgaattga ggccttgagg 1620aatgaagctt tgaaggaaaa
gaatactttg tttccagccc ccttcccaca ctcttcatgt 1680gttaaccact gccttcctgg
accttggagc cacggtgact gtattacatg ttgttataga 1740aaactgattt tagagttctg
atcgttcaag agaatgatta aatatacatt tcctaaaaaa 1800aaaaaaaaaa a
1811182972DNAHomo sapiens
18tcttcggacc taggctgccc tgccgtcatg tcgcaaggga tcctttctcc gccagcgggc
60ttgctgtccg atgacgatgt cgtagtttct cccatgtttg agtccacagc tgcagatttg
120gggtctgtgg tacgcaagaa cctgctatca gactgctctg tcgtctctac ctccctagag
180gacaagcagc aggttccatc tgaggacagt atggagaagg tgaaagtata cttgagggtt
240aggcccttgt taccttcaga gttggaacga caggaagatc agggttgtgt ccgtattgag
300aatgtggaga cccttgttct acaagcaccc aaggactcgt ttgccctgaa gagcaatgaa
360cggggaattg gccaagccac acacaggttc accttttccc agatctttgg gccagaagtg
420ggacaggcat ccttcttcaa cctaactgtg aaggagatgg taaaggatgt actcaaaggg
480cagaactggc tcatctatac atatggagtc actaactcag ggaaaaccca cacgattcaa
540ggtaccatca aggatggagg gattctcccc cggtccctgg cgctgatctt caatagcctc
600caaggccaac ttcatccaac acctgatctg aagcccttgc tctccaatga ggtaatctgg
660ctagacagca agcagatccg acaggaggaa atgaagaagc tgtccctgct aaatggaggc
720ctccaagagg aggagctgtc cacttccttg aagaggagtg tctacatcga aagtcggata
780ggtaccagca ccagcttcga cagtggcatt gctgggctct cttctatcag tcagtgtacc
840agcagtagcc agctggatga aacaagtcat cgatgggcac agccagacac tgccccacta
900cctgtcccgg caaacattcg cttctccatc tggatctcat tctttgagat ctacaacgaa
960ctgctttatg acctattaga accgcctagc caacagcgca agaggcagac tttgcggcta
1020tgcgaggatc aaaatggcaa tccctatgtg aaagatctca actggattca tgtgcaagat
1080gctgaggagg cctggaagct cctaaaagtg ggtcgtaaga accagagctt tgccagcacc
1140cacctcaacc agaactccag ccgcagtcac agcatcttct caatcaggat cctacacctt
1200cagggggaag gagatatagt ccccaagatc agcgagctgt cactctgtga tctggctggc
1260tcagagcgct gcaaagatca gaagagtggt gaacggttga aggaagcagg aaacattaac
1320acctctctac acaccctggg ccgctgtatt gctgcccttc gtcaaaacca gcagaaccgg
1380tcaaagcaga acctggttcc cttccgtgac agcaagttga ctcgagtgtt ccaaggtttc
1440ttcacaggcc gaggccgttc ctgcatgatt gtcaatgtga atccctgtgc atctacctat
1500gatgaaactc ttcatgtggc caagttctca gccattgcta gccagcttgt gcatgcccca
1560cctatgcaac tgggattccc atccctgcac tcgttcatca aggaacatag tcttcaggta
1620tcccccagct tagagaaagg ggctaaggca gacacaggcc ttgatgatga tattgaaaat
1680gaagctgaca tctccatgta tggcaaagag gagctcctac aagttgtgga agccatgaag
1740acactgcttt tgaaggaacg acaggaaaag ctacagctgg agatgcatct ccgagatgaa
1800atttgcaatg agatggtaga acagatgcaa cagcgggaac agtggtgcag tgaacatttg
1860gacacccaaa aggaactatt ggaggaaatg tatgaagaaa aactaaatat cctcaaggag
1920tcactgacaa gtttttacca agaagagatt caggagcggg atgaaaagat tgaagagcta
1980gaagctctct tgcaggaagc cagacaacag tcagtggccc atcagcaatc agggtctgaa
2040ttggccctac ggcggtcaca aaggttggca gcttctgcct ccacccagca gcttcaggag
2100gttaaagcta aattacagca gtgcaaagca gagctaaact ctaccactga agagttgcat
2160aagtatcaga aaatgttaga accaccaccc tcagccaagc ccttcaccat tgatgtggac
2220aagaagttag aagagggcca gaagaatata aggctgttgc ggacagagct tcagaaactt
2280ggtgagtctc tccaatcagc agagagagct tgttgccaca gcactggggc aggaaaactt
2340cgtcaagcct tgaccacttg tgatgacatc ttaatcaaac aggaccagac tctggctgaa
2400ctgcagaaca acatggtgct agtgaaactg gaccttcgga agaaggcagc atgtattgct
2460gagcagtatc atactgtgtt gaaactccaa ggccaggttt ctgccaaaaa gcgccttggt
2520accaaccagg aaaatcagca accaaaccaa caaccaccag ggaagaaacc attccttcga
2580aatttacttc cccgaacacc aacctgccaa agctcaacag actgcagccc ttatgcccgg
2640atcctacgct cacggcgttc ccctttactc aaatctgggc cttttggcaa aaagtactaa
2700ggctgtgggg aaagagaaga gcagtcatgg ccctgaggtg ggtcagctac tctcctgaag
2760aaataggtct cttttatgct ttaccatata tcaggaatta tatccaggat gcaatactca
2820gacactagct tttttctcac ttttgtatta taaccaccta tgtaatctca tgttgttgtt
2880tttttttatt tacttatatg atttctatgc acacaaaaac agttatatta aagatattat
2940tgttcacatt ttttattgaa aaaaaaaaaa aa
297219220DNAHomo sapiensmisc_feature(54)..(54)n is a, c, g, or t
19tccttgttac gatgaagaaa ctaaatctca ggaagaaaaa actaagtgaa gacnaaagaa
60ggatttgaac tgaggtttgt cagactctcg ggaccatgct gttgaaacca ctaaaccacg
120ctgcctctgg gtcacttggt aaacagcatt taaccattaa gaaagtcatt aataaaattc
180cttgtgctct ccttgagatt acaagccatt gatttgccaa
22020160DNAHomo sapiens 20gaacacagct aagcagatgg cttgggtcat caggacgtcc
attacatcca aaggaagaca 60gcctgtgacg tttcaaaagc aaaagtcccc taccagccag
tgaagctacc tgatttctca 120gtatcttacg cccagtgaca cgatctaccc tcaaaactta
160211172DNAHomo sapiens 21gagacattcc tcaattgctt
agacatattc tgagcctaca gcagaggaac ctccagtctc 60agcaccatga atcaaactgc
gattctgatt tgctgcctta tctttctgac tctaagtggc 120attcaaggag tacctctctc
tagaaccgta cgctgtacct gcatcagcat tagtaatcaa 180cctgttaatc caaggtcttt
agaaaaactt gaaattattc ctgcaagcca attttgtcca 240cgtgttgaga tcattgctac
aatgaaaaag aagggtgaga agagatgtct gaatccagaa 300tcgaaggcca tcaagaattt
actgaaagca gttagcaagg aaatgtctaa aagatctcct 360taaaaccaga ggggagcaaa
atcgatgcag tgcttccaag gatggaccac acagaggctg 420cctctcccat cacttcccta
catggagtat atgtcaagcc ataattgttc ttagtttgca 480gttacactaa aaggtgacca
atgatggtca ccaaatcagc tgctactact cctgtaggaa 540ggttaatgtt catcatccta
agctattcag taataactct accctggcac tataatgtaa 600gctctactga ggtgctatgt
tcttagtgga tgttctgacc ctgcttcaaa tatttccctc 660acctttccca tcttccaagg
gtactaagga atctttctgc tttggggttt atcagaattc 720tcagaatctc aaataactaa
aaggtatgca atcaaatctg ctttttaaag aatgctcttt 780acttcatgga cttccactgc
catcctccca aggggcccaa attctttcag tggctaccta 840catacaattc caaacacata
caggaaggta gaaatatctg aaaatgtatg tgtaagtatt 900cttatttaat gaaagactgt
acaaagtata agtcttagat gtatatattt cctatattgt 960tttcagtgta catggaataa
catgtaatta agtactatgt atcaatgagt aacaggaaaa 1020ttttaaaaat acagatagat
atatgctctg catgttacat aagataaatg tgctgaatgg 1080ttttcaaata aaaatgaggt
actctcctgg aaatattaag aaagactatc taaatgttga 1140aagatcaaaa ggttaataaa
gtaattataa ct 117222278DNAHomo sapiens
22tttgcaggtt tgatctcaga ctgctgtgct agtaatcagc gagattccgt gggcgtagga
60gcctccaagc caggtcctga agaaaatgaa gttgatgttt cagtgagaca cctgtatgcc
120agagagtaaa agggattatt gtggattcct gagaattttc tacatatgaa atcatgtcat
180ctatgaacag agatgggact gtctcgttgg aggaaaacaa gctcagggct cccactgatt
240ccacattatg ttgcaagctc ctacgaagct cccactca
278231743DNAHomo sapiens 23tttctccgca tgcgcgggat cccggatgtg gatcaagttg
gtgggaagcg tgcggtgccg 60cagcaatggc ggcgctcaca attgccacgg gtactggcaa
ttggttttcg gctttggcgc 120tcggggtgac tcttctcaaa tgccttctca tccccacata
ccattccaca gattttgaag 180tacaccgaaa ctggcttgct atcactcaca gtttgccaat
atcacagtgg tattatgagg 240caacttcaga gtggacgttg gattaccccc ctttctttgc
atggtttgag tatatcctgt 300cacatgttgc caaatatttt gatcaagaaa tgctgaatgt
ccataatttg aattactcca 360gctcaaggac cttacttttc cagagatttt ccgtcatctt
tatggatgta ctctttgtgt 420atgctgtccg tgagtgctgt aaatgcattg atggaaaaaa
agtgggtaaa gaacttacag 480aaaagccaaa atttattctg tcggtattac ttctgtggaa
cttcgggtta ttaattgtgg 540accatattca ttttcagtac aatggctttt tatttggatt
aatgctactc tccattgcac 600gattatttca gaaaaggcat atggaaggag catttctctt
tgctgttctc ctacatttca 660agcatatcta cctctatgta gcaccagctt atggtgtata
tctgctgcga tcctactgtt 720tcactgcaaa taaaccagat gggtctattc gatggaagag
tttcagcttt gttcgtgtta 780tttccctggg actggttgtt ttcttagttt ctgctctttc
attgggtcct ttcctggcct 840tgaatcagct gcctcaagtc ttttcccgac tctttccttt
caagaggggc ctctgtcatg 900catattgggc tccaaacttc tgggctttgt acaatgcttt
ggacaaagtg ctgtctgtca 960tcggtttgaa attgaaattt cttgatccca acaatattcc
caaggcctca atgacaagtg 1020gtttggttca gcagttccaa cacacagtcc ttccctcagt
gactcccttg gcaaccctca 1080tctgcacact gattgccata ttgccctcta ttttctgtct
ttggtttaaa ccccaagggc 1140ccagaggctt tctccgatgt ctaactcttt gtgccttgag
ctcctttatg tttgggtggc 1200atgttcatga aaaagccata cttctagcaa ttctcccaat
gagccttttg tctgtgggaa 1260aagcaggaga cgcttcgatt tttctgattc tgaccacaac
aggacattat tccctctttc 1320ctctgctctt cactgcacca gaacttccca ttaaaatctt
actcatgtta ctattcacca 1380tatatagtat ttcgtcactg aagactttat tcagacggag
tttcaccctt gttgcccagg 1440ctggagtgca atggcacgat ctcagctaac tgaaacctcc
gcctcccaga aaagaaaaac 1500ctctttttaa ttggatggaa actttctacc tgcttggcct
ggggcctctg gaagtctgct 1560gtgaatttgt attccctttc acctcctgga aggtgaagta
ccccttcatc cctttgttac 1620taacctcagt gtattgtgca gtaggcatca catatgcttg
gttcaaactg tatgtttcag 1680tattgattga ctctgctatt ggcaagacaa agaaacaatg
aataaaggaa ctgcttagat 1740atg
1743241382DNAHomo sapiens 24cattatgcta acagcataaa
catgcagggg gtgggagcag ggtcacaaaa gtgagtgttg 60tcaattctac ttggaatgaa
aggttgaaat aatttaaaca gtacgggaaa tgcagagcaa 120ttttctcctc tggtgacaat
atagtgtcca acacttggaa gtgattttta agaatgttta 180tttaaattaa aaggatggat
ttccaaggaa aaaaaataag gaaaaggaaa gaaaaaactg 240aacagaaaac gcaaaagtat
cagtttggtc actaaccttt gcaaggatac ctttttattt 300tctttaagat tcctgttgtt
tatacacaga ttttaagttt actcctactg ctgacccaag 360tgaaattcct tctccagtca
cagtgtcaac ctctaccccc caactgcaac gagagttttg 420aggggcatca atcacaccga
gaagtcacag cccctcaacc actgaggtgt gggggggtag 480ggatctgcat ttcttcatat
caaccccaca ctatagggca cctaaatggg tgggcggtgg 540gggagaccga ctcacttgag
tttcttgaag gcttcctggc ctccagccac gtaattgccc 600ccgctctgga tctggtctag
cttccggatt cggtggccag tccgcggggt gtagatgttc 660ctgacggccc caaagggtgc
ctgaacgccg ccggtcacct ccttcaggaa gacttcgaag 720ctggacacct tcttctcatg
gatgacgacg cggcgccccg cgtagaaggg gtccccgttg 780cggtacacaa gcacgctctt
cacgacgggc tgagacaggt ggctggacct ggcgctgctg 840ccgctcatct tccccgctgg
ccgccgcctc agctcgctgc ttcgcgtcgg gaggcacctc 900cgctgtccca gcggcctcac
cgcacccagg gcgcgggatc gcctcctgaa acgaacgaga 960aactgacgaa tccacaggtg
aaagagaagt aacggccgtg cgcctaggcg tccacccaga 1020ggagacacta ggagcttgca
ggactcggag tagacgctca agtttttcac cgtggcgtgc 1080acagccaatc aggacccgca
gtgcgcgcac cacaccaggt tcacctgcta cgggcagaat 1140caaggtggac agcttctgag
caggagccgg aaacgcgcgg ggccttcaaa caggcacgcc 1200tagtgagggc aggagagagg
aggacgcaca cacacacaca cacacaaata tggtgaaacc 1260caatttctta catcatatct
gtgctaccct ttccaaacag cctaattttt cttttctctc 1320ttcttgcacc tttacccctc
aatctcctgc ttcctcccaa attaaagcaa ttaagttcct 1380gg
1382251163DNAHomo sapiens
25ctcctccgag cactcgctca cggcgtcccc ttgcctggaa agataccgcg gtccctccag
60aggatttgag ggacagggtc ggagggggct cttccgccag caccggagga agaaagagga
120ggggctggct ggtcaccaga gggtggggcg gaccgcgtgc gctcggcggc tgcggagagg
180gggagagcag gcagcgggcg gcggggagca gcatggagcc ggcggcgggg agcagcatgg
240agccttcggc tgactggctg gccacggccg cggcccgggg tcgggtagag gaggtgcggg
300cgctgctgga ggcgggggcg ctgcccaacg caccgaatag ttacggtcgg aggccgatcc
360aggtcatgat gatgggcagc gcccgagtgg cggagctgct gctgctccac ggcgcggagc
420ccaactgcgc cgaccccgcc actctcaccc gacccgtgca cgacgctgcc cgggagggct
480tcctggacac gctggtggtg ctgcaccggg ccggggcgcg gctggacgtg cgcgatgcct
540ggggccgtct gcccgtggac ctggctgagg agctgggcca tcgcgatgtc gcacggtacc
600tgcgcgcggc tgcggggggc accagaggca gtaaccatgc ccgcatagat gccgcggaag
660gtccctcaga catccccgat tgaaagaacc agagaggctc tgagaaacct cgggaaactt
720agatcatcag tcaccgaagg tcctacaggg ccacaactgc ccccgccaca acccaccccg
780ctttcgtagt tttcatttag aaaatagagc ttttaaaaat gtcctgcctt ttaacgtaga
840tatatgcctt cccccactac cgtaaatgtc catttatatc attttttata tattcttata
900aaaatgtaaa aaagaaaaac accgcttctg ccttttcact gtgttggagt tttctggagt
960gagcactcac gccctaagcg cacattcatg tgggcatttc ttgcgagcct cgcagcctcc
1020ggaagctgtc gacttcatga caagcatttt gtgaactagg gaagctcagg ggggttactg
1080gcttctcttg agtcacactg ctagcaaatg gcagaaccaa agctcaaata aaaataaaat
1140aattttcatt cattcactca aaa
1163263685DNAHomo sapiens 26agtggactca cgcaggcgca ggagactaca cttcccagga
actccgggcc gcgttgttcg 60ctggtacctc cttctgactt ccggtattgc tgcggtctgt
agggccaatc gggagcctgg 120aattgctttc ccggcgctct gattggtgca ttcgactagg
ctgcctgggt tcaaaatttc 180aacgatactg aatgagtccc gcggcgggtt ggctcgcgct
tcgttgtcag atctgaggcg 240aggctaggtg agccgtggga agaaaagagg gagcagctag
ggcgcgggtc tccctcctcc 300cggagtttgg aacggctgaa gttcaccttc cagcccctag
cgccgttcgc gccgctaggc 360ctggcttctg aggcggttgc ggtgctcggt cgccgcctag
gcggggcagg gtgcgagcag 420gggcttcggg ccacgcttct cttggcgaca ggattttgct
gtgaagtccg tccgggaaac 480ggaggaaaaa aagagttgcg ggaggctgtc ggctaataac
ggttcttgat acatatttgc 540cagacttcaa gatttcagaa aaggggtgaa agagaagatt
gcaactttga gtcagacctg 600taggcctgat agactgatta aaccacagaa ggtgacctgc
tgagaaaagt ggtacaaata 660ctgggaaaaa cctgctcttc tgcgttaagt gggagacaat
gtcacaagtt aaaagctctt 720attcctatga tgccccctcg gatttcatca atttttcatc
cttggatgat gaaggagata 780ctcaaaacat agattcatgg tttgaggaga aggccaattt
ggagaataag ttactgggga 840agaatggaac tggagggctt tttcagggca aaactccttt
gagaaaggct aatcttcagc 900aagctattgt cacacctttg aaaccagttg acaacactta
ctacaaagag gcagaaaaag 960aaaatcttgt ggaacaatcc attccgtcaa atgcttgttc
ttccctggaa gttgaggcag 1020ccatatcaag aaaaactcca gcccagcctc agagaagatc
tcttaggctt tctgctcaga 1080aggatttgga acagaaagaa aagcatcatg taaaaatgaa
agccaagaga tgtgccactc 1140ctgtaatcat cgatgaaatt ctaccctcta agaaaatgaa
agtttctaac aacaaaaaga 1200agccagagga agaaggcagt gctcatcaag atactgctga
aaagaatgca tcttccccag 1260agaaagccaa gggtagacat actgtgcctt gtatgccacc
tgcaaagcag aagtttctaa 1320aaagtactga ggagcaagag ctggagaaga gtatgaaaat
gcagcaagag gtggtggaga 1380tgcggaaaaa gaatgaagaa ttcaagaaac ttgctctggc
tggaataggg caacctgtga 1440agaaatcagt gagccaggtc accaaatcag ttgacttcca
cttccgcaca gatgagcgaa 1500tcaaacaaca tcctaagaac caggaggaat ataaggaagt
gaactttaca tctgaactac 1560gaaagcatcc ttcatctcct gcccgagtga ctaagggatg
taccattgtt aagcctttca 1620acctgtccca aggaaagaaa agaacatttg atgaaacagt
ttctacatat gtgccccttg 1680cacagcaagt tgaagacttc cataaacgaa cccctaacag
atatcatttg aggagcaaga 1740aggatgatat taacctgtta ccctccaaat cttctgtgac
caagatttgc agagacccac 1800agactcctgt actgcaaacc aaacaccgtg cacgggctgt
gacctgcaaa agtacagcag 1860agctggaggc tgaggagctc gagaaattgc aacaatacaa
attcaaagca cgtgaacttg 1920atcccagaat acttgaaggt gggcccatct tgcccaagaa
accacctgtg aaaccaccca 1980ccgagcctat tggctttgat ttggaaattg agaaaagaat
ccaggagcga gaatcaaaga 2040agaaaacaga ggatgaacac tttgaatttc attccagacc
ttgccctact aagattttgg 2100aagatgttgt gggtgttcct gaaaagaagg tacttccaat
caccgtcccc aagtcaccag 2160cctttgcatt gaagaacaga attcgaatgc ccaccaaaga
agatgaggaa gaggacgaac 2220cggtagtgat aaaagctcaa cctgtgccac attatggggt
gccttttaag ccccaaatcc 2280cagaggcaag aactgtggaa atatgccctt tctcgtttga
ttctcgagac aaagaacgtc 2340agttacagaa ggagaagaaa ataaaagaac tgcagaaagg
ggaggtgccc aagttcaagg 2400cacttccctt gcctcatttt gacaccatta acctgccaga
gaagaaggta aagaatgtga 2460cccagattga acctttctgc ttggagactg acagaagagg
tgctctgaag gcacagactt 2520ggaagcacca gctggaagaa gaactgagac agcagaaaga
agcagcttgt ttcaaggctc 2580gtccaaacac cgtcatctct caggagccct ttgttcccaa
gaaagagaag aaatcagttg 2640ctgagggcct ttctggttct ctagttcagg aaccttttca
gctggctact gagaagagag 2700ccaaagagcg gcaggagctg gagaagagaa tggctgaggt
agaagcccag aaagcccagc 2760agttggagga ggccagacta caggaggaag agcagaaaaa
agaggagctg gccaggctac 2820ggagagaact ggtgcataag gcaaatccaa tacgcaagta
ccagggtctg gagataaagt 2880caagtgacca gcctctgact gtgcctgtat ctcccaaatt
ctccactcga ttccactgct 2940aaactcagct gtgagctgcg gataccgccc ggcaatggga
cctgctctta acctcaaacc 3000taggaccgtc ttgctttgtc attgggcatg gagagaaccc
atttctccag acttttacct 3060acccgtgcct gagaaagcat acttgacaac tgtggactcc
agttttgttg agaattgttt 3120tcttacatta ctaaggctaa taatgagatg taactcatga
atgtctcgat tagactccat 3180gtagttactt cctttaaacc atcagccggc cttttatatg
ggtcttcact ctgactagaa 3240tttagtctct gtgtcagcac agtgtaatct ctattgctat
tgccccttac gactctcacc 3300ctctccccac tttttttaaa aattttaacc agaaaataaa
gatagttaaa tcctaagata 3360gagattaagt catggtttaa atgaggaaca atcagtaaat
cagattctgt cctcttctct 3420gcataccgtg aatttatagt taaggatccc tttgctgtga
gggtagaaaa cctcaccaac 3480tgcaccagtg aggaagaaga ctgcgtggat tcatggggag
cctcacagca gccacgcagc 3540aggctctggg tggggctgcc gttaaggcac gttctttcct
tactggtgct gataacaaca 3600gggaaccgtg cagtgtgcat tttaagacct ggcctggaat
aaatacgttt tgtctttccc 3660tcaaaaaaaa aaaaaaaaaa aaaaa
368527823DNAHomo sapiens 27aaacgcgggc gggcgggccc
gcagtcctgc agttgcagtc gtgttctccg agttcctgtc 60tctctgccaa cgccgcccgg
atggcttccc aaaaccgcga cccagccgcc actagcgtcg 120ccgccgcccg taaaggagct
gagccgagcg ggggcgccgc ccggggtccg gtgggcaaaa 180ggctacagca ggagctgatg
accctcatga tgtctggcga taaagggatt tctgccttcc 240ctgaatcaga caaccttttc
aaatgggtag ggaccatcca tggagcagct ggaacagtat 300atgaagacct gaggtataag
ctctcgctag agttccccag tggctaccct tacaatgcgc 360ccacagtgaa gttcctcacg
ccctgctatc accccaacgt ggacacccag ggtaacatat 420gcctggacat cctgaaggaa
aagtggtctg ccctgtatga tgtcaggacc attctgctct 480ccatccagag ccttctagga
gaacccaaca ttgatagtcc cttgaacaca catgctgccg 540agctctggaa aaaccccaca
gcttttaaga agtacctgca agaaacctac tcaaagcagg 600tcaccagcca ggagccctga
cccaggctgc ccagcctgtc cttgtgtcgt ctttttaatt 660tttccttaga tggtctgtcc
tttttgtgat ttctgtatag gactctttat cttgagctgt 720ggtatttttg ttttgttttt
gtcttttaaa ttaagcctcg gttgagccct tgtatattaa 780ataaatgcat ttttgtcctt
ttttagacaa aaaaaaaaaa aaa 823283018DNAHomo sapiens
28cagctaaatt ttaaaggtgt ttttgtagag atgaggtttc actatattgc ccaggctggt
60ctcgaactcc tggacttaag tgatccttcc tctttggcct cccaaagtgc tgggattaca
120ggcatgagcc actgccccag ccaagactgt cttttctcca ttgtattgcg tttgcttcct
180tgtcaaagat cagttgacta tatttgtgtg gggctatttc tgggctccct atttgtttcc
240agtgattatg tctatttttt caccattacc accctatctt aattactgta gctttatagt
300gagtcttaaa gttgggtaat atcagtcttc tgaccttttt ctctttcaat attgtgccag
360ctattctggg tcttttgcct ttccatgtaa actttagaac cagtttgtca ggatccacaa
420aatactttgc tgggttttga ttgggattgc attgaatcca caggtcaagt tggcaaaaac
480tgacatacag caatgccagt ttattgtttt gtgatagcct taatccagct agtttcttca
540caggatgatg ttgaaaatat gggatgctca taatccctga atatttttta tgtggataat
600taaacttgtt ctgggtggat ggttggatag ccagaatagt aataacctct cttccagcca
660ctcaaagaaa atgatataaa cgtagggttg gtttaattgt tgagaggtca cgttttttcc
720attcttgctc tcaggtaagg aaagagcact gttggttcac gcattccttt ttccctcata
780cactttgttg ggcactgata tggtttggct ctgtgttccc acccaaatct catgttgaat
840tgtgatcctg agtgttggag gtggggcctc gcgggagacg actggatcat gggggcggat
900tttccccttg ctgttctcat gatagtgagt tctcatgaga tctggttgtt taaaagtgta
960tagcacttcc tgcttcactc tctcccactc caccatgtga agaaggtgcc tttgcccttc
1020cgccacgact gtgtttcctg aggcctcccc agccatgcct cctgtacagc ctgcggaact
1080gtcagttaaa cctcttttct tcattaatta cccactctca ggtggttttt tatggcagtg
1140tgagaacgga ctaatacaga aaattggtac cagagaagtg ggatattgct ataaaatacc
1200tgaaaatgtg gaagtgactt tggaactggg taatgggcag aggttggaac agtttggagg
1260gctcagaaga agacaggaag atgagggaaa gtttgcagct tcctagagac ttgttgaatg
1320gttgtgacca aagtgctgat agtgatatgg acagtgaagt ccaggctgag ttggtctcag
1380atgggagatg agaatcttat tccgaactgg agtgaaggtc actcttggct gtgctttagc
1440aaagagagtg gtggcattgt gcccctgctc tagagatctg tgaactctga actcgagagg
1500gtatctggca gaaaaaaatt tctaagcagc aaagtgttca agatgtggcc tgattgcttc
1560taaaagccta tgctcatttg catgaacaaa gtggaactta tatttaaaac agaagctgag
1620cttttataaa agtttggaga atttgcagcc caaccatgtg gtgaaaaaga aaaatccatt
1680ttctggggag gtattcaagg ctgcagaaat ttgcataaga agagcctcat gttaacagcc
1740aagagagtga ggaaaatgcc tctagagcat ttcagagacc ttcacagcag ctcctcccat
1800cacaggcatg gaagcccagg aggaagaaat gcttttgtgg gccagcccag ggccccactg
1860ttctgtgcag ccttgggaca tggtgccctg catcccagcc actccagctc cagctgtgac
1920taaaaggggc caaggtacag cttgggctgc tgcttcagag ggtgcaagcc ccaagccttg
1980gtggcttcca tgtggtgtta ggcaggtgtg cagaagagtt gaggtttagg aacctctacc
2040tagatttcag aggatgtatg gaaatgcccg gatgtccagg cagaagtttg ctgcagaggc
2100agagccctca tagataacct ctgcgagggc agtgtggagg ggaaatgtgg ggttggagct
2160atgagaagag ggccaccatc caccagaccc cagaattgta gatccactga cagcttgcac
2220tatgcacctg taaaagttgc aggcagttaa tgctagcctg tgaaagcagc tgtggggact
2280atatgcagag ccacagaggc agagctgccc agagccttgg gagcccactc cttgtgtcag
2340tgtggcctgg atgtgagacg tggagtcaaa gatcattttg gaggtttgag atttaatgac
2400tgccctcctg gattttggac ttgcatgggg cccatagccc ctttgttttg gctgatttct
2460cctatttgga atgggagcat ttacccaatg cctgtatccc cattgtatct tggagataac
2520tgacttgttt ttgattttac aggctcacag gaggaaggga cttggctggt ctcagatgag
2580acttgacttg gacatttgag ttaatgctgg aatgagttaa gactttaggg ggctattggg
2640aaggcatgat tgtgttttga aatgtgagga catgagattt gggaggggcc agggtggaat
2700gatatggttt ggctgtgtcc ccccacccaa atctcatgtt gaattgtgat cctgagtctt
2760ggaggtagag cctggtggga ggtgattgga tcatgggggc agatttcccc cttgctgttc
2820tcatgacagt gagttctcat gagatctggt taagtgtgta gcacttcccc ctttgcttgc
2880tctctccctc tgccatgtga agaaggtgct tgctttccct tcgcccttct gccatgactg
2940taagtttctt gaggcctcgc agccatgctt cctgtacagc ctgcagaact gtgagttaat
3000taaacctctt ttcttcat
301829969DNAHomo sapiens 29agctttgggg ttgtccctgg acttgtcttg gttccagaac
ctgacgaccc ggcgacggcg 60acgtctcttt tgactaaaag acagtgtcca gtgctccagc
ctaggagtct acggggaccg 120cctcccgcgc cgccaccatg cccaacttct ctggcaactg
gaaaatcatc cgatcggaaa 180acttcgagga attgctcaaa gtgctggggg tgaatgtgat
gctgaggaag attgctgtgg 240ctgcagcgtc caagccagca gtggagatca aacaggaggg
agacactttc tacatcaaaa 300cctccaccac cgtgcgcacc acagagatta acttcaaggt
tggggaggag tttgaggagc 360agactgtgga tgggaggccc tgtaagagcc tggtgaaatg
ggagagtgag aataaaatgg 420tctgtgagca gaagctcctg aagggagagg gccccaagac
ctcgtggacc agagaactga 480ccaacgatgg ggaactgatc ctgaccatga cggcggatga
cgttgtgtgc accagggtct 540acgtccgaga gtgagtggcc acaggtagaa ccgcggccga
agcccaccac tggccatgct 600caccgccctg cttcactgcc ccctccgtcc caccccctcc
ttctaggata gcgctcccct 660taccccagtc acttctgggg gtcactggga tgcctcttgc
agggtcttgc tttctttgac 720ctcttctctc ctcccctaca ccaacaaaga ggaatggctg
caagagccca gatcacccat 780tccgggttca ctccccgcct ccccaagtca gcagtcctag
ccccaaacca gcccagagca 840gggtctctct aaaggggact tgagggcctg agcaggaaag
actggccctc tagcttctac 900cctttgtccc tgtagcctat acagtttaga atatttattt
gttaatttta ttaaaatgct 960ttaaaaaaa
96930496DNAHomo sapiens 30ctcgcttttc ggttgccgtt
gtcttttttc cttgactcgg aaatgtccgg tcgtggtaag 60cagggtggca aggcgcgcgc
caaggctaag tcgcgctcgt cgcgcgcggg gctgcagttc 120cccgtgggcc gcgtgcaccg
gttgctccgc aagggcaact attcggagcg cgtgggcgcc 180ggcgccccgg tctatctggc
cgcggtgctc gagtacttga ctgccgagat cctggagctt 240gccggcaacg cggcgcgcga
caacaagaag acgcgcatca tcccgcgcca cctgcagctg 300gccatccgca acgacgagga
gctcaacaag ctgctgggcc gcgtgaccat cgcgcagggt 360ggcgtcctgc ccaacatcca
ggccgtactg ctgcccaaga agacggagag ccaccacaag 420gccaagggca agtgaggccg
cccgccgccc ccggggcccc tttgatggac ataaaggctc 480ttttcagagc caccta
49631374DNAHomo sapiens
31atgtctggcc gtggtaaagg tggaaaaggt ttgggtaagg gaggagctaa gcgtcatcgc
60aaggttttgc gcgataacat ccagggcatc actaagccag ctatccggcg ccttgctcgt
120cgcggcggtg tcaagcgaat ttctggcctt atctatgagg agactcgtgg tgttctgaag
180gtgttcctgg agaacgtgat tcgtgacgct gtcacttaca cagagcacgc caaacgcaag
240accgtgacag caatggatgt ggtctacgcg ctgaagcgac agggacgcac tctttacggc
300ttcggtggct aaggctcctg cttgctgcac tcttattttc attttcaacc aaaggccctt
360ttcagggccg ccca
374322319DNAHomo sapiens 32gcctccacag atatcaaaag aaacctgaag agcctacaaa
aaaaaaagag ataaagacaa 60aattcaagaa aacacacaca tacataattg tggtcacctg
gagcctgggg gccggcccag 120ctctctcagg attcagcaga cattggaggt ggcagtgaag
gatacagtgg tagtcaatgt 180tatttgagca gggtcagcag gccctggagc ttcctgagtg
cacaatgcag aaggctgctt 240actatgaaaa cccaggactg tttggaggct atggctacag
caaaactacg gacacttacg 300gctacagcac cccccaccag ccctacccac cccctgctgc
tgccagctcc ctggacactg 360actatccagg ttctgcctgc tccatccaga gctctgcccc
tctgagagcc ccagcccaca 420aaggagctga actcaatggc agctgcatgc ggccgggcac
tgggaacagc cagggtgggg 480gtggtggcag ccagcctcct ggtctgaact cagagcagca
gccaccacaa ccccctcctc 540caccaccgac cctgccccca tcttcaccca ccaatcctgg
aggtggagtg cctgccaaga 600agcccaaagg tgggcccaat gcttctagct cctcagccac
catcagcaag cagatcttcc 660cctggatgaa agagtctcga cagaactcca agcagaagaa
cagctgtgcc actgcaggag 720agagctgcga ggacaagagc ccgccaggcc cagcatccaa
gcgggtacgc acggcataca 780cgagcgcgca gctggtggaa ttggaaaagg aattccactt
caaccgctac ttgtgccggc 840cgcgccgcgt ggagatggcc aacctgctga atctcacgga
acgccagatc aagatctggt 900tccagaaccg gcgcatgaag tacaagaagg accagaaggc
caagggcatc ctgcactcgc 960cggctagcca gtcccctgag cgcagcccac cgctcggcgg
cgccgctggc cacgtggcct 1020actccggcca gctgccgcca gtgcccggcc tggcctacga
cgcgccctcg ccgcctgctt 1080tcgccaaatc acagcccaat atgtacggcc tggccgccta
cacggcgcca ctcagcagct 1140gcctgccaca acagaagcgc tacgcagcgc cggagttcga
gccccatccc atggcgagca 1200acggcggcgg cttcgccagc gccaacttgc agggcagccc
ggtgtacgtg ggcggcaact 1260tcgtcgagtc catggcgccc gcgtccgggc ctgtcttcaa
cctgggccac ctctcgcacc 1320cgtcgtcggc cagcgtggac tacagttgcg ccgcgcagat
tccaggcaac caccaccatg 1380gaccttgcga ccctcatccc acctacacag atctctcggc
ccaccactcg tctcagggac 1440gactgccgga ggctcccaaa ctgacgcatc tgtagcggcc
gccgccagcc cgaactcgcg 1500gcaaaattac ctctcttgct gtagtggtgg ggtagagggt
ggggcccgcg gggcagttcg 1560ggaaccccct tccccgctct tgccctgccg ccgcctcccg
ggtctcaggc ctccagcggc 1620ggaggcgcag gcgaccgggc ctcccctcca tgggcgtcct
ttgggtgact cgccataaat 1680cagccgcaag gatccttccc tgtaaatttg acagtgccac
atactgcgga ccaagggact 1740ccaatctggt aatggtgtcc caaaggtaag tctgagaccc
atcagcggcg cgccctgcag 1800agggaccaga gcttggagag tcttgggcct ggcccgcgtc
tagcttagtt tcagagacct 1860taatttatat tctccttcct gtgccgtaag gattgcatcg
gactaaacta tctgtattta 1920ttatttgaag cgagtcattt cgttccctga ttatttatcc
ttgtctgaat gtatttatgt 1980gtatatttgt agatttatcc agccgagctt aggaattcgc
ttccaggccg tgggggccac 2040atttcacctc cttagtcccc ctggtctgaa ctagttgaga
gagtagtttt gaacagtcgt 2100aaccgtggct ggtgtttgta gttgacataa aggattaaga
ccgcaaattg tccttcatgg 2160gtagagtcag gaagcccggt ggcgtggcac aacacacttt
ggtcatttct caaaaaccac 2220agtcctcacc acagtttatt gatttcaaat tgtctggtac
tattggaaca aatatttaga 2280ataaaaaaat ttcccagtca aaaaaaaaaa aaaaaaaaa
2319331702DNAHomo sapiens 33ccagccctga gattcccagg
tgtttccatt cggtgatcag cactgaacac agaactcacc 60atggagtttg gactgagctg
ggttttcctt gttgctattt taaaaggtgt ccagtgtgaa 120gtgcagctgg tggagtctgg
gggagtcgtg gtacagcctg gggggtccct gagactctcc 180tgtgcagcct ctggattcac
ctttgatgac tatgccatgc actgggtccg tcaagctccg 240gggaagggtc tggagtgggt
ctcccttatt agttgggatg gtggtagcac ctactatgca 300gactctgtga agggtcgatt
caccatctcc agagacaata gtaaaaattc cttgtatctg 360caaatgaaca gtctgagagc
tgaggacacc gccttgtatt actgtgcaac ccgggggggt 420tattccaccg ccggctttga
ctactggggc cagggaaccc tggtcaccgt ctcctcagcc 480tccaccaagg gcccatcggt
cttccccctg gcaccctcct ccaagagcac ctctgggggc 540acagcggccc tgggctgcct
ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 600aactcaggcg ccctgaccag
cggcgtgcac accttcccgg ctgtcctaca gtcctcagga 660ctctactccc tcagcagcgt
ggtgaccgtg ccctccagca gcttgggcac ccagacctac 720atctgcaacg tgaatcacaa
gcccagcaac accaaggtgg acaagaaagt tgagcccaaa 780tcttgtgaca aaactcacac
atgcccaccg tgcccagcac ctgaactcct ggggggaccg 840tcagtcttcc tcttcccccc
aaaacccaag gacaccctca tgatctcccg gacccctgag 900gtcacatgcg tggtggtgga
cgtgagccac gaagaccctg aggtcaagtt caactggtac 960gtggacggcg tggaggtgca
taatgccaag acaaagccgc gggaggagca gtacaacagc 1020acgtaccgtg tggtcagcgt
cctcaccgtc ctgcaccagg actggctgaa tggcaaggag 1080tacaagtgca aggtctccaa
caaagccctc ccagccccca tcgagaaaac catctccaaa 1140gccaaagggc agccccgaga
accacaggtg tacaccctgc ccccatcccg ggatgagctg 1200accaagaacc aggtcagcct
gacctgcctg gtcaaaggct tctatcccag cgacatcgcc 1260gtggagtggg agagcaatgg
gcagccggag aacaactaca agaccacgcc tcccgtgctg 1320gactccgacg gctccttctt
cctctacagc aagctcaccg tggacaagag caggtggcag 1380caggggaacg tcttctcatg
ctccgtgatg catgaggctc tgcacaacca ctacacgcag 1440aagagcctct ccctgtctcc
gggtaaatga gtgcgacggc cggcaagccc ccgctccccg 1500ggctctcgcg gtcgcacgag
gatgcttggc acgtaccccg tgtacatact tcccgggcgc 1560ccagcatgga aataaagcac
ccagcgctgc cctgggcccc tgcgaaaaaa aaaaaaaaaa 1620aaaaaaaaaa aaaaaaaaaa
aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1680aaaaaaaaaa aaaaaaaaaa
aa 170234975DNAHomo sapiens
34gagggaacca tggaaacccc agcgcagctt ctcttcctcc tgctactctg gctcccagat
60atcaccggag aaattgtgtt gacgcagtct ccaggcaccc tgtctttgtc tccaggagaa
120agagccgccc tctcatgcag ggccagtcag agtgttaaca gcaagtactt agcctggtac
180cagcagaagc ctggccaggc tcccaggctc ctcatgtatg ctgcatccat cagggccact
240ggcatcccag acaggttcag tggcagtggg tctgggacag acttcactct caccatcagc
300agactggaat ctgaggactt tgcactgtat ttctgtcagc aatatggtac ttcacctctc
360actttcggcg gagggaccaa ggtggagatc aaacgaactg tggctgcacc atctgtcttc
420atcttcccgc catctgatga gcagttgaaa tctggaactg cctctgttgt gtgcctgctg
480aataacttct atcccagaga ggccaaagta cagtggaagg tggataacgc cctccaatcg
540ggtaactccc aggagagtgt cacagagcag gacagcaagg acagcaccta cagcctcagc
600agcaccctga cgctgagcaa agcagactac gagaaacaca aagtctacgc ctgcgaagtc
660acccatcagg gcctgagctc gcccgtcaca aagagcttca acaggggaga gtgttagagg
720gagaagtgcc cccacctgct cctcagttcc agcctgaccc cctcccatcc tttggcctct
780gacccttttt ccacagggga cctaccccta ttgcggtcct ccagctcatc tttcacctca
840cccccctcct cctccttggc tttaattatg ctaatgttgg aggagaatga ataaataaag
900tgaatctttg cacctaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa
960aaaaaaaaaa aaaaa
975354006DNAHomo sapiens 35acgcgggggg cccgctctcg gcgagcccga gccgccgccg
gccccgcggc ggagatgagc 60aggtccgcga cgctgctgct gtgcctgctg ggctgccacg
tctggaaggc ggtgaccaag 120acgctgcggg agcccggcgc cggagcccaa gaggtgacgt
taaaggtgca catcagcgac 180gccagcaccc accagcccgt agcagatgcg ctcatcgaga
tcttcaccaa ccaggcctcc 240atagcctctg gcacctcggg gactgatggc gtcgccttta
tcaagttcca gtataagctg 300ggcagtcagt tgattgtcac cgcctcgaag catgcctacg
tgccaaactc tgccccatgg 360aagccaatcc ggttacctgt attttcctct ctgagccttg
gcctgcttcc agaacgctct 420gccactctaa tggtatatga agatgtcgtc caaatagtat
caggattcca aggtgcccgg 480ccacagcctc gcgttcattt ccagagaagg gctctgaggt
tgcctgagaa caccagctac 540agtgacctga ccgcgtttct cacggccgcc agctcccctt
cggaggtgga cagttttcct 600tatttgcgag gattagacgg aaatggaaca ggaaacagca
ccaggcatga cctgacccca 660gtcacagccg tcagcgtcca cttgctgagc agtaatggaa
cgccggtgct ggtggatggt 720cccatctatg tcactgtgcc cctggccacg cagagcagcc
tgaggcacaa tgcctatgtc 780gcggcgtggc ggtttgacca gaagctggga acgtggctga
agagcggtct gggtcttgtg 840caccaggaag gcagccagct gacgtggaca tacattgccc
cccagttggg gtactgggtg 900gccgccatgt cccctcccat cccaggtccc gttgtaacac
aggacattac cacgtatcac 960acggtgtttc ttttggccat tttaggagga atggctttca
tacttttggt tttgctgtgt 1020ctccttttat attattgcag gaggaagtgc ttgaaacctc
gtcagcacca cagaaaactg 1080cagctccctg caggactgga gagttccaaa agagaccagt
ccacgtccat gtcacacatt 1140aacttgctgt tttcacgccg agcgtcagaa ttccctggcc
cgctgtccgt caccagccac 1200ggccgccccg aggcccccgg cacgaaggaa ctgatgagtg
gagtccattt ggaaatgatg 1260tctccgggcg gcgaagggga cctgcacacc cccatgctca
agctctccta cagcacctcc 1320caggaattta gctcccggga ggagctcctc tcttgcaagg
aagaggataa aagccagatc 1380tcctttgata acctcactcc aagtgggacg ctggggaaag
actaccataa gtcagtggag 1440gtttttccct taaaggcaag aaaatctatg gaaagagaag
gctacgagtc ctcgggcaat 1500gatgactaca ggggtagtta caacaccgtg ctctcacagc
ctttatttga aaagcaggac 1560agagaaggtc cagcctccac gggaagcaaa ctcaccattc
aggaacatct gtaccccgcg 1620ccttcatcac ctgagaaaga acagctgctg gaccgcagac
ccactgaatg tatgatgtcg 1680cgatcagtag atcacctcga gagacctacg tccttcccac
ggcccggcca gttaatctgc 1740tgcagttctg tcgaccaggt caatgacagc gtttacagga
aagtactgcc tgccttggtc 1800atcccggctc attatatgaa actccccggg gaccactcct
atgtcagcca gcccctcgtc 1860gtcccggctg atcagcagct tgagatagaa agactacagg
ctgagctgtc caatccccat 1920gccgggatct tcccacaccc gtcctcacag atccagcccc
agcccctgtc ttcccaggcc 1980atctctcagc agcacctgca ggatgcgggc acccgggagt
ggagccctca gaacgcatcc 2040atgtcggagt ctctctccat cccagcttcc ctgaacgacg
cggctttggc tcagatgaac 2100agtgaggtgc agctcctgac tgaaaaggcc ctgatggagc
ttgggggtgg gaagccgctt 2160ccgcaccccc gggcgtggtt cgtctccttg gatggcaggt
ccaacgctca cgttagacat 2220tcatacattg atctccaaag agctggaagg aacggaagta
atgatgccag tttggactct 2280ggcgtagata tgaatgaacc aaaatcagcc cggaagggaa
ggggagatgc tttgtctctg 2340cagcagaact acccgcccgt ccaagagcac cagcagaaag
agcctcgagc cccagacagc 2400acggcctaca cgcagctcgt gtacctggat gacgtggaac
agagtggtag cgaatgtggg 2460accacggtct gtacccccga ggacagtgcc ctgcgatgct
tgttggaggg gtcgagtcgg 2520agaagtggtg gccagctgcc cagcctgcag gaggagacga
ccagacggac tgcggatgcc 2580ccctcggagc cagcagccag cccccaccag agaagatctg
cccacgagga agaggaagac 2640gatgatgatg atgaccaagg agaagacaag aaaagcccct
ggcagaaacg ggaggagagg 2700cccctgatgg cgtttaacat taaatgagct atcgcagacc
cacctgactg tggaatataa 2760aattgccaaa tatcctttct catggaagcg cgtacccgtt
cgtggaggaa acggaacggc 2820agcccagccg tgggacggac gtggacgttt actgcattcc
tgtttgccgt gtaaatgtta 2880gaaaggaatt aaagttatta ctcggaataa aggatgactt
tggcggatgt cgcccctgca 2940aggaggtggc tgaaagtggt gtccagatgt ccttccgagg
actcggcgta tccgccacca 3000gggacattaa gaaaccgcac gtgatgtcgc tatgctctaa
cgatcacctc agttctccct 3060cggattctgg gaacagatga aactttttgc atcgcttgag
tcatttttat cacaataatc 3120ctactgtgaa gctgtcgttg agaacttagg ttggcacgta
gcgtctcaag gtatgcgttc 3180tctcaaagga aagctatgca tcgctgcttc tttgtctgat
tttgcttaga ttttgctttg 3240gttaggttgc gttttggggt ttgccttttt ttgttgtcgc
ttaaatgcaa tttggttgta 3300aagatttgat tcctttgtgt tcatctgttc cgcttctcag
cggtccatct cagcgtctcc 3360cttcaggaac cgctgagtgt cctctcttaa catccaagcc
ttttaatgaa atcgtactga 3420aatctgtatc agctaagagt cctccaatcc tggtcccatt
aactccaagt gcctttttgt 3480cagtgacaac agacagtccc tcgctttttg ttgttgttgg
ttttcttaac ccctttaatg 3540gaactgcctg gattttatac agttattaaa ggatgtctct
tttgctttaa actgcatgct 3600gccaagtgcc atttggggtc agcatcctcg tttcaacaca
gtgtgctctc tagttatcat 3660gtgtaacgtg ggttctgttt agcgaagata gactagagga
cacgttagag atgcccttcc 3720ctgctccatc cctgtggcac cattatggtt ttttggctgt
ttgtatatac ggttacgtat 3780taactctgga atcctatggg ctcatcttgc tcacccaatg
tgggagtctg gtttgagcaa 3840gcgagctgaa tgtgactatt aaaaaaaatt taaaaaaaaa
aaagaaaatc ttatgtacta 3900tccaaaagtg ccagaatgac tcttctgtgc attcttctta
aagagctgct tggttatcca 3960aaaatgaaaa ttcaaaataa actctgaaaa aaaaaaaaaa
aaaaaa 4006361807DNAHomo sapiens 36cgtcacttcc tgttgcctta
ggggaacgtg gctttccctg cagagccggt gtctccgcct 60gcgtccctgc tgcagcaacc
ggagctggag tcggatcccg aacgcaccct cgccatggac 120tcggccctca gcgatccgca
taacggcagt gccgaggcag gcggccccac caacagcact 180acgcggccgc cttccacgcc
cgagggcatc gcgctggcct acggcagcct cctgctcatg 240gcgctgctgc ccatcttctt
cggcgccctg cgctccgtac gctgcgcccg cggcaagaat 300gcttcagaca tgcctgaaac
aatcaccagc cgggatgccg cccgcttccc catcatcgcc 360agctgcacac tcttggggct
ctacctcttt ttcaaaatat tctcccagga gtacatcaac 420ctcctgctgt ccatgtattt
cttcgtgctg ggaatcctgg ccctgtccca caccatcagc 480cccttcatga ataagttttt
tccagccagc tttccaaatc gacagtacca gctgctcttc 540acacagggtt ctggggaaaa
caaggaagag atcatcaatt atgaatttga caccaaggac 600ctggtgtgcc tgggcctgag
cagcatcgtt ggcgtctggt acctgctgag gaagcactgg 660attgccaaca acctttttgg
cctggccttc tcccttaatg gagtagagct cctgcacctc 720aacaatgtca gcactggctg
catcctgctg ggcggactct tcatctacga tgtcttctgg 780gtatttggca ccaatgtgat
ggtgacagtg gccaagtcct tcgaggcacc aataaaattg 840gtgtttcccc aggatctgct
ggagaaaggc ctcgaagcaa acaactttgc catgctggga 900cttggagatg tcgtcattcc
agggatcttc attgccttgc tgctgcgctt tgacatcagc 960ttgaagaaga atacccacac
ctacttctac accagctttg cagcctacat cttcggcctg 1020ggccttacca tcttcatcat
gcacatcttc aagcatgctc agcctgccct cctatacctg 1080gtccccgcct gcatcggttt
tcctgtcctg gtggcgctgg ccaagggaga agtgacagag 1140atgttcagct acgagtcctc
ggcggaaatc ctgcctcata ccccgaggct cacccacttc 1200cccacagtct cgggctcccc
agccagcctg gccgactcca tgcagcagaa gctagctggc 1260cctcgccgcc ggcgcccgca
gaatcccagc gccatgtaat gcccagcggg tgcccacctg 1320cccgcttccc cctactgccc
cggggcccaa gttatgagga gtcaaatcct aaggatccag 1380cggcagtgac agaatccaaa
gagggaacag aggcatcagc atcgaagggg ctggagaaga 1440aagagaaatg atgcagctgg
tgcccgagcc tctcagggcc agaccagaca gatgggggct 1500gggcccacac aggcgtgcac
cggtagaggg cacaggaggc caagggcagc tccaggacag 1560ggcagggggc agcaggatac
ctccagccag gcctctgtgg cctctgtttc cttctccctt 1620tcttggccct cctctgctcc
tccccacacc ctgcaggcaa aagaaacccc cagcttcccc 1680cctccccggg agccaggtgg
gaaaagtggg tgtgattttt agattttgta ttgtggactg 1740attttgcctc acattaaaaa
ctcatcccat ggccagggcg ggccactgtg ctcctggaaa 1800aaaaaaa
180737220DNAHomo sapiens
37tgcctcagtc tctcactgtg ccttatgccc ctcagctgaa ttctttcttc tgagcaggca
60ggaattgagg ttgctgcaga cgtgtatgca tttgccacca gtaacatact ttggtgccac
120atgactagga tatgttctct agtgctaaca tgttcgttta cagttcttag gactccctga
180tagaaaaaaa cacaaaaaaa aacacaaaaa aacccaacca
220382058DNAHomo sapiens 38gttgggaaag agcagcctgg gcggcagggg cggtggctgg
agctcggtaa agctcgtggg 60accccattgg gggaatttga tccaaggaag cggtgattgc
cgggggagga gaagctccca 120gatccttgtg tccacttgca gcgggggagg cggagacggc
ggagcgggcc ttttggcgtc 180cactgcgcgg ctgcaccctg ccccatcctg ccgggatcat
ggtctgcggc agcccgggag 240ggatgctgct gctgcgggcc gggctgcttg ccctggctgc
tctctgcctg ctccgggtgc 300ccggggctcg ggctgcagcc tgtgagcccg tccgcatccc
cctgtgcaag tccctgccct 360ggaacatgac taagatgccc aaccacctgc accacagcac
tcaggccaac gccatcctgg 420ccatcgagca gttcgaaggt ctgctgggca cccactgcag
ccccgatctg ctcttcttcc 480tctgtgccat gtacgcgccc atctgcacca ttgacttcca
gcacgagccc atcaagccct 540gtaagtctgt gtgcgagcgg gcccggcagg gctgtgagcc
catactcatc aagtaccgcc 600actcgtggcc ggagaacctg gcctgcgagg agctgccagt
gtacgacagg ggcgtgtgca 660tctctcccga ggccatcgtt actgcggacg gagctgattt
tcctatggat tctagtaacg 720gaaactgtag aggggcaagc agtgaacgct gtaaatgtaa
gcctattaga gctacacaga 780agacctattt ccggaacaat tacaactatg tcattcgggc
taaagttaaa gagataaaga 840ctaagtgcca tgatgtgact gcagtagtgg aggtgaagga
gattctaaag tcctctctgg 900taaacattcc acgggacact gtcaacctct ataccagctc
tggctgcctc tgccctccac 960ttaatgttaa tgaggaatat atcatcatgg gctatgaaga
tgaggaacgt tccagattac 1020tcttggtgga aggctctata gctgagaagt ggaaggatcg
actcggtaaa aaagttaagc 1080gctgggatat gaagcttcgt catcttggac tcagtaaaag
tgattctagc aatagtgatt 1140ccactcagag tcagaagtct ggcaggaact cgaacccccg
gcaagcacgc aactaaatcc 1200cgaaatacaa aaagtaacac agtggacttc ctattaagac
ttacttgcat tgctggacta 1260gcaaaggaaa attgcactat tgcacatcat attctattgt
ttactataaa aatcatgtga 1320taactgatta ttacttctgt ttctcttttg gtttctgctt
ctctcttctc tcaacccctt 1380tgtaatggtt tgggggcaga ctcttaagta tattgtgagt
tttctatttc actaatcatg 1440agaaaaactg ttcttttgca ataataataa attaaacatg
ctgttaccag agcctctttg 1500ctggagtctc cagatgttaa tttactttct gcaccccaat
tgggaatgca atattggatg 1560aaaagagagg tttctggtat tcacagaaag ctagatatgc
cttaaaacat actctgccga 1620tctaattaca gccttatttt tgtatgcctt ttgggcattc
tcctcatgct tagaaagttc 1680caaatgttta taaaggtaaa atggcagttt gaagtcaaat
gtcacatagg caaagcaatc 1740aagcaccagg aagtgtttat gaggaaacaa cacccaagat
gaattatttt tgagactgtc 1800aggaagtaaa ataaatagga gcttaagaaa gaacattttg
cctgattgag aagcacaact 1860gaaaccagta gccgctgggg tgttaatggt agcattcttc
ttttggcaat acatttgatt 1920tgttcatgaa tatattaatc agcattagag aaatgaatta
taactagaca tctgctgtta 1980tcaccatagt tttgtttaat ttgcttcctt ttaaataaac
ccattggtga aagtcccaaa 2040aaaaaaaaaa aaaaaaaa
2058393487DNAHomo sapiens 39actgaaagct ccggtgccag
accccacccc cggccccggc ccgggacccc ctcccctccc 60gggatccccc ggggttccca
ccccgcccgc accgccgggg acccggccgg tccggcgcga 120gcccccgtcc ggggccctgg
ctcggccccc aggttggagg agcccggagc ccgccttcgg 180agctacggcc taacggcggc
ggcgactgca gtctggaggg tccacacttg tgattctcaa 240tggagagtga aaacgcagat
tcataatgaa aactagcccc cgtcggccac tgattctcaa 300aagacggagg ctgccccttc
ctgttcaaaa tgccccaagt gaaacatcag aggaggaacc 360taagagatcc cctgcccaac
aggagtctaa tcaagcagag gcctccaagg aagtggcaga 420gtccaactct tgcaagtttc
cagctgggat caagattatt aaccacccca ccatgcccaa 480cacgcaagta gtggccatcc
ccaacaatgc taatattcac agcatcatca cagcactgac 540tgccaaggga aaagagagtg
gcagtagtgg gcccaacaaa ttcatcctca tcagctgtgg 600gggagcccca actcagcctc
caggactccg gcctcaaacc caaaccagct atgatgccaa 660aaggacagaa gtgaccctgg
agaccttggg accaaaacct gcagctaggg atgtgaatct 720tcctagacca cctggagccc
tttgcgagca gaaacgggag acctgtgcag atggtgaggc 780agcaggctgc actatcaaca
atagcctatc caacatccag tggcttcgaa agatgagttc 840tgatggactg ggctcccgca
gcatcaagca agagatggag gaaaaggaga attgtcacct 900ggagcagcga caggttaagg
ttgaggagcc ttcgagacca tcagcgtcct ggcagaactc 960tgtgtctgag cggccaccct
actcttacat ggccatgata caattcgcca tcaacagcac 1020tgagaggaag cgcatgactt
tgaaagacat ctatacgtgg attgaggacc actttcccta 1080ctttaagcac attgccaagc
caggctggaa gaactccatc cgccacaacc tttccctgca 1140cgacatgttt gtccgggaga
cgtctgccaa tggcaaggtc tccttctgga ccattcaccc 1200cagtgccaac cgctacttga
cattggacca ggtgtttaag cagcagaaac gaccgaatcc 1260agagctccgc cggaacatga
ccatcaaaac cgaactcccc ctgggcgcac ggcggaagat 1320gaagccactg ctaccacggg
tcagctcata cctggtacct atccagttcc cggtgaacca 1380gtcactggtg ttgcagccct
cggtgaaggt gccattgccc ctggcggctt ccctcatgag 1440ctcagagctt gcccgccata
gcaagcgagt ccgcattgcc cccaaggtgc tgctagctga 1500ggaggggata gctcctcttt
cttctgcagg accagggaaa gaggagaaac tcctgtttgg 1560agaagggttt tctcctttgc
ttccagttca gactatcaag gaggaagaaa tccagcctgg 1620ggaggaaatg ccacacttag
cgagacccat caaagtggag agccctccct tggaagagtg 1680gccctccccg gccccatctt
tcaaagagga atcatctcac tcctgggagg attcgtccca 1740atctcccacc ccaagaccca
agaagtccta cagtgggctt aggtccccaa cccggtgtgt 1800ctcggaaatg cttgtgattc
aacacaggga gaggagggag aggagccggt ctcggaggaa 1860acagcatcta ctgcctccct
gtgtggatga gccggagctg ctcttctcag aggggcccag 1920tacttcccgc tgggccgcag
agctcccgtt cccagcagac tcctctgacc ctgcctccca 1980gctcagctac tcccaggaag
tgggaggacc ttttaagaca cccattaagg aaacgctgcc 2040catctcctcc accccgagca
aatctgtcct ccccagaacc cctgaatcct ggaggctcac 2100gcccccagcc aaagtagggg
gactggattt cagcccagta caaacctccc agggtgcctc 2160tgaccccttg cctgaccccc
tggggctgat ggatctcagc accactccct tgcaaagtgc 2220tccccccctt gaatcaccgc
aaaggctcct cagttcagaa cccttagacc tcatctccgt 2280cccctttggc aactcttctc
cctcagatat agacgtcccc aagccaggct ccccggagcc 2340acaggtttct ggccttgcag
ccaatcgttc tctgacagaa ggcctggtcc tggacacaat 2400gaatgacagc ctcagcaaga
tcctgctgga catcagcttt cctggcctgg acgaggaccc 2460actgggccct gacaacatca
actggtccca gtttattcct gagctacagt agagccctgc 2520ccttgcccct gtgctcaagc
tgtccaccat cccgggcact ccaaggctca gtgcacccca 2580agcctctgag tgaggacagc
aggcagggac tgttctgctc ctcatagctc cctgctgcct 2640gattatgcaa aagtagcagt
cacaccctag ccactgctgg gaccttgtgt tccccaagag 2700tatctgattc ctctgctgtc
cctgccagga gctgaagggt gggaacaaca aaggcaatgg 2760tgaaaagaga ttaggaaccc
cccagcctgt ttccattctc tgcccagcag tctcttacct 2820tccctgatct ttgcagggtg
gtccgtgtaa atagtataaa ttctccaaat tatcctctaa 2880ttataaatgt aagcttattt
ccttagatca ttatccagag actgccagaa ggtgggtagg 2940atgacctggg gtttcaattg
acttctgttc cttgctttta gttttgatag aagggaagac 3000ctgcagtgca cggtttcttc
caggctgagg tacctggatc ttgggttctt cactgcaggg 3060acccagacaa gtggatctgc
ttgccagagt cctttttgcc cctccctgcc acctccccgt 3120gtttccaagt cagctttcct
gcaagaagaa atcctggtta aaaaagtctt ttgtattggg 3180tcaggagttg aatttggggt
gggaggatgg atgcaactga agcagagtgt gggtgcccag 3240atgtgcgcta ttagatgttt
ctctgataat gtccccaatc ataccaggga gactggcatt 3300gacgagaact caggtggagg
cttgagaagg ccgaaagggc ccctgacctg cctggcttcc 3360ttagcttgcc cctcagcttt
gcaaagagcc accctaggcc ccagctgacc gcatgggtgt 3420gagccagctt gagaacacta
actactcaat aaaagcgaag gtggacaaaa aaaaaaaaaa 3480aaaaaaa
3487401441DNAHomo sapiens
40gtcgaggctg cggcgcgtgg ggagcgggcg gagcgggggc gggggccgag cgcggggcac
60ccgggggcct cctgtatagg cgggcaccat gggctcctgc tccggccgct gcgcgctcgt
120cgtcctctgc gcttttcagc tggtcgccgc cctggagagg caggtgtttg acttcctggg
180ctaccagtgg gcgcccatcc tggccaactt tgtccacatc atcatcgtca tcctgggact
240cttcggcacc atccagtacc ggctgcgcta tgtcatggtg tacacgctgt gggcagccgt
300ctgggtcacc tggaacgtct tcatcatctg cttctacctg gaagtcggtg gcctcttaaa
360ggacagcgag ctactgacct tcagcctctc ccggcatcgc tcctggtggc gtgagcgctg
420gccaggctgt ctgcatgagg aggtgccagc agtgggcctc ggggcccccc atggccaggc
480cctggtgtca ggtgctggct gtgccctgga gcccagctat gtggaggccc tacacagttg
540cctgcagatc ctgatcgcgc ttctgggctt tgtctgtggc tgccaggtgg tcagcgtgtt
600tacggatgaa gaggacagct ttgatttcat tggtggattt gatccatttc ctctctacca
660tgtcaatgaa aagccatcca gtctcttgtc caagcaggtg tacttgcctg cgtaagtgag
720gaaacagctg accctgctcc tgtggcctcc agcctcagcg accgaccagt gacaatgaca
780ggagctccca ggccttggga cgcgccccca cccagcaccc cccaggcggc cggcagcacc
840tgccctgggt tctaagtact ggacaccagc cagggcggca gggcagtgcc acggctggct
900gcagcgtcaa gagagtttgt aatttccttt ctcttaaaaa aaaaaaagaa aagaaaacat
960acaaaagaaa aggcaaaacc ccacatgccc acctcctctg gcaacatggg ggtcacagct
1020ctgcccccag gctgtcgtct cgtcgaggag cccctccctc aggtgccaac ctggggctgc
1080tggaccctcg ggctgcaagc actgctgctg ggatgcagcc tccccaggaa gtcaatgtga
1140ggcccgagac ccctcaagcg gtgagggccc ctgttgaaca tggagggttc ctaaccccaa
1200actcgtgcca gaagaacccc caccccaccc aggagctgag gctgatggag ccctagggtg
1260ggggctgggc ttgaccagga acagcagagc caggccccaa ggcatagggc agggcacatg
1320gtggtgacga gcaggcagta ctcttgtaaa gggggctctt gggcaaacag tcccaaaggc
1380tcccccaggt atcatcaagt tggtaaataa acaggaacat ggcccaaaaa aaaaaaaaaa
1440a
144141282DNAHomo sapiensmisc_feature(21)..(21)n is a, c, g, or
tmisc_feature(28)..(28)n is a, c, g, or tmisc_feature(137)..(137)n is a,
c, g, or t 41aaaaaataag tatatctgtc nagaatcnta tttatgtgag atgtgtcaat
actggtcttg 60cgttatttcg gctacttgaa aataagttaa aaaagatagt gtttggttcc
aaaaaggaaa 120agtcagcctc tcctgcntga gtgggagctg caacctttta gaattgataa
tcacaaaccc 180ctcagaccca aagtggaata aagaaaaata tgtaacatta ggcattgatg
gaaaaggact 240agatcctagt gtaagcatcc taataaaagg agaggttcac aa
282421260DNAHomo sapiens 42cagccagatc tgctgggaca cctttcccaa
ggaagagccc gttgcactgg gctttgaagg 60ataagcagga gcttgttact caggcagagg
aagaaagagc atcccaggcg gggggagcag 120catatgcaaa ggcacgaagg ggccccagga
gcctagggag tctggggaag tgtgagcact 180ttggagagtg gaggctggag cgctgtggag
agtgggggct ggtggccggg aatgaagctg 240cagctggctg ggccacatgg taaaggctga
caactggacc cagaggccaa ctagcctatg 300atcagcattt cccaaaatct gtttcccgac
tcatggttct gtgagatgtg acaagggctc 360ctttttcatt cctgagacgc cggttttcat
ctgtgatgcg gggacagctg cgctccttgc 420tgcgaggcgt caggacccag gtgatagtga
agggagggtg gcgcccgcgg ttcccggcgg 480ccactgatgc ctgtctctct gtcgtgtgta
cgtgcgtgtg tgctccacgc ctggcttctc 540aggctttcaa atgtgtgtca gcagcagcag
cagcagccac gacgaggccc ccgtcctgaa 600cgacaagcac ctggacgtgc ccgacatcat
catcacgccc cccaccccca cgggcatgat 660gctgccgagg gacttgggga gcacagtctg
gctggatgag acagggtcgt gcccagatga 720tggagaaatc gacccagaag cctgaggagg
tgtcctgggt ttggctggct ggctcctgct 780ccagcggccc ggcttcaggt gtccgggggc
gtggctgcct ggagcaggtg tgctgaatac 840cctggatggg aactgagcga acccgggcct
ccgctcagag agacgtggca ggaccagcga 900ggaatccagc ctgtccactt ccagaacagt
gtttcccagg ccccgctgag tggaccggac 960ctctgacacc tccaggttct tgctgactcc
ggcctggtga aagggagcgc catggtcctg 1020gctgttgggg tcccagggag aggctctctt
ctggacaaac acaccctccc agcccccagg 1080gctgtgcaaa cacatgcccc tcccataagc
accaacaaga acttcttgca ggtggagtgg 1140ctgtttttta taagttgttt tacagatacg
gaaacagtcc aaaatgggat ttataatttc 1200ttttttgcat tataaataaa gatcctctgt
aacaaaaaaa aaaaaaaaaa aaaaaaaaaa 1260433237DNAHomo sapiens 43gcgaagtgaa
gggtggccca ggtggggcca ggctgactga atgtatctcc tagctatgga 60ctaaataata
catgggggga aataaacaag tattcatgag ggtgaaaatg tgacccagca 120ggaaaattac
aactattttc aattgacgtt gaataggatg agtcatggaa tttaagtgat 180ttactgaaga
ttatactact ggtagataga agagctaaag aaagatggat actatgatgc 240tgaatgtgcg
gaatctgttt gagcagcttg tgcgccgggt ggagattctc agtgaaggaa 300atgaagtcca
atttatccag ttggcgaagg actttgagga tttccgtaaa aagtggcaga 360ggactgacca
tgagctgggg aaatacaagg atcttttgat gaaagcagag actgagcgaa 420gtgctctgga
tgttaagctg aagcatgcac gtaatcaggt ggatgtagag atcaaacgga 480gacagagagc
tgaggctgac tgcgaaaagc tggaacgaca gattcagctg attcgagaga 540tgctcatgtg
tgacacatct ggcagcattc aactaagcga ggagcaaaaa tcagctctgg 600cttttctcaa
cagaggccaa ccatccagca gcaatgctgg gaacaaaaga ctatcaacca 660ttgatgaatc
tggttccatt ttatcagata tcagctttga caagactgat gaatcactgg 720attgggactc
ttctttggtg aagactttca aactgaagaa gagagaaaag aggcgctcta 780ctagccgaca
gtttgttgat ggtccccctg gacctgtaaa gaaaactcgt tccattggct 840ctgcagtaga
ccaggggaat gaatccatag ttgcaaaaac tacagtgact gttcccaatg 900atggcgggcc
catcgaagct gtgtccacta ttgagactgt gccatattgg accaggagcc 960gaaggaaaac
aggtacttta caaccttgga acagtgactc caccctgaac agcaggcagc 1020tggagccaag
aactgagaca gacagtgtgg gcacgccaca gagtaatgga gggatgcgcc 1080tgcatgactt
tgtttctaag acggttatta aacctgaatc ctgtgttcca tgtggaaagc 1140ggataaaatt
tggcaaatta tctctgaagt gtcgagactg tcgtgtggtc tctcatccag 1200aatgtcggga
ccgctgtccc cttccctgca ttcctaccct gataggaaca cctgtcaaga 1260ttggagaggg
aatgctggca gactttgtgt cccagacttc tccaatgatc ccctccattg 1320ttgtgcattg
tgtaaatgag attgagcaaa gaggtctgac tgagacaggc ctgtatagga 1380tctctggctg
tgaccgcaca gtaaaagagc tgaaagagaa attcctcaga gtgaaaactg 1440tacccctcct
cagcaaagtg gatgatatcc atgctatctg tagccttcta aaagactttc 1500ttcgaaacct
caaagaacct cttctgacct ttcgccttaa cagagccttt atggaagcag 1560cagaaatcac
agatgaagac aacagcatag ctgccatgta ccaagctgtt ggtgaactgc 1620cccaggccaa
cagggacaca ttagctttcc tcatgattca cttgcagaga gtggctcaga 1680gtccacatac
taaaatggat gttgccaatc tggctaaagt ctttggccct acaatagtgg 1740cccatgctgt
gcccaatcca gacccagtga caatgttaca ggacatcaag cgtcaaccca 1800aggtggttga
gcgcctgctt tccttgcctc tggagtattg gagtcagttc atgatggtgg 1860agcaagagaa
cattgacccc ctacatgtca ttgaaaactc aaatgccttt tcaacaccac 1920agacaccaga
tattaaagtg agtttactgg gacctgtgac cactcctgaa catcagcttc 1980tcaagactcc
ttcatctagt tccctgtcac agagagtccg ttccaccctc accaagaaca 2040ctcctagatt
tgggagcaaa agcaagtctg ccactaacct aggacgacaa ggcaactttt 2100ttgcttctcc
aatgctcaag tgaagtcaca tctgcctgtt acttcccagc attgactgac 2160tataagaaag
gacacatctg tactctgctc tgcagcctcc tgtactcatt actactttta 2220gcattctcca
ggcttttact caagtttaat tgtgcatgag ggttttatta aaactatata 2280tatctcccct
tccttctcct caagtcacat aatatcagca ctttgtgctg gtcattgttg 2340ggagctttta
gatgagacat ctttccaggg gtagaagggt tagtatggaa ttggttgtga 2400ttctttttgg
ggaagggggt tattgttcct ttggcttaaa gccaaatgct gctcatagaa 2460tgatctttct
ctagtttcat ttagaactga tttccgtgag acaatgacag aaaccctacc 2520tatctgataa
gattagcttg tctcagggtg ggaagtggga gggcagggca aagaaaggat 2580tagaccagag
gatttaggat gcctccttct aagaaccaga agttctcatt ccccattatg 2640aactgagcta
taatatggag ctttcataaa aatgggatgc attgaggaca gaactagtga 2700tgggagtatg
cgtagctttg atttggatga ttaggtcttt aatagtgttg agtggcacaa 2760ccttgtaaat
gtgaaagtac aactcgtatt tatctctgat gtgccgctgg ctgaactttg 2820ggttcatttg
gggtcaaagc cagtttttct tttaaaattg aattcattct gatgcttggc 2880ccccataccc
ccaaccttgt ccagtggagc ccaacttcta aaggtcaata tatcatcctt 2940tggcatccca
actaacaata aagagtaggc tataagggaa gattgtcaat attttgtggt 3000aagaaaagct
acagtcattt tttctttgca ctttggatgc tgaaattttt cccatggaac 3060atagccacat
ctagatagat gtgagctttt tcttctgtta aaattattct taatgtctgt 3120aaaaacgatt
ttcttctgta gaatgtttga cttcgtattg acccttatct gtaaaacacc 3180tatttgggat
aatatttgga aaaaaagtaa atagcttttt caaaatgaaa aaaaaaa
3237444659DNAHomo sapiens 44aggcgctaga ggcgggggcg ccgggaggcg cgggctttgc
tcctggggtc tcggccttgg 60ccggctggac ctgaccctag ggcggcttgc gcagctgtcg
ggacgtgact gcgttcagcc 120gcgtcgggcg tgcttcccag acttgcccaa gttcgggtgc
cctagctgcc cctttgcagc 180cgctggccta cccggcccgc gggtgagaag gttgcgacgg
gaggtgggtg gaactcgcca 240gcgccgggac cgcggattgg ctgcctcggc tttctctttt
ccccgtgggc tccggcgtga 300ggcgctgaag cggccggcag ccggcgaccg gccctcaccg
tccgccgggt tgcgctctgc 360ttttgcggtg aggcgttgac cacgcccata tgaattggag
ctctccgcca gtaggagttt 420ccggaaggag tttgaatttt tgtgattttt atgcttgttt
ggtcggtgga atatgttggg 480atttatgttt gcctctgaac aagtgtcttg ctcacatcgt
aaatgacttt ctctccgaaa 540cgctaaatat tctttcccgc aggagctcat atccttattt
tccatgacag atcttaacga 600caatatatgc aaaagatata taaagatgat aactaatata
gttatactga gcctgatcat 660ttgcatttcg ttagctttct ggattatatc aatgactgca
agcacctatt atggtaactt 720acgacctatt tctccgtggc gttggctgtt ttctgttgtt
gttcctgttc tgatcgtctc 780taatggcctt aaaaagaaaa gtctagatca cagtggggct
ctaggagggc tagtcgttgg 840atttatccta accattgcaa atttcagctt ttttacctct
ttgctgatgt ttttcttgtc 900ttcttcgaaa ctcactaaat ggaagggaga agtgaagaag
cgtctagatt cagaatataa 960ggaaggtggg caaaggaatt gggttcaggt gttctgtaat
ggagctgtac ccacagaact 1020ggccctgctg tacatgatag aaaatggccc cggggaaatc
ccagtcgatt tttccaagca 1080gtactccgct tcctggatgt gtttgtctct cttggctgca
ctggcctgct ctgctggaga 1140cacatgggct tcagaagttg gcccagttct gagtaaaagt
tctccaagac tgataacaac 1200ctgggagaaa gttccagttg gtaccaatgg aggagttaca
gtggtgggcc ttgtctccag 1260tctccttggt ggtacctttg tgggcattgc atacttcctc
acacagctga tttttgtgaa 1320tgatttagac atttctgccc cgcagtggcc aattattgca
tttggtggtt tagctggatt 1380actaggatca attgtggact catacttagg ggctacaatg
cagtatactg ggttggatga 1440aagcactggc atggtggtca acagcccaac aaataaggca
aggcacatag cagggaaacc 1500cattcttgat aacaacgcag tgaatctgtt ttcttctgtt
cttattgccc tcttgctccc 1560aactgctgct tggggttttt ggcccagggg gtgaacttta
tttcatttcc acaggttgaa 1620actggtgagt ccagctaaat ttgcaattcc aactttcatc
ctaagaataa taactgtaat 1680ggcaaagcgg aaatgccagt tcctcctgta ttccattgag
atgggatttc acattttcct 1740ctcatcaact cccctgtaat agctagcgtc tttctagtga
aagagaagaa ttcctagaac 1800ttatgcattt ttttcctgct gaatggaagt cttgagcaat
gaagctatat tgtccctaca 1860tattactata tattgaactg aaagttctta cataatcaat
gtcaagtttt gtcttatttt 1920gttttgtttg tttaaaccag tgtaggaaat aaaagtgatg
atatttaaaa tagttctcag 1980ttgaagcaga gaaatgccac tgtgctagtt gcccaaatgt
tgtatctatt ttaaatagtt 2040taagctgatg tgtatgggag cctaaacaag tgtagtatcc
tgaacttctc ccattaattg 2100ctattcacaa ttgggaaaag tgtggagatt ggttcctagt
gagttttgtg gcctactcca 2160catttgttct tccttcctca gggttagtga tgaaaaaaag
taaatatctt tttcatatgt 2220ccattagaat gtatgaaaaa aatcatttta actaaaagca
aaagaatttt atcttatatc 2280taaaaaatat ataacttact atatgtttca gttgctctct
gaacaaaaat tatcttcaat 2340ttaatatgtg gaatgtgttt tctagctttc tttgaattat
gtatggcaac ctggtttagc 2400actggcatcc tgaacagtta agagtcactg ggaaattatt
gtatttcttt ataaatttac 2460tgtcatatca attgctggaa aatgctatga tttttctatt
attaccttct aagttgtatt 2520ctctcttaca ctgtagcctc aactaaggca attctgctat
gtttgttctt cactatgatt 2580tactgtgtgc caaaggagtt ttgacagggt acagagtatt
ttactaaaag tatttttaaa 2640tgtttctcat gtgatttctg taccttcttc ctcctgcccc
ttttgctttt ttaaagaaac 2700tggggaagga tttatgaata caccaccacc agagtggata
atgcttagaa ttctttattg 2760gtggccctac tatggtgatg atctagaact gacttacttc
aggacagaag aaaaaacaat 2820cacaccctta acctttaagc cagttagatc agggggttgc
aacaattggg ttaaactttg 2880ggtatacatt ggaagcacca gggcatgttt gctttttttg
tttatgtgtt tgttttttga 2940gacagagtct cacactgtgg cccaggctgg actccagcac
agtggcatga tctcagctcc 3000gcctcctggg ttcacgtgat tctcatgcct cagcctccca
agtagctggg atcacaggcg 3060tgcaccatca cgcccggcta atttttgtat tttcagtaga
gacagggttt cgccacgttg 3120gctaggctgg tctcgaactc ctgacctcaa gtgatctgcc
catctcagcc tcccaaagat 3180ctattacaag atgtgagcca ctgtgcccag ccaccagggc
atgtttttaa aaaagtactg 3240atgtctgggt ttcacactgc aaaattctga tttatctgat
ctaaggtaca gcctggatat 3300tgagactttt taaagctctg actgtacatt gaatcatcat
gtaaggagtt tttaaaacat 3360tgttgccagg gcccctttct agaccaagtt agtcagaatg
ttggacaatg aggcccatgc 3420atgggtattt ttacaaagct ctctgggaga ttctaatgct
taaccaaatt gagaagcact 3480gaataagaat atcctgggcc gggcgcactg gctcatgcct
gtaatcccag cattttggaa 3540ggccgaggcg ggtggatcac ttgaggtcag gagttcgaga
ccagcctggc caacatggtg 3600aaacaccgtc tctactaaaa atacaaaaaa ttaggtgtgg
tggtgcgtgc ctgtattccc 3660agccactcag gaggctgagg caggagaatc gctggaacct
gggatgtgga ggttgcagtg 3720agccaagatt gcaccactgt actccagcct gggcaacaga
gggagactcc atctagactc 3780catctcaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa
aaaaagaata ttctaagcac 3840tagaactaca taagaatgtc ctaaagcact gtatctaagc
acttgaaaag aatgggactt 3900ttcggtttta gggagataac tattagcaac cacacaatat
gttatcttta tggatgaata 3960acttctggta atgacacagt gtcttacagc tacatcattt
ataaaatcat gtgtcagttt 4020tcacacagcc tgcacatcgt tctgacatgc cctttttttc
cctggagatt tatcctcatg 4080acatacaagg ggacaaaaat atttattggg actgtctttg
aatttagtag aatcactgta 4140tcattaacag tttggggaag tactgctttg cagtccttta
tttgaaaact taggtctagc 4200tgtgttttgc atcaaaattt ttgagctatt caaaaactaa
taggatctgt gtaaaatatt 4260tcactcaaaa ctactaaaaa aaagtctggg atggcagctc
attatcaaat atactcctat 4320ttttgtggtg atttatgaac atccccacta agtataacta
aagatcataa agagcctcag 4380atcaagtttg gtcaggtttt gtcaccaagc tttgtaaata
aactggtttt catagctttt 4440tggagatgag aattgaggat aagaaattgt gtctctgtcc
tttttttttt tttttgttaa 4500gtcttacatg tattttactg taacatcttt tgaattggat
atttaactaa ttcaacatat 4560ttttcctctt tgcagaatgg gcagttcatg ttaaaatcac
ttttcatgga aagagctcta 4620tgtaacagca taataaaact gcctacctag cagcataaa
465945333DNAHomo sapiensmisc_feature(2)..(2)n is a,
c, g, or tmisc_feature(28)..(28)n is a, c, g, or t 45cnggacacat
caaactgctt atccaggnac cactagaagt gaatctcttc ttgagtattc 60catactgctg
cccctgctat tcacttgggg tcccagtcag ttgttactat atatttgtca 120tctattgtga
gagtcgtgat atcaccttcc acatcagtga tactgagaag gaacaaatct 180gccaaagatg
cttcacagtt agttgttacc tttttaagaa gactgtgctt gaaaattatg 240gtaaaacaca
tttagaagaa ggatgtgcat tttcacatca gtctatgaag tataacttga 300catttaaatt
aaaatgctgt tcttcaaaat cga 33346261DNAHomo
sapiensmisc_feature(19)..(19)n is a, c, g, or tmisc_feature(72)..(72)n is
a, c, g, or t 46gttcccgact agctgcccnt gcacattatc ttcattttcc tggaatttga
tacagagagc 60aatttatagc cnattgatag cttatgctgt ttcaatgtaa attcgtggta
aataacttag 120gaactgcctc ttctttttct ttgaaaacct acttataact gttgctaata
agaatgtgta 180ttgttcagga caacttgtct ccatacagtt gggttgtaac cctcatgctt
ggcccaaata 240aactctctac ttatatcagt a
26147598DNAHomo sapiens 47ctaggggtcc tgacggttct ctggctccaa
gtctggcccc tcaacctccc tggtcatcag 60tgggctccag gctgaggatg aggctgatta
ctactgtgca gcatgggatg acagcctgaa 120aggtcctgcg ttcggaggag gcacccacct
gaccgtcctc ggtcagccca aggctgcccc 180ctcggtcact ctgttcccac cctcctctga
ggagcttcaa gccaacaagg ccacactggt 240gtgtctcgta agtgacttct acccgggagc
cgtgacagtg gcctggaagg cagatggcag 300ccccgtcaag gtgggagtgg agaccaccaa
accctccaaa caaagcaaca acaagtatgc 360ggccagcagc tacctgagcc tgacgcccga
gcagtggaag tcccacagaa gctacagctg 420ccgggtcacg catgaaggga gcaccgtgga
gaagacagtg gcccctgcag aatgctctta 480ggcccccgac cctcacccca cccacagggg
cctggagctg caggttccca ggggaggggt 540ctctgccccc atcccaagtc atccagccct
tctcaataaa tatcctcatc gtcaacga 598481614DNAHomo sapiens 48ggtagttggt
tgtgggcact gggttagagg tatcacgtgg gggcactttc gtcttagctt 60ttggacaaga
cgcaggcgca acccacggct gctgcgggga tccttgtggc ccttccggtc 120ggtggaacca
atccgtgcac agagaagcgg ggcgaactga ggcgagtgaa gtggactctg 180agggctaccg
ctaccgccac tgctgcggca ggggcgtgga gggcagaggg ccgcggaggc 240cgcagttgca
aacatggctc agagcagaga cggcggaaac ccgttcgccg agcccagcga 300gcttgacaac
ccctttcagg acccagctgt gatccagcac cgacccagcc ggcagtatgc 360cacgcttgac
gtctacaacc cttttgagac ccgggagcca ccaccagcct atgagcctcc 420agcccctgcc
ccattgcctc caccctcagc tccctccttg cagccctcga gaaagctcag 480ccccacagaa
cctaagaact atggctcata cagcactcag gcctcagctg cagcagccac 540agctgagctg
ctgaagaaac aggaggagct caaccggaag gcagaggagt tggaccgaag 600ggagcgagag
ctgcagcatg ctgccctggg gggcacagct actcgacaga acaattggcc 660ccctctacct
tctttttgtc cagttcagcc ctgctttttc caggacatct ccatggagat 720cccccaagaa
tttcagaaga ctgtatccac catgtactac ctctggatgt gcagcacgct 780ggctcttctc
ctgaacttcc tcgcctgcct ggccagcttc tgtgtggaaa ccaacaatgg 840cgcaggcttt
gggctttcta tcctctgggt cctccttttc actccctgct cctttgtctg 900ctggtaccgc
cccatgtata aggctttccg gagtgacagt tcattcaatt tcttcgtttt 960cttcttcatt
ttcttcgtcc aggatgtgct ctttgtcctc caggccattg gtatcccagg 1020ttggggattc
agtggctgga tctctgctct ggtggtgccg aagggcaaca cagcagtatc 1080cgtgctcatg
ctgctggtcg ccctgctctt cactggcatt gctgtgctag gaattgtcat 1140gctgaaacgg
atccactcct tataccgccg cacaggtgcc agctttcaga aggcccagca 1200agaatttgct
gctggtgtct tctccaaccc tgcggtgcga accgcagctg ccaatgcagc 1260cgctggggct
gctgaaaatg ccttccgggc cccgtgaccc ctgactggga tgccctggcc 1320ctgctacttg
agggagctga cttagctccc gtccctaagg tctctgggac ttggagagac 1380atcactaact
gatggctcct ccgtagtgct cccaatccta tggccatgac tgctgaacct 1440gacaggcgtg
tggggagttc actgtgacct agtcccccca tcaggccaca ctgctgccac 1500ctctcacacg
ccccaaccca gcttccctct gctgtgccac ggctgttgct tcggttattt 1560aaataaaaag
aaagtggaac tggaactgac aaaaaaaaaa aaaaaaaaaa aaaa 161449326DNAHomo
sapiensmisc_feature(13)..(13)n is a, c, g, or tmisc_feature(20)..(20)n is
a, c, g, or tmisc_feature(32)..(32)n is a, c, g, or
tmisc_feature(47)..(47)n is a, c, g, or t 49ctgcaagaac tantcattcn
aggtcaccag anaggagccc tgacccntcg ctgcccagcc 60tgtccttgtg tcgtcttttt
acgggagacg actggatcat gggggcggat tttccccttg 120ctgttctcat gatagtgagt
tctcatgaga tctggttgtt taaaagtgta tagcacttcc 180tgcttcactc tctcccactc
caccatgtga agaaggtgcc tttgcccttc cgccacgact 240gtgtttcctg aggcctcccc
agccatgctt cctgtacagc ctgcagaact gtgagttaat 300taaacctctt ttcttcataa
agaaca 32650944DNAHomo sapiens
50tcaagattaa acgacaagga cagacatggc tcagcggatg acaacacagc tgctgctcct
60tctagtgtgg gtggctgtag taggggaggc tcagacaagg attgcatggg ccaggactga
120gcttctcaat gtctgcatga acgccaagca ccacaaggaa aagccaggcc ccgaggacaa
180gttgcatgag cagtgtcgac cctggaggaa gaatgcctgc tgttctacca acaccagcca
240ggaagcccat aaggatgttt cctacctata tagattcaac tggaaccact gtggagagat
300ggcacctgcc tgcaaacggc atttcatcca ggacacctgc ctctacgagt gctcccccaa
360cttggggccc tggatccagc aggtggatca gagctggcgc aaagagcggg tactgaacgt
420gcccctgtgc aaagaggact gtgagcaatg gtgggaagat tgtcgcacct cctacacctg
480caagagcaac tggcacaagg gctggaactg gacttcaggg tttaacaagt gcgcagtggg
540agctgcctgc caacctttcc atttctactt ccccacaccc actgttctgt gcaatgaaat
600ctggactcac tcctacaagg tcagcaacta cagccgaggg agtggccgct gcatccagat
660gtggttcgac ccagcccagg gcaaccccaa tgaggaggtg gcgaggttct atgctgcagc
720catgagtggg gctgggccct gggcagcctg gcctttcctg cttagcctgg ccctaatgct
780gctgtggctg ctcagctgac ctccttttac cttctgatac ctggaaatcc ctgccctgtt
840cagccccaca gctcccaact atttggttcc tgctccatgg tcgggcctct gacagccact
900ttgaataaac cagacaccgc acatgtgtct tgagaattat ttgg
9445174PRTHomo sapiens 51Met Pro Val Ile Asn Ile Glu Asp Leu Thr Glu Lys
Asp Lys Leu Lys 1 5 10
15 Met Glu Val Asp Gln Leu Lys Lys Glu Val Thr Leu Glu Arg Met Leu
20 25 30 Val Ser Lys
Cys Cys Glu Glu Val Arg Asp Tyr Val Glu Glu Arg Ser 35
40 45 Gly Glu Asp Pro Leu Val Lys Gly
Ile Pro Glu Asp Lys Asn Pro Phe 50 55
60 Lys Glu Leu Lys Gly Gly Cys Val Ile Ser 65
70 52413PRTHomo sapiens 52Met Val Glu Arg Cys
Ser Arg Gln Gly Cys Thr Ile Thr Met Ala Tyr 1 5
10 15 Ile Asp Tyr Asn Met Ile Val Ala Phe Met
Leu Gly Asn Tyr Ile Asn 20 25
30 Leu Arg Glu Ser Ser Thr Glu Pro Asn Asp Ser Leu Trp Phe Ser
Leu 35 40 45 Gln
Lys Lys Asn Asp Thr Thr Glu Ile Glu Thr Leu Leu Leu Asn Thr 50
55 60 Ala Pro Lys Ile Ile Asp
Glu Gln Leu Val Cys Arg Leu Ser Lys Thr 65 70
75 80 Asp Ile Phe Ile Ile Cys Arg Asp Asn Lys Ile
Tyr Leu Asp Lys Met 85 90
95 Ile Thr Arg Asn Leu Lys Leu Arg Phe Tyr Gly His Arg Gln Tyr Leu
100 105 110 Glu Cys
Glu Val Phe Arg Val Glu Gly Ile Lys Asp Asn Leu Asp Asp 115
120 125 Ile Lys Arg Ile Ile Lys Ala
Arg Glu His Arg Asn Arg Leu Leu Ala 130 135
140 Asp Ile Arg Asp Tyr Arg Pro Tyr Ala Asp Leu Val
Ser Glu Ile Arg 145 150 155
160 Ile Leu Leu Val Gly Pro Val Gly Ser Gly Lys Ser Ser Phe Phe Asn
165 170 175 Ser Val Lys
Ser Ile Phe His Gly His Val Thr Gly Gln Ala Val Val 180
185 190 Gly Ser Asp Thr Thr Ser Ile Thr
Glu Arg Tyr Arg Ile Tyr Ser Val 195 200
205 Lys Asp Gly Lys Asn Gly Lys Ser Leu Pro Phe Met Leu
Cys Asp Thr 210 215 220
Met Gly Leu Asp Gly Ala Glu Gly Ala Gly Leu Cys Met Asp Asp Ile 225
230 235 240 Pro His Ile Leu
Lys Gly Cys Met Pro Asp Arg Tyr Gln Phe Asn Ser 245
250 255 Arg Lys Pro Ile Thr Pro Glu His Ser
Thr Phe Ile Thr Ser Pro Ser 260 265
270 Leu Lys Asp Arg Ile His Cys Val Ala Tyr Val Leu Asp Ile
Asn Ser 275 280 285
Ile Asp Asn Leu Tyr Ser Lys Met Leu Ala Lys Val Lys Gln Val His 290
295 300 Lys Glu Val Leu Asn
Cys Gly Ile Ala Tyr Val Ala Leu Leu Thr Lys 305 310
315 320 Val Asp Asp Cys Ser Glu Val Leu Gln Asp
Asn Phe Leu Asn Met Ser 325 330
335 Arg Ser Met Thr Ser Gln Ser Arg Val Met Asn Val His Lys Met
Leu 340 345 350 Gly
Ile Pro Ile Ser Asn Ile Leu Met Val Gly Asn Tyr Ala Ser Asp 355
360 365 Leu Glu Leu Asp Pro Met
Lys Asp Ile Leu Ile Leu Ser Ala Leu Arg 370 375
380 Gln Met Leu Arg Ala Ala Asp Asp Phe Leu Glu
Asp Leu Pro Leu Glu 385 390 395
400 Glu Thr Gly Ala Ile Glu Arg Ala Leu Gln Pro Cys Ile 405
410 53328PRTHomo sapiens 53Met Ser Ser Tyr
Leu Glu Tyr Val Ser Cys Ser Ser Ser Gly Gly Val 1 5
10 15 Gly Gly Asp Val Leu Ser Leu Ala Pro
Lys Phe Cys Arg Ser Asp Ala 20 25
30 Arg Pro Val Ala Leu Gln Pro Ala Phe Pro Leu Gly Asn Gly
Asp Gly 35 40 45
Ala Phe Val Ser Cys Leu Pro Leu Ala Ala Ala Arg Pro Ser Pro Ser 50
55 60 Pro Pro Ala Ala Pro
Ala Arg Pro Ser Val Pro Pro Pro Ala Ala Pro 65 70
75 80 Gln Tyr Ala Gln Cys Thr Leu Glu Gly Ala
Tyr Glu Pro Gly Ala Ala 85 90
95 Pro Ala Ala Ala Ala Gly Gly Ala Asp Tyr Gly Phe Leu Gly Ser
Gly 100 105 110 Pro
Ala Tyr Asp Phe Pro Gly Val Leu Gly Arg Ala Ala Asp Asp Gly 115
120 125 Gly Ser His Val His Tyr
Ala Thr Ser Ala Val Phe Ser Gly Gly Gly 130 135
140 Ser Phe Leu Leu Ser Gly Gln Val Asp Tyr Ala
Ala Phe Gly Glu Pro 145 150 155
160 Gly Pro Phe Pro Ala Cys Leu Lys Ala Ser Ala Asp Gly His Pro Gly
165 170 175 Ala Phe
Gln Thr Ala Ser Pro Ala Pro Gly Thr Tyr Pro Lys Ser Val 180
185 190 Ser Pro Ala Ser Gly Leu Pro
Ala Ala Phe Ser Thr Phe Glu Trp Met 195 200
205 Lys Val Lys Arg Asn Ala Ser Lys Lys Gly Lys Leu
Ala Glu Tyr Gly 210 215 220
Ala Ala Ser Pro Ser Ser Ala Ile Arg Thr Asn Phe Ser Thr Lys Gln 225
230 235 240 Leu Thr Glu
Leu Glu Lys Glu Phe His Phe Asn Lys Tyr Leu Thr Arg 245
250 255 Ala Arg Arg Ile Glu Ile Ala Asn
Cys Leu His Leu Asn Asp Thr Gln 260 265
270 Val Lys Ile Trp Phe Gln Asn Arg Arg Met Lys Gln Lys
Lys Arg Glu 275 280 285
Arg Glu Gly Leu Leu Ala Thr Ala Ile Pro Val Ala Pro Leu Gln Leu 290
295 300 Pro Leu Ser Gly
Thr Thr Pro Thr Lys Phe Ile Lys Asn Pro Gly Ser 305 310
315 320 Pro Ser Gln Ser Gln Glu Pro Ser
325 54107PRTHomo sapiens 54Met Ala Asn Glu Val
Gln Asp Leu Leu Ser Pro Arg Lys Gly Gly His 1 5
10 15 Pro Pro Ala Val Lys Ala Gly Gly Met Arg
Ile Ser Lys Lys Gln Glu 20 25
30 Ile Gly Thr Leu Glu Arg His Thr Lys Lys Thr Gly Phe Glu Lys
Thr 35 40 45 Ser
Ala Ile Ala Asn Val Ala Lys Ile Gln Thr Leu Asp Ala Leu Asn 50
55 60 Asp Thr Leu Glu Lys Leu
Asn Tyr Lys Phe Pro Ala Thr Val His Met 65 70
75 80 Ala His Gln Lys Pro Thr Pro Ala Leu Glu Lys
Val Val Pro Leu Lys 85 90
95 Arg Ile Tyr Ile Ile Gln Gln Pro Arg Lys Cys 100
105 55478PRTHomo sapiens 55Met Ser Thr Asn Gly Asp
Asp His Gln Val Lys Asp Ser Leu Glu Gln 1 5
10 15 Leu Arg Cys His Phe Thr Trp Glu Leu Ser Ile
Asp Asp Asp Glu Met 20 25
30 Pro Asp Leu Glu Asn Arg Val Leu Asp Gln Ile Glu Phe Leu Asp
Thr 35 40 45 Lys
Tyr Ser Val Gly Ile His Asn Leu Leu Ala Tyr Val Lys His Leu 50
55 60 Lys Gly Gln Asn Glu Glu
Ala Leu Lys Ser Leu Lys Glu Ala Glu Asn 65 70
75 80 Leu Met Gln Glu Glu His Asp Asn Gln Ala Asn
Val Arg Ser Leu Val 85 90
95 Thr Trp Gly Asn Phe Ala Trp Met Tyr Tyr His Met Gly Arg Leu Ala
100 105 110 Glu Ala
Gln Thr Tyr Leu Asp Lys Val Glu Asn Ile Cys Lys Lys Leu 115
120 125 Ser Asn Pro Phe Arg Tyr Arg
Met Glu Cys Pro Glu Ile Asp Cys Glu 130 135
140 Glu Gly Trp Ala Leu Leu Lys Cys Gly Gly Lys Asn
Tyr Glu Arg Ala 145 150 155
160 Lys Ala Cys Phe Glu Lys Val Leu Glu Val Asp Pro Glu Asn Pro Glu
165 170 175 Ser Ser Ala
Gly Tyr Ala Ile Ser Ala Tyr Arg Leu Asp Gly Phe Lys 180
185 190 Leu Ala Thr Lys Asn His Lys Pro
Phe Ser Leu Leu Pro Leu Arg Gln 195 200
205 Ala Val Arg Leu Asn Pro Asp Asn Gly Tyr Ile Lys Val
Leu Leu Ala 210 215 220
Leu Lys Leu Gln Asp Glu Gly Gln Glu Ala Glu Gly Glu Lys Tyr Ile 225
230 235 240 Glu Glu Ala Leu
Ala Asn Met Ser Ser Gln Thr Tyr Val Phe Arg Tyr 245
250 255 Ala Ala Lys Phe Tyr Arg Arg Lys Gly
Ser Val Asp Lys Ala Leu Glu 260 265
270 Leu Leu Lys Lys Ala Leu Gln Glu Thr Pro Thr Ser Val Leu
Leu His 275 280 285
His Gln Ile Gly Leu Cys Tyr Lys Ala Gln Met Ile Gln Ile Lys Glu 290
295 300 Ala Thr Lys Gly Gln
Pro Arg Gly Gln Asn Arg Glu Lys Leu Asp Lys 305 310
315 320 Met Ile Arg Ser Ala Ile Phe His Phe Glu
Ser Ala Val Glu Lys Lys 325 330
335 Pro Thr Phe Glu Val Ala His Leu Asp Leu Ala Arg Met Tyr Ile
Glu 340 345 350 Ala
Gly Asn His Arg Lys Ala Glu Glu Asn Phe Gln Lys Leu Leu Cys 355
360 365 Met Lys Pro Val Val Glu
Glu Thr Met Gln Asp Ile His Phe His Tyr 370 375
380 Gly Arg Phe Gln Glu Phe Gln Lys Lys Ser Asp
Val Asn Ala Ile Ile 385 390 395
400 His Tyr Leu Lys Ala Ile Lys Ile Glu Gln Ala Ser Leu Thr Arg Asp
405 410 415 Lys Ser
Ile Asn Ser Leu Lys Lys Leu Val Leu Arg Lys Leu Arg Arg 420
425 430 Lys Ala Leu Asp Leu Glu Ser
Leu Ser Leu Leu Gly Phe Val Tyr Lys 435 440
445 Leu Glu Gly Asn Met Asn Glu Ala Leu Glu Tyr Tyr
Glu Arg Ala Leu 450 455 460
Arg Leu Ala Ala Asp Phe Glu Asn Ser Val Arg Gln Gly Pro 465
470 475 561020PRTHomo sapiens 56Met
Gln Ser Cys Ala Arg Ala Trp Gly Leu Arg Leu Gly Arg Gly Val 1
5 10 15 Gly Gly Gly Arg Arg Leu
Ala Gly Gly Ser Gly Pro Cys Trp Ala Pro 20
25 30 Arg Ser Arg Asp Ser Ser Ser Gly Gly Gly
Asp Ser Ala Ala Ala Gly 35 40
45 Ala Ser Arg Leu Leu Glu Arg Leu Leu Pro Arg His Asp Asp
Phe Ala 50 55 60
Arg Arg His Ile Gly Pro Gly Asp Lys Asp Gln Arg Glu Met Leu Gln 65
70 75 80 Thr Leu Gly Leu Ala
Ser Ile Asp Glu Leu Ile Glu Lys Thr Val Pro 85
90 95 Ala Asn Ile Arg Leu Lys Arg Pro Leu Lys
Met Glu Asp Pro Val Cys 100 105
110 Glu Asn Glu Ile Leu Ala Thr Leu His Ala Ile Ser Ser Lys Asn
Gln 115 120 125 Ile
Trp Arg Ser Tyr Ile Gly Met Gly Tyr Tyr Asn Cys Ser Val Pro 130
135 140 Gln Thr Ile Leu Arg Asn
Leu Leu Glu Asn Ser Gly Trp Ile Thr Gln 145 150
155 160 Tyr Thr Pro Tyr Gln Pro Glu Val Ser Gln Gly
Arg Leu Glu Ser Leu 165 170
175 Leu Asn Tyr Gln Thr Met Val Cys Asp Ile Thr Gly Leu Asp Met Ala
180 185 190 Asn Ala
Ser Leu Leu Asp Glu Gly Thr Ala Ala Ala Glu Ala Leu Gln 195
200 205 Leu Cys Tyr Arg His Asn Lys
Arg Arg Lys Phe Leu Val Asp Pro Arg 210 215
220 Cys His Pro Gln Thr Ile Ala Val Val Gln Thr Arg
Ala Lys Tyr Thr 225 230 235
240 Gly Val Leu Thr Glu Leu Lys Leu Pro Cys Glu Met Asp Phe Ser Gly
245 250 255 Lys Asp Val
Ser Gly Val Leu Phe Gln Tyr Pro Asp Thr Glu Gly Lys 260
265 270 Val Glu Asp Phe Thr Glu Leu Val
Glu Arg Ala His Gln Ser Gly Ser 275 280
285 Leu Ala Cys Cys Ala Thr Asp Leu Leu Ala Leu Cys Ile
Leu Arg Pro 290 295 300
Pro Gly Glu Phe Gly Val Asp Ile Ala Leu Gly Ser Ser Gln Arg Phe 305
310 315 320 Gly Val Pro Leu
Gly Tyr Gly Gly Pro His Ala Ala Phe Phe Ala Val 325
330 335 Arg Glu Ser Leu Val Arg Met Met Pro
Gly Arg Met Val Gly Val Thr 340 345
350 Arg Asp Ala Thr Gly Lys Glu Val Tyr Arg Leu Ala Leu Gln
Thr Arg 355 360 365
Glu Gln His Ile Arg Arg Asp Lys Ala Thr Ser Asn Ile Cys Thr Ala 370
375 380 Gln Ala Leu Leu Ala
Asn Met Ala Ala Met Phe Arg Ile Tyr His Gly 385 390
395 400 Ser His Gly Leu Glu His Ile Ala Arg Arg
Val His Asn Ala Thr Leu 405 410
415 Ile Leu Ser Glu Gly Leu Lys Arg Ala Gly His Gln Leu Gln His
Asp 420 425 430 Leu
Phe Phe Asp Thr Leu Lys Ile His Cys Gly Cys Ser Val Lys Glu 435
440 445 Val Leu Gly Arg Ala Ala
Gln Arg Gln Ile Asn Phe Arg Leu Phe Glu 450 455
460 Asp Gly Thr Leu Gly Ile Ser Leu Asp Glu Thr
Val Asn Glu Lys Asp 465 470 475
480 Leu Asp Asp Leu Leu Trp Ile Phe Gly Cys Glu Ser Ser Ala Glu Leu
485 490 495 Val Ala
Glu Ser Met Gly Glu Glu Cys Arg Gly Ile Pro Gly Ser Val 500
505 510 Phe Lys Arg Thr Ser Pro Phe
Leu Thr His Gln Val Phe Asn Ser Tyr 515 520
525 His Ser Glu Thr Asn Ile Val Arg Tyr Met Lys Lys
Leu Glu Asn Lys 530 535 540
Asp Ile Ser Leu Val His Ser Met Ile Pro Leu Gly Ser Cys Thr Met 545
550 555 560 Lys Leu Asn
Ser Ser Ser Glu Leu Ala Pro Ile Thr Trp Lys Glu Phe 565
570 575 Ala Asn Ile His Pro Phe Val Pro
Leu Asp Gln Ala Gln Gly Tyr Gln 580 585
590 Gln Leu Phe Arg Glu Leu Glu Lys Asp Leu Cys Glu Leu
Thr Gly Tyr 595 600 605
Asp Gln Val Cys Phe Gln Pro Asn Ser Gly Ala Gln Gly Glu Tyr Ala 610
615 620 Gly Leu Ala Thr
Ile Arg Ala Tyr Leu Asn Gln Lys Gly Glu Gly His 625 630
635 640 Arg Thr Val Cys Leu Ile Pro Lys Ser
Ala His Gly Thr Asn Pro Ala 645 650
655 Ser Ala His Met Ala Gly Met Lys Ile Gln Pro Val Glu Val
Asp Lys 660 665 670
Tyr Gly Asn Ile Asp Ala Val His Leu Lys Ala Met Val Asp Lys His
675 680 685 Lys Glu Asn Leu
Ala Ala Ile Met Ile Thr Tyr Pro Ser Thr Asn Gly 690
695 700 Val Phe Glu Glu Asn Ile Ser Asp
Val Cys Asp Leu Ile His Gln His 705 710
715 720 Gly Gly Gln Val Tyr Leu Asp Gly Ala Asn Met Asn
Ala Gln Val Gly 725 730
735 Ile Cys Arg Pro Gly Asp Phe Gly Ser Asp Val Ser His Leu Asn Leu
740 745 750 His Lys Thr
Phe Cys Ile Pro His Gly Gly Gly Gly Pro Gly Met Gly 755
760 765 Pro Ile Gly Val Lys Lys His Leu
Ala Pro Phe Leu Pro Asn His Pro 770 775
780 Val Ile Ser Leu Lys Arg Asn Glu Asp Ala Cys Pro Val
Gly Thr Val 785 790 795
800 Ser Ala Ala Pro Trp Gly Ser Ser Ser Ile Leu Pro Ile Ser Trp Ala
805 810 815 Tyr Ile Lys Met
Met Gly Gly Lys Gly Leu Lys Gln Ala Thr Glu Thr 820
825 830 Ala Ile Leu Asn Ala Asn Tyr Met Ala
Lys Arg Leu Glu Thr His Tyr 835 840
845 Arg Ile Leu Phe Arg Gly Ala Arg Gly Tyr Val Gly His Glu
Phe Ile 850 855 860
Leu Asp Thr Arg Pro Phe Lys Lys Ser Ala Asn Ile Glu Ala Val Asp 865
870 875 880 Val Ala Lys Arg Leu
Gln Asp Tyr Gly Phe His Ala Pro Thr Met Ser 885
890 895 Trp Pro Val Ala Gly Thr Leu Met Val Glu
Pro Thr Glu Ser Glu Asp 900 905
910 Lys Ala Glu Leu Asp Arg Phe Cys Asp Ala Met Ile Ser Ile Arg
Gln 915 920 925 Glu
Ile Ala Asp Ile Glu Glu Gly Arg Ile Asp Pro Arg Val Asn Pro 930
935 940 Leu Lys Met Ser Pro His
Ser Leu Thr Cys Val Thr Ser Ser His Trp 945 950
955 960 Asp Arg Pro Tyr Ser Arg Glu Val Ala Ala Phe
Pro Leu Pro Phe Met 965 970
975 Lys Pro Glu Asn Lys Phe Trp Pro Thr Ile Ala Arg Ile Asp Asp Ile
980 985 990 Tyr Gly
Asp Gln His Leu Val Cys Thr Cys Pro Pro Met Glu Val Tyr 995
1000 1005 Glu Ser Pro Phe Ser
Glu Gln Lys Arg Ala Ser Ser 1010 1015
1020 57513PRTHomo sapiens 57Met Ile Arg Thr Pro Leu Ser Ala Ser Ala His
Arg Leu Leu Leu Pro 1 5 10
15 Gly Ser Arg Gly Arg Pro Pro Arg Asn Met Gln Pro Thr Gly Arg Glu
20 25 30 Gly Ser
Arg Ala Leu Ser Arg Arg Tyr Leu Arg Arg Leu Leu Leu Leu 35
40 45 Leu Leu Leu Leu Leu Leu Arg
Gln Pro Val Thr Arg Ala Glu Thr Thr 50 55
60 Pro Gly Ala Pro Arg Ala Leu Ser Thr Leu Gly Ser
Pro Ser Leu Phe 65 70 75
80 Thr Thr Pro Gly Val Pro Ser Ala Leu Thr Thr Pro Gly Leu Thr Thr
85 90 95 Pro Gly Thr
Pro Lys Thr Leu Asp Leu Arg Gly Arg Ala Gln Ala Leu 100
105 110 Met Arg Ser Phe Pro Leu Val Asp
Gly His Asn Asp Leu Pro Gln Val 115 120
125 Leu Arg Gln Arg Tyr Lys Asn Val Leu Gln Asp Val Asn
Leu Arg Asn 130 135 140
Phe Ser His Gly Gln Thr Ser Leu Asp Arg Leu Arg Asp Gly Leu Val 145
150 155 160 Gly Ala Gln Phe
Trp Ser Ala Ser Val Ser Cys Gln Ser Gln Asp Gln 165
170 175 Thr Ala Val Arg Leu Ala Leu Glu Gln
Ile Asp Leu Ile His Arg Met 180 185
190 Cys Ala Ser Tyr Ser Glu Leu Glu Leu Val Thr Ser Ala Glu
Gly Leu 195 200 205
Asn Ser Ser Gln Lys Leu Ala Cys Leu Ile Gly Val Glu Gly Gly His 210
215 220 Ser Leu Asp Ser Ser
Leu Ser Val Leu Arg Ser Phe Tyr Val Leu Gly 225 230
235 240 Val Arg Tyr Leu Thr Leu Thr Phe Thr Cys
Ser Thr Pro Trp Ala Glu 245 250
255 Ser Ser Thr Lys Phe Arg His His Met Tyr Thr Asn Val Ser Gly
Leu 260 265 270 Thr
Ser Phe Gly Glu Lys Val Val Glu Glu Leu Asn Arg Leu Gly Met 275
280 285 Met Ile Asp Leu Ser Tyr
Ala Ser Asp Thr Leu Ile Arg Arg Val Leu 290 295
300 Glu Val Ser Gln Ala Pro Val Ile Phe Ser His
Ser Ala Ala Arg Ala 305 310 315
320 Val Cys Asp Asn Leu Leu Asn Val Pro Asp Asp Ile Leu Gln Leu Leu
325 330 335 Lys Lys
Asn Gly Gly Ile Val Met Val Thr Leu Ser Met Gly Val Leu 340
345 350 Gln Cys Asn Leu Leu Ala Asn
Val Ser Thr Val Ala Asp His Phe Asp 355 360
365 His Ile Arg Ala Val Ile Gly Ser Glu Phe Ile Gly
Ile Gly Gly Asn 370 375 380
Tyr Asp Gly Thr Gly Arg Phe Pro Gln Gly Leu Glu Asp Val Ser Thr 385
390 395 400 Tyr Pro Val
Leu Ile Glu Glu Leu Leu Ser Arg Ser Trp Ser Glu Glu 405
410 415 Glu Leu Gln Gly Val Leu Arg Gly
Asn Leu Leu Arg Val Phe Arg Gln 420 425
430 Val Glu Lys Val Arg Glu Glu Ser Arg Ala Gln Ser Pro
Val Glu Ala 435 440 445
Glu Phe Pro Tyr Gly Gln Leu Ser Thr Ser Cys His Ser His Leu Val 450
455 460 Pro Gln Asn Gly
His Gln Ala Thr His Leu Glu Val Thr Lys Gln Pro 465 470
475 480 Thr Asn Arg Val Pro Trp Arg Ser Ser
Asn Ala Ser Pro Tyr Leu Val 485 490
495 Pro Gly Leu Val Ala Ala Ala Thr Ile Pro Thr Phe Thr Gln
Trp Leu 500 505 510
Cys 58174PRTHomo sapiens 58Met Leu Arg Thr Glu Ser Cys Arg Pro Arg Ser
Pro Ala Gly Gln Val 1 5 10
15 Ala Ala Ala Ser Pro Leu Leu Leu Leu Leu Leu Leu Leu Ala Trp Cys
20 25 30 Ala Gly
Ala Cys Arg Gly Ala Pro Ile Leu Pro Gln Gly Leu Gln Pro 35
40 45 Glu Gln Gln Leu Gln Leu Trp
Asn Glu Ile Asp Asp Thr Cys Ser Ser 50 55
60 Phe Leu Ser Ile Asp Ser Gln Pro Gln Ala Ser Asn
Ala Leu Glu Glu 65 70 75
80 Leu Cys Phe Met Ile Met Gly Met Leu Pro Lys Pro Gln Glu Gln Asp
85 90 95 Glu Lys Asp
Asn Thr Lys Arg Phe Leu Phe His Tyr Ser Lys Thr Gln 100
105 110 Lys Leu Gly Lys Ser Asn Val Val
Ser Ser Val Val His Pro Leu Leu 115 120
125 Gln Leu Val Pro His Leu His Glu Arg Arg Met Lys Arg
Phe Arg Val 130 135 140
Asp Glu Glu Phe Gln Ser Pro Phe Ala Ser Gln Ser Arg Gly Tyr Phe 145
150 155 160 Leu Phe Arg Pro
Arg Asn Gly Arg Arg Ser Ala Gly Phe Ile 165
170 59431PRTHomo sapiens 59Met His Val Arg Ser Leu Arg
Ala Ala Ala Pro His Ser Phe Val Ala 1 5
10 15 Leu Trp Ala Pro Leu Phe Leu Leu Arg Ser Ala
Leu Ala Asp Phe Ser 20 25
30 Leu Asp Asn Glu Val His Ser Ser Phe Ile His Arg Arg Leu Arg
Ser 35 40 45 Gln
Glu Arg Arg Glu Met Gln Arg Glu Ile Leu Ser Ile Leu Gly Leu 50
55 60 Pro His Arg Pro Arg Pro
His Leu Gln Gly Lys His Asn Ser Ala Pro 65 70
75 80 Met Phe Met Leu Asp Leu Tyr Asn Ala Met Ala
Val Glu Glu Gly Gly 85 90
95 Gly Pro Gly Gly Gln Gly Phe Ser Tyr Pro Tyr Lys Ala Val Phe Ser
100 105 110 Thr Gln
Gly Pro Pro Leu Ala Ser Leu Gln Asp Ser His Phe Leu Thr 115
120 125 Asp Ala Asp Met Val Met Ser
Phe Val Asn Leu Val Glu His Asp Lys 130 135
140 Glu Phe Phe His Pro Arg Tyr His His Arg Glu Phe
Arg Phe Asp Leu 145 150 155
160 Ser Lys Ile Pro Glu Gly Glu Ala Val Thr Ala Ala Glu Phe Arg Ile
165 170 175 Tyr Lys Asp
Tyr Ile Arg Glu Arg Phe Asp Asn Glu Thr Phe Arg Ile 180
185 190 Ser Val Tyr Gln Val Leu Gln Glu
His Leu Gly Arg Glu Ser Asp Leu 195 200
205 Phe Leu Leu Asp Ser Arg Thr Leu Trp Ala Ser Glu Glu
Gly Trp Leu 210 215 220
Val Phe Asp Ile Thr Ala Thr Ser Asn His Trp Val Val Asn Pro Arg 225
230 235 240 His Asn Leu Gly
Leu Gln Leu Ser Val Glu Thr Leu Asp Gly Gln Ser 245
250 255 Ile Asn Pro Lys Leu Ala Gly Leu Ile
Gly Arg His Gly Pro Gln Asn 260 265
270 Lys Gln Pro Phe Met Val Ala Phe Phe Lys Ala Thr Glu Val
His Phe 275 280 285
Arg Ser Ile Arg Ser Thr Gly Ser Lys Gln Arg Ser Gln Asn Arg Ser 290
295 300 Lys Thr Pro Lys Asn
Gln Glu Ala Leu Arg Met Ala Asn Val Ala Glu 305 310
315 320 Asn Ser Ser Ser Asp Gln Arg Gln Ala Cys
Lys Lys His Glu Leu Tyr 325 330
335 Val Ser Phe Arg Asp Leu Gly Trp Gln Asp Trp Ile Ile Ala Pro
Glu 340 345 350 Gly
Tyr Ala Ala Tyr Tyr Cys Glu Gly Glu Cys Ala Phe Pro Leu Asn 355
360 365 Ser Tyr Met Asn Ala Thr
Asn His Ala Ile Val Gln Thr Leu Val His 370 375
380 Phe Ile Asn Pro Glu Thr Val Pro Lys Pro Cys
Cys Ala Pro Thr Gln 385 390 395
400 Leu Asn Ala Ile Ser Val Leu Tyr Phe Asp Asp Ser Ser Asn Val Ile
405 410 415 Leu Lys
Lys Tyr Arg Asn Met Val Val Arg Ala Cys Gly Cys His 420
425 430 60212PRTHomo sapiens 60Met Lys Pro
Pro Ser Ser Ile Gln Thr Ser Glu Phe Asp Ser Ser Asp 1 5
10 15 Glu Glu Pro Ile Glu Asp Glu Gln
Thr Pro Ile His Ile Ser Trp Leu 20 25
30 Ser Leu Ser Arg Val Asn Cys Ser Gln Phe Leu Gly Leu
Cys Ala Leu 35 40 45
Pro Gly Cys Lys Phe Lys Asp Val Arg Arg Asn Val Gln Lys Asp Thr 50
55 60 Glu Glu Leu Lys
Ser Cys Gly Ile Gln Asp Ile Phe Val Phe Cys Thr 65 70
75 80 Arg Gly Glu Leu Ser Lys Tyr Arg Val
Pro Asn Leu Leu Asp Leu Tyr 85 90
95 Gln Gln Cys Gly Ile Ile Thr His His His Pro Ile Ala Asp
Gly Gly 100 105 110
Thr Pro Asp Ile Ala Ser Cys Cys Glu Ile Met Glu Glu Leu Thr Thr
115 120 125 Cys Leu Lys Asn
Tyr Arg Lys Thr Leu Ile His Cys Tyr Gly Gly Leu 130
135 140 Gly Arg Ser Cys Leu Val Ala Ala
Cys Leu Leu Leu Tyr Leu Ser Asp 145 150
155 160 Thr Ile Ser Pro Glu Gln Ala Ile Asp Ser Leu Arg
Asp Leu Arg Gly 165 170
175 Ser Gly Ala Ile Gln Thr Ile Lys Gln Tyr Asn Tyr Leu His Glu Phe
180 185 190 Arg Asp Lys
Leu Ala Ala His Leu Ser Ser Arg Asp Ser Gln Ser Arg 195
200 205 Ser Val Ser Arg 210
6179PRTHomo sapiens 61Met Ser His Lys Gln Ile Tyr Tyr Ser Asp Lys Tyr Asp
Asp Glu Glu 1 5 10 15
Phe Glu Tyr Arg His Val Met Leu Pro Lys Asp Ile Ala Lys Leu Val
20 25 30 Pro Lys Thr His
Leu Met Ser Glu Ser Glu Trp Arg Asn Leu Gly Val 35
40 45 Gln Gln Ser Gln Gly Trp Val His Tyr
Met Ile His Glu Pro Glu Pro 50 55
60 His Ile Leu Leu Phe Arg Arg Pro Leu Pro Lys Lys Pro
Lys Lys 65 70 75
62509PRTHomo sapiens 62Met Glu Arg Arg Arg Leu Trp Gly Ser Ile Gln Ser
Arg Tyr Ile Ser 1 5 10
15 Met Ser Val Trp Thr Ser Pro Arg Arg Leu Val Glu Leu Ala Gly Gln
20 25 30 Ser Leu Leu
Lys Asp Glu Ala Leu Ala Ile Ala Ala Leu Glu Leu Leu 35
40 45 Pro Arg Glu Leu Phe Pro Pro Leu
Phe Met Ala Ala Phe Asp Gly Arg 50 55
60 His Ser Gln Thr Leu Lys Ala Met Val Gln Ala Trp Pro
Phe Thr Cys 65 70 75
80 Leu Pro Leu Gly Val Leu Met Lys Gly Gln His Leu His Leu Glu Thr
85 90 95 Phe Lys Ala Val
Leu Asp Gly Leu Asp Val Leu Leu Ala Gln Glu Val 100
105 110 Arg Pro Arg Arg Trp Lys Leu Gln Val
Leu Asp Leu Arg Lys Asn Ser 115 120
125 His Gln Asp Phe Trp Thr Val Trp Ser Gly Asn Arg Ala Ser
Leu Tyr 130 135 140
Ser Phe Pro Glu Pro Glu Ala Ala Gln Pro Met Thr Lys Lys Arg Lys 145
150 155 160 Val Asp Gly Leu Ser
Thr Glu Ala Glu Gln Pro Phe Ile Pro Val Glu 165
170 175 Val Leu Val Asp Leu Phe Leu Lys Glu Gly
Ala Cys Asp Glu Leu Phe 180 185
190 Ser Tyr Leu Ile Glu Lys Val Lys Arg Lys Lys Asn Val Leu Arg
Leu 195 200 205 Cys
Cys Lys Lys Leu Lys Ile Phe Ala Met Pro Met Gln Asp Ile Lys 210
215 220 Met Ile Leu Lys Met Val
Gln Leu Asp Ser Ile Glu Asp Leu Glu Val 225 230
235 240 Thr Cys Thr Trp Lys Leu Pro Thr Leu Ala Lys
Phe Ser Pro Tyr Leu 245 250
255 Gly Gln Met Ile Asn Leu Arg Arg Leu Leu Leu Ser His Ile His Ala
260 265 270 Ser Ser
Tyr Ile Ser Pro Glu Lys Glu Glu Gln Tyr Ile Ala Gln Phe 275
280 285 Thr Ser Gln Phe Leu Ser Leu
Gln Cys Leu Gln Ala Leu Tyr Val Asp 290 295
300 Ser Leu Phe Phe Leu Arg Gly Arg Leu Asp Gln Leu
Leu Arg His Val 305 310 315
320 Met Asn Pro Leu Glu Thr Leu Ser Ile Thr Asn Cys Arg Leu Ser Glu
325 330 335 Gly Asp Val
Met His Leu Ser Gln Ser Pro Ser Val Ser Gln Leu Ser 340
345 350 Val Leu Ser Leu Ser Gly Val Met
Leu Thr Asp Val Ser Pro Glu Pro 355 360
365 Leu Gln Ala Leu Leu Glu Arg Ala Ser Ala Thr Leu Gln
Asp Leu Val 370 375 380
Phe Asp Glu Cys Gly Ile Thr Asp Asp Gln Leu Leu Ala Leu Leu Pro 385
390 395 400 Ser Leu Ser His
Cys Ser Gln Leu Thr Thr Leu Ser Phe Tyr Gly Asn 405
410 415 Ser Ile Ser Ile Ser Ala Leu Gln Ser
Leu Leu Gln His Leu Ile Gly 420 425
430 Leu Ser Asn Leu Thr His Val Leu Tyr Pro Val Pro Leu Glu
Ser Tyr 435 440 445
Glu Asp Ile His Gly Thr Leu His Leu Glu Arg Leu Ala Tyr Leu His 450
455 460 Ala Arg Leu Arg Glu
Leu Leu Cys Glu Leu Gly Arg Pro Ser Met Val 465 470
475 480 Trp Leu Ser Ala Asn Pro Cys Pro His Cys
Gly Asp Arg Thr Phe Tyr 485 490
495 Asp Pro Glu Pro Ile Leu Cys Pro Cys Phe Met Pro Asn
500 505 63165PRTHomo sapiens 63Met
Gly Trp Asp Leu Thr Val Lys Met Leu Ala Gly Asn Glu Phe Gln 1
5 10 15 Val Ser Leu Ser Ser Ser
Met Ser Val Ser Glu Leu Lys Ala Gln Ile 20
25 30 Thr Gln Lys Ile Gly Val His Ala Phe Gln
Gln Arg Leu Ala Val His 35 40
45 Pro Ser Gly Val Ala Leu Gln Asp Arg Val Pro Leu Ala Ser
Gln Gly 50 55 60
Leu Gly Pro Gly Ser Thr Val Leu Leu Val Val Asp Lys Cys Asp Glu 65
70 75 80 Pro Leu Ser Ile Leu
Val Arg Asn Asn Lys Gly Arg Ser Ser Thr Tyr 85
90 95 Glu Val Arg Leu Thr Gln Thr Val Ala His
Leu Lys Gln Gln Val Ser 100 105
110 Gly Leu Glu Gly Val Gln Asp Asp Leu Phe Trp Leu Thr Phe Glu
Gly 115 120 125 Lys
Pro Leu Glu Asp Gln Leu Pro Leu Gly Glu Tyr Gly Leu Lys Pro 130
135 140 Leu Ser Thr Val Phe Met
Asn Leu Arg Leu Arg Gly Gly Gly Thr Glu 145 150
155 160 Pro Gly Gly Arg Ser 165
64363PRTHomo sapiens 64Met Arg Trp Val Arg His Asp Ala Pro Ala Arg Arg
Gly Gln Leu Arg 1 5 10
15 Arg Leu Leu Glu His Val Arg Leu Pro Leu Leu Ala Pro Ala Tyr Phe
20 25 30 Leu Glu Lys
Val Glu Ala Asp Glu Leu Leu Gln Ala Cys Gly Glu Cys 35
40 45 Arg Pro Leu Leu Leu Glu Ala Arg
Ala Cys Phe Ile Leu Gly Arg Glu 50 55
60 Ala Gly Ala Leu Arg Thr Arg Pro Arg Arg Phe Met Asp
Leu Ala Glu 65 70 75
80 Val Ile Val Val Ile Gly Gly Cys Asp Arg Lys Gly Leu Leu Lys Leu
85 90 95 Pro Phe Ala Asp
Ala Tyr His Pro Glu Ser Gln Arg Trp Thr Pro Leu 100
105 110 Pro Ser Leu Pro Gly Tyr Thr Arg Ser
Glu Phe Ala Ala Cys Ala Leu 115 120
125 Arg Asn Asp Val Tyr Val Ser Gly Gly His Ile Asn Ser His
Asp Val 130 135 140
Trp Met Phe Ser Ser His Leu His Thr Trp Ile Lys Val Ala Ser Leu 145
150 155 160 His Lys Gly Arg Trp
Arg His Lys Met Ala Val Val Gln Gly Gln Leu 165
170 175 Phe Ala Val Gly Gly Phe Asp Gly Leu Arg
Arg Leu His Ser Val Glu 180 185
190 Arg Tyr Asp Pro Phe Ser Asn Thr Trp Ala Ala Ala Ala Pro Leu
Pro 195 200 205 Glu
Ala Val Ser Ser Ala Ala Val Ala Ser Cys Ala Gly Lys Leu Phe 210
215 220 Val Ile Gly Gly Ala Arg
Gln Gly Gly Val Asn Thr Asp Lys Val Gln 225 230
235 240 Cys Phe Asp Pro Lys Glu Asp Arg Trp Ser Leu
Arg Ser Pro Ala Pro 245 250
255 Phe Ser Gln Arg Cys Leu Glu Ala Val Ser Leu Glu Asp Thr Ile Tyr
260 265 270 Val Met
Gly Gly Leu Met Ser Lys Ile Phe Thr Tyr Asp Pro Gly Thr 275
280 285 Asp Val Trp Gly Glu Ala Ala
Val Leu Pro Ser Pro Val Glu Ser Cys 290 295
300 Gly Val Thr Val Cys Asp Gly Lys Val His Ile Leu
Gly Gly Arg Asp 305 310 315
320 Asp Arg Gly Glu Ser Thr Asp Lys Val Phe Thr Phe Asp Pro Ser Ser
325 330 335 Gly Gln Val
Glu Val Gln Pro Ser Leu Gln Arg Cys Thr Ser Ser His 340
345 350 Gly Cys Val Thr Ile Ile Gln Ser
Leu Gly Arg 355 360 65282PRTHomo
sapiens 65Met Ala Ser Leu Gly Gln Ile Leu Phe Trp Ser Ile Ile Ser Ile Ile
1 5 10 15 Ile Ile
Leu Ala Gly Ala Ile Ala Leu Ile Ile Gly Phe Gly Ile Ser 20
25 30 Gly Arg His Ser Ile Thr Val
Thr Thr Val Ala Ser Ala Gly Asn Ile 35 40
45 Gly Glu Asp Gly Ile Gln Ser Cys Thr Phe Glu Pro
Asp Ile Lys Leu 50 55 60
Ser Asp Ile Val Ile Gln Trp Leu Lys Glu Gly Val Leu Gly Leu Val 65
70 75 80 His Glu Phe
Lys Glu Gly Lys Asp Glu Leu Ser Glu Gln Asp Glu Met 85
90 95 Phe Arg Gly Arg Thr Ala Val Phe
Ala Asp Gln Val Ile Val Gly Asn 100 105
110 Ala Ser Leu Arg Leu Lys Asn Val Gln Leu Thr Asp Ala
Gly Thr Tyr 115 120 125
Lys Cys Tyr Ile Ile Thr Ser Lys Gly Lys Gly Asn Ala Asn Leu Glu 130
135 140 Tyr Lys Thr Gly
Ala Phe Ser Met Pro Glu Val Asn Val Asp Tyr Asn 145 150
155 160 Ala Ser Ser Glu Thr Leu Arg Cys Glu
Ala Pro Arg Trp Phe Pro Gln 165 170
175 Pro Thr Val Val Trp Ala Ser Gln Val Asp Gln Gly Ala Asn
Phe Ser 180 185 190
Glu Val Ser Asn Thr Ser Phe Glu Leu Asn Ser Glu Asn Val Thr Met
195 200 205 Lys Val Val Ser
Val Leu Tyr Asn Val Thr Ile Asn Asn Thr Tyr Ser 210
215 220 Cys Met Ile Glu Asn Asp Ile Ala
Lys Ala Thr Gly Asp Ile Lys Val 225 230
235 240 Thr Glu Ser Glu Ile Lys Arg Arg Ser His Leu Gln
Leu Leu Asn Ser 245 250
255 Lys Ala Ser Leu Cys Val Ser Ser Phe Phe Ala Ile Ser Trp Ala Leu
260 265 270 Leu Pro Leu
Ser Pro Tyr Leu Met Leu Lys 275 280
66890PRTHomo sapiens 66Met Ser Gln Gly Ile Leu Ser Pro Pro Ala Gly Leu
Leu Ser Asp Asp 1 5 10
15 Asp Val Val Val Ser Pro Met Phe Glu Ser Thr Ala Ala Asp Leu Gly
20 25 30 Ser Val Val
Arg Lys Asn Leu Leu Ser Asp Cys Ser Val Val Ser Thr 35
40 45 Ser Leu Glu Asp Lys Gln Gln Val
Pro Ser Glu Asp Ser Met Glu Lys 50 55
60 Val Lys Val Tyr Leu Arg Val Arg Pro Leu Leu Pro Ser
Glu Leu Glu 65 70 75
80 Arg Gln Glu Asp Gln Gly Cys Val Arg Ile Glu Asn Val Glu Thr Leu
85 90 95 Val Leu Gln Ala
Pro Lys Asp Ser Phe Ala Leu Lys Ser Asn Glu Arg 100
105 110 Gly Ile Gly Gln Ala Thr His Arg Phe
Thr Phe Ser Gln Ile Phe Gly 115 120
125 Pro Glu Val Gly Gln Ala Ser Phe Phe Asn Leu Thr Val Lys
Glu Met 130 135 140
Val Lys Asp Val Leu Lys Gly Gln Asn Trp Leu Ile Tyr Thr Tyr Gly 145
150 155 160 Val Thr Asn Ser Gly
Lys Thr His Thr Ile Gln Gly Thr Ile Lys Asp 165
170 175 Gly Gly Ile Leu Pro Arg Ser Leu Ala Leu
Ile Phe Asn Ser Leu Gln 180 185
190 Gly Gln Leu His Pro Thr Pro Asp Leu Lys Pro Leu Leu Ser Asn
Glu 195 200 205 Val
Ile Trp Leu Asp Ser Lys Gln Ile Arg Gln Glu Glu Met Lys Lys 210
215 220 Leu Ser Leu Leu Asn Gly
Gly Leu Gln Glu Glu Glu Leu Ser Thr Ser 225 230
235 240 Leu Lys Arg Ser Val Tyr Ile Glu Ser Arg Ile
Gly Thr Ser Thr Ser 245 250
255 Phe Asp Ser Gly Ile Ala Gly Leu Ser Ser Ile Ser Gln Cys Thr Ser
260 265 270 Ser Ser
Gln Leu Asp Glu Thr Ser His Arg Trp Ala Gln Pro Asp Thr 275
280 285 Ala Pro Leu Pro Val Pro Ala
Asn Ile Arg Phe Ser Ile Trp Ile Ser 290 295
300 Phe Phe Glu Ile Tyr Asn Glu Leu Leu Tyr Asp Leu
Leu Glu Pro Pro 305 310 315
320 Ser Gln Gln Arg Lys Arg Gln Thr Leu Arg Leu Cys Glu Asp Gln Asn
325 330 335 Gly Asn Pro
Tyr Val Lys Asp Leu Asn Trp Ile His Val Gln Asp Ala 340
345 350 Glu Glu Ala Trp Lys Leu Leu Lys
Val Gly Arg Lys Asn Gln Ser Phe 355 360
365 Ala Ser Thr His Leu Asn Gln Asn Ser Ser Arg Ser His
Ser Ile Phe 370 375 380
Ser Ile Arg Ile Leu His Leu Gln Gly Glu Gly Asp Ile Val Pro Lys 385
390 395 400 Ile Ser Glu Leu
Ser Leu Cys Asp Leu Ala Gly Ser Glu Arg Cys Lys 405
410 415 Asp Gln Lys Ser Gly Glu Arg Leu Lys
Glu Ala Gly Asn Ile Asn Thr 420 425
430 Ser Leu His Thr Leu Gly Arg Cys Ile Ala Ala Leu Arg Gln
Asn Gln 435 440 445
Gln Asn Arg Ser Lys Gln Asn Leu Val Pro Phe Arg Asp Ser Lys Leu 450
455 460 Thr Arg Val Phe Gln
Gly Phe Phe Thr Gly Arg Gly Arg Ser Cys Met 465 470
475 480 Ile Val Asn Val Asn Pro Cys Ala Ser Thr
Tyr Asp Glu Thr Leu His 485 490
495 Val Ala Lys Phe Ser Ala Ile Ala Ser Gln Leu Val His Ala Pro
Pro 500 505 510 Met
Gln Leu Gly Phe Pro Ser Leu His Ser Phe Ile Lys Glu His Ser 515
520 525 Leu Gln Val Ser Pro Ser
Leu Glu Lys Gly Ala Lys Ala Asp Thr Gly 530 535
540 Leu Asp Asp Asp Ile Glu Asn Glu Ala Asp Ile
Ser Met Tyr Gly Lys 545 550 555
560 Glu Glu Leu Leu Gln Val Val Glu Ala Met Lys Thr Leu Leu Leu Lys
565 570 575 Glu Arg
Gln Glu Lys Leu Gln Leu Glu Met His Leu Arg Asp Glu Ile 580
585 590 Cys Asn Glu Met Val Glu Gln
Met Gln Gln Arg Glu Gln Trp Cys Ser 595 600
605 Glu His Leu Asp Thr Gln Lys Glu Leu Leu Glu Glu
Met Tyr Glu Glu 610 615 620
Lys Leu Asn Ile Leu Lys Glu Ser Leu Thr Ser Phe Tyr Gln Glu Glu 625
630 635 640 Ile Gln Glu
Arg Asp Glu Lys Ile Glu Glu Leu Glu Ala Leu Leu Gln 645
650 655 Glu Ala Arg Gln Gln Ser Val Ala
His Gln Gln Ser Gly Ser Glu Leu 660 665
670 Ala Leu Arg Arg Ser Gln Arg Leu Ala Ala Ser Ala Ser
Thr Gln Gln 675 680 685
Leu Gln Glu Val Lys Ala Lys Leu Gln Gln Cys Lys Ala Glu Leu Asn 690
695 700 Ser Thr Thr Glu
Glu Leu His Lys Tyr Gln Lys Met Leu Glu Pro Pro 705 710
715 720 Pro Ser Ala Lys Pro Phe Thr Ile Asp
Val Asp Lys Lys Leu Glu Glu 725 730
735 Gly Gln Lys Asn Ile Arg Leu Leu Arg Thr Glu Leu Gln Lys
Leu Gly 740 745 750
Glu Ser Leu Gln Ser Ala Glu Arg Ala Cys Cys His Ser Thr Gly Ala
755 760 765 Gly Lys Leu Arg
Gln Ala Leu Thr Thr Cys Asp Asp Ile Leu Ile Lys 770
775 780 Gln Asp Gln Thr Leu Ala Glu Leu
Gln Asn Asn Met Val Leu Val Lys 785 790
795 800 Leu Asp Leu Arg Lys Lys Ala Ala Cys Ile Ala Glu
Gln Tyr His Thr 805 810
815 Val Leu Lys Leu Gln Gly Gln Val Ser Ala Lys Lys Arg Leu Gly Thr
820 825 830 Asn Gln Glu
Asn Gln Gln Pro Asn Gln Gln Pro Pro Gly Lys Lys Pro 835
840 845 Phe Leu Arg Asn Leu Leu Pro Arg
Thr Pro Thr Cys Gln Ser Ser Thr 850 855
860 Asp Cys Ser Pro Tyr Ala Arg Ile Leu Arg Ser Arg Arg
Ser Pro Leu 865 870 875
880 Leu Lys Ser Gly Pro Phe Gly Lys Lys Tyr 885
890 67235PRTHomo sapiens 67Met Phe Ile Trp Thr Ser Gly Arg Thr Ser
Ser Ser Tyr Arg His Asp 1 5 10
15 Glu Lys Arg Asn Ile Tyr Gln Lys Ile Arg Asp His Asp Leu Leu
Asp 20 25 30 Lys
Arg Lys Thr Val Thr Ala Leu Lys Ala Gly Glu Asp Arg Ala Ile 35
40 45 Leu Leu Gly Leu Ala Met
Met Val Cys Ser Ile Met Met Tyr Phe Leu 50 55
60 Leu Gly Ile Thr Leu Leu Arg Ser Tyr Met Gln
Ser Val Trp Thr Glu 65 70 75
80 Glu Ser Gln Cys Thr Leu Leu Asn Ala Ser Ile Thr Glu Thr Phe Asn
85 90 95 Cys Ser
Phe Ser Cys Gly Pro Asp Cys Trp Lys Leu Ser Gln Tyr Pro 100
105 110 Cys Leu Gln Val Tyr Val Asn
Leu Thr Ser Ser Gly Glu Lys Leu Leu 115 120
125 Leu Tyr His Thr Glu Glu Thr Ile Lys Ile Asn Gln
Lys Cys Ser Tyr 130 135 140
Ile Pro Lys Cys Gly Lys Asn Phe Glu Glu Ser Met Ser Leu Val Asn 145
150 155 160 Val Val Met
Glu Asn Phe Arg Lys Tyr Gln His Phe Ser Cys Tyr Ser 165
170 175 Asp Pro Glu Gly Asn Gln Lys Ser
Val Ile Leu Thr Lys Leu Tyr Ser 180 185
190 Ser Asn Val Leu Phe His Ser Leu Phe Trp Pro Thr Cys
Met Met Ala 195 200 205
Gly Gly Val Ala Ile Val Ala Met Val Lys Leu Thr Gln Tyr Leu Ser 210
215 220 Leu Leu Cys Glu
Arg Ile Gln Arg Ile Asn Arg 225 230 235
6898PRTHomo sapiens 68 Met Asn Gln Thr Ala Ile Leu Ile Cys Cys Leu Ile
Phe Leu Thr Leu 1 5 10
15 Ser Gly Ile Gln Gly Val Pro Leu Ser Arg Thr Val Arg Cys Thr Cys
20 25 30 Ile Ser Ile
Ser Asn Gln Pro Val Asn Pro Arg Ser Leu Glu Lys Leu 35
40 45 Glu Ile Ile Pro Ala Ser Gln Phe
Cys Pro Arg Val Glu Ile Ile Ala 50 55
60 Thr Met Lys Lys Lys Gly Glu Lys Arg Cys Leu Asn Pro
Glu Ser Lys 65 70 75
80 Ala Ile Lys Asn Leu Leu Lys Ala Val Ser Lys Glu Met Ser Lys Arg
85 90 95 Ser Pro
69467PRTHomo sapiens 69Met Ala Ala Leu Thr Ile Ala Thr Gly Thr Gly Asn
Trp Phe Ser Ala 1 5 10
15 Leu Ala Leu Gly Val Thr Leu Leu Lys Cys Leu Leu Ile Pro Thr Tyr
20 25 30 His Ser Thr
Asp Phe Glu Val His Arg Asn Trp Leu Ala Ile Thr His 35
40 45 Ser Leu Pro Ile Ser Gln Trp Tyr
Tyr Glu Ala Thr Ser Glu Trp Thr 50 55
60 Leu Asp Tyr Pro Pro Phe Phe Ala Trp Phe Glu Tyr Ile
Leu Ser His 65 70 75
80 Val Ala Lys Tyr Phe Asp Gln Glu Met Leu Asn Val His Asn Leu Asn
85 90 95 Tyr Ser Ser Ser
Arg Thr Leu Leu Phe Gln Arg Phe Ser Val Ile Phe 100
105 110 Met Asp Val Leu Phe Val Tyr Ala Val
Arg Glu Cys Cys Lys Cys Ile 115 120
125 Asp Gly Lys Lys Val Gly Lys Glu Leu Thr Glu Lys Pro Lys
Phe Ile 130 135 140
Leu Ser Val Leu Leu Leu Trp Asn Phe Gly Leu Leu Ile Val Asp His 145
150 155 160 Ile His Phe Gln Tyr
Asn Gly Phe Leu Phe Gly Leu Met Leu Leu Ser 165
170 175 Ile Ala Arg Leu Phe Gln Lys Arg His Met
Glu Gly Ala Phe Leu Phe 180 185
190 Ala Val Leu Leu His Phe Lys His Ile Tyr Leu Tyr Val Ala Pro
Ala 195 200 205 Tyr
Gly Val Tyr Leu Leu Arg Ser Tyr Cys Phe Thr Ala Asn Lys Pro 210
215 220 Asp Gly Ser Ile Arg Trp
Lys Ser Phe Ser Phe Val Arg Val Ile Ser 225 230
235 240 Leu Gly Leu Val Val Phe Leu Val Ser Ala Leu
Ser Leu Gly Pro Phe 245 250
255 Leu Ala Leu Asn Gln Leu Pro Gln Val Phe Ser Arg Leu Phe Pro Phe
260 265 270 Lys Arg
Gly Leu Cys His Ala Tyr Trp Ala Pro Asn Phe Trp Ala Leu 275
280 285 Tyr Asn Ala Leu Asp Lys Val
Leu Ser Val Ile Gly Leu Lys Leu Lys 290 295
300 Phe Leu Asp Pro Asn Asn Ile Pro Lys Ala Ser Met
Thr Ser Gly Leu 305 310 315
320 Val Gln Gln Phe Gln His Thr Val Leu Pro Ser Val Thr Pro Leu Ala
325 330 335 Thr Leu Ile
Cys Thr Leu Ile Ala Ile Leu Pro Ser Ile Phe Cys Leu 340
345 350 Trp Phe Lys Pro Gln Gly Pro Arg
Gly Phe Leu Arg Cys Leu Thr Leu 355 360
365 Cys Ala Leu Ser Ser Phe Met Phe Gly Trp His Val His
Glu Lys Ala 370 375 380
Ile Leu Leu Ala Ile Leu Pro Met Ser Leu Leu Ser Val Gly Lys Ala 385
390 395 400 Gly Asp Ala Ser
Ile Phe Leu Ile Leu Thr Thr Thr Gly His Tyr Ser 405
410 415 Leu Phe Pro Leu Leu Phe Thr Ala Pro
Glu Leu Pro Ile Lys Ile Leu 420 425
430 Leu Met Leu Leu Phe Thr Ile Tyr Ser Ile Ser Ser Leu Lys
Thr Leu 435 440 445
Phe Arg Arg Ser Phe Thr Leu Val Ala Gln Ala Gly Val Gln Trp His 450
455 460 Asp Leu Ser 465
7084PRTHomo sapiens 70Met Asp Asp Asp Ala Ala Pro Arg Val Glu Gly Val
Pro Val Ala Val 1 5 10
15 His Lys His Ala Leu His Asp Gly Leu Arg Gln Val Ala Gly Pro Gly
20 25 30 Ala Ala Ala
Ala His Leu Pro Arg Trp Pro Pro Pro Gln Leu Ala Ala 35
40 45 Ser Arg Arg Glu Ala Pro Pro Leu
Ser Gln Arg Pro His Arg Thr Gln 50 55
60 Gly Ala Gly Ser Pro Pro Glu Thr Asn Glu Lys Leu Thr
Asn Pro Gln 65 70 75
80 Val Lys Glu Lys 71156PRTHomo sapiens 71Met Glu Pro Ala Ala Gly Ser
Ser Met Glu Pro Ser Ala Asp Trp Leu 1 5
10 15 Ala Thr Ala Ala Ala Arg Gly Arg Val Glu Glu
Val Arg Ala Leu Leu 20 25
30 Glu Ala Gly Ala Leu Pro Asn Ala Pro Asn Ser Tyr Gly Arg Arg
Pro 35 40 45 Ile
Gln Val Met Met Met Gly Ser Ala Arg Val Ala Glu Leu Leu Leu 50
55 60 Leu His Gly Ala Glu Pro
Asn Cys Ala Asp Pro Ala Thr Leu Thr Arg 65 70
75 80 Pro Val His Asp Ala Ala Arg Glu Gly Phe Leu
Asp Thr Leu Val Val 85 90
95 Leu His Arg Ala Gly Ala Arg Leu Asp Val Arg Asp Ala Trp Gly Arg
100 105 110 Leu Pro
Val Asp Leu Ala Glu Glu Leu Gly His Arg Asp Val Ala Arg 115
120 125 Tyr Leu Arg Ala Ala Ala Gly
Gly Thr Arg Gly Ser Asn His Ala Arg 130 135
140 Ile Asp Ala Ala Glu Gly Pro Ser Asp Ile Pro Asp
145 150 155 72747PRTHomo sapiens
72Met Ser Gln Val Lys Ser Ser Tyr Ser Tyr Asp Ala Pro Ser Asp Phe 1
5 10 15 Ile Asn Phe Ser
Ser Leu Asp Asp Glu Gly Asp Thr Gln Asn Ile Asp 20
25 30 Ser Trp Phe Glu Glu Lys Ala Asn Leu
Glu Asn Lys Leu Leu Gly Lys 35 40
45 Asn Gly Thr Gly Gly Leu Phe Gln Gly Lys Thr Pro Leu Arg
Lys Ala 50 55 60
Asn Leu Gln Gln Ala Ile Val Thr Pro Leu Lys Pro Val Asp Asn Thr 65
70 75 80 Tyr Tyr Lys Glu
Ala Glu Lys Glu Asn Leu Val Glu Gln Ser Ile Pro 85
90 95 Ser Asn Ala Cys Ser Ser Leu Glu Val
Glu Ala Ala Ile Ser Arg Lys 100 105
110 Thr Pro Ala Gln Pro Gln Arg Arg Ser Leu Arg Leu Ser Ala
Gln Lys 115 120 125
Asp Leu Glu Gln Lys Glu Lys His His Val Lys Met Lys Ala Lys Arg 130
135 140 Cys Ala Thr Pro Val
Ile Ile Asp Glu Ile Leu Pro Ser Lys Lys Met 145 150
155 160 Lys Val Ser Asn Asn Lys Lys Lys Pro Glu
Glu Glu Gly Ser Ala His 165 170
175 Gln Asp Thr Ala Glu Lys Asn Ala Ser Ser Pro Glu Lys Ala Lys
Gly 180 185 190 Arg
His Thr Val Pro Cys Met Pro Pro Ala Lys Gln Lys Phe Leu Lys 195
200 205 Ser Thr Glu Glu Gln Glu
Leu Glu Lys Ser Met Lys Met Gln Gln Glu 210 215
220 Val Val Glu Met Arg Lys Lys Asn Glu Glu Phe
Lys Lys Leu Ala Leu 225 230 235
240 Ala Gly Ile Gly Gln Pro Val Lys Lys Ser Val Ser Gln Val Thr Lys
245 250 255 Ser Val
Asp Phe His Phe Arg Thr Asp Glu Arg Ile Lys Gln His Pro 260
265 270 Lys Asn Gln Glu Glu Tyr Lys
Glu Val Asn Phe Thr Ser Glu Leu Arg 275 280
285 Lys His Pro Ser Ser Pro Ala Arg Val Thr Lys Gly
Cys Thr Ile Val 290 295 300
Lys Pro Phe Asn Leu Ser Gln Gly Lys Lys Arg Thr Phe Asp Glu Thr 305
310 315 320 Val Ser Thr
Tyr Val Pro Leu Ala Gln Gln Val Glu Asp Phe His Lys 325
330 335 Arg Thr Pro Asn Arg Tyr His Leu
Arg Ser Lys Lys Asp Asp Ile Asn 340 345
350 Leu Leu Pro Ser Lys Ser Ser Val Thr Lys Ile Cys Arg
Asp Pro Gln 355 360 365
Thr Pro Val Leu Gln Thr Lys His Arg Ala Arg Ala Val Thr Cys Lys 370
375 380 Ser Thr Ala Glu
Leu Glu Ala Glu Glu Leu Glu Lys Leu Gln Gln Tyr 385 390
395 400 Lys Phe Lys Ala Arg Glu Leu Asp Pro
Arg Ile Leu Glu Gly Gly Pro 405 410
415 Ile Leu Pro Lys Lys Pro Pro Val Lys Pro Pro Thr Glu Pro
Ile Gly 420 425 430
Phe Asp Leu Glu Ile Glu Lys Arg Ile Gln Glu Arg Glu Ser Lys Lys
435 440 445 Lys Thr Glu Asp
Glu His Phe Glu Phe His Ser Arg Pro Cys Pro Thr 450
455 460 Lys Ile Leu Glu Asp Val Val Gly
Val Pro Glu Lys Lys Val Leu Pro 465 470
475 480 Ile Thr Val Pro Lys Ser Pro Ala Phe Ala Leu Lys
Asn Arg Ile Arg 485 490
495 Met Pro Thr Lys Glu Asp Glu Glu Glu Asp Glu Pro Val Val Ile Lys
500 505 510 Ala Gln Pro
Val Pro His Tyr Gly Val Pro Phe Lys Pro Gln Ile Pro 515
520 525 Glu Ala Arg Thr Val Glu Ile Cys
Pro Phe Ser Phe Asp Ser Arg Asp 530 535
540 Lys Glu Arg Gln Leu Gln Lys Glu Lys Lys Ile Lys Glu
Leu Gln Lys 545 550 555
560 Gly Glu Val Pro Lys Phe Lys Ala Leu Pro Leu Pro His Phe Asp Thr
565 570 575 Ile Asn Leu Pro
Glu Lys Lys Val Lys Asn Val Thr Gln Ile Glu Pro 580
585 590 Phe Cys Leu Glu Thr Asp Arg Arg Gly
Ala Leu Lys Ala Gln Thr Trp 595 600
605 Lys His Gln Leu Glu Glu Glu Leu Arg Gln Gln Lys Glu Ala
Ala Cys 610 615 620
Phe Lys Ala Arg Pro Asn Thr Val Ile Ser Gln Glu Pro Phe Val Pro 625
630 635 640 Lys Lys Glu Lys Lys
Ser Val Ala Glu Gly Leu Ser Gly Ser Leu Val 645
650 655 Gln Glu Pro Phe Gln Leu Ala Thr Glu Lys
Arg Ala Lys Glu Arg Gln 660 665
670 Glu Leu Glu Lys Arg Met Ala Glu Val Glu Ala Gln Lys Ala Gln
Gln 675 680 685 Leu
Glu Glu Ala Arg Leu Gln Glu Glu Glu Gln Lys Lys Glu Glu Leu 690
695 700 Ala Arg Leu Arg Arg Glu
Leu Val His Lys Ala Asn Pro Ile Arg Lys 705 710
715 720 Tyr Gln Gly Leu Glu Ile Lys Ser Ser Asp Gln
Pro Leu Thr Val Pro 725 730
735 Val Ser Pro Lys Phe Ser Thr Arg Phe His Cys 740
745 73179PRTHomo sapiens 73Met Ala Ser Gln Asn Arg
Asp Pro Ala Ala Thr Ser Val Ala Ala Ala 1 5
10 15 Arg Lys Gly Ala Glu Pro Ser Gly Gly Ala Ala
Arg Gly Pro Val Gly 20 25
30 Lys Arg Leu Gln Gln Glu Leu Met Thr Leu Met Met Ser Gly Asp
Lys 35 40 45 Gly
Ile Ser Ala Phe Pro Glu Ser Asp Asn Leu Phe Lys Trp Val Gly 50
55 60 Thr Ile His Gly Ala Ala
Gly Thr Val Tyr Glu Asp Leu Arg Tyr Lys 65 70
75 80 Leu Ser Leu Glu Phe Pro Ser Gly Tyr Pro Tyr
Asn Ala Pro Thr Val 85 90
95 Lys Phe Leu Thr Pro Cys Tyr His Pro Asn Val Asp Thr Gln Gly Asn
100 105 110 Ile Cys
Leu Asp Ile Leu Lys Glu Lys Trp Ser Ala Leu Tyr Asp Val 115
120 125 Arg Thr Ile Leu Leu Ser Ile
Gln Ser Leu Leu Gly Glu Pro Asn Ile 130 135
140 Asp Ser Pro Leu Asn Thr His Ala Ala Glu Leu Trp
Lys Asn Pro Thr 145 150 155
160 Ala Phe Lys Lys Tyr Leu Gln Glu Thr Tyr Ser Lys Gln Val Thr Ser
165 170 175 Gln Glu Pro
74138PRTHomo sapiens 74Met Pro Asn Phe Ser Gly Asn Trp Lys Ile Ile Arg
Ser Glu Asn Phe 1 5 10
15 Glu Glu Leu Leu Lys Val Leu Gly Val Asn Val Met Leu Arg Lys Ile
20 25 30 Ala Val Ala
Ala Ala Ser Lys Pro Ala Val Glu Ile Lys Gln Glu Gly 35
40 45 Asp Thr Phe Tyr Ile Lys Thr Ser
Thr Thr Val Arg Thr Thr Glu Ile 50 55
60 Asn Phe Lys Val Gly Glu Glu Phe Glu Glu Gln Thr Val
Asp Gly Arg 65 70 75
80 Pro Cys Lys Ser Leu Val Lys Trp Glu Ser Glu Asn Lys Met Val Cys
85 90 95 Glu Gln Lys Leu
Leu Lys Gly Glu Gly Pro Lys Thr Ser Trp Thr Arg 100
105 110 Glu Leu Thr Asn Asp Gly Glu Leu Ile
Leu Thr Met Thr Ala Asp Asp 115 120
125 Val Val Cys Thr Arg Val Tyr Val Arg Glu 130
135 75130PRTHomo sapiens 75Met Ser Gly Arg Gly Lys
Gln Gly Gly Lys Ala Arg Ala Lys Ala Lys 1 5
10 15 Ser Arg Ser Ser Arg Ala Gly Leu Gln Phe Pro
Val Gly Arg Val His 20 25
30 Arg Leu Leu Arg Lys Gly Asn Tyr Ser Glu Arg Val Gly Ala Gly
Ala 35 40 45 Pro
Val Tyr Leu Ala Ala Val Leu Glu Tyr Leu Thr Ala Glu Ile Leu 50
55 60 Glu Leu Ala Gly Asn Ala
Ala Arg Asp Asn Lys Lys Thr Arg Ile Ile 65 70
75 80 Pro Arg His Leu Gln Leu Ala Ile Arg Asn Asp
Glu Glu Leu Asn Lys 85 90
95 Leu Leu Gly Arg Val Thr Ile Ala Gln Gly Gly Val Leu Pro Asn Ile
100 105 110 Gln Ala
Val Leu Leu Pro Lys Lys Thr Glu Ser His His Lys Ala Lys 115
120 125 Gly Lys 130
76103PRTHomo sapiens 76Met Ser Gly Arg Gly Lys Gly Gly Lys Gly Leu Gly
Lys Gly Gly Ala 1 5 10
15 Lys Arg His Arg Lys Val Leu Arg Asp Asn Ile Gln Gly Ile Thr Lys
20 25 30 Pro Ala Ile
Arg Arg Leu Ala Arg Arg Gly Gly Val Lys Arg Ile Ser 35
40 45 Gly Leu Ile Tyr Glu Glu Thr Arg
Gly Val Leu Lys Val Phe Leu Glu 50 55
60 Asn Val Ile Arg Asp Ala Val Thr Tyr Thr Glu His Ala
Lys Arg Lys 65 70 75
80 Thr Val Thr Ala Met Asp Val Val Tyr Ala Leu Lys Arg Gln Gly Arg
85 90 95 Thr Leu Tyr Gly
Phe Gly Gly 100 77432PRTHomo sapiens 77Met Leu
Phe Glu Gln Gly Gln Gln Ala Leu Glu Leu Pro Glu Cys Thr 1 5
10 15 Met Gln Lys Ala Ala Tyr Tyr
Glu Asn Pro Gly Leu Phe Gly Gly Tyr 20 25
30 Gly Tyr Ser Lys Thr Thr Asp Thr Tyr Gly Tyr Ser
Thr Pro His Gln 35 40 45
Pro Tyr Pro Pro Pro Ala Ala Ala Ser Ser Leu Asp Thr Asp Tyr Pro
50 55 60 Gly Ser Ala
Cys Ser Ile Gln Ser Ser Ala Pro Leu Arg Ala Pro Ala 65
70 75 80 His Lys Gly Ala Glu Leu Asn
Gly Ser Cys Met Arg Pro Gly Thr Gly 85
90 95 Asn Ser Gln Gly Gly Gly Gly Gly Ser Gln Pro
Pro Gly Leu Asn Ser 100 105
110 Glu Gln Gln Pro Pro Gln Pro Pro Pro Pro Pro Pro Thr Leu Pro
Pro 115 120 125 Ser
Ser Pro Thr Asn Pro Gly Gly Gly Val Pro Ala Lys Lys Pro Lys 130
135 140 Gly Gly Pro Asn Ala Ser
Ser Ser Ser Ala Thr Ile Ser Lys Gln Ile 145 150
155 160 Phe Pro Trp Met Lys Glu Ser Arg Gln Asn Ser
Lys Gln Lys Asn Ser 165 170
175 Cys Ala Thr Ala Gly Glu Ser Cys Glu Asp Lys Ser Pro Pro Gly Pro
180 185 190 Ala Ser
Lys Arg Val Arg Thr Ala Tyr Thr Ser Ala Gln Leu Val Glu 195
200 205 Leu Glu Lys Glu Phe His Phe
Asn Arg Tyr Leu Cys Arg Pro Arg Arg 210 215
220 Val Glu Met Ala Asn Leu Leu Asn Leu Thr Glu Arg
Gln Ile Lys Ile 225 230 235
240 Trp Phe Gln Asn Arg Arg Met Lys Tyr Lys Lys Asp Gln Lys Ala Lys
245 250 255 Gly Ile Leu
His Ser Pro Ala Ser Gln Ser Pro Glu Arg Ser Pro Pro 260
265 270 Leu Gly Gly Ala Ala Gly His Val
Ala Tyr Ser Gly Gln Leu Pro Pro 275 280
285 Val Pro Gly Leu Ala Tyr Asp Ala Pro Ser Pro Pro Ala
Phe Ala Lys 290 295 300
Ser Gln Pro Asn Met Tyr Gly Leu Ala Ala Tyr Thr Ala Pro Leu Ser 305
310 315 320 Ser Cys Leu Pro
Gln Gln Lys Arg Tyr Ala Ala Pro Glu Phe Glu Pro 325
330 335 His Pro Met Ala Ser Asn Gly Gly Gly
Phe Ala Ser Ala Asn Leu Gln 340 345
350 Gly Ser Pro Val Tyr Val Gly Gly Asn Phe Val Glu Ser Met
Ala Pro 355 360 365
Ala Ser Gly Pro Val Phe Asn Leu Gly His Leu Ser His Pro Ser Ser 370
375 380 Ala Ser Val Asp Tyr
Ser Cys Ala Ala Gln Ile Pro Gly Asn His His 385 390
395 400 His Gly Pro Cys Asp Pro His Pro Thr Tyr
Thr Asp Leu Ser Ala His 405 410
415 His Ser Ser Gln Gly Arg Leu Pro Glu Ala Pro Lys Leu Thr His
Leu 420 425 430
78469PRTHomo sapiens 78Met Glu Phe Gly Leu Ser Trp Val Phe Leu Val Ala
Ile Leu Lys Gly 1 5 10
15 Val Gln Cys Glu Val Gln Leu Val Glu Ser Gly Gly Val Val Val Gln
20 25 30 Pro Gly Gly
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe 35
40 45 Asp Asp Tyr Ala Met His Trp Val
Arg Gln Ala Pro Gly Lys Gly Leu 50 55
60 Glu Trp Val Ser Leu Ile Ser Trp Asp Gly Gly Ser Thr
Tyr Tyr Ala 65 70 75
80 Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn
85 90 95 Ser Leu Tyr Leu
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu 100
105 110 Tyr Tyr Cys Ala Thr Arg Gly Gly Tyr
Ser Thr Ala Gly Phe Asp Tyr 115 120
125 Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr
Lys Gly 130 135 140
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly 145
150 155 160 Thr Ala Ala Leu Gly
Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val 165
170 175 Thr Val Ser Trp Asn Ser Gly Ala Leu Thr
Ser Gly Val His Thr Phe 180 185
190 Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val
Val 195 200 205 Thr
Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val 210
215 220 Asn His Lys Pro Ser Asn
Thr Lys Val Asp Lys Lys Val Glu Pro Lys 225 230
235 240 Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys
Pro Ala Pro Glu Leu 245 250
255 Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
260 265 270 Leu Met
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 275
280 285 Ser His Glu Asp Pro Glu Val
Lys Phe Asn Trp Tyr Val Asp Gly Val 290 295
300 Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
Gln Tyr Asn Ser 305 310 315
320 Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
325 330 335 Asn Gly Lys
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala 340
345 350 Pro Ile Glu Lys Thr Ile Ser Lys
Ala Lys Gly Gln Pro Arg Glu Pro 355 360
365 Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr
Lys Asn Gln 370 375 380
Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 385
390 395 400 Val Glu Trp Glu
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 405
410 415 Pro Pro Val Leu Asp Ser Asp Gly Ser
Phe Phe Leu Tyr Ser Lys Leu 420 425
430 Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser
Cys Ser 435 440 445
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser 450
455 460 Leu Ser Pro Gly Lys
465 79235PRTHomo sapiens 79Met Glu Thr Pro Ala Gln Leu
Leu Phe Leu Leu Leu Leu Trp Leu Pro 1 5
10 15 Asp Ile Thr Gly Glu Ile Val Leu Thr Gln Ser
Pro Gly Thr Leu Ser 20 25
30 Leu Ser Pro Gly Glu Arg Ala Ala Leu Ser Cys Arg Ala Ser Gln
Ser 35 40 45 Val
Asn Ser Lys Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala 50
55 60 Pro Arg Leu Leu Met Tyr
Ala Ala Ser Ile Arg Ala Thr Gly Ile Pro 65 70
75 80 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp
Phe Thr Leu Thr Ile 85 90
95 Ser Arg Leu Glu Ser Glu Asp Phe Ala Leu Tyr Phe Cys Gln Gln Tyr
100 105 110 Gly Thr
Ser Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 115
120 125 Arg Thr Val Ala Ala Pro Ser
Val Phe Ile Phe Pro Pro Ser Asp Glu 130 135
140 Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu
Leu Asn Asn Phe 145 150 155
160 Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
165 170 175 Ser Gly Asn
Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 180
185 190 Thr Tyr Ser Leu Ser Ser Thr Leu
Thr Leu Ser Lys Ala Asp Tyr Glu 195 200
205 Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly
Leu Ser Ser 210 215 220
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 225 230
235 80890PRTHomo sapiens 80Met Ser Arg Ser Ala Thr Leu Leu
Leu Cys Leu Leu Gly Cys His Val 1 5 10
15 Trp Lys Ala Val Thr Lys Thr Leu Arg Glu Pro Gly Ala
Gly Ala Gln 20 25 30
Glu Val Thr Leu Lys Val His Ile Ser Asp Ala Ser Thr His Gln Pro
35 40 45 Val Ala Asp Ala
Leu Ile Glu Ile Phe Thr Asn Gln Ala Ser Ile Ala 50
55 60 Ser Gly Thr Ser Gly Thr Asp Gly
Val Ala Phe Ile Lys Phe Gln Tyr 65 70
75 80 Lys Leu Gly Ser Gln Leu Ile Val Thr Ala Ser Lys
His Ala Tyr Val 85 90
95 Pro Asn Ser Ala Pro Trp Lys Pro Ile Arg Leu Pro Val Phe Ser Ser
100 105 110 Leu Ser Leu
Gly Leu Leu Pro Glu Arg Ser Ala Thr Leu Met Val Tyr 115
120 125 Glu Asp Val Val Gln Ile Val Ser
Gly Phe Gln Gly Ala Arg Pro Gln 130 135
140 Pro Arg Val His Phe Gln Arg Arg Ala Leu Arg Leu Pro
Glu Asn Thr 145 150 155
160 Ser Tyr Ser Asp Leu Thr Ala Phe Leu Thr Ala Ala Ser Ser Pro Ser
165 170 175 Glu Val Asp Ser
Phe Pro Tyr Leu Arg Gly Leu Asp Gly Asn Gly Thr 180
185 190 Gly Asn Ser Thr Arg His Asp Leu Thr
Pro Val Thr Ala Val Ser Val 195 200
205 His Leu Leu Ser Ser Asn Gly Thr Pro Val Leu Val Asp Gly
Pro Ile 210 215 220
Tyr Val Thr Val Pro Leu Ala Thr Gln Ser Ser Leu Arg His Asn Ala 225
230 235 240 Tyr Val Ala Ala Trp
Arg Phe Asp Gln Lys Leu Gly Thr Trp Leu Lys 245
250 255 Ser Gly Leu Gly Leu Val His Gln Glu Gly
Ser Gln Leu Thr Trp Thr 260 265
270 Tyr Ile Ala Pro Gln Leu Gly Tyr Trp Val Ala Ala Met Ser Pro
Pro 275 280 285 Ile
Pro Gly Pro Val Val Thr Gln Asp Ile Thr Thr Tyr His Thr Val 290
295 300 Phe Leu Leu Ala Ile Leu
Gly Gly Met Ala Phe Ile Leu Leu Val Leu 305 310
315 320 Leu Cys Leu Leu Leu Tyr Tyr Cys Arg Arg Lys
Cys Leu Lys Pro Arg 325 330
335 Gln His His Arg Lys Leu Gln Leu Pro Ala Gly Leu Glu Ser Ser Lys
340 345 350 Arg Asp
Gln Ser Thr Ser Met Ser His Ile Asn Leu Leu Phe Ser Arg 355
360 365 Arg Ala Ser Glu Phe Pro Gly
Pro Leu Ser Val Thr Ser His Gly Arg 370 375
380 Pro Glu Ala Pro Gly Thr Lys Glu Leu Met Ser Gly
Val His Leu Glu 385 390 395
400 Met Met Ser Pro Gly Gly Glu Gly Asp Leu His Thr Pro Met Leu Lys
405 410 415 Leu Ser Tyr
Ser Thr Ser Gln Glu Phe Ser Ser Arg Glu Glu Leu Leu 420
425 430 Ser Cys Lys Glu Glu Asp Lys Ser
Gln Ile Ser Phe Asp Asn Leu Thr 435 440
445 Pro Ser Gly Thr Leu Gly Lys Asp Tyr His Lys Ser Val
Glu Val Phe 450 455 460
Pro Leu Lys Ala Arg Lys Ser Met Glu Arg Glu Gly Tyr Glu Ser Ser 465
470 475 480 Gly Asn Asp Asp
Tyr Arg Gly Ser Tyr Asn Thr Val Leu Ser Gln Pro 485
490 495 Leu Phe Glu Lys Gln Asp Arg Glu Gly
Pro Ala Ser Thr Gly Ser Lys 500 505
510 Leu Thr Ile Gln Glu His Leu Tyr Pro Ala Pro Ser Ser Pro
Glu Lys 515 520 525
Glu Gln Leu Leu Asp Arg Arg Pro Thr Glu Cys Met Met Ser Arg Ser 530
535 540 Val Asp His Leu Glu
Arg Pro Thr Ser Phe Pro Arg Pro Gly Gln Leu 545 550
555 560 Ile Cys Cys Ser Ser Val Asp Gln Val Asn
Asp Ser Val Tyr Arg Lys 565 570
575 Val Leu Pro Ala Leu Val Ile Pro Ala His Tyr Met Lys Leu Pro
Gly 580 585 590 Asp
His Ser Tyr Val Ser Gln Pro Leu Val Val Pro Ala Asp Gln Gln 595
600 605 Leu Glu Ile Glu Arg Leu
Gln Ala Glu Leu Ser Asn Pro His Ala Gly 610 615
620 Ile Phe Pro His Pro Ser Ser Gln Ile Gln Pro
Gln Pro Leu Ser Ser 625 630 635
640 Gln Ala Ile Ser Gln Gln His Leu Gln Asp Ala Gly Thr Arg Glu Trp
645 650 655 Ser Pro
Gln Asn Ala Ser Met Ser Glu Ser Leu Ser Ile Pro Ala Ser 660
665 670 Leu Asn Asp Ala Ala Leu Ala
Gln Met Asn Ser Glu Val Gln Leu Leu 675 680
685 Thr Glu Lys Ala Leu Met Glu Leu Gly Gly Gly Lys
Pro Leu Pro His 690 695 700
Pro Arg Ala Trp Phe Val Ser Leu Asp Gly Arg Ser Asn Ala His Val 705
710 715 720 Arg His Ser
Tyr Ile Asp Leu Gln Arg Ala Gly Arg Asn Gly Ser Asn 725
730 735 Asp Ala Ser Leu Asp Ser Gly Val
Asp Met Asn Glu Pro Lys Ser Ala 740 745
750 Arg Lys Gly Arg Gly Asp Ala Leu Ser Leu Gln Gln Asn
Tyr Pro Pro 755 760 765
Val Gln Glu His Gln Gln Lys Glu Pro Arg Ala Pro Asp Ser Thr Ala 770
775 780 Tyr Thr Gln Leu
Val Tyr Leu Asp Asp Val Glu Gln Ser Gly Ser Glu 785 790
795 800 Cys Gly Thr Thr Val Cys Thr Pro Glu
Asp Ser Ala Leu Arg Cys Leu 805 810
815 Leu Glu Gly Ser Ser Arg Arg Ser Gly Gly Gln Leu Pro Ser
Leu Gln 820 825 830
Glu Glu Thr Thr Arg Arg Thr Ala Asp Ala Pro Ser Glu Pro Ala Ala
835 840 845 Ser Pro His Gln
Arg Arg Ser Ala His Glu Glu Glu Glu Asp Asp Asp 850
855 860 Asp Asp Asp Gln Gly Glu Asp Lys
Lys Ser Pro Trp Gln Lys Arg Glu 865 870
875 880 Glu Arg Pro Leu Met Ala Phe Asn Ile Lys
885 890 81394PRTHomo sapiens 81Met Asp Ser Ala Leu
Ser Asp Pro His Asn Gly Ser Ala Glu Ala Gly 1 5
10 15 Gly Pro Thr Asn Ser Thr Thr Arg Pro Pro
Ser Thr Pro Glu Gly Ile 20 25
30 Ala Leu Ala Tyr Gly Ser Leu Leu Leu Met Ala Leu Leu Pro Ile
Phe 35 40 45 Phe
Gly Ala Leu Arg Ser Val Arg Cys Ala Arg Gly Lys Asn Ala Ser 50
55 60 Asp Met Pro Glu Thr Ile
Thr Ser Arg Asp Ala Ala Arg Phe Pro Ile 65 70
75 80 Ile Ala Ser Cys Thr Leu Leu Gly Leu Tyr Leu
Phe Phe Lys Ile Phe 85 90
95 Ser Gln Glu Tyr Ile Asn Leu Leu Leu Ser Met Tyr Phe Phe Val Leu
100 105 110 Gly Ile
Leu Ala Leu Ser His Thr Ile Ser Pro Phe Met Asn Lys Phe 115
120 125 Phe Pro Ala Ser Phe Pro Asn
Arg Gln Tyr Gln Leu Leu Phe Thr Gln 130 135
140 Gly Ser Gly Glu Asn Lys Glu Glu Ile Ile Asn Tyr
Glu Phe Asp Thr 145 150 155
160 Lys Asp Leu Val Cys Leu Gly Leu Ser Ser Ile Val Gly Val Trp Tyr
165 170 175 Leu Leu Arg
Lys His Trp Ile Ala Asn Asn Leu Phe Gly Leu Ala Phe 180
185 190 Ser Leu Asn Gly Val Glu Leu Leu
His Leu Asn Asn Val Ser Thr Gly 195 200
205 Cys Ile Leu Leu Gly Gly Leu Phe Ile Tyr Asp Val Phe
Trp Val Phe 210 215 220
Gly Thr Asn Val Met Val Thr Val Ala Lys Ser Phe Glu Ala Pro Ile 225
230 235 240 Lys Leu Val Phe
Pro Gln Asp Leu Leu Glu Lys Gly Leu Glu Ala Asn 245
250 255 Asn Phe Ala Met Leu Gly Leu Gly Asp
Val Val Ile Pro Gly Ile Phe 260 265
270 Ile Ala Leu Leu Leu Arg Phe Asp Ile Ser Leu Lys Lys Asn
Thr His 275 280 285
Thr Tyr Phe Tyr Thr Ser Phe Ala Ala Tyr Ile Phe Gly Leu Gly Leu 290
295 300 Thr Ile Phe Ile Met
His Ile Phe Lys His Ala Gln Pro Ala Leu Leu 305 310
315 320 Tyr Leu Val Pro Ala Cys Ile Gly Phe Pro
Val Leu Val Ala Leu Ala 325 330
335 Lys Gly Glu Val Thr Glu Met Phe Ser Tyr Glu Ser Ser Ala Glu
Ile 340 345 350 Leu
Pro His Thr Pro Arg Leu Thr His Phe Pro Thr Val Ser Gly Ser 355
360 365 Pro Ala Ser Leu Ala Asp
Ser Met Gln Gln Lys Leu Ala Gly Pro Arg 370 375
380 Arg Arg Arg Pro Gln Asn Pro Ser Ala Met 385
390 82325PRTHomo sapiens 82Met Val Cys
Gly Ser Pro Gly Gly Met Leu Leu Leu Arg Ala Gly Leu 1 5
10 15 Leu Ala Leu Ala Ala Leu Cys Leu
Leu Arg Val Pro Gly Ala Arg Ala 20 25
30 Ala Ala Cys Glu Pro Val Arg Ile Pro Leu Cys Lys Ser
Leu Pro Trp 35 40 45
Asn Met Thr Lys Met Pro Asn His Leu His His Ser Thr Gln Ala Asn 50
55 60 Ala Ile Leu Ala
Ile Glu Gln Phe Glu Gly Leu Leu Gly Thr His Cys 65 70
75 80 Ser Pro Asp Leu Leu Phe Phe Leu Cys
Ala Met Tyr Ala Pro Ile Cys 85 90
95 Thr Ile Asp Phe Gln His Glu Pro Ile Lys Pro Cys Lys Ser
Val Cys 100 105 110
Glu Arg Ala Arg Gln Gly Cys Glu Pro Ile Leu Ile Lys Tyr Arg His
115 120 125 Ser Trp Pro Glu
Asn Leu Ala Cys Glu Glu Leu Pro Val Tyr Asp Arg 130
135 140 Gly Val Cys Ile Ser Pro Glu Ala
Ile Val Thr Ala Asp Gly Ala Asp 145 150
155 160 Phe Pro Met Asp Ser Ser Asn Gly Asn Cys Arg Gly
Ala Ser Ser Glu 165 170
175 Arg Cys Lys Cys Lys Pro Ile Arg Ala Thr Gln Lys Thr Tyr Phe Arg
180 185 190 Asn Asn Tyr
Asn Tyr Val Ile Arg Ala Lys Val Lys Glu Ile Lys Thr 195
200 205 Lys Cys His Asp Val Thr Ala Val
Val Glu Val Lys Glu Ile Leu Lys 210 215
220 Ser Ser Leu Val Asn Ile Pro Arg Asp Thr Val Asn Leu
Tyr Thr Ser 225 230 235
240 Ser Gly Cys Leu Cys Pro Pro Leu Asn Val Asn Glu Glu Tyr Ile Ile
245 250 255 Met Gly Tyr Glu
Asp Glu Glu Arg Ser Arg Leu Leu Leu Val Glu Gly 260
265 270 Ser Ile Ala Glu Lys Trp Lys Asp Arg
Leu Gly Lys Lys Val Lys Arg 275 280
285 Trp Asp Met Lys Leu Arg His Leu Gly Leu Ser Lys Ser Asp
Ser Ser 290 295 300
Asn Ser Asp Ser Thr Gln Ser Gln Lys Ser Gly Arg Asn Ser Asn Pro 305
310 315 320 Arg Gln Ala Arg Asn
325 83748PRTHomo sapiens 83Met Lys Thr Ser Pro Arg Arg
Pro Leu Ile Leu Lys Arg Arg Arg Leu 1 5
10 15 Pro Leu Pro Val Gln Asn Ala Pro Ser Glu Thr
Ser Glu Glu Glu Pro 20 25
30 Lys Arg Ser Pro Ala Gln Gln Glu Ser Asn Gln Ala Glu Ala Ser
Lys 35 40 45 Glu
Val Ala Glu Ser Asn Ser Cys Lys Phe Pro Ala Gly Ile Lys Ile 50
55 60 Ile Asn His Pro Thr Met
Pro Asn Thr Gln Val Val Ala Ile Pro Asn 65 70
75 80 Asn Ala Asn Ile His Ser Ile Ile Thr Ala Leu
Thr Ala Lys Gly Lys 85 90
95 Glu Ser Gly Ser Ser Gly Pro Asn Lys Phe Ile Leu Ile Ser Cys Gly
100 105 110 Gly Ala
Pro Thr Gln Pro Pro Gly Leu Arg Pro Gln Thr Gln Thr Ser 115
120 125 Tyr Asp Ala Lys Arg Thr Glu
Val Thr Leu Glu Thr Leu Gly Pro Lys 130 135
140 Pro Ala Ala Arg Asp Val Asn Leu Pro Arg Pro Pro
Gly Ala Leu Cys 145 150 155
160 Glu Gln Lys Arg Glu Thr Cys Ala Asp Gly Glu Ala Ala Gly Cys Thr
165 170 175 Ile Asn Asn
Ser Leu Ser Asn Ile Gln Trp Leu Arg Lys Met Ser Ser 180
185 190 Asp Gly Leu Gly Ser Arg Ser Ile
Lys Gln Glu Met Glu Glu Lys Glu 195 200
205 Asn Cys His Leu Glu Gln Arg Gln Val Lys Val Glu Glu
Pro Ser Arg 210 215 220
Pro Ser Ala Ser Trp Gln Asn Ser Val Ser Glu Arg Pro Pro Tyr Ser 225
230 235 240 Tyr Met Ala Met
Ile Gln Phe Ala Ile Asn Ser Thr Glu Arg Lys Arg 245
250 255 Met Thr Leu Lys Asp Ile Tyr Thr Trp
Ile Glu Asp His Phe Pro Tyr 260 265
270 Phe Lys His Ile Ala Lys Pro Gly Trp Lys Asn Ser Ile Arg
His Asn 275 280 285
Leu Ser Leu His Asp Met Phe Val Arg Glu Thr Ser Ala Asn Gly Lys 290
295 300 Val Ser Phe Trp Thr
Ile His Pro Ser Ala Asn Arg Tyr Leu Thr Leu 305 310
315 320 Asp Gln Val Phe Lys Gln Gln Lys Arg Pro
Asn Pro Glu Leu Arg Arg 325 330
335 Asn Met Thr Ile Lys Thr Glu Leu Pro Leu Gly Ala Arg Arg Lys
Met 340 345 350 Lys
Pro Leu Leu Pro Arg Val Ser Ser Tyr Leu Val Pro Ile Gln Phe 355
360 365 Pro Val Asn Gln Ser Leu
Val Leu Gln Pro Ser Val Lys Val Pro Leu 370 375
380 Pro Leu Ala Ala Ser Leu Met Ser Ser Glu Leu
Ala Arg His Ser Lys 385 390 395
400 Arg Val Arg Ile Ala Pro Lys Val Leu Leu Ala Glu Glu Gly Ile Ala
405 410 415 Pro Leu
Ser Ser Ala Gly Pro Gly Lys Glu Glu Lys Leu Leu Phe Gly 420
425 430 Glu Gly Phe Ser Pro Leu Leu
Pro Val Gln Thr Ile Lys Glu Glu Glu 435 440
445 Ile Gln Pro Gly Glu Glu Met Pro His Leu Ala Arg
Pro Ile Lys Val 450 455 460
Glu Ser Pro Pro Leu Glu Glu Trp Pro Ser Pro Ala Pro Ser Phe Lys 465
470 475 480 Glu Glu Ser
Ser His Ser Trp Glu Asp Ser Ser Gln Ser Pro Thr Pro 485
490 495 Arg Pro Lys Lys Ser Tyr Ser Gly
Leu Arg Ser Pro Thr Arg Cys Val 500 505
510 Ser Glu Met Leu Val Ile Gln His Arg Glu Arg Arg Glu
Arg Ser Arg 515 520 525
Ser Arg Arg Lys Gln His Leu Leu Pro Pro Cys Val Asp Glu Pro Glu 530
535 540 Leu Leu Phe Ser
Glu Gly Pro Ser Thr Ser Arg Trp Ala Ala Glu Leu 545 550
555 560 Pro Phe Pro Ala Asp Ser Ser Asp Pro
Ala Ser Gln Leu Ser Tyr Ser 565 570
575 Gln Glu Val Gly Gly Pro Phe Lys Thr Pro Ile Lys Glu Thr
Leu Pro 580 585 590
Ile Ser Ser Thr Pro Ser Lys Ser Val Leu Pro Arg Thr Pro Glu Ser
595 600 605 Trp Arg Leu Thr
Pro Pro Ala Lys Val Gly Gly Leu Asp Phe Ser Pro 610
615 620 Val Gln Thr Ser Gln Gly Ala Ser
Asp Pro Leu Pro Asp Pro Leu Gly 625 630
635 640 Leu Met Asp Leu Ser Thr Thr Pro Leu Gln Ser Ala
Pro Pro Leu Glu 645 650
655 Ser Pro Gln Arg Leu Leu Ser Ser Glu Pro Leu Asp Leu Ile Ser Val
660 665 670 Pro Phe Gly
Asn Ser Ser Pro Ser Asp Ile Asp Val Pro Lys Pro Gly 675
680 685 Ser Pro Glu Pro Gln Val Ser Gly
Leu Ala Ala Asn Arg Ser Leu Thr 690 695
700 Glu Gly Leu Val Leu Asp Thr Met Asn Asp Ser Leu Ser
Lys Ile Leu 705 710 715
720 Leu Asp Ile Ser Phe Pro Gly Leu Asp Glu Asp Pro Leu Gly Pro Asp
725 730 735 Asn Ile Asn Trp
Ser Gln Phe Ile Pro Glu Leu Gln 740 745
84208PRTHomo sapiens 84Met Gly Ser Cys Ser Gly Arg Cys Ala Leu Val
Val Leu Cys Ala Phe 1 5 10
15 Gln Leu Val Ala Ala Leu Glu Arg Gln Val Phe Asp Phe Leu Gly Tyr
20 25 30 Gln Trp
Ala Pro Ile Leu Ala Asn Phe Val His Ile Ile Ile Val Ile 35
40 45 Leu Gly Leu Phe Gly Thr Ile
Gln Tyr Arg Leu Arg Tyr Val Met Val 50 55
60 Tyr Thr Leu Trp Ala Ala Val Trp Val Thr Trp Asn
Val Phe Ile Ile 65 70 75
80 Cys Phe Tyr Leu Glu Val Gly Gly Leu Leu Lys Asp Ser Glu Leu Leu
85 90 95 Thr Phe Ser
Leu Ser Arg His Arg Ser Trp Trp Arg Glu Arg Trp Pro 100
105 110 Gly Cys Leu His Glu Glu Val Pro
Ala Val Gly Leu Gly Ala Pro His 115 120
125 Gly Gln Ala Leu Val Ser Gly Ala Gly Cys Ala Leu Glu
Pro Ser Tyr 130 135 140
Val Glu Ala Leu His Ser Cys Leu Gln Ile Leu Ile Ala Leu Leu Gly 145
150 155 160 Phe Val Cys Gly
Cys Gln Val Val Ser Val Phe Thr Asp Glu Glu Asp 165
170 175 Ser Phe Asp Phe Ile Gly Gly Phe Asp
Pro Phe Pro Leu Tyr His Val 180 185
190 Asn Glu Lys Pro Ser Ser Leu Leu Ser Lys Gln Val Tyr Leu
Pro Ala 195 200 205
8564PRTHomo sapiens 85Met Cys Val Ser Ser Ser Ser Ser Ser His Asp Glu Ala
Pro Val Leu 1 5 10 15
Asn Asp Lys His Leu Asp Val Pro Asp Ile Ile Ile Thr Pro Pro Thr
20 25 30 Pro Thr Gly Met
Met Leu Pro Arg Asp Leu Gly Ser Thr Val Trp Leu 35
40 45 Asp Glu Thr Gly Ser Cys Pro Asp Asp
Gly Glu Ile Asp Pro Glu Ala 50 55
60 86632PRTHomo sapiens 86Met Asp Thr Met Met Leu Asn
Val Arg Asn Leu Phe Glu Gln Leu Val 1 5
10 15 Arg Arg Val Glu Ile Leu Ser Glu Gly Asn Glu
Val Gln Phe Ile Gln 20 25
30 Leu Ala Lys Asp Phe Glu Asp Phe Arg Lys Lys Trp Gln Arg Thr
Asp 35 40 45 His
Glu Leu Gly Lys Tyr Lys Asp Leu Leu Met Lys Ala Glu Thr Glu 50
55 60 Arg Ser Ala Leu Asp Val
Lys Leu Lys His Ala Arg Asn Gln Val Asp 65 70
75 80 Val Glu Ile Lys Arg Arg Gln Arg Ala Glu Ala
Asp Cys Glu Lys Leu 85 90
95 Glu Arg Gln Ile Gln Leu Ile Arg Glu Met Leu Met Cys Asp Thr Ser
100 105 110 Gly Ser
Ile Gln Leu Ser Glu Glu Gln Lys Ser Ala Leu Ala Phe Leu 115
120 125 Asn Arg Gly Gln Pro Ser Ser
Ser Asn Ala Gly Asn Lys Arg Leu Ser 130 135
140 Thr Ile Asp Glu Ser Gly Ser Ile Leu Ser Asp Ile
Ser Phe Asp Lys 145 150 155
160 Thr Asp Glu Ser Leu Asp Trp Asp Ser Ser Leu Val Lys Thr Phe Lys
165 170 175 Leu Lys Lys
Arg Glu Lys Arg Arg Ser Thr Ser Arg Gln Phe Val Asp 180
185 190 Gly Pro Pro Gly Pro Val Lys Lys
Thr Arg Ser Ile Gly Ser Ala Val 195 200
205 Asp Gln Gly Asn Glu Ser Ile Val Ala Lys Thr Thr Val
Thr Val Pro 210 215 220
Asn Asp Gly Gly Pro Ile Glu Ala Val Ser Thr Ile Glu Thr Val Pro 225
230 235 240 Tyr Trp Thr Arg
Ser Arg Arg Lys Thr Gly Thr Leu Gln Pro Trp Asn 245
250 255 Ser Asp Ser Thr Leu Asn Ser Arg Gln
Leu Glu Pro Arg Thr Glu Thr 260 265
270 Asp Ser Val Gly Thr Pro Gln Ser Asn Gly Gly Met Arg Leu
His Asp 275 280 285
Phe Val Ser Lys Thr Val Ile Lys Pro Glu Ser Cys Val Pro Cys Gly 290
295 300 Lys Arg Ile Lys Phe
Gly Lys Leu Ser Leu Lys Cys Arg Asp Cys Arg 305 310
315 320 Val Val Ser His Pro Glu Cys Arg Asp Arg
Cys Pro Leu Pro Cys Ile 325 330
335 Pro Thr Leu Ile Gly Thr Pro Val Lys Ile Gly Glu Gly Met Leu
Ala 340 345 350 Asp
Phe Val Ser Gln Thr Ser Pro Met Ile Pro Ser Ile Val Val His 355
360 365 Cys Val Asn Glu Ile Glu
Gln Arg Gly Leu Thr Glu Thr Gly Leu Tyr 370 375
380 Arg Ile Ser Gly Cys Asp Arg Thr Val Lys Glu
Leu Lys Glu Lys Phe 385 390 395
400 Leu Arg Val Lys Thr Val Pro Leu Leu Ser Lys Val Asp Asp Ile His
405 410 415 Ala Ile
Cys Ser Leu Leu Lys Asp Phe Leu Arg Asn Leu Lys Glu Pro 420
425 430 Leu Leu Thr Phe Arg Leu Asn
Arg Ala Phe Met Glu Ala Ala Glu Ile 435 440
445 Thr Asp Glu Asp Asn Ser Ile Ala Ala Met Tyr Gln
Ala Val Gly Glu 450 455 460
Leu Pro Gln Ala Asn Arg Asp Thr Leu Ala Phe Leu Met Ile His Leu 465
470 475 480 Gln Arg Val
Ala Gln Ser Pro His Thr Lys Met Asp Val Ala Asn Leu 485
490 495 Ala Lys Val Phe Gly Pro Thr Ile
Val Ala His Ala Val Pro Asn Pro 500 505
510 Asp Pro Val Thr Met Leu Gln Asp Ile Lys Arg Gln Pro
Lys Val Val 515 520 525
Glu Arg Leu Leu Ser Leu Pro Leu Glu Tyr Trp Ser Gln Phe Met Met 530
535 540 Val Glu Gln Glu
Asn Ile Asp Pro Leu His Val Ile Glu Asn Ser Asn 545 550
555 560 Ala Phe Ser Thr Pro Gln Thr Pro Asp
Ile Lys Val Ser Leu Leu Gly 565 570
575 Pro Val Thr Thr Pro Glu His Gln Leu Leu Lys Thr Pro Ser
Ser Ser 580 585 590
Ser Leu Ser Gln Arg Val Arg Ser Thr Leu Thr Lys Asn Thr Pro Arg
595 600 605 Phe Gly Ser Lys
Ser Lys Ser Ala Thr Asn Leu Gly Arg Gln Gly Asn 610
615 620 Phe Phe Ala Ser Pro Met Leu Lys
625 630 87336PRTHomo sapiens 87Met Thr Asp Leu
Asn Asp Asn Ile Cys Lys Arg Tyr Ile Lys Met Ile 1 5
10 15 Thr Asn Ile Val Ile Leu Ser Leu Ile
Ile Cys Ile Ser Leu Ala Phe 20 25
30 Trp Ile Ile Ser Met Thr Ala Ser Thr Tyr Tyr Gly Asn Leu
Arg Pro 35 40 45
Ile Ser Pro Trp Arg Trp Leu Phe Ser Val Val Val Pro Val Leu Ile 50
55 60 Val Ser Asn Gly Leu
Lys Lys Lys Ser Leu Asp His Ser Gly Ala Leu 65 70
75 80 Gly Gly Leu Val Val Gly Phe Ile Leu Thr
Ile Ala Asn Phe Ser Phe 85 90
95 Phe Thr Ser Leu Leu Met Phe Phe Leu Ser Ser Ser Lys Leu Thr
Lys 100 105 110 Trp
Lys Gly Glu Val Lys Lys Arg Leu Asp Ser Glu Tyr Lys Glu Gly 115
120 125 Gly Gln Arg Asn Trp Val
Gln Val Phe Cys Asn Gly Ala Val Pro Thr 130 135
140 Glu Leu Ala Leu Leu Tyr Met Ile Glu Asn Gly
Pro Gly Glu Ile Pro 145 150 155
160 Val Asp Phe Ser Lys Gln Tyr Ser Ala Ser Trp Met Cys Leu Ser Leu
165 170 175 Leu Ala
Ala Leu Ala Cys Ser Ala Gly Asp Thr Trp Ala Ser Glu Val 180
185 190 Gly Pro Val Leu Ser Lys Ser
Ser Pro Arg Leu Ile Thr Thr Trp Glu 195 200
205 Lys Val Pro Val Gly Thr Asn Gly Gly Val Thr Val
Val Gly Leu Val 210 215 220
Ser Ser Leu Leu Gly Gly Thr Phe Val Gly Ile Ala Tyr Phe Leu Thr 225
230 235 240 Gln Leu Ile
Phe Val Asn Asp Leu Asp Ile Ser Ala Pro Gln Trp Pro 245
250 255 Ile Ile Ala Phe Gly Gly Leu Ala
Gly Leu Leu Gly Ser Ile Val Asp 260 265
270 Ser Tyr Leu Gly Ala Thr Met Gln Tyr Thr Gly Leu Asp
Glu Ser Thr 275 280 285
Gly Met Val Val Asn Ser Pro Thr Asn Lys Ala Arg His Ile Ala Gly 290
295 300 Lys Pro Ile Leu
Asp Asn Asn Ala Val Asn Leu Phe Ser Ser Val Leu 305 310
315 320 Ile Ala Leu Leu Leu Pro Thr Ala Ala
Trp Gly Phe Trp Pro Arg Gly 325 330
335 88347PRTHomo sapiens 88Met Ala Gln Ser Arg Asp Gly Gly
Asn Pro Phe Ala Glu Pro Ser Glu 1 5 10
15 Leu Asp Asn Pro Phe Gln Asp Pro Ala Val Ile Gln His
Arg Pro Ser 20 25 30
Arg Gln Tyr Ala Thr Leu Asp Val Tyr Asn Pro Phe Glu Thr Arg Glu
35 40 45 Pro Pro Pro Ala
Tyr Glu Pro Pro Ala Pro Ala Pro Leu Pro Pro Pro 50
55 60 Ser Ala Pro Ser Leu Gln Pro Ser
Arg Lys Leu Ser Pro Thr Glu Pro 65 70
75 80 Lys Asn Tyr Gly Ser Tyr Ser Thr Gln Ala Ser Ala
Ala Ala Ala Thr 85 90
95 Ala Glu Leu Leu Lys Lys Gln Glu Glu Leu Asn Arg Lys Ala Glu Glu
100 105 110 Leu Asp Arg
Arg Glu Arg Glu Leu Gln His Ala Ala Leu Gly Gly Thr 115
120 125 Ala Thr Arg Gln Asn Asn Trp Pro
Pro Leu Pro Ser Phe Cys Pro Val 130 135
140 Gln Pro Cys Phe Phe Gln Asp Ile Ser Met Glu Ile Pro
Gln Glu Phe 145 150 155
160 Gln Lys Thr Val Ser Thr Met Tyr Tyr Leu Trp Met Cys Ser Thr Leu
165 170 175 Ala Leu Leu Leu
Asn Phe Leu Ala Cys Leu Ala Ser Phe Cys Val Glu 180
185 190 Thr Asn Asn Gly Ala Gly Phe Gly Leu
Ser Ile Leu Trp Val Leu Leu 195 200
205 Phe Thr Pro Cys Ser Phe Val Cys Trp Tyr Arg Pro Met Tyr
Lys Ala 210 215 220
Phe Arg Ser Asp Ser Ser Phe Asn Phe Phe Val Phe Phe Phe Ile Phe 225
230 235 240 Phe Val Gln Asp Val
Leu Phe Val Leu Gln Ala Ile Gly Ile Pro Gly 245
250 255 Trp Gly Phe Ser Gly Trp Ile Ser Ala Leu
Val Val Pro Lys Gly Asn 260 265
270 Thr Ala Val Ser Val Leu Met Leu Leu Val Ala Leu Leu Phe Thr
Gly 275 280 285 Ile
Ala Val Leu Gly Ile Val Met Leu Lys Arg Ile His Ser Leu Tyr 290
295 300 Arg Arg Thr Gly Ala Ser
Phe Gln Lys Ala Gln Gln Glu Phe Ala Ala 305 310
315 320 Gly Val Phe Ser Asn Pro Ala Val Arg Thr Ala
Ala Ala Asn Ala Ala 325 330
335 Ala Gly Ala Ala Glu Asn Ala Phe Arg Ala Pro 340
345 89257PRTHomo sapiens 89Met Ala Gln Arg Met Thr
Thr Gln Leu Leu Leu Leu Leu Val Trp Val 1 5
10 15 Ala Val Val Gly Glu Ala Gln Thr Arg Ile Ala
Trp Ala Arg Thr Glu 20 25
30 Leu Leu Asn Val Cys Met Asn Ala Lys His His Lys Glu Lys Pro
Gly 35 40 45 Pro
Glu Asp Lys Leu His Glu Gln Cys Arg Pro Trp Arg Lys Asn Ala 50
55 60 Cys Cys Ser Thr Asn Thr
Ser Gln Glu Ala His Lys Asp Val Ser Tyr 65 70
75 80 Leu Tyr Arg Phe Asn Trp Asn His Cys Gly Glu
Met Ala Pro Ala Cys 85 90
95 Lys Arg His Phe Ile Gln Asp Thr Cys Leu Tyr Glu Cys Ser Pro Asn
100 105 110 Leu Gly
Pro Trp Ile Gln Gln Val Asp Gln Ser Trp Arg Lys Glu Arg 115
120 125 Val Leu Asn Val Pro Leu Cys
Lys Glu Asp Cys Glu Gln Trp Trp Glu 130 135
140 Asp Cys Arg Thr Ser Tyr Thr Cys Lys Ser Asn Trp
His Lys Gly Trp 145 150 155
160 Asn Trp Thr Ser Gly Phe Asn Lys Cys Ala Val Gly Ala Ala Cys Gln
165 170 175 Pro Phe His
Phe Tyr Phe Pro Thr Pro Thr Val Leu Cys Asn Glu Ile 180
185 190 Trp Thr His Ser Tyr Lys Val Ser
Asn Tyr Ser Arg Gly Ser Gly Arg 195 200
205 Cys Ile Gln Met Trp Phe Asp Pro Ala Gln Gly Asn Pro
Asn Glu Glu 210 215 220
Val Ala Arg Phe Tyr Ala Ala Ala Met Ser Gly Ala Gly Pro Trp Ala 225
230 235 240 Ala Trp Pro Phe
Leu Leu Ser Leu Ala Leu Met Leu Leu Trp Leu Leu 245
250 255 Ser 9043DNAArtificial
SequenceSynthetic Oligonucleotide 90actgtactaa ccctgcggcc gctttttttt
tttttttttt ttv 439147DNAArtificial
SequenceSynthetic Oligonucleotide 91ggaattctaa tacgactcac tatagggaga
cgaagacagt agacagg 479250DNAArtificial
SequenceSynthetic Oligonucleotide 92cgcgcctgtc tactgtcttc gtctccctat
agtgagtcgt attagaattc 509352DNAArtificial
SequenceSynthetic Oligonucleotide 93ggaattctaa tacgactcac tatagggaga
gcctgcacca acagttaaca gg 529455DNAArtificial
SequenceSynthetic Oligonucleotide 94cgcgcctgtt aactgttggt gcaggctctc
cctatagtga gtcgtattag aattc 559519DNAArtificial
SequenceSynthetic Oligonucleotide 95gggagacgaa gacagtaga
199620DNAArtificial SequenceSynthetic
Oligonucleotide 96gcctgcacca acagttaaca
209728DNAArtificial SequenceSynthetic Oligonucleotide
97ggaattctaa tacgactcac tataggga
289831DNAArtificial SequenceSynthetic Oligonucleotide 98cgcgtcccta
tagtgagtcg tattagaatt c
31992757DNAArtificial SequenceVector sequence 99ttttcccagt cacgacgttg
taaaacgacg gccagtgaat tctaatacga ctcactatag 60ggagatggag aaaaaaatca
ctggacgcgt ggcgcgccat taattaatgc ggccgctagc 120tcgagtgata ataagcggat
gaatggctgc aggcatgcaa gcttggcgta atcatggtca 180tagctgtttc ctgtgtgaaa
ttgttatccg ctcacaattc cacacaacat acgagccgga 240agcataaagt gtaaagcctg
gggtgcctaa tgagtgagct aactcacatt aattgcgttg 300cgctcactgc ccgctttcca
gtcgggaaac ctgtcgtgcc agctgcatta atgaatcggc 360caacgcgcgg ggagaggcgg
tttgcgtatt gggcgctctt ccgcttcctc gctcactgac 420tcgctgcgct cggtcgttcg
gctgcggcga gcggtatcag ctcactcaaa ggcggtaata 480cggttatcca cagaatcagg
ggataacgca ggaaagaaca tgtgagcaaa aggccagcaa 540aaggccagga accgtaaaaa
ggccgcgttg ctggcgtttt tccataggct ccgcccccct 600gacgagcatc acaaaaatcg
acgctcaagt cagaggtggc gaaacccgac aggactataa 660agataccagg cgtttccccc
tggaagctcc ctcgtgcgct ctcctgttcc gaccctgccg 720cttaccggat acctgtccgc
ctttctccct tcgggaagcg tggcgctttc tcaatgctca 780cgctgtaggt atctcagttc
ggtgtaggtc gttcgctcca agctgggctg tgtgcacgaa 840ccccccgttc agcccgaccg
ctgcgcctta tccggtaact atcgtcttga gtccaacccg 900gtaagacacg acttatcgcc
actggcagca gccactggta acaggattag cagagcgagg 960tatgtaggcg gtgctacaga
gttcttgaag tggtggccta actacggcta cactagaagg 1020acagtatttg gtatctgcgc
tctgctgaag ccagttacct tcggaaaaag agttggtagc 1080tcttgatccg gcaaacaaac
caccgctggt agcggtggtt tttttgtttg caagcagcag 1140attacgcgca gaaaaaaagg
atctcaagaa gatcctttga tcttttctac ggggtctgac 1200gctcagtgga acgaaaactc
acgttaaggg attttggtca tgagattatc aaaaaggatc 1260ttcacctaga tccttttaaa
ttaaaaatga agttttaaat caatctaaag tatatatgag 1320taaacttggt ctgacagtta
ccaatgctta atcagtgagg cacctatctc agcgatctgt 1380ctatttcgtt catccatagt
tgcctgactc cccgtcgtgt agataactac gatacgggag 1440ggcttaccat ctggccccag
tgctgcaatg ataccgcgag acccacgctc accggctcca 1500gatttatcag caataaacca
gccagccgga agggccgagc gcagaagtgg tcctgcaact 1560ttatccgcct ccatccagtc
tattaattgt tgccgggaag ctagagtaag tagttcgcca 1620gttaatagtt tgcgcaacgt
tgttgccatt gctacaggca tcgtggtgtc acgctcgtcg 1680tttggtatgg cttcattcag
ctccggttcc caacgatcaa ggcgagttac atgatccccc 1740atgttgtgca aaaaagcggt
tagctccttc ggtcctccga tcgttgtcag aagtaagttg 1800gccgcagtgt tatcactcat
ggttatggca gcactgcata attctcttac tgtcatgcca 1860tccgtaagat gcttttctgt
gactggtgag tactcaacca agtcattctg agaatagtgt 1920atgcggcgac cgagttgctc
ttgcccggcg tcaatacggg ataataccgc gccacatagc 1980agaactttaa aagtgctcat
cattggaaaa cgttcttcgg ggcgaaaact ctcaaggatc 2040ttaccgctgt tgagatccag
ttcgatgtaa cccactcgtg cacccaactg atcttcagca 2100tcttttactt tcaccagcgt
ttctgggtga gcaaaaacag gaaggcaaaa tgccgcaaaa 2160aagggaataa gggcgacacg
gaaatgttga atactcatac tcttcctttt tcaatattat 2220tgaagcattt atcagggtta
ttgtctcatg agcggataca tatttgaatg tatttagaaa 2280aataaacaaa taggggttcc
gcgcacattt ccccgaaaag tgccacctga cgtctaagaa 2340accattatta tcatgacatt
aacctataaa aataggcgta tcacgaggcc ctttcgtctc 2400gcgcgtttcg gtgatgacgg
tgaaaacctc tgacacatgc agctcccgga gacggtcaca 2460gcttgtctgt aagcggatgc
cgggagcaga caagcccgtc agggcgcgtc agcgggtgtt 2520ggcgggtgtc ggggctggct
taactatgcg gcatcagagc agattgtact gagagtgcac 2580catatgcggt gtgaaatacc
gcacagatgc gtaaggagaa aataccgcat caggcgccat 2640tcgccattca ggctgcgcaa
ctgttgggaa gggcgatcgg tgcgggcctc ttcgctatta 2700cgccagctgg cgaaaggggg
atgtgctgca aggcgattaa gttgggtaac gccaggg 27571002995DNAArtificial
SequenceVector Sequence 100ttttcccagt cacgacgttg taaaacgacg gccagtgaat
tcaattaacc ctcactaaag 60ggagacttgt tccaaatgtg ttaggcgcgc cgcatgcgtc
gacggatcct gagaacttca 120ggctcctggg caacgtgctg gttattgtgc tgtctcatca
ttttggcaaa gaattcactc 180ctcaggtgca ggctgcctat cagaaggtgg tggctggtgt
ggccaatgcc ctggctcaca 240aataccactg agatcttttt ccctctgcca aaaattatgg
ggacatcatg aagccccttg 300agcatctgac ttctggctaa taaaggaaat ttattttcat
tgcaaaaaaa aaaagcggcc 360gctcttctat agtgtcacct aaatggccca gcggccgagc
ttggcgtaat catggtcata 420gctgtttcct gtgtgaaatt gttatccgct cacaattcca
cacaacatac gagccggaag 480cataaagtgt aaagcctggg gtgcctaatg agtgagctaa
ctcacattaa ttgcgttgcg 540ctcactgccc gctttccagt cgggaaacct gtcgtgccag
ctgcattaat gaatcggcca 600acgcgcgggg agaggcggtt tgcgtattgg gcgctcttcc
gcttcctcgc tcactgactc 660gctgcgctcg gtcgttcggc tgcggcgagc ggtatcagct
cactcaaagg cggtaatacg 720gttatccaca gaatcagggg ataacgcagg aaagaacatg
tgagcaaaag gccagcaaaa 780ggccaggaac cgtaaaaagg ccgcgttgct ggcgtttttc
cataggctcc gcccccctga 840cgagcatcac aaaaatcgac gctcaagtca gaggtggcga
aacccgacag gactataaag 900ataccaggcg tttccccctg gaagctccct cgtgcgctct
cctgttccga ccctgccgct 960taccggatac ctgtccgcct ttctcccttc gggaagcgtg
gcgctttctc aaagctcacg 1020ctgtaggtat ctcagttcgg tgtaggtcgt tcgctccaag
ctgggctgtg tgcacgaacc 1080ccccgttcag cccgaccgct gcgccttatc cggtaactat
cgtcttgagt ccaacccggt 1140aagacacgac ttatcgccac tggcagcagc cactggtaac
aggattagca gagcgaggta 1200tgtaggcggt gctacagagt tcttgaagtg gtggcctaac
tacggctaca ctagaagaac 1260agtatttggt atctgcgctc tgctgaagcc agttaccttc
ggaaaaagag ttggtagctc 1320ttgatccggc aaacaaacca ccgctggtag cggtggtttt
tttgtttgca agcagcagat 1380tacgcgcaga aaaaaaggat ctcaagaaga tcctttgatc
ttttctacgg ggtctgacgc 1440tcagtggaac gaaaactcac gttaagggat tttggtcatg
agattatcaa aaaggatctt 1500cacctagatc cttttaaatt aaaaatgaag ttttaaatca
atctaaagta tatatgagta 1560aacttggtct gacagttacc aatgcttaat cagtgaggca
cctatctcag cgatctgtct 1620atttcgttca tccatagttg cctgactccc cgtcgtgtag
ataactacga tacgggaggg 1680cttaccatct ggccccagtg ctgcaatgat accgcgagac
ccacgctcac cggctccaga 1740tttatcagca ataaaccagc cagccggaag ggccgagcgc
agaagtggtc ctgcaacttt 1800atccgcctcc atccagtcta ttaattgttg ccgggaagct
agagtaagta gttcgccagt 1860taatagtttg cgcaacgttg ttgccattgc tacaggcatc
gtggtgtcac gctcgtcgtt 1920tggtatggct tcattcagct ccggttccca acgatcaagg
cgagttacat gatcccccat 1980gttgtgcaaa aaagcggtta gctccttcgg tcctccgatc
gttgtcagaa gtaagttggc 2040cgcagtgtta tcactcatgg ttatggcagc actgcataat
tctcttactg tcatgccatc 2100cgtaagatgc ttttctgtga ctggtgagta ctcaaccaag
tcattctgag aatagtgtat 2160gcggcgaccg agttgctctt gcccggcgtc aatacgggat
aataccgcgc cacatagcag 2220aactttaaaa gtgctcatca ttggaaaacg ttcttcgggg
cgaaaactct caaggatctt 2280accgctgttg agatccagtt cgatgtaacc cactcgtgca
cccaactgat cttcagcatc 2340ttttactttc accagcgttt ctgggtgagc aaaaacagga
aggcaaaatg ccgcaaaaaa 2400gggaataagg gcgacacgga aatgttgaat actcatactc
ttcctttttc aatattattg 2460aagcatttat cagggttatt gtctcatgag cggatacata
tttgaatgta tttagaaaaa 2520taaacaaata ggggttccgc gcacatttcc ccgaaaagtg
ccacctgacg tctaagaaac 2580cattattatc atgacattaa cctataaaaa taggcgtatc
acgaggccct ttcgtctcgc 2640gcgtttcggt gatgacggtg aaaacctctg acacatgcag
ctcccggaga cggtcacagc 2700ttgtctgtaa gcggatgccg ggagcagaca agcccgtcag
ggcgcgtcag cgggtgttgg 2760cgggtgtcgg ggctggctta actatgcggc atcagagcag
attgtactga gagtgcacca 2820tatgcggtgt gaaataccgc acagatgcgt aaggagaaaa
taccgcatca ggcgccattc 2880gccattcagg ctgcgcaact gttgggaagg gcgatcggtg
cgggcctctt cgctattacg 2940ccagctggcg aaagggggat gtgctgcaag gcgattaagt
tgggtaacgc caggg 29951014455DNAArtificial SequenceVector sequence
101tcgcgcgttt cggtgatgac ggtgaaaacc tctgacacat gcagctcccg gagacggtca
60cagcttgtct gtaagcggat gccgggagca gacaagcccg tcagggcgcg tcagcgggtg
120ttggcgggtg tcggggctgg cttaactatg cggcatcaga gcagattgta ctgagagtgc
180accatatgcg gtgtgaaata ccgcacagat gcgtaaggag aaaataccgc atcaggcgcc
240attcgccatt caggctgcgc aactgttggg aagggcgatc ggtgcgggcc tcttcgctat
300tacgccagct ggcgaaaggg ggatgtgctg caaggcgatt aagttgggta acgccagggt
360tttcccagtc acgacgttgt aaaacgacgg ccagtgccaa gcttttccaa aaaactaccg
420ttgttatagg tgtctcttga acacctataa caacggtagt ggatcccgcg tcctttccac
480aagatatata aacccaagaa atcgaaatac tttcaagtta cggtaagcat atgatagtcc
540attttaaaac ataattttaa aactgcaaac tacccaagaa attattactt tctacgtcac
600gtattttgta ctaatatctt tgtgtttaca gtcaaattaa ttctaattat ctctctaaca
660gccttgtatc gtatatgcaa atatgaagga atcatgggaa ataggccctc ttcctgcccg
720accttggcgc gcgctcggcg cgcggtcacg ctccgtcacg tggtgcgttt tgcctgcgcg
780tctttccact ggggaattca tgcttctcct ccctttagtg agggtaattc tctctctctc
840cctatagtga gtcgtattaa ttccttctct tctatagtgt cacctaaatc gttgcaattc
900gtaatcatgt catagctgtt tcctgtgtga aattgttatc cgctcacaat tccacacaac
960atacgagccg gaagcataaa gtgtaaagcc tggggtgcct aatgagtgag ctaactcaca
1020ttaattgcgt tgcgctcact gcccgctttc cagtcgggaa acctgtcgtg ccagctgcat
1080taatgaatcg gccaacgcgc ggggagaggc ggtttgcgta ttgggcgctc ttccgcttcc
1140tcgctcactg actcgctgcg ctcggtcgtt cggctgcggc gagcggtatc agctcactca
1200aaggcggtaa tacggttatc cacagaatca ggggataacg caggaaagaa catgtgagca
1260aaaggccagc aaaaggccag gaaccgtaaa aaggccgcgt tgctggcgtt tttccatagg
1320ctccgccccc ctgacgagca tcacaaaaat cgacgctcaa gtcagaggtg gcgaaacccg
1380acaggactat aaagatacca ggcgtttccc cctggaagct ccctcgtgcg ctctcctgtt
1440ccgaccctgc cgcttaccgg atacctgtcc gcctttctcc cttcgggaag cgtggcgctt
1500tctcatagct cacgctgtag gtatctcagt tcggtgtagg tcgttcgctc caagctgggc
1560tgtgtgcacg aaccccccgt tcagcccgac cgctgcgcct tatccggtaa ctatcgtctt
1620gagtccaacc cggtaagaca cgacttatcg ccactggcag cagccactgg taacaggatt
1680agcagagcga ggtatgtagg cggtgctaca gagttcttga agtggtggcc taactacggc
1740tacactagaa gaacagtatt tggtatctgc gctctgctga agccagttac cttcggaaaa
1800agagttggta gctcttgatc cggcaaaaaa accaccgctg gtagcggtgg tttttttgtt
1860tgcaagcagc agattacgcg cagaaaaaaa ggatctcaag aagatccttt gatcttttct
1920acggggtctg acgctcagtg gaacgaaaac tcacgttaag ggattttggt catgagatta
1980tcaaaaagga tcttcaccta gatcctttta aattaaaaat gaagttttaa atcaatctaa
2040agtatatatg agtaaacttg gtctgacagt taccaatgct taatcagtga ggcacctatc
2100tcagcgatct gtctatttcg ttcatccata gttgcctgac tccccgtcgt gtagataact
2160acgatacggg agggcttacc atctggcccc agtgctgcaa tgataccgcg agacccacgc
2220tcaccggctc cagatttatc agcaataaac cagccagccg gaagggccga gcgcagaagt
2280ggtcctgcaa ctttatccgc ctccatccag tctattaatt gttgccggga agctagagta
2340agtagttcgc cagttaatag tttgcgcaac gttgttgcca ttgctacagg catcgtggtg
2400tcacgctcgt cgtttggtat ggcttcattc agctccggtt cccaacgatc aaggcgagtt
2460acatgatccc ccatgttgtg caaaaaagcg gttagctcct tcggtcctcc gatcgttgtc
2520agaagtaagt tggccgcagt gttatcactc atggttatgg cagcactgca taattctctt
2580actgtcatgc catccgtaag atgcttttct gtgactggtg agtactcaac caagtcattc
2640tgagaatagt gtatgcggcg accgagttgc tcttgcccgg cgtcaatacg ggataatacc
2700gcgccacata gcagaacttt aaaagtgctc atcattggaa aacgttcttc ggggcgaaaa
2760ctctcaagga tcttaccgct gttgagatcc agttcgatgt aacccactcg tgcacccaac
2820tgatcttcag catcttttac tttcaccagc gtttctgggt gagcaaaaac aggaaggcaa
2880aatgccgcaa aaaagggaat aagggcgaca cggaaatgtt gaatactcat actcttcctt
2940tttcaatatt attgaagcat ttatcagggt tattgtctca tgagcggata catatttgaa
3000tgtatttaga aaaataaaca aataggggtt ccgcgcacat ttccccgaaa agtgccacct
3060attggtgtgg aaagtcccca ggctccccag caggcagaag tatgcaaagc atgcatctca
3120attagtcagc aaccaggtgt ggaaagtccc caggctcccc agcaggcaga agtatgcaaa
3180gcatgcatct caattagtca gcaaccatag tcccgcccct aactccgccc atcccgcccc
3240taactccgcc cagttccgcc cattctccgc cccatggctg actaattttt tttatttatg
3300cagaggccga ggccgcctcg gcctctgagc tattccagaa gtagtgagga ggcttttttg
3360gaggcctagg cttttgcaaa aagctagctt gcatgcctgc aggtcggccg ccacgaccgg
3420tgccgccacc atcccctgac ccacgcccct gacccctcac aaggagacga ccttccatga
3480ccgagtacaa gcccacggtg cgcctcgcca cccgcgacga cgtcccccgg gccgtacgca
3540ccctcgccgc cgcgttcgcc gactaccccg ccacgcgcca caccgtcgac ccggaccgcc
3600acatcgagcg ggtcaccgag ctgcaagaac tcttcctcac gcgcgtcggg ctcgacatcg
3660gcaaggtgtg ggtcgcggac gacggcgccg cggtggcggt ctggaccacg ccggagagcg
3720tcgaagcggg ggcggtgttc gccgagatcg gcccgcgcat ggccgagttg agcggttccc
3780ggctggccgc gcagcaacag atggaaggcc tcctggcgcc gcaccggccc aaggagcccg
3840cgtggttcct ggccaccgtc ggcgtctcgc ccgaccacca gggcaagggt ctgggcagcg
3900ccgtcgtgct ccccggagtg gaggcggccg agcgcgccgg ggtgcccgcc ttcctggaga
3960cctccgcgcc ccgcaacctc cccttctacg agcggctcgg cttcaccgtc accgccgacg
4020tcgaggtgcc cgaaggaccg cgcacctggt gcatgacccg caagcccggt gcctgacgcc
4080cgccccacga cccgcagcgc ccgaccgaaa ggagcgcacg accccatggc tccgaccgaa
4140gccacccggg gcggccccgc cgaccccgca cccgcccccg aggcccaccg actctagagg
4200atcataatca gccataccac atttgtagag gttttacttg ctttaaaaaa cctcccacac
4260ctccccctga acctgaaaca taaaatgaat gcaattgttg ttgttaactt gtttattgca
4320gcttataatg gttacaaata aagcaatagc atcacaaatt tcacaaataa agcatttttt
4380tcactgcaat ctaagaaacc attattatca tgacattaac ctataaaaat aggcgtatca
4440cgaggccctt tcgtc
445510252DNAArtificial SequenceSEQUENCE UNKNOWNmisc_feature(1)..(52)n is
a, c, g, or t 102nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nn 5210319DNAArtificial SequenceSynthetic Oligonucleotide
103gtcaagaaac cacacttta
1910419DNAArtificial SequenceSynthetic Oligonucleotide 104gtgacatgga
acccagcga
1910519DNAArtificial SequenceSynthetic Oligonucleotide 105accgtggctg
ctcgataaa
1910619DNAArtificial SequenceSynthetic Oligonucleotide 106gccagagagc
acagaaata
1910719DNAArtificial SequenceSynthetic Oligonucleotide 107gaggaatgcc
tctaagaaa
1910819DNAArtificial SequenceSynthetic Oligonucleotide 108gggaacgaga
agggcttct
1910919DNAArtificial SequenceSynthetic Oligonucleotide 109agctggagga
atgagaatt
1911019DNAArtificial SequenceSynthetic Oligonucleotide 110agggccaaag
ctttccata
1911119DNAArtificial SequenceSynthetic Oligonucleotide 111ggcaggctgt
ccgcttaaa
1911219DNAArtificial SequenceSynthetic Oligonucleotide 112ggtccttagg
cacccagat
1911319DNAArtificial SequenceSynthetic Oligonucleotide 113gcggagccca
gggagaata
1911419DNAArtificial SequenceSynthetic Oligonucleotide 114gcccggattg
atgacatat
1911519DNAArtificial SequenceSynthetic Oligonucleotide 115gtggaggctg
agtttccat
1911619DNAArtificial SequenceSynthetic Oligonucleotide 116ggatgttaac
ctgcgaaat
1911719DNAArtificial SequenceSynthetic Oligonucleotide 117ggtcagcagg
gttcattta
1911819DNAArtificial SequenceSynthetic Oligonucleotide 118gcctcaggaa
caagatgaa
1911919DNAArtificial SequenceSynthetic Oligonucleotide 119gcgcgagatc
ctctccatt
1912019DNAArtificial SequenceSynthetic Oligonucleotide 120gcgccagagg
agcgggaag
1912119DNAArtificial SequenceSynthetic Oligonucleotide 121gccgcccagt
tcaatacaa
1912219DNAArtificial SequenceSynthetic Oligonucleotide 122gagcttacaa
cctgcctta
1912319DNAArtificial SequenceSynthetic Oligonucleotide 123ggcgcccact
acccaagaa
1912419DNAArtificial SequenceSynthetic Oligonucleotide 124gagtcaggga
tgggtccat
1912519DNAArtificial SequenceSynthetic Oligonucleotide 125gggccagtct
gtactcatt
1912619DNAArtificial SequenceSynthetic Oligonucleotide 126gggaattcca
tctccatat
1912719DNAArtificial SequenceSynthetic Oligonucleotide 127ggcgcagatc
acccagaag
1912819DNAArtificial SequenceSynthetic Oligonucleotide 128gagcatcctg
gtgaggaat
1912919DNAArtificial SequenceSynethtic Oligonucleotide 129ggtgccacat
gactaggat
1913019DNAArtificial SequenceSynthetic Oligonucleotide 130gctgcagacg
tgtatgcat
1913119DNAArtificial SequenceSynthetic Oligonucleotide 131gcggaggcac
tgggcttat
1913219DNAArtificial SequenceSynthetic Oligonucleotide 132gcccgcttac
ttcctggag
1913319DNAArtificial SequenceSynthetic Oligonucleotide 133gctctgctca
agttggata
1913419DNAArtificial SequenceSynthetic Oligonucleotide 134gctgctgcct
tgcagtttg
1913519DNAArtificial SequenceSynthetic Oligonucleotide 135gcccttacct
gatgctaaa
1913619DNAArtificial SequenceSynthetic Oligonucleotide 136ggcacctaca
aatgttata
1913719DNAArtificial SequenceSynthetic Oligonucleotide 137gaggcctgga
agctcctaa
1913819DNAArtificial SequenceSynthetic Oligonucleotide 138gcagcttcag
gaggttaaa
1913919DNAArtificial SequenceSynthetic Oligonucleotide 139gccggacctc
ttcatctta
1914019DNAArtificial SequenceSynthetic Oligonucleotide 140gcgtccatca
cggaaacat
1914119DNAArtificial SequenceSynthetic Oligonucleotide 141gtcatcagga
cgtccatta
1914219DNAArtificial SequenceSynthetic Oligonucleotide 142gacacgatct
accctcaaa
1914319DNAArtificial SequenceSynthetic Oligonucleotide 143gggccatagg
gaagcttga
1914419DNAArtificial SequenceSynthetic Oligonucleotide 144gcccacgtgt
tgagatcaa
1914519DNAArtificial SequenceSynthetic Oligonucleotide 145gctcccactg
attccacat
1914619DNAArtificial SequenceSynthetic Oligonucleotide 146gccagagagt
aaaagggat
1914719DNAArtificial SequenceSynthetic Oligonucleotide 147ggcatatgga
aggagcatt
1914819DNAArtificial SequenceSynthetic Oligonucleotide 148gtggtttggt
tcagcagtt
1914919DNAArtificial SequenceSynthetic Oligonucleotide 149ggcctccagc
cacgtaatt
1915019DNAArtificial SequenceSynthetic Oligonucleotide 150ggcgctgctg
ccgctcatc
1915119DNAArtificial SequenceSynthetic Oligonucleotide 151gggctggaac
tggacttca
1915219DNAArtificial SequenceSynthetic Oligonucleotide 152gcccataagg
atgtttcct
1915323DNAArtificial SequenceSynthetic Oligonucleotide 153gcgtccgggc
ctgtcttcaa cct
2315424DNAArtificial SequenceSynthetic Oligonucleotide 154gccccaccct
ctaccccacc acta
2415522DNAArtificial SequenceSynthetic Oligonucleotide 155gagatcctga
tcaaggtgca gg
2215621DNAArtificial SequenceSynthetic Oligonucleotide 156tgcacgctca
cagcagtcag g
2115722DNAArtificial SequenceSynthetic Oligonucleotide 157aacatgacta
agatgcccaa cc
2215823DNAArtificial SequenceSynthetic Oligonucleotide 158aatctccttc
acctccacta ctg
2315922DNAArtificial SequenceSynthetic Oligonucleotide 159aagcatagcc
ataggtgatt gg
2216023DNAArtificial SequenceSynthetic Oligonucleotide 160acaggtatca
gacaagggag cag
2316121DNAArtificial SequenceSynthetic Oligonucleotide 161ttacgaccta
tttctccgtg g
2116221DNAArtificial SequenceSynthetic Oligonucleotide 162aatgcaataa
ttggccactg c
2116323DNAArtificial SequenceSynthetic Oligonucleotide 163acacatcaaa
ctgcttatcc agg
2316422DNAArtificial SequenceSynthetic Oligonucleotide 164actgatgtga
aaatgcacat cc
2216521DNAArtificial SequenceSynthetic Oligonucleotide 165atggctcata
cagcactcag g
2116622DNAArtificial SequenceSynthetic Oligonucleotide 166gaactgtcac
tccggaaagc ct
2216726DNAArtificial SequenceSynthetic Oligonucleotide 167tgaaggtcgg
agtcaacgga tttggt
2616824DNAArtificial SequenceSynthetic Oligonucleotide 168catgtgggcc
atgaggtcca ccac
241694419DNAHomo sapiens 169ccctaatgcc tccaacaata actgttgact ttttattttc
agtcagagaa gcctggcaac 60caagaactgt ttttttggtg gtttacgaga acttaactga
attggaaaat atttgcttta 120atgaaacaat ttactcttgt gcaacactaa attgtgtcaa
tcaagcaaat aaggaagaaa 180gtcttattta taaaattgcc tgctcctgat tttacttcat
ttcttctcag gctccaagaa 240ggggaaaaaa atgaagattt tgatacttgg tatttttctg
tttttatgta gtaccccagc 300ctgggcgaaa gaaaagcatt attacattgg aattattgaa
acgacttggg attatgcctc 360tgaccatggg gaaaagaaac ttatttctgt tgacacggaa
cattccaata tctatcttca 420aaatggccca gatagaattg ggagactata taagaaggcc
ctttatcttc agtacacaga 480tgaaaccttt aggacaacta tagaaaaacc ggtctggctt
gggtttttag gccctattat 540caaagctgaa actggagata aagtttatgt acacttaaaa
aaccttgcct ctaggcccta 600cacctttcat tcacatggaa taacttacta taaggaacat
gagggggcca tctaccctga 660taacaccaca gattttcaaa gagcagatga caaagtatat
ccaggagagc agtatacata 720catgttgctt gccactgaag aacaaagtcc tggggaagga
gatggcaatt gtgtgactag 780gatttaccat tcccacattg atgctccaaa agatattgcc
tcaggactca tcggaccttt 840aataatctgt aaaaaagatt ctctagataa agaaaaagaa
aaacatattg accgagaatt 900tgtggtgatg ttttctgtgg tggatgaaaa tttcagctgg
tacctagaag acaacattaa 960aacctactgc tcagaaccag agaaagttga caaagacaac
gaagacttcc aggagagtaa 1020cagaatgtat tctgtgaatg gatacacttt tggaagtctc
ccaggactct ccatgtgtgc 1080tgaagacaga gtaaaatggt acctttttgg tatgggtaat
gaagttgatg tgcacgcagc 1140tttctttcac gggcaagcac tgactaacaa gaactaccgt
attgacacaa tcaacctctt 1200tcctgctacc ctgtttgatg cttatatggt ggcccagaac
cctggagaat ggatgctcag 1260ctgtcagaat ctaaaccatc tgaaagccgg tttgcaagcc
tttttccagg tccaggagtg 1320taacaagtct tcatcaaagg ataatatccg tgggaagcat
gttagacact actacattgc 1380cgctgaggaa atcatctgga actatgctcc ctctggtata
gacatcttca ctaaagaaaa 1440cttaacagca cctggaagtg actcagcggt gttttttgaa
caaggtacca caagaattgg 1500aggctcttat aaaaagctgg tttatcgtga gtacacagat
gcctccttca caaatcgaaa 1560ggagagaggc cctgaagaag agcatcttgg catcctgggt
cctgtcattt gggcagaggt 1620gggagacacc atcagagtaa ccttccataa caaaggagca
tatcccctca gtattgagcc 1680gattggggtg agattcaata agaacaacga gggcacatac
tattccccaa attacaaccc 1740ccagagcaga agtgtgcctc cttcagcctc ccatgtggca
cccacagaaa cattcaccta 1800tgaatggact gtccccaaag aagtaggacc cactaatgca
gatcctgtgt gtctagctaa 1860gatgtattat tctgctgtgg atcccactaa agatatattc
actgggctta ttgggccaat 1920gaaaatatgc aagaaaggaa gtttacatgc aaatgggaga
cagaaagatg tagacaagga 1980attctatttg tttcctacag tatttgatga gaatgagagt
ttactcctgg aagataatat 2040tagaatgttt acaactgcac ctgatcaggt ggataaggaa
gatgaagact ttcaggaatc 2100taataaaatg cactccatga atggattcat gtatgggaat
cagccgggtc tcactatgtg 2160caaaggagat tcggtcgtgt ggtacttatt cagcgccgga
aatgaggccg atgtacatgg 2220aatatacttt tcaggaaaca catatctgtg gagaggagaa
cggagagaca cagcaaacct 2280cttccctcaa acaagtctta cgctccacat gtggcctgac
acagagggga cttttaatgt 2340tgaatgcctt acaactgatc attacacagg cggcatgaag
caaaaatata ctgtgaacca 2400atgcaggcgg cagtctgagg attccacctt ctacctggga
gagaggacat actatatcgc 2460agcagtggag gtggaatggg attattcccc acaaagggag
tgggaaaagg agctgcatca 2520tttacaagag cagaatgttt caaatgcatt tttagataag
ggagagtttt acataggctc 2580aaagtacaag aaagttgtgt atcggcagta tactgatagc
acattccgtg ttccagtgga 2640gagaaaagct gaagaagaac atctgggaat tctaggtcca
caacttcatg cagatgttgg 2700agacaaagtc aaaattatct ttaaaaacat ggccacaagg
ccctactcaa tacatgccca 2760tggggtacaa acagagagtt ctacagttac tccaacatta
ccaggtgaaa ctctcactta 2820cgtatggaaa atcccagaaa gatctggagc tggaacagag
gattctgctt gtattccatg 2880ggcttattat tcaactgtgg atcaagttaa ggacctctac
agtggattaa ttggccccct 2940gattgtttgt cgaagacctt acttgaaagt attcaatccc
agaaggaaac tggaatttgc 3000ccttctgttt ctagtttttg atgagaatga atcttggtac
ttagatgaca acatcaaaac 3060atactctgat caccccgaga aagtaaacaa agatgatgag
gaattcatag aaagcaataa 3120aatgcatgct attaatggaa gaatgtttgg aaacctacaa
ggcctcacaa tgcacgtggg 3180agatgaagtc aactggtatc tgatgggaat gggcaatgaa
atagacttac acactgtaca 3240ttttcacggc catagcttcc aatacaagca caggggagtt
tatagttctg atgtctttga 3300cattttccct ggaacatacc aaaccctaga aatgtttcca
agaacacctg gaatttggtt 3360actccactgc catgtgaccg accacattca tgctggaatg
gaaaccactt acaccgttct 3420acaaaatgaa gacaccaaat ctggctgaat gaaataaatt
ggtgataagt ggaaaaaaga 3480gaaaaaccaa tgattcataa caatgtatgt gaaagtgtaa
aatagaatgt tactttggaa 3540tgactataaa cattaaaaga agactggaag catacaactt
tgtacatttg tgggggaaaa 3600ctattaattt tttgcaaatg gaaagatcaa cagactatat
aatgatacat gactgacact 3660tgtacactag gtaataaaac tgattcatac agtctaatga
tatcaccgct gttagggttt 3720tataaaactg catttaaaaa aagatctatg accagatatt
ctcctgggtg ctcctcaaag 3780gaacactatt aaggttcatt gaaatgtttt caatcattgc
cttcccattg atccttctaa 3840catgctgttg acatcacacc taatattcag agggaatggg
caaggtatga gggaaggaaa 3900taaaaaataa aataaataaa atagaatgac acaaatttga
gttttgtgaa cccctgaaca 3960gatggtctta aggacgttat ctggaactgg agaaaagcag
agttgagaga caattctata 4020gattaaatcc tggtaaggac aaacattgcc attagaagaa
aagcttcaaa atagacctgt 4080ggcagatgtc acatgagtag aatttctgcc cagccttaac
tgcattcaga ggataatatc 4140aatgaactaa acttgaacta aaaatttttt aaacaaaaag
ttataaatga agacacatgg 4200ttgtgaatac aatgatgtat ttctttattt tcacatacac
tctagctaaa agagcaagag 4260tacacatcaa caaaaatgga aacaaggctt tggctgaaaa
aaacatgcat ttgacaaatc 4320atgttaatag ctagacaaga agaaagttag ctttgtaaac
ttctacttca tttgattcag 4380agaaacagag catgagtttt cttaaaagta acaagaaaa
44191701065PRTHomo sapiens 170Met Lys Ile Leu Ile
Leu Gly Ile Phe Leu Phe Leu Cys Ser Thr Pro 1 5
10 15 Ala Trp Ala Lys Glu Lys His Tyr Tyr Ile
Gly Ile Ile Glu Thr Thr 20 25
30 Trp Asp Tyr Ala Ser Asp His Gly Glu Lys Lys Leu Ile Ser Val
Asp 35 40 45 Thr
Glu His Ser Asn Ile Tyr Leu Gln Asn Gly Pro Asp Arg Ile Gly 50
55 60 Arg Leu Tyr Lys Lys Ala
Leu Tyr Leu Gln Tyr Thr Asp Glu Thr Phe 65 70
75 80 Arg Thr Thr Ile Glu Lys Pro Val Trp Leu Gly
Phe Leu Gly Pro Ile 85 90
95 Ile Lys Ala Glu Thr Gly Asp Lys Val Tyr Val His Leu Lys Asn Leu
100 105 110 Ala Ser
Arg Pro Tyr Thr Phe His Ser His Gly Ile Thr Tyr Tyr Lys 115
120 125 Glu His Glu Gly Ala Ile Tyr
Pro Asp Asn Thr Thr Asp Phe Gln Arg 130 135
140 Ala Asp Asp Lys Val Tyr Pro Gly Glu Gln Tyr Thr
Tyr Met Leu Leu 145 150 155
160 Ala Thr Glu Glu Gln Ser Pro Gly Glu Gly Asp Gly Asn Cys Val Thr
165 170 175 Arg Ile Tyr
His Ser His Ile Asp Ala Pro Lys Asp Ile Ala Ser Gly 180
185 190 Leu Ile Gly Pro Leu Ile Ile Cys
Lys Lys Asp Ser Leu Asp Lys Glu 195 200
205 Lys Glu Lys His Ile Asp Arg Glu Phe Val Val Met Phe
Ser Val Val 210 215 220
Asp Glu Asn Phe Ser Trp Tyr Leu Glu Asp Asn Ile Lys Thr Tyr Cys 225
230 235 240 Ser Glu Pro Glu
Lys Val Asp Lys Asp Asn Glu Asp Phe Gln Glu Ser 245
250 255 Asn Arg Met Tyr Ser Val Asn Gly Tyr
Thr Phe Gly Ser Leu Pro Gly 260 265
270 Leu Ser Met Cys Ala Glu Asp Arg Val Lys Trp Tyr Leu Phe
Gly Met 275 280 285
Gly Asn Glu Val Asp Val His Ala Ala Phe Phe His Gly Gln Ala Leu 290
295 300 Thr Asn Lys Asn Tyr
Arg Ile Asp Thr Ile Asn Leu Phe Pro Ala Thr 305 310
315 320 Leu Phe Asp Ala Tyr Met Val Ala Gln Asn
Pro Gly Glu Trp Met Leu 325 330
335 Ser Cys Gln Asn Leu Asn His Leu Lys Ala Gly Leu Gln Ala Phe
Phe 340 345 350 Gln
Val Gln Glu Cys Asn Lys Ser Ser Ser Lys Asp Asn Ile Arg Gly 355
360 365 Lys His Val Arg His Tyr
Tyr Ile Ala Ala Glu Glu Ile Ile Trp Asn 370 375
380 Tyr Ala Pro Ser Gly Ile Asp Ile Phe Thr Lys
Glu Asn Leu Thr Ala 385 390 395
400 Pro Gly Ser Asp Ser Ala Val Phe Phe Glu Gln Gly Thr Thr Arg Ile
405 410 415 Gly Gly
Ser Tyr Lys Lys Leu Val Tyr Arg Glu Tyr Thr Asp Ala Ser 420
425 430 Phe Thr Asn Arg Lys Glu Arg
Gly Pro Glu Glu Glu His Leu Gly Ile 435 440
445 Leu Gly Pro Val Ile Trp Ala Glu Val Gly Asp Thr
Ile Arg Val Thr 450 455 460
Phe His Asn Lys Gly Ala Tyr Pro Leu Ser Ile Glu Pro Ile Gly Val 465
470 475 480 Arg Phe Asn
Lys Asn Asn Glu Gly Thr Tyr Tyr Ser Pro Asn Tyr Asn 485
490 495 Pro Gln Ser Arg Ser Val Pro Pro
Ser Ala Ser His Val Ala Pro Thr 500 505
510 Glu Thr Phe Thr Tyr Glu Trp Thr Val Pro Lys Glu Val
Gly Pro Thr 515 520 525
Asn Ala Asp Pro Val Cys Leu Ala Lys Met Tyr Tyr Ser Ala Val Asp 530
535 540 Pro Thr Lys Asp
Ile Phe Thr Gly Leu Ile Gly Pro Met Lys Ile Cys 545 550
555 560 Lys Lys Gly Ser Leu His Ala Asn Gly
Arg Gln Lys Asp Val Asp Lys 565 570
575 Glu Phe Tyr Leu Phe Pro Thr Val Phe Asp Glu Asn Glu Ser
Leu Leu 580 585 590
Leu Glu Asp Asn Ile Arg Met Phe Thr Thr Ala Pro Asp Gln Val Asp
595 600 605 Lys Glu Asp Glu
Asp Phe Gln Glu Ser Asn Lys Met His Ser Met Asn 610
615 620 Gly Phe Met Tyr Gly Asn Gln Pro
Gly Leu Thr Met Cys Lys Gly Asp 625 630
635 640 Ser Val Val Trp Tyr Leu Phe Ser Ala Gly Asn Glu
Ala Asp Val His 645 650
655 Gly Ile Tyr Phe Ser Gly Asn Thr Tyr Leu Trp Arg Gly Glu Arg Arg
660 665 670 Asp Thr Ala
Asn Leu Phe Pro Gln Thr Ser Leu Thr Leu His Met Trp 675
680 685 Pro Asp Thr Glu Gly Thr Phe Asn
Val Glu Cys Leu Thr Thr Asp His 690 695
700 Tyr Thr Gly Gly Met Lys Gln Lys Tyr Thr Val Asn Gln
Cys Arg Arg 705 710 715
720 Gln Ser Glu Asp Ser Thr Phe Tyr Leu Gly Glu Arg Thr Tyr Tyr Ile
725 730 735 Ala Ala Val Glu
Val Glu Trp Asp Tyr Ser Pro Gln Arg Glu Trp Glu 740
745 750 Lys Glu Leu His His Leu Gln Glu Gln
Asn Val Ser Asn Ala Phe Leu 755 760
765 Asp Lys Gly Glu Phe Tyr Ile Gly Ser Lys Tyr Lys Lys Val
Val Tyr 770 775 780
Arg Gln Tyr Thr Asp Ser Thr Phe Arg Val Pro Val Glu Arg Lys Ala 785
790 795 800 Glu Glu Glu His Leu
Gly Ile Leu Gly Pro Gln Leu His Ala Asp Val 805
810 815 Gly Asp Lys Val Lys Ile Ile Phe Lys Asn
Met Ala Thr Arg Pro Tyr 820 825
830 Ser Ile His Ala His Gly Val Gln Thr Glu Ser Ser Thr Val Thr
Pro 835 840 845 Thr
Leu Pro Gly Glu Thr Leu Thr Tyr Val Trp Lys Ile Pro Glu Arg 850
855 860 Ser Gly Ala Gly Thr Glu
Asp Ser Ala Cys Ile Pro Trp Ala Tyr Tyr 865 870
875 880 Ser Thr Val Asp Gln Val Lys Asp Leu Tyr Ser
Gly Leu Ile Gly Pro 885 890
895 Leu Ile Val Cys Arg Arg Pro Tyr Leu Lys Val Phe Asn Pro Arg Arg
900 905 910 Lys Leu
Glu Phe Ala Leu Leu Phe Leu Val Phe Asp Glu Asn Glu Ser 915
920 925 Trp Tyr Leu Asp Asp Asn Ile
Lys Thr Tyr Ser Asp His Pro Glu Lys 930 935
940 Val Asn Lys Asp Asp Glu Glu Phe Ile Glu Ser Asn
Lys Met His Ala 945 950 955
960 Ile Asn Gly Arg Met Phe Gly Asn Leu Gln Gly Leu Thr Met His Val
965 970 975 Gly Asp Glu
Val Asn Trp Tyr Leu Met Gly Met Gly Asn Glu Ile Asp 980
985 990 Leu His Thr Val His Phe His Gly
His Ser Phe Gln Tyr Lys His Arg 995 1000
1005 Gly Val Tyr Ser Ser Asp Val Phe Asp Ile Phe
Pro Gly Thr Tyr 1010 1015 1020
Gln Thr Leu Glu Met Phe Pro Arg Thr Pro Gly Ile Trp Leu Leu
1025 1030 1035 His Cys His
Val Thr Asp His Ile His Ala Gly Met Glu Thr Thr 1040
1045 1050 Tyr Thr Val Leu Gln Asn Glu Asp
Thr Lys Ser Gly 1055 1060 1065
17123DNAArtificial SequenceSynthetic Oligonucleotide 171gcttaaaaga
gtcctcctgt ggc
2317223DNAArtificial SequenceSynthetic Oligonucleotide 172tggacattgt
tcttaaagtg tgg
2317321DNAArtificial SequenceSynthetic Oligonucleotide 173aggttttatg
gccaccgtca g
2117422DNAArtificial SequenceSynthetic Oligonucleotide 174atcctatacc
gctcggttat gc
2217522DNAArtificial SequenceSynthetic Oligonucleotide 175gggcggcggc
tctttcctcc tc
2217619DNAArtificial SequenceSynthetic Oligonucleotide 176gctagcggcc
ccatactcg
1917724DNAArtificial SequenceSynthetic Oligonucleotide 177acactggatg
ccctgaatga caca
2417820DNAArtificial SequenceSynthetic Oligonucleotide 178gctttggccc
tttttgctaa
2017922DNAArtificial SequenceSynthetic Oligonucleotide 179cccacttctg
tcttactgca tc
2218022DNAArtificial SequenceSynthetic Oligonucleotide 180catagtactc
cagggcttat tc
2218123DNAArtificial SequenceSynthetic Oligonucleotide 181aacgattgcc
cggattgatg aca
2318224DNAArtificial SequenceSynthetic Oligonucleotide 182tacttgaggc
tggggtggga gatg
2418322DNAArtificial SequenceSynthetic Oligonucleotide 183cactacgcca
ggcaccccca aa
2218418DNAArtificial SequenceSynthetic Oligonucleotide 184cgaggcgcac
ggcagtct
1818524DNAArtificial SequenceSynthetic Oligonucleotide 185atccgttgct
gcagctcgtt cctc
2418624DNAArtificial SequenceSynthetic Oligonucleotide 186accctgctga
ccttcttcca ttcc
2418724DNAArtificial SequenceSynthetic Oligonucleotide 187tcggaggagg
gctggctggt gttt
2418824DNAArtificial SequenceSynthetic Oligonucleotide 188cttgggcgtc
ttggagcggt tctg
2418922DNAArtificial SequenceSynthetic Oligonucleotide 189agagcctatt
gaagatgaac ag
2219023DNAArtificial SequenceSynthetic Oligonucleotide 190tgattgcccc
ggatcctctt agg
2319120DNAArtificial SequenceSynthetic Oligonucleotide 191ggacaaatac
gacgacgagg
2019219DNAArtificial SequenceSynthetic Oligonucleotide 192ggtttcttgg
gtagtgggc
1919322DNAArtificial SequenceSynthetic Oligonucleotide 193ccccggagaa
ggaagagcag ta
2219424DNAArtificial SequenceSynthetic Oligonucleotide 194cgaaagccgg
cagttagtta ttga
2419524DNAArtificial SequenceSynthetic Oligonucleotide 195ggcgggcaac
gaattccagg tgtc
2419624DNAArtificial SequenceSynthetic Oligonucleotide 196tcagaggttc
gtcgcatttg tcca
2419722DNAArtificial SequenceSynthetic Oligonucleotide 197caacagtcat
gatgtgtgga tg
2219822DNAArtificial SequenceSynthetic Oligonucleotide 198actgcacctt
gtccgtgttg ac
2219920DNAArtificial SequenceSynthetic Oligonucleotide 199ccggctggct
gctttgttta
2020024DNAArtificial SequenceSynthetic Oligonucleotide 200atgatcagca
ggttcgttgg tagg
2420119DNAArtificial SequenceSynthetic Oligonucleotide 201atgccggaag
tgaatgtgg
1920219DNAArtificial SequenceSynthetic Oligonucleotide 202ggtgactccg
ccttttgat
1920320DNAArtificial SequenceSynthetic Oligonucleotide 203acattcgctt
ctccatctgg
2020420DNAArtificial SequenceSynthetic Oligonucleotide 204tgtcacggaa
gggaaccagg
2020520DNAArtificial SequenceSynthetic Oligonucleotide 205acgctgcctc
tgggtcactt
2020623DNAArtificial SequenceSynthetic Oligonucleotide 206ttggcaaatc
aatggcttgt aat
2320720DNAArtificial SequenceSynthetic Oligonucleotide 207atggcttggg
tcatcaggac
2020823DNAArtificial SequenceSynthetic Oligonucleotide 208gtgtcactgg
gcgtaagata ctg
2320924DNAArtificial SequenceSynthetic Oligonucleotide 209caccaaatca
gctgctacta ctcc
2421024DNAArtificial SequenceSynthetic Oligonucleotide 210gataaacccc
aaagcagaaa gatt
2421120DNAArtificial SequenceSynthetic Oligonucleotide 211cgagattccg
tgggcgtagg
2021219DNAArtificial SequenceSynthetic Oligonucleotide 212tgagtgggag
cttcgtagg
1921321DNAArtificial SequenceSynthetic Oligonucleotide 213tcagagtgga
cgttggatta c
2121421DNAArtificial SequenceSynthetic Oligonucleotide 214tgcttgaaat
gtaggagaac a
2121524DNAArtificial SequenceSynthetic Oligonucleotide 215gaggggcatc
aatcacaccg agaa
2421622DNAArtificial SequenceSynthetic Oligonucleotide 216ccccaccgcc
cacccattta gg
2221720DNAArtificial SequenceSynthetic Oligonucleotide 217gggggcacca
gaggcagtaa
2021822DNAArtificial SequenceSynthetic Oligonucleotide 218ggttgtggcg
ggggcagttg tg
2221922DNAArtificial SequenceSynthetic Oligonucleotide 219acagactcct
gtactgcaaa cc
2222021DNAArtificial SequenceSynthetic Oligonucleotide 220taccggttcg
tcctcttcct c
2122123DNAArtificial SequenceSynthetic Oligonucleotide 221gaagttcctc
acgccctgct atc
2322224DNAArtificial SequenceSynthetic Oligonucleotide 222ctggctggtg
acctgctttg agta
2422331DNAArtificial SequenceSynthetic Oligonucleotide 223taggcgcgcc
tgacatacag caatgccagt t
3122436DNAArtificial SequenceSynthetic Oligonucleotide 224taagaatgcg
gccgcgccac atcttgaaca ctttgc
3622524DNAArtificial SequenceSynthetic Oligonucleotide 225tggggaggag
tttgaggagc agac
2422623DNAArtificial SequenceSynthetic Oligonucleotide 226gtgggacgga
gggggcagtg aag
2322720DNAArtificial SequenceSynthetic Oligonucleotide 227gcaactattc
ggagcgcgtg
2022820DNAArtificial SequenceSynthetic Oligonucleotide 228ccagcagctt
gttgagctcc
2022921DNAArtificial SequenceSynthetic Oligonucleotide 229ggaggagcta
agcgtcatcg c
2123019DNAArtificial SequenceSynthetic Oligonucleotide 230tcgcttcagc
gcgtagacc
1923124DNAArtificial SequenceSynthetic Oligonucleotide 231tattagttgg
gatggtggta gcac
2423222DNAArtificial SequenceSynthetic Oligonucleotide 232gagaattcga
gtcgacgatg ac
2223323DNAArtificial SequenceSynthetic Oligonucleotide 233gaaattgtgt
tgacgcagtc tcc
2323422DNAArtificial SequenceSynthetic Oligonucleotide 234aggcacacaa
cagaggcagt tc
2223522DNAArtificial SequenceSynthetic Oligonucleotide 235gtacatcaac
ctcctgctgt cc
2223622DNAArtificial SequenceSynthetic Oligonucleotide 236gacatctcca
agtcccagca tg
2223723DNAArtificial SequenceSynthetic Oligonucleotide 237agtctctcac
tgtgccttat gcc
2323820DNAArtificial SequenceSynthetic Oligonucleotide 238agtcctaaga
actgtaaacg
2023921DNAArtificial SequenceSynthetic Oligonucleotide 239catctatacg
tggattgagg a
2124021DNAArtificial SequenceSynthetic Oligonucleotide 240ataggtacca
ggtatgagct g
2124123DNAArtificial SequenceSynthetic Oligonucleotide 241tgtccacatc
atcatcgtca tcc
2324222DNAArtificial SequenceSynthetic Oligonucleotide 242tgtcactggt
cggtcgctga gg
2224318DNAArtificial SequenceSynthetic Oligonucleotide 243catggggctt
aagatgtc
1824420DNAArtificial SequenceSynthetic Oligonucleotide 244gtcgatttct
ccatcatctg
2024520DNAArtificial SequenceSynthetic Oligonucleotide 245aagaggcgct
ctactagccg
2024620DNAArtificial SequenceSynthetic Oligonucleotide 246ctttccacat
ggaacacagg
2024723DNAArtificial SequenceSynthetic Oligonucleotide 247cattttcctg
gaatttgata cag
2324823DNAArtificial SequenceSynthetic Oligonucleotide 248gtagagagtt
tatttgggcc aag
2324921DNAArtificial SequenceSynthetic Oligonucleotide 249catctatggt
aactacaatc g
2125022DNAArtificial SequenceSynthetic Oligonucleotide 250gtagaagtca
ctgatcagac ac
2225124DNAArtificial SequenceSynthetic Oligonucleotide 251ctgcctgcca
acctttccat ttct
2425223DNAArtificial SequenceSynthetic Oligonucleotide 252tgagcagcca
cagcagcatt agg
2325321DNAArtificial SequenceSynthetic Oligonucleotide 253cacctgatca
ggtggataag g
2125422DNAArtificial SequenceSynthetic Oligonucleotide 254tcccaggtag
aaggtggaat cc 22
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