POLYNUCLEOTIDES AND POLYPEPTIDE SEQUENCES INVOLVED IN CANCER

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.

Description

PRIORITY CLAIM

[0001] This patent application is a divisional of U.S. Ser. No. 12/305,648 filed on Jun. 22, 2007, now U.S. Pat. No. 8,216,582 which is a national stage filing under 35 U.S.C. §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 on Jun. 23, 2006 and U.S. provisional application No. 60/874,471 filed 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. §1.52(e)(5), a Sequence Listing in the form of a text file (entitled "Sequence Listing", created on May 30, 2012 and of 279 kilobytes) 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 ˜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 a 80% 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, librairies 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 untranslated 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 3-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.

Use of NSEQ for Development of an Expression System

[0036] 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.

[0037] 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.

[0038] 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.

[0039] 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.

[0040] 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.

[0041] 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.

[0042] 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.

[0043] 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.

[0044] The present invention additionally relates to a bioassay for evaluating compounds as potential antagonists of the polypeptide described herein, the bioassay may comprise: [0045] 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 [0046] 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.

[0047] 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: [0048] 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 [0049] 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

[0050] 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.

[0051] 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.

[0052] 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.

[0053] 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.

[0054] 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.

[0055] 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')₂ fragment, and Fv fragment; CDRs, or a single-chain antibody comprising an antigen-binding fragment (e.g., a single chain Fv).

[0056] The antibody may originate for example, from a mouse, rat or any other mammal or from other sources such as through recombinant DNA technologies.

[0057] 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.

[0058] 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.

[0059] 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.

[0060] 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.

[0061] 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).

[0062] 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.

[0063] 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.

[0064] 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.

[0065] 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.

[0066] 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.

[0067] 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.

[0068] 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.

[0069] 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.

[0070] 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.

[0071] 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, (2-10×10¹⁰) 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.

[0072] 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.

[0073] 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.

[0074] The antibody may further comprise a detectable label (reporter molecule) attached thereto.

[0075] 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: [0076] 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; [0077] b) collecting the serum from the mammal; and [0078] c) isolating the polypeptide-specific antibodies from the serum of the mammal.

[0079] The method may further comprise the step of administering a second dose to the mammal (e.g., animal).

[0080] 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.

[0081] The method may comprise: [0082] a) immunizing a mammal (e.g., mouse, a transgenic mammal capable of producing human Ig, etc.) with a suitable amount of a PSEQ thereof; [0083] b) obtaining lymphoid cells from the immunized animal obtained from (a); [0084] c) fusing the lymphoid cells with an immortalizing cell to produce hybrid cells; and [0085] d) selecting hybrid cells which produce antibody that specifically binds to a PSEQ thereof.

[0086] 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: [0087] a) synthesizing a library of antibodies (e.g., antigen binding fragment) on phage or ribosomes; [0088] 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; [0089] c) isolating phage which binds to the polypeptide or polypeptide fragment, and; [0090] d) obtaining an antibody from the phage or ribosomes.

[0091] 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 [0092] a) extracting cells which are responsible for production of antibodies from a host mammal; [0093] b) isolating RNA from the cells of (a); [0094] c) reverse transcribing mRNA to produce cDNA; [0095] d) amplifying the cDNA using a (antibody-specific) primer; and [0096] 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.

[0097] 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.

[0098] 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.

[0099] For in vivo detection purposes, antibodies may be those which preferably recognize an epitope present at the surface of a tumor cell.

[0100] 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.

[0101] 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.

[0102] 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.

[0103] 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.

[0104] In accordance with the present invention, the kit may be a diagnostic kit, which may comprise: [0105] a) one or more antibodies described herein; and [0106] b) a detection reagent which may comprise a reporter group.

[0107] 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

[0108] 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.

[0109] 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.

[0110] 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.

[0111] 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.

[0112] 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.

[0113] 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.

[0114] 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)

[0115] 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.

[0116] 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.

[0117] 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.

[0118] 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.

[0119] 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.

[0120] 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 ED₅₀ (the dose therapeutically effective in 50% of the population) and LD₅₀ (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.

[0121] 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.

[0122] 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

[0123] 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.

[0124] 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.

[0125] 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.

[0126] 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.

[0127] 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).

[0128] 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; [0129] 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, [0130] 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, [0131] 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), [0132] 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), [0133] 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); [0134] 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; [0135] g) a fragment of any one of a) to f) including polynucleotides which consist in the above.

[0136] More specifically, the present invention relates to expressed polynucleotides which are selected from the group consisting of; [0137] 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, [0138] 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, [0139] 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), [0140] 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), [0141] 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); [0142] 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; [0143] g) a fragment of any one of a) to f) including polynucleotides which consist in the above.

[0144] 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.

[0145] 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.

[0146] 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.

[0147] In yet a further aspect the present invention relates to a composition comprising the polynucleotide and/or polypeptide described herein.

[0148] 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.

[0149] 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.

[0150] 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.

[0151] 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.

[0152] 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.

[0153] 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.

[0154] 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).

[0155] 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.

[0156] 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.

[0157] 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.

[0158] 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.

[0159] 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.

[0160] 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.

[0161] Detection of NSEQ may require an amplification (e.g., PCR) step in order to have sufficient material for detection purposes.

[0162] 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.

[0163] 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).

[0164] 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.

[0165] 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).

[0166] 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.

[0167] 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.

[0168] 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.

[0169] 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.

[0170] 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.

[0171] 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.

[0172] Therapeutic uses and methods are also encompassed herewith.

[0173] 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).

[0174] 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 [0175] 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 [0176] 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, [0177] 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; [0178] d) a fragment of any one of a) to c) [0179] for reducing, lowering or inhibiting the growth of a cancer cell.

[0180] 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).

[0181] Of course, the present invention encompasses immunizing an individual by administering a NSEQ (e.g., in an expression vector) or a PSEQ.

[0182] 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 [0183] 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, [0184] 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, [0185] 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; [0186] d) a fragment of any one of a) to c).

[0187] 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 [0188] 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, [0189] 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, [0190] 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; [0191] d) a polynucleotide which may comprise a sequence substantially identical to a), b), or c).

[0192] 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.

[0193] 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.

[0194] In a further aspect, the present invention relates to an isolated polypeptide encoded by the polynucleotide described herein.

[0195] The present invention more particularly provides an isolated polypeptide which may be selected from the group consisting of [0196] a) a polypeptide which may comprise any one of SEQ ID NO.:51 to 88 and 170 [0197] b) a polypeptide which may be encoded by any one of the polynucleotide described herein, [0198] c) a fragment of any one of a) or b), [0199] d) a derivative of any one of a) or b) and; [0200] e) an analog of any one of a) or b).

[0201] 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.

[0202] 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.

[0203] 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.

[0204] 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.

[0205] 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.

[0206] 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.

[0207] 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.

[0208] 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.

[0209] 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.

[0210] 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.

[0211] 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.

[0212] 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.

[0213] 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.

[0214] Detection of the complex may also be indicative of a late stage malignant ovarian cancer.

[0215] 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).

[0216] 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.

[0217] 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.

[0218] 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.

[0219] 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.

[0220] 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; [0221] a) a polypeptide comprising or consisting of any one of SEQ ID NO.:51 to 89 or 170, and; [0222] 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).

[0223] 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.

[0224] 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.

[0225] 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; [0226] a) a polypeptide which may comprise any one of SEQ ID NO.:51 to 88, 89 and 170, and; [0227] 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.

[0228] 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.

[0229] 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.

[0230] The present invention also relates to a composition which may comprise an antibody described herein.

[0231] 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; [0232] 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; [0233] b) a polypeptide which may comprise a polypeptide sequence encoded by any one of the polynucleotide sequence described herein or a portion thereof.

[0234] 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.

[0235] 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.

[0236] 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.

[0237] 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.

[0238] 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.

[0239] 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.

[0240] 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.

[0241] 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.

[0242] 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.

[0243] 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.

[0244] 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.

[0245] 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.

[0246] 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).

[0247] "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×SCC, 65° 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.

[0248] 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.

[0249] 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).

[0250] 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).

[0251] 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.

[0252] "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.

[0253] 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.

[0254] 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.

[0255] 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.

[0256] 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.

[0257] 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.

[0258] 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.

[0259] 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).

[0260] 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.

[0261] 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.

[0262] 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 NH₂(CH₂)_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.

[0263] 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.

[0264] 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 (Gln), Histidine (His), Lysine (Lys), Arginine (Arg) (5) residues that influence chain orientation: Glycine (Gly), Proline (Pro); and aromatic: Tryptophan (Trp), Tyrosine (Tyr), Phenylalanine (Phe)

[0265] 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

[0266] 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. . . .

[0267] 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

[0268] In the appended drawings:

[0269] 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 (C10), 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.

[0270] 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.

[0271] 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 NCl-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.

[0272] More particularly,

[0273] 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 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);

[0274] 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 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;

[0275] 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 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;

[0276] 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 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;

[0277] 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 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;

[0278] 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 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;

[0279] 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 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;

[0280] 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 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;

[0281] 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 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);

[0282] 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 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);

[0283] 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 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);

[0284] 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 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);

[0285] 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 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);

[0286] 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 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;

[0287] 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 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;

[0288] 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 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;

[0289] 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 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;

[0290] 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 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));

[0291] 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 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);

[0292] 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);

[0293] 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 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;

[0294] 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 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;

[0295] 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 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;

[0296] 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 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);

[0297] 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 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);

[0298] 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 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);

[0299] 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 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;

[0300] 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 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;

[0301] 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 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;

[0302] 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 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;

[0303] 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 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;

[0304] 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 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. 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;

[0306] 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 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;

[0307] 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 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;

[0308] 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;

[0309] 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 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;

[0310] 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 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;

[0311] 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;

[0312] 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 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;

[0313] 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 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;

[0314] 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;

[0315] 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 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;

[0316] 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 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;

[0317] 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;

[0318] 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;

[0319] 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 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;

[0320] 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 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;

[0321] 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;

[0322] 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 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;

[0323] 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 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;

[0324] FIG. 51 is a picture showing an example of STAR subtraction for the ovarian cancer samples. The housekeeping genes, GAPDH (Panel A) and β-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);

[0325] 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;

[0326] 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;

[0327] 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;

[0328] 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;

[0329] 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 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;

[0330] 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 NCl-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;

[0331] 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 NCl-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;

[0332] 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 NCl-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;

[0333] 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 NCl-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;

[0334] 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 NCl-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;

[0335] 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 NCl-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;

[0336] 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 NCl-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;

[0337] 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 NCl-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;

[0338] 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 NCl-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;

[0339] 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 NCl-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;

[0340] 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 NCl-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;

[0341] 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 NCl-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;

[0342] 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 NCl-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;

[0343] 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 NCl-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;

[0344] 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 NCl-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;

[0345] 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 NCl-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;

[0346] 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 NCl-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;

[0347] 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 NCl-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;

[0348] 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 NCl-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;

[0349] 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 NCl-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;

[0350] 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 NCl-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;

[0351] 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 NCl-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;

[0352] 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 NCl-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;

[0353] 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 NCl-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;

[0354] 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 NCl-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;

[0355] 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 NCl-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;

[0356] 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 NCl-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;

[0357] 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 NCl-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;

[0358] 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 NCl-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;

[0359] 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 NCl-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;

[0360] 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 NCl-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;

[0361] 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 NCl-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;

[0362] 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 NCl-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;

[0363] 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 NCl-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;

[0364] 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 NCl-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;

[0365] 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 NCl-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;

[0366] 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 NCl-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;

[0367] 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 NCl-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;

[0368] 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 NCl-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;

[0369] 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 NCl-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;

[0370] 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 NCl-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;

[0371] 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 NCl-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;

[0372] 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 NCl-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;

[0373] 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 NCl-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;

[0374] 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 NCl-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;

[0375] 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 NCl-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;

[0376] 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 NCl-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;

[0377] 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 NCl-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;

[0378] 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 NCl-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

[0379] 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.

[0380] The present invention is illustrated in further details below in a non-limiting fashion.

A--Material and Methods

[0381] 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

[0382] LMP and malignant ovarian tumor samples were selected based on histopathology to identify the respective stage and grade (Table B). LMP was choosen 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® (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 Code Position 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 CE 3b 3 G3 endometrioide 40 Carcinoma CE 3c 3 F3 endometrioide 44 Carcinoma CE 3c 3 C4 endometrioide 39 Carcinoma CE 3c 2 E3 endometrioide 50 Carcinoma CE 1c 1 G4 endometrioide 46 Carcinoma CE 1a 2 E4 endometrioide 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

[0383] 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.

[0384] 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.

[0385] 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

[0386] 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 μg 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 dT₁₁ 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 (OGS 458 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.).

[0387] Next, in order to prepare 3'-represented tester and driver libraries, a 10-μg 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 A₂60nm. Thereafter, 6×1-μg aliquots of each double-stranded cDNA was digested individually with one of the following 4-base recognition restriction enzymes Rsa I, Sau3A1, Mse I, Msp I, HinPl I 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 I recognition site. Each linker-adapted pooled DNA sample was digested with Asc I and Not I 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 A₂60nm. 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:

[0388] Tester 1 (MF-22)--human malignant ovarian cancer donor 1

[0389] Tester 2 (MF-25)--human malignant ovarian cancer donor 2

[0390] Tester 3 (MF-27)--human malignant ovarian cancer donor 3

[0391] Tester 4 (MF-28)--human malignant ovarian cancer donor 4

[0392] Tester 5 (MF-30)--human malignant ovarian cancer donor 5

[0393] Driver 1 (MF-15)--human ovarian LMP donor 1

[0394] Driver 2 (MF-16)--human ovarian LMP donor 2

[0395] Driver 3 (MF-18)--human ovarian LMP donor 3

[0396] Driver 4 (MF-19)--human ovarian LMP donor 4

[0397] Driver 5 (MF-20)--human ovarian LMP donor 5

[0398] 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.

[0399] 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)

[0400] A 5-μL 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 β-actin (Accession #X00351), which are typically non-differentially expressed house-keeping genes, it was evident that there was subtraction of both GAPDH and β-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:

[0401] Approximately ˜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 μL of autoclaved water. Then, 42 μL of each was used in a 100-μL standard PCR reaction containing oligonucleotide primers, OGS 1 and OGS 142 and amplified for 40-cycles (94° C. for 10 minutes, 40× (94° C. for 40 seconds, 55° C. for 30 seconds and 72° C. for 2 minutes) followed by 72° C. for 7 minutes) in 96-wells microtitre plates using HotStart® Taq polymerase (Qiagen, Mississauga, ON). The completed PCR reactions were desalted using the 96-well filter plates (Corning) and the amplicons recovered in 100 μL 10 mM Tris (pH 8.0). A 5-μL 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.

[0402] 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.

[0403] 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

[0404] 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 μL of the PCR reactions prepared in the previous section was lyophilized and each reconstituted in 20 μL of spotting solution comprising 3×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.).

[0405] 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.

[0406] 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:

[0407] 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/μL in 3×SSC and 0.1% sarkosyl in a 96-well microtitre plate and 1 μL spotted onto Hybond N+ nylon membranes using the specialized MULTI-PRINT® apparatus (VP Scientific, San Diego, Calif.), air dried and UV-cross linked. Of the ˜750 different sequences selected from SL123 to SL127 for macroarray analysis, only 250 sequences were individually radiolabeled with α-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.

[0408] 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 μg 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.

[0409] 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.

[0410] 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.

[0411] 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.

[0412] The method of the present invention may comprise the following steps or some of the following steps; [0413] 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 endogeneously differentially expressed sequence, [0414] 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; [0415] 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; [0416] 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, [0417] 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), [0418] f) generating single-stranded complementary first or second tagged DNA from one of e), [0419] g) hybridizing the single-stranded complementary first or second tagged DNA of f) with the other linearly amplified sense RNA of e), [0420] h) recovering unhybridized RNA with the help of the first or second sequence tag (for example by PCR or hybridization), and; [0421] i) identifying (determining) the nucleotide sequence of unhybridized RNA.

[0422] 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 isoalted 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 fis, 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, H4h (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 biinding (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 biinding (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 μg 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 μg/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® 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 inhibition in Alethia's TOV-21G Gene SEQ. ID. Gene 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 and 104 47.9 SEQ. ID. NO. 2 0478 SEQ. ID. NOs. 105 and 106 41.7 SEQ. ID. NO. 3 0671 SEQ. ID. NOs. 107 and 108 65.7 SEQ. ID. NO. 4 0851 SEQ. ID. NOs. 109 and 110 21.5 SEQ. ID. NO. 5 0713 SEQ. ID. NOs. 111 and 112 42.3 SEQ. ID. NO. 6 1064 SEQ. ID. NOs. 113 and 114 28.9 SEQ. ID. NO. 7 1096 SEQ. ID. NOs. 115 and 116 25.8 SEQ. ID. NO. 8 0065 SEQ. ID. NOs. 117 and 118 32.5 SEQ. ID. NO. 9 1313 SEQ. ID. NOs. 119 and 120 50.5 SEQ. ID. NO. 10 0059 SEQ. ID. NOs. 121 and 122 52.4 SEQ. ID. NO. 11 0239 SEQ. ID. NOs. 123 and 124 22.8 SEQ. ID. NO. 12 0291 SEQ. ID. NOs. 125 and 126 <20 SEQ. ID. NO. 13 0972 SEQ. ID. NOs. 127 and 128 <20 SEQ. ID. NO. 14 0875 SEQ. ID. NOs. 129 and 130 <20 SEQ. ID. NO. 15 0420 SEQ. ID. NOs. 131 and 132 <20 SEQ. ID. NO. 16 0125 SEQ. ID. NOs. 133 and 134 <20 SEQ. ID. NO. 17 0531 SEQ. ID. NOs. 135 and 136 0 SEQ. ID. NO. 18 0967B SEQ. ID. NOs. 137 and 138 0 SEQ. ID. NO. 19 0889 SEQ. ID. NOs. 139 and 140 <20 SEQ. ID. NO. 20 0313 SEQ. ID. NOs. 141 and 142 <20 SEQ. ID. NO. 21 1134 SEQ. ID. NOs. 143 and 144 <20 SEQ. ID. NO. 22 0488 SEQ. ID. NOs. 145 and 146 0 SEQ. ID. NO. 23 0216 SEQ. ID. NOs. 147 and 148 <20 SEQ. ID. NO. 24 0447 SEQ. ID. NOs. 149 and 150 0 SEQ. ID. NO. 50 0967A SEQ. ID. NOs. 151 and 152 47.4

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 μg of pSil-shRNA vector, the same plasmids used in the previous assay. The next day, fresh medium was applied containing 2 μg/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 sytem, breast, colon, lung, melanoma, ovarian, prostate, and renal cancer (see Table C). These RNA samples were obtained from the Developmental Therapeutics Program at the NCl/NIH. Using the same RAMP RNA samples that amplified from the total RNA samples obtained from the NCl, 500 μg 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 may be 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 may be 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. ORF Nucleotide NCBI Positions/ Nucleotide Unigene #/Gene Accession Polypeptide Sequence No. Symbol/Gene ID Number sequence No. Function SEQ ID NO. 1 STAR clone BX094904 Unknown Transcribed locus but possibly NM_021955 149-373 for guanine nucleotide binding belonging to for Hs.555871 Hs.555871 protein (G protein), cluster Hs.555871 encoding SEQ gamma transducing ID NO.: 51 activity polypeptide 1 SEQ ID NO. 2 Hs.389724/ NM_006820 242-1483 interferon-induced protein IFI44L/ encoding SEQ 44-like; function unknown 10964 ID NO.: 52 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 protein IFIT1/ encoding SEQ with tetratricopeptide 3434 ID NO.: 55 repeats 1; function unknown SEQ ID NO. 6 Hs.584238/ NM_000170 151-3213 glycine dehydrogenase GLDC/ encoding SEQ (decarboxylating; glycine 2731 ID NO.: 56 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; proteolysis DPEP3/ encoding SEQ and peptidolysis 64180 ID NO.: 57 SEQ ID NO. 8 Hs.418367/ NM_006681 106..630 neuromedin U (NMU); NMU/ encoding SEQ neuropeptide signaling 10874 ID NO.: 58 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 kinase CDKN3/ encoding SEQ inhibitor 3; a cyclin- 1033 ID NO.: 60 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 expressed PRAME/ encoding SEQ antigen in melanoma; 23532 ID NO.: 62 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 containing T VTCN1/ encoding SEQ cell activation inhibitor 1; 79679 ID NO.: 65 function unknown SEQ ID NO. 18 Hs.73625/ NM_005733 28..2700 kinesin family member KIF20A/ encoding SEQ 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 of NM_005832 encoding SEQ potassium large it belonging to for ID NO.: 67 conductance calcium- cluster Hs.478368 activated channel, Hs.478368 subfamily M, beta member according to 2 for Hs.478368 NCBI 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 motif) CXCL10/ encoding SEQ ligand 10; chemokine 3627 ID NO.: 68 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 homolog 79053 ID NO.: 69 (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 antigen KAAG1 encoding SEQ 1; fumction unknown ID NO.: 70 SEQ ID NO. 25 Hs.512599/ NM_000077 213-683 cyclin-dependent kinase CDKN2A/ encoding SEQ 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; required for 11065 ID NO.: 73 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 play a HOXD3/ encoding SEQ role in the regulation of 3232 ID NO.: 77 cell adhesion processes SEQ ID NO. 33 Hs.525641/ BC092518 61-1470 Immunoglobulin heavy IGHG1/ encoding SEQ constant gamma 1; may 3500 ID NO.: 78 play a role in immune response and antigen binding SEQ ID NO. 34 Hs.592988/ BC073793 10-717 Immunoglobulin kappa IGKC/ encoding SEQ constant; may play a role 3514 ID NO.: 79 in immune response and antigen binding SEQ ID NO. 35 Hs.66762 AY683003 55-2727 Chromosome 10 ORF 38; encoding SEQ unknown function ID NO.: 80 SEQ ID NO. 36 Hs.373741/ NM_178580 115-1299 Histocompatibility (minor) SPP/ encoding SEQ 13; unknown function 81502 ID NO.: 81 SEQ ID NO. 37 STAR clone AL157931 Novel genomic hit SEQ ID NO. 38 Hs.128453/ NM_001463 219-1196 Frizzled-related protein; FRZB/ encoding SEQ Wnt receptor signaling 2487 ID NO.: 82 pathway, development, skeletal, transmembrane receptor activity SEQ ID NO. 39 Hs.239/ NM_202003 266-2512 Forkhead box M1; FOXM1/ encoding SEQ transcriptional regulation 2305 ID NO.: 83 SEQ ID NO. 40 Hs.46627 NM_152864 89-715 Chromosome 20 ORF 58; encoding SEQ unknown function ID NO.: 84 SEQ ID NO. 41 STAR clone AK092936 Novel genomic hit SEQ ID NO. 42 Gene ID 404550 BC009078 552-746 Chromosome 16 ORF 74; encoding SEQ unknown function ID NO.: 85 SEQ ID NO. 43 Hs.645513/ NM_013277 225-2123 Rac GTPase activating RACGAP1/ encoding SEQ protein 1; electron 29127 ID NO.: 86 transport, intracellular signaling cascade; iron ion binding SEQ ID NO. 44 Hs.645522/ NM_018279 584-1594 Transmembrane protein TMEM19/ encoding SEQ 19; unknown function 55266 ID NO.: 87 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; post- 10067 ID NO.: 88 Golgi transport, protein transport SEQ ID NO. 49 STAR clone AC068288 SEQ ID NO. 50 Hs.73769/ NM_000802 26-799 folate receptor 1 (adult); FOLR1/ encoding SEQ mediate delivery of 5- 2348 ID NO.: 89 methyltetrahydrofolate to the interior of cells SEQ ID NO. Hs.558314/ NM_000096 251-3448 Ceruloplasmin; secreted 169 CP/ encoding SEQ protein; copper ion binding 1356 ID NO.: 170 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 dT₁₁ + 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 for shRNA vector 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. NucleotideSequence (5'-3') ORFs SEQ. ID NO. 1 SEQ. ID NO. 51 STAR clone: MPVINIEDLTEKDKLKMEVDQ CTGGAAGCTGAAGAATCACCGGCTTCAGTGACATGGAACCCAGCGATTTGATTTTTGACGAGTATCGGGTGACT- TTGAGG LKKEVTLERMLVSKCCEEVRD TGGTCAAGAAACCACACTTTAAGAACAATGTCCA YVEERSGEDPLVKGIPEDKNP NM_021955: FKELKGGCVIS AATCATATTAGTGAAGATTAGGAAGAAGCTTTAAAATCCCAAGGCTAGTGTGCATTGCTAGAATTGTTAAGAGA- GAGAGC TCATATGAAATTGGTTATCGTGGGATATTTAAAATAAAACAAAGAACAGTTTACTTTCAGGCAAAAAGATGCCA- GTAATC AATATTGAGGACCTGACAGAAAAGGACAAATTGAAGATGGAAGTTGACCAGCTCAAGAAAGAAGTGACACTGGA- AAGAAT GCTAGTTTCCAAATGTTGTGAAGAAGTAAGAGATTACGTTGAAGAACGATCTGGCGAGGATCCACTGGTAAAGG- GCATCC CAGAGGACAAAAATCCCTTCAAGGAGCTCAAAGGAGGCTGTGTGATTTCATAATACAAACAAAAAGAAAAAAAA- TTAAAC AAATTCTTGGAAATATCTCAAATGTTAATAACAATATGAATTTTTCTCATGCATACTATTACTACTAAGCATGT- ACGTGA ATTTTTAAATTTATAGATGTAAACTTTTAATAAAAATTGGGGTGTGGTAACCCATCATTCTATGTTTTTCTTAA- CATAGC TGGCACAGGGTTTAACACATAATTGCCAATAAATATTGCTTAAAGTTCTTTAAAAAGAACTATGTTTT SEQ. ID NO. 2 SEQ. ID NO. 52 GCACGAGGAAGCCACAGATCTCTTAAGAACTTTCTGTCTCCAAACCGTGGCTGCTCGATAAATCAGACAGAACA- GTTAAT MVERCSRQGCTITMAYIDYNM CCTCAATTTAAGCCTGATCTAACCCCTAGAAACAGATATAGAACAATGGAAGTGACAACAAGATTGACATGGAA- TGATGA IVAFMLGNYINLRESSTEPND AAATCATCTGCGCAACTGCTTGGAAATGTTTCTTTGAGTCTTCTCTATAAGTCTAGTGTTCATGGAGGTAGCAT- TGAAGA SLWFSLQKKNDTTEIETLLLN TATGGTTGAAAGATGCAGCCGTCAGGGATGTACTATAACAATGGCTTACATTGATTACAATATGATTGTAGCCT- TTATGC TAPKIIDEQLVCRLSKTDIFI TTGGAAATTATATTAATTTACGTGAAAGTTCTACAGAGCCAAATGATTCCCTATGGTTTTCACTTCAAAAGAAA- AATGAC ICRDNKIYLDKMITRNLKLRF ACCACTGAAATAGAAACTTTACTCTTAAATACAGCACCAAAAATTATTGATGAGCAACTGGTGTGTCGTTTATC- GAAAAC YGHRQYLECEVFRVEGIKDNL GGATATTTTCATTATATGTCGAGATAATAAAATTTATCTAGATAAAATGATAACAAGAAACTTGAAACTAAGGT- TTTATG DDIKRIIKAREHRNRLLADIR GCCACCGTCAGTATTTGGAATGTGAAGTTTTTCGAGTTGAAGGAATTAAGGATAACCTAGACGACATAAAGAGG- ATAATT DYRPYADLVSEIRILLVGPVG AAAGCCAGAGAGCACAGAAATAGGCTTCTAGCAGACATCAGAGACTATAGGCCCTATGCAGACTTGGTTTCAGA- AATTCG SGKSSFFNSVKSIFHGHVTG TATTCTTTTGGTGGGTCCAGTTGGGTCTGGAAAGTCCAGTTTTTTCAATTCAGTCAAGTCTATTTTTCATGGCC- ATGTGA QAVVGSDTTSITERYRIYSV CTGGCCAAGCCGTAGTGGGGTCTGATACCACCAGCATAACCGAGCGGTATAGGATATATTCTGTTAAAGATGGA- AAAAAT KDGKNGKSLPFMLCDTMGLD GGAAAATCTCTGCCATTTATGTTGTGTGACACTATGGGGCTAGATGGGGCAGAAGGAGCAGGACTGTGCATGGA- TGACAT GAEGAGLCMDDIPHILKGCM TCCCCACATCTTAAAAGGTTGTATGCCAGACAGATATCAGTTTAATTCCCGTAAACCAATTACACCTGAGCATT- CTACTT PDRYQFNSRKPITPEHSTFI TTATCACCTCTCCATCTCTGAAGGACAGGATTCACTGTGTGGCTTATGTCTTAGACATCAACTCTATTGACAAT- CTCTAC TSPSLKDRIHCVAYVLDINS TCTAAAATGTTGGCAAAAGTGAAGCAAGTTCACAAAGAAGTATTAAACTGTGGTATAGCATATGTGGCCTTGCT- TACTAA IDNLYSKMLAKVKQVHKEVL AGTGGATGATTGCAGTGAGGTTCTTCAAGACAACTTTTTAAACATGAGTAGATCTATGACTTCTCAAAGCCGGG- TCATGA NCGIAYVALLTKVDDCSEVL ATGTCCATAAAATGCTAGGCATTCCTATTTCCAATATTTTGATGGTTGGAAATTATGCTTCAGATTTGGAACTG- GACCCC QDNFLNMSRSMTSQSRVMNV ATGAAGGATATTCTCATCCTCTCTGCACTGAGGCAGATGCTGCGGGCTGCAGATGATTTTTTAGAAGATTTGCC- TCTTGA HKMLGIPISNILMVGNYASD GGAAACTGGTGCAATTGAGAGAGCGTTACAGCCCTGCATTTGAGATAAGTTGCCTTGATTCTGACATTTGGCCC- AGCCTG LELDPMKDILILSALRQMLR TACTGGTGTGCCGCAATGAGAGTCAATCTCTATTGACAGCCTGCTTCAGATTTTGCTTTTGTTCGTTTTGCCTT- CTGTCC AADDFLEDLPLEETGAIERA TTGGAACAGTCATATCTCAAGTTCAAAGGCCAAAACCTGAGAAGCGGTGGGCTAAGATAGGTCCTACTGCAAAC- CACCCC LQPCI TCCATATTTCCGTACCATTTACAATTCAGTTTCTGTGACATCTTTTTAAACCACTGGAGGAAAAATGAGATATT- CTCTAA TTTATTCTTCTATAACACTCTATATAGAGCTATGTGAGTACTAATCACATTGAATAATAGTTATAAAATTATTG- TATAGA CATCTGCTTCTTAAACAGATTGTGAGTTCTTTGAGAAACAGCGTGGATTTTACTTATCTGTGTATTCACAGAGC- TTAGCA CAGTGCCTGGTAATGAGCAAGCATACTTGCCATTACTTTTCCTTCCCACTCTCTCCAACATCACATTCACTTTA- AATTTT TCTGTATATAGAAAGGAAAACTAGCCTGGGCAACATGATGAAACCCCATCTCCACTGC SEQ. ID NO. 3 SEQ. ID NO. 53 GCCGAGCGGAGAGGCCGCCCATTGGCCGGCCAGCGCCACGTGGCCGCCCCCGCCGGTATATTAGGCCACTATTT- ACCTCC MSSYLEYVSCSSSGGVGGDV GGCTCACTCGCCATGGGTTGGAGAGGGCAGCTCGGGTAGAGAGGGCTGGCGGAGCGGCGCAGACGGCGGCAGTC- CTGCTC LSLAPKFCRSDARPVALQPA AGCCTCTGCCCGGCTCCGTACTCCGGCCCCGGCCTGCGCCCTCAGAAAGGTGGGGCCCGAACCATGAGCTCCTA- CCTGGA FPLGNGDGAFVSCLPLAAAR GTACGTGTCATGCAGCAGCAGCGGCGGGGTCGGCGGCGACGTGCTCAGCTTGGCACCCAAGTTCTGCCGCTCCG- ACGCCC PSPSPPAAPARPSVPPPAAP GGCCCGTGGCTCTGCAGCCCGCCTTCCCTCTGGGCAACGGCGACGGCGCCTTCGTCAGCTGTCTGCCCCTGGCC- GCCGCC QYAQCTLEGAYEPGAAPAAA CGACCCTCGCCTTCGCCCCCGGCCGCCCCCGCGCGGCCGTCCGTACCGCCTCCGGCCGCGCCCCAGTACGCGCA- GTGCAC AGGADYGFLGSGPAYDFPGV CCTGGAGGGGGCCTACGAACCTGGTGCCGCACCTGCCGCGGCAGCTGGGGGCGCGGACTACGGCTTCCTGGGGT- CCGGGC LGRAADDGGSHVHYATSAVF CGGCGTACGACTTCCCGGGCGTGCTGGGGCGGGCGGCCGACGACGGCGGGTCTCACGTCCACTACGCCACCTCG- GCCGTC SGGGSFLLSGQVDYAAFGEP TTCTCGGGCGGCGGCTCTTTCCTCCTCAGCGGCCAGGTGGATTACGCGGCCTTCGGCGAACCCGGCCCTTTTCC- GGCTTG GPFPACLKASADGHPGAFQT TCTCAAAGCGTCAGCCGACGGCCACCCTGGTGCTTTCCAGACCGCATCCCCGGCCCCAGGCACCTACCCCAAGT- CCGTCT ASPAPGTYPKSVSPASGLPA CTCCCGCCTCCGGCCTCCCTGCCGCCTTCAGCACGTTCGAGTGGATGAAAGTGAAGAGGAATGCCTCTAAGAAA- GGTAAA AFSTFEWMKVKRNASKKGKL CTCGCCGAGTATGGGGCCGCTAGCCCCTCCAGCGCGATCCGCACGAATTTCAGCACCAAGCAACTGACAGAACT- GGAAAA AEYGAASPSSAIRTNFSTKQ AGAGTTTCATTTCAATAAGTACTTAACTCGAGCCCGGCGCATCGAGATAGCCAACTGCTTGCACCTGAATGACA- CGCAAG LTELEKEFHFNKYLTRARRI TCAAAATCTGGTTCCAGAACCGCAGGATGAAACAGAAGAAAAGGGAACGAGAAGGGCTTCTGGCCACGGCCATT- CCTGTG EIANCLHLNDTQVKIWFQNR GCTCCCCTCCAACTTCCCCTCTCTGGAACAACCCCCACTAAGTTTATCAAGAACCCCGGCAGCCCTTCTCAGTC- CCAAGA RMKQKKREREGLLATAIPVA GCCTTCGTGAGGCCGGTACTTGGGGCCGAAAAACTGTGGCCTGCAGAAGTCCCAGGCGACCCCCATCCCTATCT- AGACTT PLQLPLSGTTPTKFIKNPGS AGGAGCTCAGTTTGGGATGGAGGTGGGAGAACAAAAATGAATAGGGATTTCACTTGGGAAATGAAGTACTTTAG- TTGGCT PSQSQEPS TCCGAGTTCCAGACTATATGTCCAGATATTAATTGACTGTCTTGTAAGCCACTTGTTTGGTTATGATTTGTGTC- TTATCA GGGAAAAGGTGCCCAGCTGCCAGCCCAGCTCCGCTGCTATCTTTGCCTCACTTAGTCATGTGCAATTCGCGTTG- CAGAGT GGCAGACCATTAGTTGCTGAGTTCTGTCAGCACTCTGATGTGCTCAGAAGAGCACCTGCCCAAAGTTTTTCTGG- TTTTAA TTTAAAGGACAAGGCTACATATATTCAGCTTTTTGAGATGACCAAAGCTAGTTAGGGTCTCCTTGATGTAGCTA- AGCTGC TTCAGTGATCTTCACATTTGCACTCCAGTTTTTTTTTCTTTAAAAAAGCGGTTTCTACCTCTCTATGTGCCTGA- GTGATG ATACAATCGCTGTTTAGTTACTAGATGAACAAATCCACAGAATGGGTAAAGAGTAGAATCTGAACTATATCTTG- ACAAAT ATTATTCAAACTTGAATGTAAATATATACAGTATGTATATTTTTTAAAAAGATTTGCTTGCAATGACCTTATAA- GTGACA TTTAATGTCATAGCATGTAAAGGGTTTTTTTTGTAATAAAAATTATAGAATCTGCAAAAAAAAAAAAAAAA SEQ. ID NO. 4 SEQ. ID NO. 54 CAGCCTCCAGAGCACCAGCACTGGCACTGGCACTGGCACACGCTATGGCAAATGAAGTGCAAGACCTGCTCTCC- CCTCGG MANEVQDLLSPRKGGHPPAV AAAGGGGGACATCCTCCTGCAGTAAAAGCTGGAGGAATGAGAATTTCCAAAAAACAAGAAATTGGCACCTTGGA- AAGACA KAGGMRISKKQEIGTLERHT TACCAAAAAAACAGGATTCGAGAAAACAAGTGCCATTGCAAATGTTGCCAAAATACAGACACTGGATGCCCTGA- ATGACA KKTGFEKTSAIANVAKIQTL CACTGGAGAAGCTCAACTATAAATTTCCAGCAACAGTGCACATGGCACATCAAAAACCCACACCTGCTCTGGAA- AAGGTT DALNDTLEKLNYKFPATVHM GTTCCACTGAAAAGGATCTACATTATTCAGCAGCCTCGAAAATGTTAAGCCTGGATTTAAAACACAGCCGTCTG- GCCAGC AHQKPTPALEKVVPLKRIYI TGCCTCGAATATCTGACAGCTTAGCAAAAAGGGCCAAAGCTTTCCATAGGCGTGCTGCACTTGCTTGGTAAATT- AAACAG IQQPRKC CTTTTGTATCTTCCCCTTTGACTTTAGGTAATAAAGCATCCAAACTTGTAAAAAAAAAA SEQ. ID NO. 5 SEQ. ID NO. 55 GTAACTGAAAATCCACAAGACAGAATAGCCAGATCTCAGAGGAGCCTGGCTAAGCAAAACCCTGCAGAACGGCT- GCCTAA MSTNGDDHQVKDSLEQLRCH TTTACAGCAACCATGAGTACAAATGGTGATGATCATCAGGTCAAGGATAGTCTGGAGCAATTGAGATGTCACTT- TACATG FTWELSIDDDEMPDLENRVL GGAGTTATCCATTGATGACGATGAAATGCCTGATTTAGAAAACAGAGTCTTGGATCAGATTGAATTCCTAGACA- CCAAAT DQIEFLDTKYSVGIHNLLAY ACAGTGTGGGAATACACAACCTACTAGCCTATGTGAAACACCTGAAAGGCCAGAATGAGGAAGCCCTGAAGAGC- TTAAAA VKHLKGQNEEALKSLKEAEN GAAGCTGAAAACTTAATGCAGGAAGAACATGACAACCAAGCAAATGTGAGGAGTCTGGTGACCTGGGGCAACTT- TGCCTG LMQEEHDNQANVRSLVTWGN GATGTATTACCACATGGGCAGACTGGCAGAAGCCCAGACTTACCTGGACAAGGTGGAGAACATTTGCAAGAAGC- TTTCAA FAWMYYHMGRLAEAQTYLDK ATCCCTTCCGCTATAGAATGGAGTGTCCAGAAATAGACTGTGAGGAAGGATGGGCCTTGCTGAAGTGTGGAGGA- AAGAAT VENICKKLSNPFRYRMECPE TATGAACGGGCCAAGGCCTGCTTTGAAAAGGTGCTTGAAGTGGACCCTGAAAACCCTGAATCCAGCGCTGGGTA- TGCGAT IDCEEGWALLKCGGKNYERA CTCTGCCTATCGCCTGGATGGCTTTAAATTAGCCACAAAAAATCACAAGCCATTTTCTTTGCTTCCCCTAAGGC- AGGCTG KACFEKVLEVDPENPESSAG TCCGCTTAAATCCAGACAATGGATATATTAAGGTTCTCCTTGCCCTGAAGCTTCAGGATGAAGGACAGGAAGCT- GAAGGA YAISAYRLDGFKLATKNHKP GAAAAGTACATTGAAGAAGCTCTAGCCAACATGTCCTCACAGACCTATGTCTTTCGATATGCAGCCAAGTTTTA- CCGAAG FSLLPLRQAVRLNPDNGYIK AAAAGGCTCTGTGGATAAAGCTCTTGAGTTATTAAAAAAGGCCTTGCAGGAAACACCCACTTCTGTCTTACTGC- ATCACC VLLALKLQDEGQEAEGEKYI AGATAGGGCTTTGCTACAAGGCACAAATGATCCAAATCAAGGAGGCTACAAAAGGGCAGCCTAGAGGGCAGAAC- AGAGAA EEALANMSSQTYVFRYAAKF AAGCTAGACAAAATGATAAGATCAGCCATATTTCATTTTGAATCTGCAGTGGAAAAAAAGCCCACATTTGAGGT- GGCTCA YRRKGSVDKALELLKKALQE TCTAGACCTGGCAAGAATGTATATAGAAGCAGGCAATCACAGAAAAGCTGAAGAGAATTTTCAAAAATTGTTAT- GCATGA TPTSVLLHHQIGLCYKAQMI AACCAGTGGTAGAAGAAACAATGCAAGACATACATTTCCACTATGGTCGGTTTCAGGAATTTCAAAAGAAATCT- GACGTC QIKEATKGQPRGQNREKLDK AATGCAATTATCCATTATTTAAAAGCTATAAAAATAGAACAGGCATCATTAACAAGGGATAAAAGTATCAATTC- TTTGAA MIRSAIFHFESAVEKKPTFE GAAATTGGTTTTAAGGAAACTTCGGAGAAAGGCATTAGATCTGGAAAGCTTGAGCCTCCTTGGGTTCGTCTACA- AATTGG VAHLDLARMYIEAGNHRKAE AAGGAAATATGAATGAAGCCCTGGAGTACTATGAGCGGGCCCTGAGACTGGCTGCTGACTTTGAGAACTCTGTG- AGACAA ENFQKLLCMKPVVEETMQDI GGTCCTTAGGCACCCAGATATCAGCCACTTTCACATTTCATTTCATTTTATGCTAACATTTACTAATCATCTTT- TCTGCT HFHYGRFQEFQKKSDVNAII TACTGTTTTCAGAAACATTATAATTCACTGTAATGATGTAATTCTTGAATAATAAATCTGACAAAAAAAAAAAA- AAAAAA HYLKAIKIEQASLTRDKSIN AAAAAAAAAA SLKKLVLRKLRRKALDLESL SLLGFVYKLEGNMNEALEYY ERALRLAADFENSVRQGP SEQ. ID NO. 6 SEQ. ID NO. 56 CCCGCGAGCGTCCATCCATCTGTCCGGCCGACTGTCCAGCGAAAGGGGCTCCAGGCCGGGCGCACGTCGACCCG- GGGGAC MQSCARAWGLRLGRGVGGGRR CGAGGCCAGGAGAGGGGCCAAGAGCGCGGCTGACCCTTGCGGGCCGGGGCAGGGGACGGTGGCCGCGGCCATGC- AGTCCT LAGGSGPCWAPRSRDSSSGGG GTGCCAGGGCGTGGGGGCTGCGCCTGGGCCGCGGGGTCGGGGGCGGCCGCCGCCTGGCTGGGGGATCGGGGCCG- TGCTGG DSAAAGASRLLERLLPRHDDF GCGCCGCGGAGCCGGGACAGCAGCAGTGGCGGCGGGGACAGCGCCGCGGCTGGGGCCTCGCGCCTCCTGGAGCG- CCTTCT ARRHIGPGDKDQREMLQTLGL GCCCAGACACGACGACTTCGCTCGGAGGCACATCGGCCCTGGGGACAAAGACCAGAGAGAGATGCTGCAGACCT- TGGGGC ASIDELIEKTVPANIRLKRPL TGGCGAGCATTGATGAATTGATCGAGAAGACGGTCCCTGCCAACATCCGTTTGAAAAGACCCTTGAAAATGGAA- GACCCT KMEDPVCENEILATLHAISSK GTTTGTGAAAATGAAATCCTTGCAACTCTGCATGCCATTTCAAGCAAAAACCAGATCTGGAGATCGTATATTGG- CATGGG NQIWRSYIGMGYYNCSVPQTI CTATTATAACTGCTCAGTGCCACAGACGATTTTGCGGAACTTACTGGAGAACTCAGGATGGATCACCCAGTATA- CTCCAT LRNLLENSGWITQYTPYQPEV ACCAGCCTGAGGTGTCTCAGGGGAGGCTGGAGAGTTTACTCAACTACCAGACCATGGTGTGTGACATCACAGGC- CTGGAC SQGRLESLLNYQTMVCDITGL ATGGCCAATGCATCCCTGCTGGATGAGGGGACTGCAGCCGCAGAGGCACTGCAGCTGTGCTACAGACACAACAA- GAGGAG DMANASLLDEGTAAAEALQLC GAAATTTCTCGTTGATCCCCGTTGCCACCCACAGACAATAGCTGTTGTCCAGACTCGAGCCAAATATACTGGAG- TCCTCA YRHNKRRKFLVDPRCHPQTIA CTGAGCTGAAGTTACCCTGTGAAATGGACTTCAGTGGAAAAGATGTCAGTGGAGTGTTGTTCCAGTACCCAGAC- ACGGAG VVQTRAKYTGVLTELKLPCEM GGGAAGGTGGAAGACTTTACGGAACTCGTGGAGAGAGCTCATCAGAGTGGGAGCCTGGCCTGCTGTGCTACTGA- CCTTTT DFSGKDVSGVLFQYPDTEGKV AGCTTTGTGCATCTTGAGGCCACCTGGAGAATTTGGGGTAGACATCGCCCTGGGCAGCTCCCAGAGATTTGGAG- TGCCAC EDFTELVERAHQSGSLACCAT TGGGCTATGGGGGACCCCATGCAGCATTTTTTGCTGTCCGAGAAAGCTTGGTGAGAATGATGCCTGGAAGAATG- GTGGGG DLLALCILRPPGEFGVDIALG GTAACAAGAGATGCCACTGGGAAAGAAGTGTATCGTCTTGCTCTTCAAACCAGGGAGCAACACATTCGGAGAGA- CAAGGC SSQRFGVPLGYGGPHAAFFAV TACCAGCAACATCTGTACAGCTCAGGCCCTCTTGGCGAATATGGCTGCCATGTTTCGAATCTACCATGGTTCCC- ATGGGC RESLVRMMPGRMVGVTRDATG TGGAGCATATTGCTAGGAGGGTACATAATGCCACTTTGATTTTGTCAGAAGGTCTCAAGCGAGCAGGGCATCAA- CTCCAG KEVYRLALQTREQHIRRDKAT CATGACCTGTTCTTTGATACCTTGAAGATTCATTGTGGCTGCTCAGTGAAGGAGGTCTTGGGCAGGGCGGCTCA- GCGGCA SNICTAQALLANMAAMFRIYH GATCAATTTTCGGCTTTTTGAGGATGGCACACTTGGTATTTCTCTTGATGAAACAGTCAATGAAAAAGATCTGG- ACGATT GSHGLEHIARRVHNATLILSE TGTTGTGGATCTTTGGTTGTGAGTCATCTGCAGAACTGGTTGCTGAAAGCATGGGAGAGGAGTGCAGAGGTATT- CCAGGG GLKRAGHQLQHDLFFDTLKIH TCTGTGTTCAAGAGGACCAGCCCGTTCCTCACCCATCAAGTGTTCAACAGCTACCACTCTGAAACAAACATTGT- CCGGTA CGCSVKEVLGRAAQRQINFRL CATGAAGAAACTGGAAAATAAAGACATTTCCCTTGTTCACAGCATGATTCCACTGGGATCCTGCACCATGAAAC- TGAACA FEDGTLGISLDETVNEKDLDD GTTCGTCTGAACTCGCACCTATCACATGGAAAGAATTTGCAAACATCCACCCCTTTGTGCCTCTGGATCAAGCT- CAAGGA LLWIFGCESSAELVAESMGEE TATCAGCAGCTTTTCCGAGAGCTTGAGAAGGATTTGTGTGAACTCACAGGTTATGACCAGGTCTGTTTCCAGCC- AAACAG CRGIPGSVFKRTSPFLTHQVF CGGAGCCCAGGGAGAATATGCTGGACTGGCCACTATCCGAGCCTACTTAAACCAGAAAGGAGAGGGGCACAGAA- CGGTTT NSYHSETNIVRYMKKLENKDI GCCTCATTCCGAAATCAGCACATGGGACCAACCCAGCAAGTGCCCACATGGCAGGCATGAAGATTCAGCCTGTG- GAGGTG SLVHSMIPLGSCTMKLNSSSE GATAAATATGGGAATATCGATGCAGTTCACCTCAAGGCCATGGTGGATAAGCACAAGGAGAACCTAGCAGCTAT-

CATGAT LAPITWKEFANIHPFVPLDQA TACATACCCATCCACCAATGGGGTGTTTGAAGAGAACATCAGTGACGTGTGTGACCTCATCCATCAACATGGAG- GACAGG QGYQQLFRELEKDLCELTGYD TCTACCTAGACGGGGCAAATATGAATGCTCAGGTGGGAATCTGTCGCCCTGGAGACTTCGGGTCTGATGTCTCG- CACCTA QVCFQPNSGAQGEYAGLATIR AATCTTCACAAGACCTTCTGCATTCCCCACGGAGGAGGTGGTCCTGGCATGGGGCCCATCGGAGTGAAGAAACA- TCTCGC AYLNQKGEGHRTVCLIPKSAH CCCGTTTTTGCCCAATCATCCCGTCATTTCACTAAAGCGGAATGAGGATGCCTGTCCTGTGGGAACCGTCAGTG- CGGCCC GTNPASAHMAGMKIQPVEVDK CATGGGGCTCCAGTTCCATCTTGCCCATTTCCTGGGCTTATATCAAGATGATGGGAGGCAAGGGTCTTAAACAA- GCCACG YGNIDAVHLKAMVDKHKENLA GAAACTGCGATATTAAATGCCAACTACATGGCCAAGCGATTAGAAACACACTACAGAATTCTTTTCAGGGGTGC- AAGAGG AIMITYPSTNGVFEENISDVC TTATGTGGGTCATGAATTTATTTTGGACACGAGACCCTTCAAAAAGTCTGCAAATATTGAGGCTGTGGATGTGG- CCAAGA DLIHQHGGQVYLDGANMNAQV GACTCCAGGATTATGGATTTCACGCCCCTACCATGTCCTGGCCTGTGGCAGGGACCCTCATGGTGGAGCCCACT- GAGTCG GICRPGDFGSDVSHLNLHKTF GAGGACAAGGCAGAGCTGGACAGATTCTGTGATGCCATGATCAGCATTCGGCAGGAAATTGCTGACATTGAGGA- GGGCCG CIPHGGGGPGMGPIGVKKHLA CATCGACCCCAGGGTCAATCCGCTGAAGATGTCTCCACACTCCCTGACCTGCGTTACATCTTCCCACTGGGACC- GGCCTT PFLPNHPVISLKRNEDACPVG ATTCCAGAGAGGTGGCAGCATTCCCACTCCCCTTCATGAAACCAGAGAACAAATTCTGGCCAACGATTGCCCGG- ATTGAT TVSAAPWGSSSILPISWAYIK GACATATATGGAGATCAGCACCTGGTTTGTACCTGCCCACCCATGGAAGTTTATGAGTCTCCATTTTCTGAACA- AAAGAG MMGGKGLKQATETAILNANYM GGCGTCTTCTTAGTCCTCTCTCCCTAAGTTTAAAGGACTGATTTGATGCCTCTCCCCAGAGCATTTGATAAGCA- AGAAAG AKRLETHYRILFRGARGYVGH ATTTCATCTCCCACCCCAGCCTCAAGTAGGAGTTTTATATACTGTGTATATCTCTGTAATCTCTGTCAAGGTAA- ATGTAA EFILDTRPFKKSANIEAVDVA ATACAGTAGCTGGAGGGAGTCGAAGCTGATGGTTGGAAGACGGATTTGCTTTGGTATTCTGCTTCCACATGTGC- CAGTTG KRLQDYGFHAPTMSWPVAGTL CCTGGATTGGGAGCCATTTTGTGTTTTGCGTAGAAAGTTTTAGGAACTTTAACTTTTAATGTGGCAAGTTTGCA- GATGTC MVEPTESEDKAELDRFCDAMI ATAGAGGCTATCCTGGAGACTTAATAGACATTTTTTTGTTCCAAAAGAGTCCATGTGGACTGTGCCATCTGTGG- GAAATC SIRQEIADIEEGRIDPRVNPL CCAGGGCAAATGTTTACATTTTGTATACCCTGAAGAACTCTTTTTCCTCTAATATGCCTAATCTGTAATCACAT- TTCTGA KMSPHSLTCVTSSHWDRPYSR GTGTTTTCCTCTTTTTCTGTGTGAGGTTTTTTTTTTTTTTAATCTGCATTTATTAGTATTCTAATAAAAGCATT- TTGATC EVAAFPLPFMKPENKFWPTIA GGAAAAAAAAAAAAAAAAAAAAA RIDDIYGDQHLVCTCPPMEVY ESPFSEQKRASS SEQ. ID NO. 7 SEQ. ID NO. 57 GGGTCGTCATGATCCGGACCCCATTGTCGGCCTCTGCCCATCGCCTGCTCCTCCCAGGCTCCCGCGGCCGACCC- CCGCGC MIRTPLSASAHRLLLPGSRGR AACATGCAGCCCACGGGCCGCGAGGGTTCCCGCGCGCTCAGCCGGCGGTATCTGCGGCGTCTGCTGCTCCTGCT- ACTGCT PPRNMQPTGREGSRALSRRYL GCTGCTGCTGCGGCAGCCCGTAACCCGCGCGGAGACCACGCCGGGCGCCCCCAGAGCCCTCTCCACGCTGGGCT- CCCCCA RRLLLLLLLLLLRQPVTRAET GCCTCTTCACCACGCCGGGTGTCCCCAGCGCCCTCACTACCCCAGGCCTCACTACGCCAGGCACCCCCAAAACC- CTGGAC TPGAPRALSTLGSPSLFTTPG CTTCGGGGTCGCGCGCAGGCCCTGATGCGGAGTTTCCCACTCGTGGACGGCCACAATGACCTGCCCCAGGTCCT- GAGACA VPSALTTPGLTTPGTPKTLDL GCGTTACAAGAATGTGCTTCAGGATGTTAACCTGCGAAATTTCAGCCATGGTCAGACCAGCCTGGACAGGCTTA- GAGACG RGRAQALMRSFPLVDGHNDLP GCCTCGTGGGTGCCCAGTTCTGGTCAGCCTCCGTCTCATGCCAGTCCCAGGACCAGACTGCCGTGCGCCTCGCC- CTGGAG QVLRQRYKNVLQDVNLRNFSH CAGATTGACCTCATTCACCGCATGTGTGCCTCCTACTCTGAACTCGAGCTTGTGACCTCAGCTGAAGGTCTGAA- CAGCTC GQTSLDRLRDGLVGAQFWSAS TCAAAAGCTGGCCTGCCTCATTGGCGTGGAGGGTGGTCACTCACTGGACAGCAGCCTCTCTGTGCTGCGCAGTT- TCTATG VSCQSQDQTAVRLALEQIDLI TGCTGGGGGTGCGCTACCTGACACTTACCTTCACCTGCAGTACACCATGGGCAGAGAGTTCCACCAAGTTCAGA- CACCAC HRMCASYSELELVTSAEGLNS ATGTACACCAACGTCAGCGGATTGACAAGCTTTGGTGAGAAAGTAGTAGAGGAGTTGAACCGCCTGGGCATGAT- GATAGA SQKLACLIGVEGGHSLDSSLS TTTGTCCTATGCATCGGACACCTTGATAAGAAGGGTCCTGGAAGTGTCTCAGGCTCCTGTGATCTTCTCCCACT- CAGCTG VLRSFYVLGVRYLTLTFTCST CCAGAGCTGTGTGTGACAATTTGTTGAATGTTCCCGATGATATCCTGCAGCTTCTGAAGAAGAACGGTGGCATC- GTGATG PWAESSTKFRHHMYTNVSGLT GTGACACTGTCCATGGGGGTGCTGCAGTGCAACCTGCTTGCTAACGTGTCCACTGTGGCAGATCACTTTGACCA- CATCAG SFGEKVVEELNRLGMMIDLSY GGCAGTCATTGGATCTGAGTTCATCGGGATTGGTGGAAATTATGACGGGACTGGCCGGTTCCCTCAGGGGCTGG- AGGATG ASDTLIRRVLEVSQAPVIFSH TGTCCACATACCCAGTCCTGATAGAGGAGTTGCTGAGTCGTAGCTGGAGCGAGGAAGAGCTTCAAGGTGTCCTT- CGTGGA SAARAVCDNLLNVPDDILQLL AACCTGCTGCGGGTCTTCAGACAAGTGGAAAAGGTGAGAGAGGAGAGCAGGGCGCAGAGCCCCGTGGAGGCTGA- GTTTCC KKNGGIVMVTLSMGVLQCNLL ATATGGGCAACTGAGCACATCCTGCCACTCCCACCTCGTGCCTCAGAATGGACACCAGGCTACTCATCTGGAGG- TGACCA ANVSTVADHFDHIRAVIGSEF AGCAGCCAACCAATCGGGTCCCCTGGAGGTCCTCAAATGCCTCCCCATACCTTGTTCCAGGCCTTGTGGCTGCT- GCCACC IGIGGNYDGTGRFPQGLEDVS ATCCCAACCTTCACCCAGTGGCTCTGCTGACACAGTCGGTCCCCGCAGAGGTCACTGTGGCAAAGCCTCACAAA- GCCCCC TYPVLIEELLSRSWSEEELQG TCTCCTAGTTCATTCACAAGCATATGCTGAGAATAAACATGTTACACATGGAAAAAAAAAAAAAAAAAAA VLRGNLLRVFRQVEKVREESR AQSPVEAEFPYGQLSTSCHSH LVPQNGHQATHLEVTKQPTNR VPWRSSNASPYLVPGLVAAAT IPTFTQWLC SEQ. ID NO. 8 SEQ. ID NO. 58 AGTCCTGCGTCCGGGCCCCGAGGCGCAGCAGGGCACCAGGTGGAGCACCAGCTACGCGTGGCGCAGCGCAGCGT- CCCTAG MLRTESCRPRSPAGQVAAASP CACCGAGCCTCCCGCAGCCGCCGAGATGCTGCGAACAGAGAGCTGCCGCCCCAGGTCGCCCGCCGGACAGGTGG- CCGCGG LLLLLLLLAWCAGACRGAPIL CGTCCCCGCTCCTGCTGCTGCTGCTGCTGCTCGCCTGGTGCGCGGGCGCCTGCCGAGGTGCTCCAATATTACCT- CAAGGA PQGLQPEQQLQLWNEIDDTCS TTACAGCCTGAACAACAGCTACAGTTGTGGAATGAGATAGATGATACTTGTTCGTCTTTTCTGTCCATTGATTC- TCAGCC SFLSIDSQPQASNALEELCFM TCAGGCATCCAACGCACTGGAGGAGCTTTGCTTTATGATTATGGGAATGCTACCAAAGCCTCAGGAACAAGATG- AAAAAG IMGMLPKPQEQDEKDNTKRFL ATAATACTAAAAGGTTCTTATTTCATTATTCGAAGACACAGAAGTTGGGCAAGTCAAATGTTGTGTCGTCAGTT- GTGCAT FHYSKTQKLGKSNVVSSVVHP CCGTTGCTGCAGCTCGTTCCTCACCTGCATGAGAGAAGAATGAAGAGATTCAGAGTGGACGAAGAATTCCAAAG- TCCCTT LLQLVPHLHERRMKRFRVDEE TGCAAGTCAAAGTCGAGGATATTTTTTATTCAGGCCACGGAATGGAAGAAGGTCAGCAGGGTTCATTTAAAATG- GATGCC FQSPFASQSRGYFLFRPRNGR AGCTAATTTTCCACAGAGCAATGCTATGGAATACAAAATGTACTGACATTTTGTTTTCTTCTGAAAAAAATCCT- TGCTAA RSAGFI ATGTACTCTGTTGAAAATCCCTGTGTTGTCAATGTTCTCAGTTGTAACAATGTTGTAAATGTTCAATTTGTTGA- AAATTA AAAAATCTAAAAATAAA SEQ. ID NO. 9 SEQ. ID NO. 59 GGGCGCAGCGGGGCCCGTCTGCAGCAAGTGACCGACGGCCGGGACGGCCGCCTGCCCCCTCTGCCACCTGGGGC- GGTGCG MHVRSLRAAAPHSFVALWAPL GGCCCGGAGCCCGGAGCCCGGGTAGCGCGTAGAGCCGGCGCGATGCACGTGCGCTCACTGCGAGCTGCGGCGCC- GCACAG FLLRSALADFSLDNEVHSSFI CTTCGTGGCGCTCTGGGCACCCCTGTTCCTGCTGCGCTCCGCCCTGGCCGACTTCAGCCTGGACAACGAGGTGC- ACTCGA HRRLRSQERREMQREILSILG GCTTCATCCACCGGCGCCTCCGCAGCCAGGAGCGGCGGGAGATGCAGCGCGAGATCCTCTCCATTTTGGGCTTG- CCCCAC LPHRPRPHLQGKHNSAPMFML CGCCCGCGCCCGCACCTCCAGGGCAAGCACAACTCGGCACCCATGTTCATGCTGGACCTGTACAACGCCATGGC- GGTGGA DLYNAMAVEEGGGPGGQGFSY GGAGGGCGGCGGGCCCGGCGGCCAGGGCTTCTCCTACCCCTACAAGGCCGTCTTCAGTACCCAGGGCCCCCCTC- TGGCCA PYKAVFSTQGPPLASLQDSHF GCCTGCAAGATAGCCATTTCCTCACCGACGCCGACATGGTCATGAGCTTCGTCAACCTCGTGGAACATGACAAG- GAATTC LTDADMVMSFVNLVEHDKEFF TTCCACCCACGCTACCACCATCGAGAGTTCCGGTTTGATCTTTCCAAGATCCCAGAAGGGGAAGCTGTCACGGC- AGCCGA HPRYHHREFRFDLSKIPEGEA ATTCCGGATCTACAAGGACTACATCCGGGAACGCTTCGACAATGAGACGTTCCGGATCAGCGTTTATCAGGTGC- TCCAGG VTAAEFRIYKDYIRERFDNET AGCACTTGGGCAGGGAATCGGATCTCTTCCTGCTCGACAGCCGTACCCTCTGGGCCTCGGAGGAGGGCTGGCTG- GTGTTT FRISVYQVLQEHLGRESDLFL GACATCACAGCCACCAGCAACCACTGGGTGGTCAATCCGCGGCACAACCTGGGCCTGCAGCTCTCGGTGGAGAC- GCTGGA LDSRTLWASEEGWLVFDITAT TGGGCAGAGCATCAACCCCAAGTTGGCGGGCCTGATTGGGCGGCACGGGCCCCAGAACAAGCAGCCCTTCATGG- TGGCTT SNHWVVNPRHNLGLQLSVETL TCTTCAAGGCCACGGAGGTCCACTTCCGCAGCATCCGGTCCACGGGGAGCAAACAGCGCAGCCAGAACCGCTCC- AAGACG DGQSINPKLAGLIGRHGPQNK CCCAAGAACCAGGAAGCCCTGCGGATGGCCAACGTGGCAGAGAACAGCAGCAGCGACCAGAGGCAGGCCTGTAA- GAAGCA QPFMVAFFKATEVHFRSIRST CGAGCTGTATGTCAGCTTCCGAGACCTGGGCTGGCAGGACTGGATCATCGCGCCTGAAGGCTACGCCGCCTACT- ACTGTG GSKQRSQNRSKTPKNQEALRM AGGGGGAGTGTGCCTTCCCTCTGAACTCCTACATGAACGCCACCAACCACGCCATCGTGCAGACGCTGGTCCAC- TTCATC ANVAENSSSDQRQACKKHELY AACCCGGAAACGGTGCCCAAGCCCTGCTGTGCGCCCACGCAGCTCAATGCCATCTCCGTCCTCTACTTCGATGA- CAGCTC VSFRDLGWQDWIIAPEGYAAY CAACGTCATCCTGAAGAAATACAGAAACATGGTGGTCCGGGCCTGTGGCTGCCACTAGCTCCTCCGAGAATTCA- GACCCT YCEGECAFPLNSYMNATNHAI TTGGGGCCAAGTTTTTCTGGATCCTCCATTGCTCGCCTTGGCCAGGAACCAGCAGACCAACTGCCTTTTGTGAG- ACCTTC VQTLVHFINPETVPKPCCAPT CCCTCCCTATCCCCAACTTTAAAGGTGTGAGAGTATTAGGAAACATGAGCAGCATATGGCTTTTGATCAGTTTT- TCAGTG QLNAISVLYFDDSSNVILKKY GCAGCATCCAATGAACAAGATCCTACAAGCTGTGCAGGCAAAACCTAGCAGGAAAAAAAAACAACGCATAAAGA- AAAATG RNMVVRACGCH GCCGGGCCAGGTCATTGGCTGGGAAGTCTCAGCCATGCACGGACTCGTTTCCAGAGGTAATTATGAGCGCCTAC- CAGCCA GGCCACCCAGCCGTGGGAGGAAGGGGGCGTGGCAAGGGGTGGGCACATTGGTGTCTGTGCGAAAGGAAAATTGA- CCCGGA AGTTCCTGTAATAAATGTCACAATAAAACGAATGAATG SEQ. ID NO. 10 SEQ. ID NO. 60 CCGGTGAGTCGCCGGCGCTGCAGAGGGAGGCGGCACTGGTCTCGACGTGGGGCGGCCAGCGATGAAGCCGCCCA- GTTCAA MKPPSSIQTSEFDSSDEEPIE TACAAACAAGTGAGTTTGACTCATCAGATGAAGAGCCTATTGAAGATGAACAGACTCCAATTCATATATCATGG- CTATCT DEQTPIHISWLSLSRVNCSQF TTGTCACGAGTGAATTGTTCTCAGTTTCTCGGTTTATGTGCTCTTCCAGGTTGTAAATTTAAAGATGTTAGAAG- AAATGT LGLCALPGCKFKDVRRNVQK CCAAAAAGATACAGAAGAACTAAAGAGCTGTGGTATACAAGACATATTTGTTTTCTGCACCAGAGGGGAACTGT- CAAAAT DTEELKSCGIQDIFVFCTRGE ATAGAGTCCCAAACCTTCTGGATCTCTACCAGCAATGTGGAATTATCACCCATCATCATCCAATCGCAGATGGA- GGGACT LSKYRVPNLLDLYQQCGIITH CCTGACATAGCCAGCTGCTGTGAAATAATGGAAGAGCTTACAACCTGCCTTAAAAATTACCGAAAAACCTTAAT- ACACTG HHPIADGGTPDIASCCEIME CTATGGAGGACTTGGGAGATCTTGTCTTGTAGCTGCTTGTCTCCTACTATACCTGTCTGACACAATATCACCAG- AGCAAG ELTTCLKNYRKTLIHCYGGLG CCATAGACAGCCTGCGAGACCTAAGAGGATCCGGGGCAATACAGACCATCAAGCAATACAATTATCTTCATGAG- TTTCGG RSCLVAACLLLYLSDTISPE GACAAATTAGCTGCACATCTATCATCAAGAGATTCACAATCAAGATCTGTATCAAGATAAAGGAATTCAAATAG- CATATA QAIDSLRDLRGSGAIQTIKQY TATGACCATGTCTGAAATGTCAGTTCTCTAGCATAATTTGTATTGAAATGAAACCACCAGTGTTATCAACTTGA- ATGTAA NYLHEFRDKLAAHLSSRDSQ ATGTACATGTGCAGATATTCCTAAAGTTTTATTGAC SRSVSR SEQ. ID NO. 11 SEQ. ID NO. 61 AGAGCGATCATGTCGCACAAACAAATTTACTATTCGGACAAATACGACGACGAGGAGTTTGAGTATCGACATGT- CATGCT MSHKQIYYSDKYDDEEFEYRH GCCCAAGGACATAGCCAAGCTGGTCCCTAAAACCCATCTGATGTCTGAATCTGAATGGAGGAATCTTGGCGTTC- AGCAGA VMLPKDIAKLVPKTHLMSESE GTCAGGGATGGGTCCATTATATGATCCATGAACCAGAACCTCACATCTTGCTGTTCCGGCGCCCACTACCCAAG- AAACCA WRNLGVQQSQGWVHYMIHEP AAGAAATGAAGCTGGCAAGCTACTTTTCAGCCTCAAGCTTTACACAGCTGTCCTTACTTCCTAACATCTTTCTG- ATAACA EPHILLFRRPLPKKPKK TTATTATGTTGCCTTCTTGTTTCTCACTTTGATATTTAAAAGATGTTCAATACACTGTTTGAATGTGCTGGTAA- CTGCTT TGCTTCTTGAGTAGAGCCACCACCACCATAGCCCAGCCAGATGAGTGCTCTGTGGACCCACAGCCTAAGCTGAG- TGTGAC CCCAGAAGCCACGATGTGCTCTGTATCCAGAACACACTTGGCAGATGGAGGAAGCATCTGAGTTTGAGACCATG- GCTGTT ACAGGGATCATGTAAACTTGCTGTTTTTGTTTTTTCTGCCGGGTGTTGTATGTGTGGTGACTTGCGGATTTATG- TTTCAG TGTACTGGAAACTTTCCATTTTATTCAAGAAATCTGTTCATGTTAAAAGCCTTGATTAAAGAGGAAGTTTTTAT- AAT SEQ. ID NO. 12 SEQ. ID NO. 62 CGAGTTCCGGCGAGGCTTCAGGGTACAGCTCCCCCGCAGCCAGAAGCCGGGCCTGCAGCGCCTCAGCACCGCTC- CGGGAC MERRRLWGSIQSRYISMSVWT ACCCCACCCGCTTCCCAGGCGTGACCTGTCAACAGCAACTTCGCGGTGTGGTGAACTCTCTGAGGAAAAACCAT- TTTGAT SPRRLVELAGQSLLKDEALAI TATTACTCTCAGACGTGCGTGGCAACAAGTGACTGAGACCTAGAAATCCAAGCGTTGGAGGTCCTGAGGCCAGC- CTAAGT AALELLPRELFPPLFMAAFDG CGCTTCAAAATGGAACGAAGGCGTTTGTGGGGTTCCATTCAGAGCCGATACATCAGCATGAGTGTGTGGACAAG- CCCACG RHSQTLKAMVQAWPFTCLPLG GAGACTTGTGGAGCTGGCAGGGCAGAGCCTGCTGAAGGATGAGGCCCTGGCCATTGCCGCCCTGGAGTTGCTGC- CCAGGG VLMKGQHLHLETFKAVLDGLD AGCTCTTCCCGCCACTCTTCATGGCAGCCTTTGACGGGAGACACAGCCAGACCCTGAAGGCAATGGTGCAGGCC- TGGCCC VLLAQEVRPRRWKLQVLDLRK TTCACCTGCCTCCCTCTGGGAGTGCTGATGAAGGGACAACATCTTCACCTGGAGACCTTCAAAGCTGTGCTTGA- TGGACT NSHQDFWTVWSGNRASLYSFP TGATGTGCTCCTTGCCCAGGAGGTTCGCCCCAGGAGGTGGAAACTTCAAGTGCTGGATTTACGGAAGAACTCTC- ATCAGG EPEAAQPMTKKRKVDGLSTEA ACTTCTGGACTGTATGGTCTGGAAACAGGGCCAGTCTGTACTCATTTCCAGAGCCAGAAGCAGCTCAGCCCATG- ACAAAG EQPFIPVEVLVDLFLKEGACD AAGCGAAAAGTAGATGGTTTGAGCACAGAGGCAGAGCAGCCCTTCATTCCAGTAGAGGTGCTCGTAGACCTGTT- CCTCAA ELFSYLIEKVKRKKNVLRLCC GGAAGGTGCCTGTGATGAATTGTTCTCCTACCTCATTGAGAAAGTGAAGCGAAAGAAAAATGTACTACGCCTGT- GCTGTA KKLKIFAMPMQDIKMILKMVQ AGAAGCTGAAGATTTTTGCAATGCCCATGCAGGATATCAAGATGATCCTGAAAATGGTGCAGCTGGACTCTATT- GAAGAT LDSIEDLEVTCTWKLPTLAKF TTGGAAGTGACTTGTACCTGGAAGCTACCCACCTTGGCGAAATTTTCTCCTTACCTGGGCCAGATGATTAATCT- GCGTAG SPYLGQMINLRRLLLSHIHAS ACTCCTCCTCTCCCACATCCATGCATCTTCCTACATTTCCCCGGAGAAGGAAGAGCAGTATATCGCCCAGTTCA- CCTCTC SYISPEKEEQYIAQFTSQFLS AGTTCCTCAGTCTGCAGTGCCTGCAGGCTCTCTATGTGGACTCTTTATTTTTCCTTAGAGGCCGCCTGGATCAG- TTGCTC LQCLQALYVDSLFFLRGRLDQ AGGCACGTGATGAACCCCTTGGAAACCCTCTCAATAACTAACTGCCGGCTTTCGGAAGGGGATGTGATGCATCT- GTCCCA LLRHVMNPLETLSITNCRLSE GAGTCCCAGCGTCAGTCAGCTAAGTGTCCTGAGTCTAAGTGGGGTCATGCTGACCGATGTAAGTCCCGAGCCCC- TCCAAG GDVMHLSQSPSVSQLSVLSLS CTCTGCTGGAGAGAGCCTCTGCCACCCTCCAGGACCTGGTCTTTGATGAGTGTGGGATCACGGATGATCAGCTC- CTTGCC GVMLTDVSPEPLQALLERASA CTCCTGCCTTCCCTGAGCCACTGCTCCCAGCTTACAACCTTAAGCTTCTACGGGAATTCCATCTCCATATCTGC- CTTGCA TLQDLVFDECGITDDQLLALL GAGTCTCCTGCAGCACCTCATCGGGCTGAGCAATCTGACCCACGTGCTGTATCCTGTCCCCCTGGAGAGTTATG- AGGACA PSLSHCSQLTTLSFYGNSISI TCCATGGTACCCTCCACCTGGAGAGGCTTGCCTATCTGCATGCCAGGCTCAGGGAGTTGCTGTGTGAGTTGGGG- CGGCCC SALQSLLQHLIGLSNLTHVLY AGCATGGTCTGGCTTAGTGCCAACCCCTGTCCTCACTGTGGGGACAGAACCTTCTATGACCCGGAGCCCATCCT- GTGCCC PVPLESYEDIHGTLHLERLAY CTGTTTCATGCCTAACTAGCTGGGTGCACATATCAAATGCTTCATTCTGCATACTTGGACACTAAAGCCAGGAT-

GTGCAT LHARLRELLCELGRPSMVWLS GCATCTTGAAGCAACAAAGCAGCCACAGTTTCAGACAAATGTTCAGTGTGAGTGAGGAAAACATGTTCAGTGAG- GAAAAA ANPCPHCGDRTFYDPEPILCP ACATTCAGACAAATGTTCAGTGAGGAAAAAAAGGGGAAGTTGGGGATAGGCAGATGTTGACTTGAGGAGTTAAT- GTGATC CFMPN TTTGGGGAGATACATCTTATAGAGTTAGAAATAGAATCTGAATTTCTAAAGGGAGATTCTGGCTTGGGAAGTAC- ATGTAG GAGTTAATCCCTGTGTAGACTGTTGTAAAGAAACTGTTGAAAATAAAGAGAAGCAATGTGAAGCAAAAAAAAAA- AAAAAA AA SEQ. ID NO. 13 SEQ. ID NO. 63 CGGCTGAGAGGCAGCGAACTCATCTTTGCCAGTACAGGAGCTTGTGCCGTGGCCCACAGCCCACAGCCCACAGC- CATGGG MGWDLTVKMLAGNEFQVSLSS CTGGGACCTGACGGTGAAGATGCTGGCGGGCAACGAATTCCAGGTGTCCCTGAGCAGCTCCATGTCGGTGTCAG- AGCTGA SMSVSELKAQITQKIGVHAFQ AGGCGCAGATCACCCAGAAGATTGGCGTGCACGCCTTCCAGCAGCGTCTGGCTGTCCACCCGAGCGGTGTGGCG- CTGCAG QRLAVHPSGVALQDRVPLASQ GACAGGGTCCCCCTTGCCAGCCAGGGCCTGGGCCCTGGCAGCACGGTCCTGCTGGTGGTGGACAAATGCGACGA- ACCTCT GLGPGSTVLLVVDKCDEPLSI GAGCATCCTGGTGAGGAATAACAAGGGCCGCAGCAGCACCTACGAGGTCCGGCTGACGCAGACCGTGGCCCACC- TGAAGC LVRNNKGRSSTYEVRLTQTVA AGCAAGTGAGCGGGCTGGAGGGTGTGCAGGACGACCTGTTCTGGCTGACCTTCGAGGGGAAGCCCCTGGAGGAC- CAGCTC HLKQQVSGLEGVQDDLFWLTF CCGCTGGGGGAGTACGGCCTCAAGCCCCTGAGCACCGTGTTCATGAATCTGCGCCTGCGGGGAGGCGGCACAGA- GCCTGG EGKPLEDQLPLGEYGLKPLST CGGGCGGAGCTAAGGGCCTCCACCAGCATCCGAGCAGGATCAAGGGCCGGAAATAAAGGCTGTTGTAAGAGAAT VFMNLRLRGGGTEPGGRS SEQ. ID NO. 14 STAR clone: TGCCCACTTGGCCCCTCCTTCCAAGGTGTACTTTACTTCCTTTCATTCCTGCTCTAATACTGTTTAGTACATTT- TCACTC CTGCTCTAAAACTTGCCTCAGTCTCTCACTGTGCCTTATGCCCCTCAGCTGAATTCTTTCTTCTGAGCAGGCAG- GAATTG AGGTTGCTGCAGACGTGTATGCATTTGCCACCAGTAACATACTTTGGTGCCACATGACTAGGATATGTTCTCTA- GTGCTA ACATGTTCGTTTACAGTTCTTAGGACTCCCTGATA SEQ. ID NO. 15 SEQ. ID NO. 64 GGCCGCCTGCGCGCCGCCAACAGCCTAGCGCTGCGCCGCGTGGCCGCCGCCTTCTCGCTGGCCCCGCTGGCCGA- GCGCTG MRWVRHDAPARRGQLRRLLEH CGGCCGCGTCCTGCGTCAGGCCTTCGCCGAGGTGGCGCGCCACGCCGACTTCCTGGAGCTGGCGCCTGACGAGG- TGGTGG VRLPLLAPAYFLEKVEADELL CGCTGCTGGCGGACCCCGCGCTGGGCGTGGCGCGCGAGGAGGCCGTGTTTGAAGCGGCCATGCGCTGGGTGCGC- CACGAC QACGECRPLLLEARACFILGR GCGCCGGCCCGCCGCGGCCAGCTGCGACGCCTGCTGGAGCACGTGCGCCTGCCGCTACTGGCGCCCGCTTACTT- CCTGGA EAGALRTRPRRFMDLAEVIVV GAAGGTGGAGGCGGACGAGCTGCTGCAGGCCTGCGGCGAGTGCCGCCCGCTGCTGCTCGAGGCTCGCGCCTGCT- TCATCC IGGCDRKGLLKLPFADAYHPE TGGGCCGCGAGGCCGGTGCGCTGCGGACCCGGCCGCGGAGATTCATGGACCTAGCTGAAGTGATCGTGGTCATC- GGCGGT SQRWTPLPSLPGYTRSEFAAC TGCGACCGCAAAGGTCTCCTGAAGCTGCCCTTCGCCGATGCCTACCATCCAGAGAGCCAGCGGTGGACCCCACT- GCCCAG ALRNDVYVSGGHINSHDVWMF CCTGCCCGGCTACACTCGCTCAGAATTCGCCGCCTGTGCTCTCCGCAATGACGTCTACGTCTCCGGAGGCCACA- TCAACA SSHLHTWIKVASLHKGRWRHK GTCATGATGTGTGGATGTTTAGCTCCCATCTGCACACCTGGATCAAGGTAGCCTCTCTGCACAAGGGCAGGTGG- AGGCAC MAVVQGQLFAVGGFDGLRRLH AAGATGGCAGTTGTGCAGGGGCAGCTGTTCGCGGTGGGTGGCTTCGACGGCCTGAGGCGCCTGCACAGCGTGGA- GCGCTA SVERYDPFSNTWAAAAPLPEA CGACCCCTTCTCCAACACCTGGGCGGCCGCCGCGCCCCTCCCGGAGGCCGTGAGCTCGGCGGCGGTGGCGTCCT- GCGCGG VSSAAVASCAGKLFVIGGARQ GCAAGCTCTTCGTGATTGGGGGCGCCAGGCAGGGCGGCGTCAACACGGACAAGGTGCAGTGCTTTGACCCCAAG- GAGGAC GGVNTDKVQCFDPKEDRWSLR CGGTGGAGCCTGCGGTCACCAGCACCCTTCTCACAGCGGTGTCTCGAGGCTGTCTCCCTTGAGGACACCATCTA- TGTCAT SPAPFSQRCLEAVSLEDTIYV GGGGGGTCTCATGAGCAAAATCTTCACCTATGATCCAGGCACAGATGTGTGGGGGGAGGCAGCTGTCCTCCCCA- GCCCTG MGGLMSKIFTYDPGTDVWGEA TGGAAAGCTGTGGAGTCACTGTGTGTGACGGGAAGGTCCACATCCTTGGCGGGCGGGATGATCGCGGAGAAAGC- ACCGAT AVLPSPVESCGVTVCDGKVHI AAGGTCTTCACCTTTGACCCCAGCAGTGGGCAGGTGGAGGTCCAGCCATCCCTGCAGCGCTGCACCAGCTCCCA- CGGCTG LGGRDDRGESTDKVFTFDPSS TGTCACCATCATCCAGAGCTTGGGCAGGTGATTCAGATTTGGACAGCCTGAGCCAGGAGGCGGAGAGGCAGGCG- GAGCTC GQVEVQPSLQRCTSSHGCVTI AGATGCACACTCTGCTCCCTCATGGCACCTCCACGCAAACAGCCCTTAACTTAATGGTCCCTTTTCTTGTATAA- ATAAAA IQSLGR SEQ. ID NO. 16 STAR clone: TTTCTAGCAGCCTGGGCAATGGCGGGCGCCCCTCCCCCAGCCTCGCTGCTGCCTTGCAGTTTGATCTCAGACTG- CTGTGC TAGCAATCAGCAAGACTCCGTGGGCGTAGGACCCTCCGAGCCAGGTTGCAAGAAAGCTCAAGTAGCCTATGGAG- AGGATG CAAGGCTTCCAGCTGATGCCCTCAGCCAGGCTCAGTAGCAGCCAGAACTAGCCTACCAACGAACCTGCTGATCA- TGTGCA TAAGCCACCTTGAACGTCGATCCTCCTGCCTGGTGGAGCCATCCCAGCTGATGCCACATGAAGCAGACACAAGC- TGTCCC TACTAAGCTCTGCTCAAGTTGGATATTCATGAGTGAAATAAATGACTGTTACTAA SEQ. ID NO. 17 SEQ. ID NO. 65 GAGTCACCAAGGAAGGCAGCGGCAGCTCCACTCAGCCAGTACCCAGATACGCTGGGAACCTTCCCCAGCCATGG- CTTCCC MASLGQILFWSIISIIIILA TGGGGCAGATCCTCTTCTGGAGCATAATTAGCATCATCATTATTCTGGCTGGAGCAATTGCACTCATCATTGGC- TTTGGT GAIALIIGFGISGRHSITVT ATTTCAGGGAGACACTCCATCACAGTCACTACTGTCGCCTCAGCTGGGAACATTGGGGAGGATGGAATCCAGAG- CTGCAC TVASAGNIGEDGIQSCTFEP TTTTGAACCTGACATCAAACTTTCTGATATCGTGATACAATGGCTGAAGGAAGGTGTTTTAGGCTTGGTCCATG- AGTTCA DIKLSDIVIQWLKEGVLGLV AAGAAGGCAAAGATGAGCTGTCGGAGCAGGATGAAATGTTCAGAGGCCGGACAGCAGTGTTTGCTGATCAAGTG- ATAGTT HEFKEGKDELSEQDEMFRGR GGCAATGCCTCTTTGCGGCTGAAAAACGTGCAACTCACAGATGCTGGCACCTACAAATGTTATATCATCACTTC- TAAAGG TAVFADQVIVGNASLRLKNV CAAGGGGAATGCTAACCTTGAGTATAAAACTGGAGCCTTCAGCATGCCGGAAGTGAATGTGGACTATAATGCCA- GCTCAG QLTDAGTYKCYIITSKGKGN AGACCTTGCGGTGTGAGGCTCCCCGATGGTTCCCCCAGCCCACAGTGGTCTGGGCATCCCAAGTTGACCAGGGA- GCCAAC ANLEYKTGAFSMPEVNVDYN TTCTCGGAAGTCTCCAATACCAGCTTTGAGCTGAACTCTGAGAATGTGACCATGAAGGTTGTGTCTGTGCTCTA- CAATGT ASSETLRCEAPRWFPQPTVV TACGATCAACAACACATACTCCTGTATGATTGAAAATGACATTGCCAAAGCAACAGGGGATATCAAAGTGACAG- AATCGG WASQVDQGANFSEVSNTSFE AGATCAAAAGGCGGAGTCACCTACAGCTGCTAAACTCAAAGGCTTCTCTGTGTGTCTCTTCTTTCTTTGCCATC- AGCTGG LNSENVTMKVVSVLYNVTIN GCACTTCTGCCTCTCAGCCCTTACCTGATGCTAAAATAATGTGCCTCGGCCACAAAAAAGCATGCAAAGTCATT- GTTACA NTYSCMIENDIAKATGDIKV ACAGGGATCTACAGAACTATTTCACCACCAGATATGACCTAGTTTTATATTTCTGGGAGGAAATGAATTCATAT- CTAGAA TESEIKRRSHLQLLNSKASL GTCTGGAGTGAGCAAACAAGAGCAAGAAACAAAAAGAAGCCAAAAGCAGAAGGCTCCAATATGAACAAGATAAA- TCTATC CVSSFFAISWALLPLSPYL TTCAAAGACATATTAGAAGTTGGGAAAATAATTCATGTGAACTAGAGTCAACTGTGTCAGGGCTAAGAAACCCT- GGTTTT MLK GAGTAGAAAAGGGCCTGGAAAGAGGGGAGCCAACAAATCTGTCTGCTTCCTCACATTAGTCATTGGCAAATAAG- CATTCT GTCTCTTTGGCTGCTGCCTCAGCACAGAGAGCCAGAACTCTATCGGGCACCAGGATAACATCTCTCAGTGAACA- GAGTTG ACAAGGCCTATGGGAAATGCCTGATGGGATTATCTTCAGCTTGTTGAGCTTCTAAGTTTCTTTCCCTTCATTCT- ACCCTG CAAGCCAAGTTCTGTAAGAGAAATGCCTGAGTTCTAGCTCAGGTTTTCTTACTCTGAATTTAGATCTCCAGACC- CTGCCT GGCCACAATTCAAATTAAGGCAACAAACATATACCTTCCATGAAGCACACACAGACTTTTGAAAGCAAGGACAA- TGACTG CTTGAATTGAGGCCTTGAGGAATGAAGCTTTGAAGGAAAAGAATACTTTGTTTCCAGCCCCCTTCCCACACTCT- TCATGT GTTAACCACTGCCTTCCTGGACCTTGGAGCCACGGTGACTGTATTACATGTTGTTATAGAAAACTGATTTTAGA- GTTCTG ATCGTTCAAGAGAATGATTAAATATACATTTCCTAAAAAAAAAAAAAAAAA SEQ. ID NO. 18 SEQ. ID NO. 66 TCTTCGGACCTAGGCTGCCCTGCCGTCATGTCGCAAGGGATCCTTTCTCCGCCAGCGGGCTTGCTGTCCGATGA- CGATGT MSQGILSPPAGLLSDDDVVV CGTAGTTTCTCCCATGTTTGAGTCCACAGCTGCAGATTTGGGGTCTGTGGTACGCAAGAACCTGCTATCAGACT- GCTCTG SPMFESTAADLGSVVRKNLL TCGTCTCTACCTCCCTAGAGGACAAGCAGCAGGTTCCATCTGAGGACAGTATGGAGAAGGTGAAAGTATACTTG- AGGGTT SDCSVVSTSLEDKQQVPSED AGGCCCTTGTTACCTTCAGAGTTGGAACGACAGGAAGATCAGGGTTGTGTCCGTATTGAGAATGTGGAGACCCT- TGTTCT SMEKVKVYLRVRPLLPSELE ACAAGCACCCAAGGACTCGTTTGCCCTGAAGAGCAATGAACGGGGAATTGGCCAAGCCACACACAGGTTCACCT- TTTCCC RQEDQGCVRIENVETLVLQA AGATCTTTGGGCCAGAAGTGGGACAGGCATCCTTCTTCAACCTAACTGTGAAGGAGATGGTAAAGGATGTACTC- AAAGGG PKDSFALKSNERGIGQATHR CAGAACTGGCTCATCTATACATATGGAGTCACTAACTCAGGGAAAACCCACACGATTCAAGGTACCATCAAGGA- TGGAGG FTFSQIFGPEVGQASFFNLT GATTCTCCCCCGGTCCCTGGCGCTGATCTTCAATAGCCTCCAAGGCCAACTTCATCCAACACCTGATCTGAAGC- CCTTGC VKEMVKDVLKGQNWLIYTYG TCTCCAATGAGGTAATCTGGCTAGACAGCAAGCAGATCCGACAGGAGGAAATGAAGAAGCTGTCCCTGCTAAAT- GGAGGC VTNSGKTHTIQGTIKDGGIL CTCCAAGAGGAGGAGCTGTCCACTTCCTTGAAGAGGAGTGTCTACATCGAAAGTCGGATAGGTACCAGCACCAG- CTTCGA PRSLALIFNSLQGQLHPTPD CAGTGGCATTGCTGGGCTCTCTTCTATCAGTCAGTGTACCAGCAGTAGCCAGCTGGATGAAACAAGTCATCGAT- GGGCAC LKPLLSNEVIWLDSKQIRQE AGCCAGACACTGCCCCACTACCTGTCCCGGCAAACATTCGCTTCTCCATCTGGATCTCATTCTTTGAGATCTAC- AACGAA EMKKLSLLNGGLQEEELSTS CTGCTTTATGACCTATTAGAACCGCCTAGCCAACAGCGCAAGAGGCAGACTTTGCGGCTATGCGAGGATCAAAA- TGGCAA LKRSVYIESRIGTSTSFDSG TCCCTATGTGAAAGATCTCAACTGGATTCATGTGCAAGATGCTGAGGAGGCCTGGAAGCTCCTAAAAGTGGGTC- GTAAGA IAGLSSISQCTSSSQLDETS ACCAGAGCTTTGCCAGCACCCACCTCAACCAGAACTCCAGCCGCAGTCACAGCATCTTCTCAATCAGGATCCTA- CACCTT HRWAQPDTAPLPVPANIRFS CAGGGGGAAGGAGATATAGTCCCCAAGATCAGCGAGCTGTCACTCTGTGATCTGGCTGGCTCAGAGCGCTGCAA- AGATCA IWISFFEIYNELLYDLLEPP GAAGAGTGGTGAACGGTTGAAGGAAGCAGGAAACATTAACACCTCTCTACACACCCTGGGCCGCTGTATTGCTG- CCCTTC SQQRKRQTLRLCEDQNGNPY GTCAAAACCAGCAGAACCGGTCAAAGCAGAACCTGGTTCCCTTCCGTGACAGCAAGTTGACTCGAGTGTTCCAA- GGTTTC VKDLNWIHVQDAEEAWKLLK TTCACAGGCCGAGGCCGTTCCTGCATGATTGTCAATGTGAATCCCTGTGCATCTACCTATGATGAAACTCTTCA- TGTGGC VGRKNQSFASTHLNQNSSRS CAAGTTCTCAGCCATTGCTAGCCAGCTTGTGCATGCCCCACCTATGCAACTGGGATTCCCATCCCTGCACTCGT- TCATCA HSIFSIRILHLQGEGDIVPK AGGAACATAGTCTTCAGGTATCCCCCAGCTTAGAGAAAGGGGCTAAGGCAGACACAGGCCTTGATGATGATATT- GAAAAT ISELSLCDLAGSERCKDQKS GAAGCTGACATCTCCATGTATGGCAAAGAGGAGCTCCTACAAGTTGTGGAAGCCATGAAGACACTGCTTTTGAA- GGAACG GERLKEAGNINTSLHTLGRC ACAGGAAAAGCTACAGCTGGAGATGCATCTCCGAGATGAAATTTGCAATGAGATGGTAGAACAGATGCAACAGC- GGGAAC IAALRQNQQNRSKQNLVPFR AGTGGTGCAGTGAACATTTGGACACCCAAAAGGAACTATTGGAGGAAATGTATGAAGAAAAACTAAATATCCTC- AAGGAG DSKLTRVFQGFFTGRGRSCM TCACTGACAAGTTTTTACCAAGAAGAGATTCAGGAGCGGGATGAAAAGATTGAAGAGCTAGAAGCTCTCTTGCA- GGAAGC IVNVNPCASTYDETLHVAKF CAGACAACAGTCAGTGGCCCATCAGCAATCAGGGTCTGAATTGGCCCTACGGCGGTCACAAAGGTTGGCAGCTT- CTGCCT SAIASQLVHAPPMQLGFPSL CCACCCAGCAGCTTCAGGAGGTTAAAGCTAAATTACAGCAGTGCAAAGCAGAGCTAAACTCTACCACTGAAGAG- TTGCAT HSFIKEHSLQVSPSLEKGAK AAGTATCAGAAAATGTTAGAACCACCACCCTCAGCCAAGCCCTTCACCATTGATGTGGACAAGAAGTTAGAAGA- GGGCCA ADTGLDDDIENEADISMYGK GAAGAATATAAGGCTGTTGCGGACAGAGCTTCAGAAACTTGGTGAGTCTCTCCAATCAGCAGAGAGAGCTTGTT- GCCACA EELLQVVEAMKTLLLKERQE GCACTGGGGCAGGAAAACTTCGTCAAGCCTTGACCACTTGTGATGACATCTTAATCAAACAGGACCAGACTCTG- GCTGAA KLQLEMHLRDEICNEMVEQM CTGCAGAACAACATGGTGCTAGTGAAACTGGACCTTCGGAAGAAGGCAGCATGTATTGCTGAGCAGTATCATAC- TGTGTT QQREQWCSEHLDTQKELLEE GAAACTCCAAGGCCAGGTTTCTGCCAAAAAGCGCCTTGGTACCAACCAGGAAAATCAGCAACCAAACCAACAAC- CACCAG MYEEKLNILKESLTSFYQEE GGAAGAAACCATTCCTTCGAAATTTACTTCCCCGAACACCAACCTGCCAAAGCTCAACAGACTGCAGCCCTTAT- GCCCGG IQERDEKIEELEALLQEARQ ATCCTACGCTCACGGCGTTCCCCTTTACTCAAATCTGGGCCTTTTGGCAAAAAGTACTAAGGCTGTGGGGAAAG- AGAAGA QSVAHQQSGSELALRRSQRL GCAGTCATGGCCCTGAGGTGGGTCAGCTACTCTCCTGAAGAAATAGGTCTCTTTTATGCTTTACCATATATCAG- GAATTA AASASTQQLQEVKAKLQQCK TATCCAGGATGCAATACTCAGACACTAGCTTTTTTCTCACTTTTGTATTATAACCACCTATGTAATCTCATGTT- GTTGTT AELNSTTEELHKYQKMLEPP TTTTTTTATTTACTTATATGATTTCTATGCACACAAAAACAGTTATATTAAAGATATTAT PSAKPFTIDVDKKLEEGQKN TGTTCACATTTTTTATTGAAAAAAAAAAAAAA IRLLRTELQKLGESLQSAER ACCHSTGAGKLRQALTTCDD ILIKQDQTLAELQNNMVLVK LDLRKKAACIAEQYHTVLKL QGQVSAKKRLGTNQENQQPN QQPPGKKPFLRNLLPRTPTC QSSTDCSPYARILRSRRSPL LKSGPFGKKY STAR clone (SEQ. ID NO. 19): SEQ. ID NO. 67 TCCTTGTTACGATGAAGAAACTAAATCTCAGGAAGAAAAAACTAAGTGAAGACNAAAGAAGGATTTGAACTGAG- GTTTGT MFIWTSGRTSSSYRHDEKRN CAGACTCTCGGGACCATGCTGTTGAAACCACTAAACCACGCTGCCTCTGGGTCACTTGGTAAACAGCATTTAAC- CATTAA IYQKIRDHDLLDKRKTVTAL GAAAGTCATTAATAAAATTCCTTGTGCTCTCCTTGAGATTACAAGCCATTGATTTGCCAA KAGEDRAILLGLAMMVCSIM NM_005832: MYFLLGITLLRSYMQSVWTE GCTGGGCACCGTTCTGTTTTCTTTCTTTTCTTAATCCTATCCAAGTATGCAGTACGCTCTTGGGTCGTCTCATG- AGACCC ESQCTLLNASITETFNCSFS AGGGGCATGTTGGAAAGAACTGAGAGAAAGAGCAACAAAGCGGCGAGTGGTGTGAGAGGGCAGCACGCGCTGTG- GGGCCC CGPDCWKLSQYPCLQVYVNL TTCCAGAGAAATGTACTGAAAAAGTCTACGCAATGTCTGGGATTTGCTAAACAATACCTGGAAAGCAGACAGGT- CTTTTT TSSGEKLLLYHTEETIKINQ GCCATTCCTCCAGGACATCCACCATAAGGAAAGGAGACCCTGGACCAACATTCTCTAAGATGTTTATATGGACC- AGTGGC KCSYIPKCGKNFEESMSLVN CGGACCTCTTCATCTTATAGACATGATGAAAAAAGAAATATTTACCAGAAAATCAGGGACCATGACCTCCTGGA- CAAAAG VVMENFRKYQHFSCYSDPEG GAAAACAGTCACAGCACTGAAGGCAGGAGAGGACCGAGCTATTCTCCTGGGACTGGCTATGATGGTGTGCTCCA- TCATGA NQKSVILTKLYSSNVLFHSL TGTATTTTCTGCTGGGAATCACACTCCTGCGCTCATACATGCAGAGCGTGTGGACCGAAGAGTCTCAATGCACC- TTGCTG FWPTCMMAGGVAIVAMVKLT AATGCGTCCATCACGGAAACATTTAATTGCTCCTTCAGCTGTGGTCCAGACTGCTGGAAACTTTCTCAGTACCC- CTGCCT QYLSLLCERIQRINR CCAGGTGTACGTTAACCTGACTTCTTCCGGGGAAAAGCTCCTCCTCTACCACACAGAAGAGACAATAAAAATCA- ATCAGA AGTGCTCCTATATACCTAAATGTGGAAAAAATTTTGAAGAATCCATGTCCCTGGTGAATGTTGTCATGGAAAAC- TTCAGG AAGTATCAACACTTCTCCTGCTATTCTGACCCAGAAGGAAACCAGAAGAGTGTTATCCTAACAAAACTCTACAG- TTCCAA CGTGCTGTTCCATTCACTCTTCTGGCCAACCTGTATGATGGCTGGGGGTGTGGCAATTGTTGCCATGGTGAAAC-

TTACAC AGTACCTCTCCCTACTATGTGAGAGGATCCAACGGATCAATAGATAAATGCAAAAATGGATAAAATAATTTTTG- TTAAAG CTCAAATACTGTTTTCTTTCATTCTTCACCAAAGAACCTTAAGTTTGTAACGTGCAGTCTGTTATGAGTTCCCT- AATATA TTCTTATATGTAGAGCAATAATGCAAAAGCTGTTCTATATGCAAACATGATGTCTTTATTATTCAGGAGAATAA- ATAACT GTTTTGTGTTGGTTGGTGGTTTTCATAATCTTATTTCTGTACTGGAACTAGTACTTTCTTCTCTCATTCCGCCA- AAACAG GGCTCAGTTATTCATTTGCCAAGCTTCGTGGAGGAATGTAGGTGACATCAATGTGATAAAGTCTGTGTTCTGAG- TTGTCA GATCTCTTGAAGACAATATTTTTCATCACTTATTGTTTACTAAAGCTACAGCCAAAAATATTTTTTTTTCTTAT- TCTAAA CTGAGCCCTATAGCAAGTGAAGGGACCAGATTTCCTAATTAAAGGAAGTTAGGTACTTTTCTTGTATTTTTTAC- CATATC ACTGTAAAGAAGAGGGGAAACCCAGCCAGCTACTTTTTTTCATCACTTTTTATTCATAACTTCAGATTTGTAAA- ACTAAT TTCCAAAATATAAGCTGTTTTCATTAGCCAGTTCTATAATATCTTCCTGTGATTTATGTAGAAAATGAACACAC- CCCTTT TCCATTTAAGACCCTGCTACTGTGTGAAGAGATGATACTTACAAGGAGTGTCATTACCTGTGAGCTGACTGAAT- GTTGGT AGGTGCTCCATTACAATCCAGGAAAGTCTGTGTTACTGATATTTGTGTGGAAATCTTTATTTCACTTCAATTTA- ACCATT AGATGGTAAAATTAAGATGCTACTTGTTGGTAAAAATTGGTGGACTGGTTTCAATGGGTAAATGTGTTGTGGCA- AATTAA TGTGTTGGAATATTGCTCTTTGTGAATTTGTGCTTAAGTCAATGAATGTGTAGTATCTCCTTCTGACAAGCATT- CCCTAT TGGGATTTTAAAGCTATGTGCACAGAATATTAGTCTCTTCTACATGTTTTATTTTTCTATTTATAATTCCCTTT- TTTGTT GTTATATTTTATACACAGAATAGATCTTTTTTCTAACACATATTTGAACTGAATAACAGACTTAAAGAAAGCCT- TTGTTC ACATTGCTATTTACTTTTGTGTTTGGGGGAAAATACGAGGGATTGATTTTAAATAAAAAACATTCCATCTTTCA- TTTAAT ATCAATATCAAAAGAAGAAGACAAACATCTATCTTTCTCATCTATATTTAAGTACCTTTTTGTAATGTAGTATC- AAAGTT TTTTAGGTAATGCAAAATTTTACAAATCATTTGTGGAATGAATGGTAAAACTAATCTGATGAAATGGAAAATTA- TTCTGC AATATTGTAATTCATAGTTTGACTTTTCATAAGCAAATAAATCCCTAGGA TGTAATCAGGACTTCAAATGTGTAATTAAATTTTTTTAAAAAAAATCTA SEQ. ID NO. 20 STAR clone: GAACACAGCTAAGCAGATGGCTTGGGTCATCAGGACGTCCATTACATCCAAAGGAAGACAGCCTGTGACGTTTC- AAAAGC AAAAGTCCCCTACCAGCCAGTGAAGCTACCTGATTTCTCAGTATCTTACGCCCAGTGACACGATCTACCCTCAA- AACTTA SEQ. ID NO. 21 SEQ. ID NO. 68 GAGACATTCCTCAATTGCTTAGACATATTCTGAGCCTACAGCAGAGGAACCTCCAGTCTCAGCACCATGAATCA- AACTGC MNQTAILICCLIFLTLSGIQG GATTCTGATTTGCTGCCTTATCTTTCTGACTCTAAGTGGCATTCAAGGAGTACCTCTCTCTAGAACCGTACGCT- GTACCT VPLSRTVRCTCISISNQPVNP GCATCAGCATTAGTAATCAACCTGTTAATCCAAGGTCTTTAGAAAAACTTGAAATTATTCCTGCAAGCCAATTT- TGTCCA RSLEKLEIIPASQFCPRVEII CGTGTTGAGATCATTGCTACAATGAAAAAGAAGGGTGAGAAGAGATGTCTGAATCCAGAATCGAAGGCCATCAA- GAATTT TMKKKGEKRCLNPESKAIKNL ACTGAAAGCAGTTAGCAAGGAAATGTCTAAAAGATCTCCTTAAAACCAGAGGGGAGCAAAATCGATGCAGTGCT- TCCAAG LKAVSKEMSKRSP GATGGACCACACAGAGGCTGCCTCTCCCATCACTTCCCTACATGGAGTATATGTCAAGCCATAATTGTTCTTAG- TTTGCA GTTACACTAAAAGGTGACCAATGATGGTCACCAAATCAGCTGCTACTACTCCTGTAGGAAGGTTAATGTTCATC- ATCCTA AGCTATTCAGTAATAACTCTACCCTGGCACTATAATGTAAGCTCTACTGAGGTGCTATGTTCTTAGTGGATGTT- CTGACC CTGCTTCAAATATTTCCCTCACCTTTCCCATCTTCCAAGGGTACTAAGGAATCTTTCTGCTTTGGGGTTTATCA- GAATTC TCAGAATCTCAAATAACTAAAAGGTATGCAATCAAATCTGCTTTTTAAAGAATGCTCTTTACTTCATGGACTTC- CACTGC CATCCTCCCAAGGGGCCCAAATTCTTTCAGTGGCTACCTACATACAATTCCAAACACATACAGGAAGGTAGAAA- TATCTG AAAATGTATGTGTAAGTATTCTTATTTAATGAAAGACTGTACAAAGTATAAGTCTTAGATGTATATATTTCCTA- TATTGT TTTCAGTGTACATGGAATAACATGTAATTAAGTACTATGTATCAATGAGTAACAGGAAAATTTTAAAAATACAG- ATAGAT ATATGCTCTGCATGTTACATAAGATAAATGTGCTGAATGGTTTTCAAATAAAAATGAGGTACTCTCCTGGAAAT- ATTAAG AAAGACTATCTAAATGTTGAAAGATCAAAAGGTTAATAAAGTAATTATAACT SEQ. ID NO. 22 STAR clone: TTTGCAGGTTTGATCTCAGACTGCTGTGCTAGTAATCAGCGAGATTCCGTGGGCGTAGGAGCCTCCAAGCCAGG- TCCTGA AGAAAATGAAGTTGATGTTTCAGTGAGACACCTGTATGCCAGAGAGTAAAAGGGATTATTGTGGATTCCTGAGA- ATTTTC TACATATGAAATCATGTCATCTATGAACAGAGATGGGACTGTCTCGTTGGAGGAAAACAAGCTCAGGGCTCCCA- CTGATT CCACATTATGTTGCAAGCTCCTACGAAGCTCCCACTCA SEQ. ID NO. 23 SEQ. ID NO. 69 TTTCTCCGCATGCGCGGGATCCCGGATGTGGATCAAGTTGGTGGGAAGCGTGCGGTGCCGCAGCAATGGCGGCG- CTCACA MAALTIATGTGNWFSALALGV ATTGCCACGGGTACTGGCAATTGGTTTTCGGCTTTGGCGCTCGGGGTGACTCTTCTCAAATGCCTTCTCATCCC- CACATA TLLKCLLIPTYHSTDFEVHRN CCATTCCACAGATTTTGAAGTACACCGAAACTGGCTTGCTATCACTCACAGTTTGCCAATATCACAGTGGTATT- ATGAGG LAITHSLPISQWYYEATSEWT CAACTTCAGAGTGGACGTTGGATTACCCCCCTTTCTTTGCATGGTTTGAGTATATCCTGTCACATGTTGCCAAA- TATTTT LDYPPFFAWFEYILSHVAKYF GATCAAGAAATGCTGAATGTCCATAATTTGAATTACTCCAGCTCAAGGACCTTACTTTTCCAGAGATTTTCCGT- CATCTT DQEMLNVHNLNYSSSRTLLFQ TATGGATGTACTCTTTGTGTATGCTGTCCGTGAGTGCTGTAAATGCATTGATGGAAAAAAAGTGGGTAAAGAAC- TTACAG RFSVIFMDVLFVYAVRECCKC AAAAGCCAAAATTTATTCTGTCGGTATTACTTCTGTGGAACTTCGGGTTATTAATTGTGGACCATATTCATTTT- CAGTAC IDGKKVGKELTEKPKFILSVL AATGGCTTTTTATTTGGATTAATGCTACTCTCCATTGCACGATTATTTCAGAAAAGGCATATGGAAGGAGCATT- TCTCTT LLWNFGLLIVDHIHFQYNGFL TGCTGTTCTCCTACATTTCAAGCATATCTACCTCTATGTAGCACCAGCTTATGGTGTATATCTGCTGCGATCCT- ACTGTT FGLMLLSIARLFQKRHMEGAF TCACTGCAAATAAACCAGATGGGTCTATTCGATGGAAGAGTTTCAGCTTTGTTCGTGTTATTTCCCTGGGACTG- GTTGTT LFAVLLHFKHIYLYVAPAYGV TTCTTAGTTTCTGCTCTTTCATTGGGTCCTTTCCTGGCCTTGAATCAGCTGCCTCAAGTCTTTTCCCGACTCTT- TCCTTT YLLRSYCFTANKPDGSIRWKS CAAGAGGGGCCTCTGTCATGCATATTGGGCTCCAAACTTCTGGGCTTTGTACAATGCTTTGGACAAAGTGCTGT- CTGTCA FSFVRVISLGLVVFLVSALSL TCGGTTTGAAATTGAAATTTCTTGATCCCAACAATATTCCCAAGGCCTCAATGACAAGTGGTTTGGTTCAGCAG- TTCCAA GPFLALNQLPQVFSRLFPFKR CACACAGTCCTTCCCTCAGTGACTCCCTTGGCAACCCTCATCTGCACACTGATTGCCATATTGCCCTCTATTTT- CTGTCT GLCHAYWAPNFWALYNALDKV TTGGTTTAAACCCCAAGGGCCCAGAGGCTTTCTCCGATGTCTAACTCTTTGTGCCTTGAGCTCCTTTATGTTTG- GGTGGC LSVIGLKLKFLDPNNIPKASM ATGTTCATGAAAAAGCCATACTTCTAGCAATTCTCCCAATGAGCCTTTTGTCTGTGGGAAAAGCAGGAGACGCT- TCGATT TSGLVQQFQHTVLPSVTPLAT TTTCTGATTCTGACCACAACAGGACATTATTCCCTCTTTCCTCTGCTCTTCACTGCACCAGAACTTCCCATTAA- AATCTT LICTLIAILPSIFCLWFKPQG ACTCATGTTACTATTCACCATATATAGTATTTCGTCACTGAAGACTTTATTCAGACGGAGTTTCACCCTTGTTG- CCCAGG PRGFLRCLTLCALSSFMFGWH CTGGAGTGCAATGGCACGATCTCAGCTAACTGAAACCTCCGCCTCCCAGAAAAGAAAAACCTCTTTTTAATTGG- ATGGAA VHEKAILLAILPMSLLSVGKA ACTTTCTACCTGCTTGGCCTGGGGCCTCTGGAAGTCTGCTGTGAATTTGTATTCCCTTTCACCTCCTGGAAGGT- GAAGTA GDASIFLILTTTGHYSLFPLL CCCCTTCATCCCTTTGTTACTAACCTCAGTGTATTGTGCAGTAGGCATCACATATGCTTGGTTCAAACTGTATG- TTTCAG FTAPELPIKILLMLLFTIYSI TATTGATTGACTCTGCTATTGGCAAGACAAAGAAACAATGAATAAAGGAACTGCTTAGATATG SSLKTLFRRSFTLVAQAGVQW HDLS SEQ. ID NO. 24 SEQ. ID NO. 70 CATTATGCTAACAGCATAAACATGCAGGGGGTGGGAGCAGGGTCACAAAAGTGAGTGTTGTCAATTCTACTTGG- AATGAA MDDDAAPRVEGVPVAVHKHAL AGGTTGAAATAATTTAAACAGTACGGGAAATGCAGAGCAATTTTCTCCTCTGGTGACAATATAGTGTCCAACAC- TTGGAA HDGLRQVAGPGAAAAHLPRWP GTGATTTTTAAGAATGTTTATTTAAATTAAAAGGATGGATTTCCAAGGAAAAAAAATAAGGAAAAGGAAAGAAA- AAACTG PPQLAASRREAPPLSQRPHRT AACAGAAAACGCAAAAGTATCAGTTTGGTCACTAACCTTTGCAAGGATACCTTTTTATTTTCTTTAAGATTCCT- GTTGTT QGAGSPPETNEKLTNPQVKEK TATACACAGATTTTAAGTTTACTCCTACTGCTGACCCAAGTGAAATTCCTTCTCCAGTCACAGTGTCAACCTCT- ACCCCC CAACTGCAACGAGAGTTTTGAGGGGCATCAATCACACCGAGAAGTCACAGCCCCTCAACCACTGAGGTGTGGGG- GGGTAG GGATCTGCATTTCTTCATATCAACCCCACACTATAGGGCACCTAAATGGGTGGGCGGTGGGGGAGACCGACTCA- CTTGAG TTTCTTGAAGGCTTCCTGGCCTCCAGCCACGTAATTGCCCCCGCTCTGGATCTGGTCTAGCTTCCGGATTCGGT- GGCCAG TCCGCGGGGTGTAGATGTTCCTGACGGCCCCAAAGGGTGCCTGAACGCCGCCGGTCACCTCCTTCAGGAAGACT- TCGAAG CTGGACACCTTCTTCTCATGGATGACGACGCGGCGCCCCGCGTAGAAGGGGTCCCCGTTGCGGTACACAAGCAC- GCTCTT CACGACGGGCTGAGACAGGTGGCTGGACCTGGCGCTGCTGCCGCTCATCTTCCCCGCTGGCCGCCGCCTCAGCT- CGCTGC TTCGCGTCGGGAGGCACCTCCGCTGTCCCAGCGGCCTCACCGCACCCAGGGCGCGGGATCGCCTCCTGAAACGA- ACGAGA AACTGACGAATCCACAGGTGAAAGAGAAGTAACGGCCGTGCGCCTAGGCGTCCACCCAGAGGAGACACTAGGAG- CTTGCA GGACTCGGAGTAGACGCTCAAGTTTTTCACCGTGGCGTGCACAGCCAATCAGGACCCGCAGTGCGCGCACCACA- CCAGGT TCACCTGCTACGGGCAGAATCAAGGTGGACAGCTTCTGAGCAGGAGCCGGAAACGCGCGGGGCCTTCAAACAGG- CACGCC TAGTGAGGGCAGGAGAGAGGAGGACGCACACACACACACACACACAAATATGGTGAAACCCAATTTCTTACATC- ATATCT GTGCTACCCTTTCCAAACAGCCTAATTTTTCTTTTCTCTCTTCTTGCACCTTTACCCCTCAATCTCCTGCTTCC- TCCCAA ATTAAAGCAATTAAGTTCCTGG SEQ. ID NO. 25 SEQ. ID NO. 71 CTCCTCCGAGCACTCGCTCACGGCGTCCCCTTGCCTGGAAAGATACCGCGGTCCCTCCAGAGGATTTGAGGGAC- AGGGTC MEPAAGSSMEPSADWLATAAA GGAGGGGGCTCTTCCGCCAGCACCGGAGGAAGAAAGAGGAGGGGCTGGCTGGTCACCAGAGGGTGGGGCGGACC- GCGTGC RGRVEEVRALLEAGALPNAPN GCTCGGCGGCTGCGGAGAGGGGGAGAGCAGGCAGCGGGCGGCGGGGAGCAGCATGGAGCCGGCGGCGGGGAGCA- GCATGG SYGRRPIQVMMMGSARVAELL AGCCTTCGGCTGACTGGCTGGCCACGGCCGCGGCCCGGGGTCGGGTAGAGGAGGTGCGGGCGCTGCTGGAGGCG- GGGGCG LLHGAEPNCADPATLTRPVHD CTGCCCAACGCACCGAATAGTTACGGTCGGAGGCCGATCCAGGTCATGATGATGGGCAGCGCCCGAGTGGCGGA- GCTGCT AAREGFLDTLVVLHRAGARLD GCTGCTCCACGGCGCGGAGCCCAACTGCGCCGACCCCGCCACTCTCACCCGACCCGTGCACGACGCTGCCCGGG- AGGGCT VRDAWGRLPVDLAEELGHRDV TCCTGGACACGCTGGTGGTGCTGCACCGGGCCGGGGCGCGGCTGGACGTGCGCGATGCCTGGGGCCGTCTGCCC- GTGGAC ARYLRAAAGGTRGSNHARIDA CTGGCTGAGGAGCTGGGCCATCGCGATGTCGCACGGTACCTGCGCGCGGCTGCGGGGGGCACCAGAGGCAGTAA- CCATGC AEGPSDIPD CCGCATAGATGCCGCGGAAGGTCCCTCAGACATCCCCGATTGAAAGAACCAGAGAGGCTCTGAGAAACCTCGGG- AAACTT AGATCATCAGTCACCGAAGGTCCTACAGGGCCACAACTGCCCCCGCCACAACCCACCCCGCTTTCGTAGTTTTC- ATTTAG AAAATAGAGCTTTTAAAAATGTCCTGCCTTTTAACGTAGATATATGCCTTCCCCCACTACCGTAAATGTCCATT- TATATC ATTTTTTATATATTCTTATAAAAATGTAAAAAAGAAAAACACCGCTTCTGCCTTTTCACTGTGTTGGAGTTTTC- TGGAGT GAGCACTCACGCCCTAAGCGCACATTCATGTGGGCATTTCTTGCGAGCCTCGCAGCCTCCGGAAGCTGTCGACT- TCATGA CAAGCATTTTGTGAACTAGGGAAGCTCAGGGGGGTTACTGGCTTCTCTTGAGTCACACTGCTAGCAAATGGCAG- AACCAA AGCTCAAATAAAAATAAAATAATTTTCATTCATTCACTCAAAA SEQ. ID NO. 26 SEQ. ID NO. 72 AGTGGACTCACGCAGGCGCAGGAGACTACACTTCCCAGGAACTCCGGGCCGCGTTGTTCGCTGGTACCTCCTTC- TGACTT MSQVKSSYSYDAPSDFINFSS CCGGTATTGCTGCGGTCTGTAGGGCCAATCGGGAGCCTGGAATTGCTTTCCCGGCGCTCTGATTGGTGCATTCG- ACTAGG LDDEGDTQNIDSWFEEKANLE CTGCCTGGGTTCAAAATTTCAACGATACTGAATGAGTCCCGCGGCGGGTTGGCTCGCGCTTCGTTGTCAGATCT- GAGGCG NKLLGKNGTGGLFQGKTPLRK AGGCTAGGTGAGCCGTGGGAAGAAAAGAGGGAGCAGCTAGGGCGCGGGTCTCCCTCCTCCCGGAGTTTGGAACG- GCTGAA ANLQQAIVTPLKPVDNTYYKE GTTCACCTTCCAGCCCCTAGCGCCGTTCGCGCCGCTAGGCCTGGCTTCTGAGGCGGTTGCGGTGCTCGGTCGCC- GCCTAG AEKENLVEQSIPSNACSSLEV GCGGGGCAGGGTGCGAGCAGGGGCTTCGGGCCACGCTTCTCTTGGCGACAGGATTTTGCTGTGAAGTCCGTCCG- GGAAAC EAAISRKTPAQPQRRSLRLSA GGAGGAAAAAAAGAGTTGCGGGAGGCTGTCGGCTAATAACGGTTCTTGATACATATTTGCCAGACTTCAAGATT- TCAGAA QKDLEQKEKHHVKMKAKRCAT AAGGGGTGAAAGAGAAGATTGCAACTTTGAGTCAGACCTGTAGGCCTGATAGACTGATTAAACCACAGAAGGTG- ACCTGC PVIIDEILPSKKMKVSNNKKK TGAGAAAAGTGGTACAAATACTGGGAAAAACCTGCTCTTCTGCGTTAAGTGGGAGACAATGTCACAAGTTAAAA- GCTCTT PEEEGSAHQDTAEKNASSPEK ATTCCTATGATGCCCCCTCGGATTTCATCAATTTTTCATCCTTGGATGATGAAGGAGATACTCAAAACATAGAT- TCATGG AKGRHTVPCMPPAKQKFLKST TTTGAGGAGAAGGCCAATTTGGAGAATAAGTTACTGGGGAAGAATGGAACTGGAGGGCTTTTTCAGGGCAAAAC- TCCTTT EEQELEKSMKMQQEVVEMRKK GAGAAAGGCTAATCTTCAGCAAGCTATTGTCACACCTTTGAAACCAGTTGACAACACTTACTACAAAGAGGCAG- AAAAAG NEEFKKLALAGIGQPVKKSVS AAAATCTTGTGGAACAATCCATTCCGTCAAATGCTTGTTCTTCCCTGGAAGTTGAGGCAGCCATATCAAGAAAA- ACTCCA QVTKSVDFHFRTDERIKQHPK GCCCAGCCTCAGAGAAGATCTCTTAGGCTTTCTGCTCAGAAGGATTTGGAACAGAAAGAAAAGCATCATGTAAA- AATGAA NQEEYKEVNFTSELRKHPSSP AGCCAAGAGATGTGCCACTCCTGTAATCATCGATGAAATTCTACCCTCTAAGAAAATGAAAGTTTCTAACAACA- AAAAGA ARVTKGCTIVKPFNLSQGKKR AGCCAGAGGAAGAAGGCAGTGCTCATCAAGATACTGCTGAAAAGAATGCATCTTCCCCAGAGAAAGCCAAGGGT- AGACAT TFDETVSTYVPLAQQVEDFHK ACTGTGCCTTGTATGCCACCTGCAAAGCAGAAGTTTCTAAAAAGTACTGAGGAGCAAGAGCTGGAGAAGAGTAT- GAAAAT RTPNRYHLRSKKDDINLLPSK GCAGCAAGAGGTGGTGGAGATGCGGAAAAAGAATGAAGAATTCAAGAAACTTGCTCTGGCTGGAATAGGGCAAC- CTGTGA SSVTKICRDPQTPVLQTKHRA AGAAATCAGTGAGCCAGGTCACCAAATCAGTTGACTTCCACTTCCGCACAGATGAGCGAATCAAACAACATCCT- AAGAAC RAVTCKSTAELEAEELEKLQQ CAGGAGGAATATAAGGAAGTGAACTTTACATCTGAACTACGAAAGCATCCTTCATCTCCTGCCCGAGTGACTAA- GGGATG YKFKARELDPRILEGGPILPK TACCATTGTTAAGCCTTTCAACCTGTCCCAAGGAAAGAAAAGAACATTTGATGAAACAGTTTCTACATATGTGC- CCCTTG KPPVKPPTEPIGFDLEIEKRI CACAGCAAGTTGAAGACTTCCATAAACGAACCCCTAACAGATATCATTTGAGGAGCAAGAAGGATGATATTAAC- CTGTTA QERESKKKTEDEHFEFHSRPC CCCTCCAAATCTTCTGTGACCAAGATTTGCAGAGACCCACAGACTCCTGTACTGCAAACCAAACACCGTGCACG- GGCTGT PTKILEDVVGVPEKKVLPITV GACCTGCAAAAGTACAGCAGAGCTGGAGGCTGAGGAGCTCGAGAAATTGCAACAATACAAATTCAAAGCACGTG-

AACTTG PKSPAFALKNRIRMPTKEDEE ATCCCAGAATACTTGAAGGTGGGCCCATCTTGCCCAAGAAACCACCTGTGAAACCACCCACCGAGCCTATTGGC- TTTGAT EDEPVVIKAQPVPHYGVPFKP TTGGAAATTGAGAAAAGAATCCAGGAGCGAGAATCAAAGAAGAAAACAGAGGATGAACACTTTGAATTTCATTC- CAGACC QIPEARTVEICPFSFDSRDKE TTGCCCTACTAAGATTTTGGAAGATGTTGTGGGTGTTCCTGAAAAGAAGGTACTTCCAATCACCGTCCCCAAGT- CACCAG RQLQKEKKIKELQKGEVPKFK CCTTTGCATTGAAGAACAGAATTCGAATGCCCACCAAAGAAGATGAGGAAGAGGACGAACCGGTAGTGATAAAA- GCTCAA ALPLPHFDTINLPEKKVKNVT CCTGTGCCACATTATGGGGTGCCTTTTAAGCCCCAAATCCCAGAGGCAAGAACTGTGGAAATATGCCCTTTCTC- GTTTGA QIEPFCLETDRRGALKAQTWK TTCTCGAGACAAAGAACGTCAGTTACAGAAGGAGAAGAAAATAAAAGAACTGCAGAAAGGGGAGGTGCCCAAGT- TCAAGG HQLEEELRQQKEAACFKARPN CACTTCCCTTGCCTCATTTTGACACCATTAACCTGCCAGAGAAGAAGGTAAAGAATGTGACCCAGATTGAACCT- TTCTGC TVISQEPFVPKKEKKSVAEGL TTGGAGACTGACAGAAGAGGTGCTCTGAAGGCACAGACTTGGAAGCACCAGCTGGAAGAAGAACTGAGACAGCA- GAAAGA SGSLVQEPFQLATEKRAKERQ AGCAGCTTGTTTCAAGGCTCGTCCAAACACCGTCATCTCTCAGGAGCCCTTTGTTCCCAAGAAAGAGAAGAAAT- CAGTTG ELEKRMAEVEAQKAQQLEEAR CTGAGGGCCTTTCTGGTTCTCTAGTTCAGGAACCTTTTCAGCTGGCTACTGAGAAGAGAGCCAAAGAGCGGCAG- GAGCTG LQEEEQKKEELARLRRELVHK GAGAAGAGAATGGCTGAGGTAGAAGCCCAGAAAGCCCAGCAGTTGGAGGAGGCCAGACTACAGGAGGAAGAGCA- GAAAAA ANPIRKYQGLEIKSSDQPLTV AGAGGAGCTGGCCAGGCTACGGAGAGAACTGGTGCATAAGGCAAATCCAATACGCAAGTACCAGGGTCTGGAGA- TAAAGT PVSPKFSTRFHC CAAGTGACCAGCCTCTGACTGTGCCTGTATCTCCCAAATTCTCCACTCGATTCCACTGCTAAACTCAGCTGTGA- GCTGCG GATACCGCCCGGCAATGGGACCTGCTCTTAACCTCAAACCTAGGACCGTCTTGCTTTGTCATTGGGCATGGAGA- GAACCC ATTTCTCCAGACTTTTACCTACCCGTGCCTGAGAAAGCATACTTGACAACTGTGGACTCCAGTTTTGTTGAGAA- TTGTTT TCTTACATTACTAAGGCTAATAATGAGATGTAACTCATGAATGTCTCGATTAGACTCCATGTAGTTACTTCCTT- TAAACC ATCAGCCGGCCTTTTATATGGGTCTTCACTCTGACTAGAATTTAGTCTCTGTGTCAGCACAGTGTAATCTCTAT- TGCTAT TGCCCCTTACGACTCTCACCCTCTCCCCACTTTTTTTAAAAATTTTAACCAGAAAATAAAGATAGTTAAATCCT- AAGATA GAGATTAAGTCATGGTTTAAATGAGGAACAATCAGTAAATCAGATTCTGTCCTCTTCTCTGCATACCGTGAATT- TATAGT TAAGGATCCCTTTGCTGTGAGGGTAGAAAACCTCACCAACTGCACCAGTGAGGAAGAAGACTGCGTGGATTCAT- GGGGAG CCTCACAGCAGCCACGCAGCAGGCTCTGGGTGGGGCTGCCGTTAAGGCACGTTCTTTCCTTACTGGTGCTGATA- ACAACA GGGAACCGTGCAGTGTGCATTTTAAGACCTGGCCTGGAATAAATACGTTTTGTCTTTCCCTCAAAAAAAAAAAA- AAAAAA AAAAA SEQ. ID NO. 27 SEQ. ID NO. 73 AAACGCGGGCGGGCGGGCCCGCAGTCCTGCAGTTGCAGTCGTGTTCTCCGAGTTCCTGTCTCTCTGCCAACGCC- GCCCGG MASQNRDPAATSVAAARKGAE ATGGCTTCCCAAAACCGCGACCCAGCCGCCACTAGCGTCGCCGCCGCCCGTAAAGGAGCTGAGCCGAGCGGGGG- CGCCGC PSGGAARGPVGKRLQQELMTL CCGGGGTCCGGTGGGCAAAAGGCTACAGCAGGAGCTGATGACCCTCATGATGTCTGGCGATAAAGGGATTTCTG- CCTTCC MMSGDKGISAFPESDNLFKWV CTGAATCAGACAACCTTTTCAAATGGGTAGGGACCATCCATGGAGCAGCTGGAACAGTATATGAAGACCTGAGG- TATAAG GTIHGAAGTVYEDLRYKLSLE CTCTCGCTAGAGTTCCCCAGTGGCTACCCTTACAATGCGCCCACAGTGAAGTTCCTCACGCCCTGCTATCACCC- CAACGT FPSGYPYNAPTVKFLTPCYHP GGACACCCAGGGTAACATATGCCTGGACATCCTGAAGGAAAAGTGGTCTGCCCTGTATGATGTCAGGACCATTC- TGCTCT NVDTQGNICLDILKEKWSALY CCATCCAGAGCCTTCTAGGAGAACCCAACATTGATAGTCCCTTGAACACACATGCTGCCGAGCTCTGGAAAAAC- CCCACA DVRTILLSIQSLLGEPNIDSP GCTTTTAAGAAGTACCTGCAAGAAACCTACTCAAAGCAGGTCACCAGCCAGGAGCCCTGACCCAGGCTGCCCAG- CCTGTC LNTHAAELWKNPTAFKKYLQE CTTGTGTCGTCTTTTTAATTTTTCCTTAGATGGTCTGTCCTTTTTGTGATTTCTGTATAGGACTCTTTATCTTG- AGCTGT TYSKQVTSQEP GGTATTTTTGTTTTGTTTTTGTCTTTTAAATTAAGCCTCGGTTGAGCCCTTGTATATTAAATAAATGCATTTTT- GTCCTT TTTTAGACAAAAAAAAAAAAAAA SEQ. ID NO. 28 CAGCTAAATTTTAAAGGTGTTTTTGTAGAGATGAGGTTTCACTATATTGCCCAGGCTGGTCTCGAACTCCTGGA- CTTAAG TGATCCTTCCTCTTTGGCCTCCCAAAGTGCTGGGATTACAGGCATGAGCCACTGCCCCAGCCAAGACTGTCTTT- TCTCCA TTGTATTGCGTTTGCTTCCTTGTCAAAGATCAGTTGACTATATTTGTGTGGGGCTATTTCTGGGCTCCCTATTT- GTTTCC AGTGATTATGTCTATTTTTTCACCATTACCACCCTATCTTAATTACTGTAGCTTTATAGTGAGTCTTAAAGTTG- GGTAAT ATCAGTCTTCTGACCTTTTTCTCTTTCAATATTGTGCCAGCTATTCTGGGTCTTTTGCCTTTCCATGTAAACTT- TAGAAC CAGTTTGTCAGGATCCACAAAATACTTTGCTGGGTTTTGATTGGGATTGCATTGAATCCACAGGTCAAGTTGGC- AAAAAC TGACATACAGCAATGCCAGTTTATTGTTTTGTGATAGCCTTAATCCAGCTAGTTTCTTCACAGGATGATGTTGA- AAATAT GGGATGCTCATAATCCCTGAATATTTTTTATGTGGATAATTAAACTTGTTCTGGGTGGATGGTTGGATAGCCAG- AATAGT AATAACCTCTCTTCCAGCCACTCAAAGAAAATGATATAAACGTAGGGTTGGTTTAATTGTTGAGAGGTCACGTT- TTTTCC ATTCTTGCTCTCAGGTAAGGAAAGAGCACTGTTGGTTCACGCATTCCTTTTTCCCTCATACACTTTGTTGGGCA- CTGATA TGGTTTGGCTCTGTGTTCCCACCCAAATCTCATGTTGAATTGTGATCCTGAGTGTTGGAGGTGGGGCCTCGCGG- GAGACG ACTGGATCATGGGGGCGGATTTTCCCCTTGCTGTTCTCATGATAGTGAGTTCTCATGAGATCTGGTTGTTTAAA- AGTGTA TAGCACTTCCTGCTTCACTCTCTCCCACTCCACCATGTGAAGAAGGTGCCTTTGCCCTTCCGCCACGACTGTGT- TTCCTG AGGCCTCCCCAGCCATGCCTCCTGTACAGCCTGCGGAACTGTCAGTTAAACCTCTTTTCTTCATTAATTACCCA- CTCTCA GGTGGTTTTTTATGGCAGTGTGAGAACGGACTAATACAGAAAATTGGTACCAGAGAAGTGGGATATTGCTATAA- AATACC TGAAAATGTGGAAGTGACTTTGGAACTGGGTAATGGGCAGAGGTTGGAACAGTTTGGAGGGCTCAGAAGAAGAC- AGGAAG ATGAGGGAAAGTTTGCAGCTTCCTAGAGACTTGTTGAATGGTTGTGACCAAAGTGCTGATAGTGATATGGACAG- TGAAGT CCAGGCTGAGTTGGTCTCAGATGGGAGATGAGAATCTTATTCCGAACTGGAGTGAAGGTCACTCTTGGCTGTGC- TTTAGC AAAGAGAGTGGTGGCATTGTGCCCCTGCTCTAGAGATCTGTGAACTCTGAACTCGAGAGGGTATCTGGCAGAAA- AAAATT TCTAAGCAGCAAAGTGTTCAAGATGTGGCCTGATTGCTTCTAAAAGCCTATGCTCATTTGCATGAACAAAGTGG- AACTTA TATTTAAAACAGAAGCTGAGCTTTTATAAAAGTTTGGAGAATTTGCAGCCCAACCATGTGGTGAAAAAGAAAAA- TCCATT TTCTGGGGAGGTATTCAAGGCTGCAGAAATTTGCATAAGAAGAGCCTCATGTTAACAGCCAAGAGAGTGAGGAA- AATGCC TCTAGAGCATTTCAGAGACCTTCACAGCAGCTCCTCCCATCACAGGCATGGAAGCCCAGGAGGAAGAAATGCTT- TTGTGG GCCAGCCCAGGGCCCCACTGTTCTGTGCAGCCTTGGGACATGGTGCCCTGCATCCCAGCCACTCCAGCTCCAGC- TGTGAC TAAAAGGGGCCAAGGTACAGCTTGGGCTGCTGCTTCAGAGGGTGCAAGCCCCAAGCCTTGGTGGCTTCCATGTG- GTGTTA GGCAGGTGTGCAGAAGAGTTGAGGTTTAGGAACCTCTACCTAGATTTCAGAGGATGTATGGAAATGCCCGGATG- TCCAGG CAGAAGTTTGCTGCAGAGGCAGAGCCCTCATAGATAACCTCTGCGAGGGCAGTGTGGAGGGGAAATGTGGGGTT- GGAGCT ATGAGAAGAGGGCCACCATCCACCAGACCCCAGAATTGTAGATCCACTGACAGCTTGCACTATGCACCTGTAAA- AGTTGC AGGCAGTTAATGCTAGCCTGTGAAAGCAGCTGTGGGGACTATATGCAGAGCCACAGAGGCAGAGCTGCCCAGAG- CCTTGG GAGCCCACTCCTTGTGTCAGTGTGGCCTGGATGTGAGACGTGGAGTCAAAGATCATTTTGGAGGTTTGAGATTT- AATGAC TGCCCTCCTGGATTTTGGACTTGCATGGGGCCCATAGCCCCTTTGTTTTGGCTGATTTCTCCTATTTGGAATGG- GAGCAT TTACCCAATGCCTGTATCCCCATTGTATCTTGGAGATAACTGACTTGTTTTTGATTTTACAGGCTCACAGGAGG- AAGGGA CTTGGCTGGTCTCAGATGAGACTTGACTTGGACATTTGAGTTAATGCTGGAATGAGTTAAGACTTTAGGGGGCT- ATTGGG AAGGCATGATTGTGTTTTGAAATGTGAGGACATGAGATTTGGGAGGGGCCAGGGTGGAATGATATGGTTTGGCT- GTGTCC CCCCACCCAAATCTCATGTTGAATTGTGATCCTGAGTCTTGGAGGTAGAGCCTGGTGGGAGGTGATTGGATCAT- GGGGGC AGATTTCCCCCTTGCTGTTCTCATGACAGTGAGTTCTCATGAGATCTGGTTAAGTGTGTAGCACTTCCCCCTTT- GCTTGC TCTCTCCCTCTGCCATGTGAAGAAGGTGCTTGCTTTCCCTTCGCCCTTCTGCCATGACTGTAAGTTTCTTGAGG- CCTCGC AGCCATGCTTCCTGTACAGCCTGCAGAACTGTGAGTTAATTAAACCTCTTTTCTTCAT SEQ. ID NO. 29 SEQ. ID NO. 74 AGCTTTGGGGTTGTCCCTGGACTTGTCTTGGTTCCAGAACCTGACGACCCGGCGACGGCGACGTCTCTTTTGAC- TAAAAG MPNFSGNWKIIRSENFEELLK ACAGTGTCCAGTGCTCCAGCCTAGGAGTCTACGGGGACCGCCTCCCGCGCCGCCACCATGCCCAACTTCTCTGG- CAACTG VLGVNVMLRKIAVAAASKPAV GAAAATCATCCGATCGGAAAACTTCGAGGAATTGCTCAAAGTGCTGGGGGTGAATGTGATGCTGAGGAAGATTG- CTGTGG EIKQEGDTFYIKTSTTVRTTE CTGCAGCGTCCAAGCCAGCAGTGGAGATCAAACAGGAGGGAGACACTTTCTACATCAAAACCTCCACCACCGTG- CGCACC INFKVGEEFEEQTVDGRPCKS ACAGAGATTAACTTCAAGGTTGGGGAGGAGTTTGAGGAGCAGACTGTGGATGGGAGGCCCTGTAAGAGCCTGGT- GAAATG LVKWESENKMVCEQKLLKGEG GGAGAGTGAGAATAAAATGGTCTGTGAGCAGAAGCTCCTGAAGGGAGAGGGCCCCAAGACCTCGTGGACCAGAG- AACTGA PKTSWTRELTNDGELILTMTA CCAACGATGGGGAACTGATCCTGACCATGACGGCGGATGACGTTGTGTGCACCAGGGTCTACGTCCGAGAGTGA- GTGGCC DDVVCTRVYVRE ACAGGTAGAACCGCGGCCGAAGCCCACCACTGGCCATGCTCACCGCCCTGCTTCACTGCCCCCTCCGTCCCACC- CCCTCC TTCTAGGATAGCGCTCCCCTTACCCCAGTCACTTCTGGGGGTCACTGGGATGCCTCTTGCAGGGTCTTGCTTTC- TTTGAC CTCTTCTCTCCTCCCCTACACCAACAAAGAGGAATGGCTGCAAGAGCCCAGATCACCCATTCCGGGTTCACTCC- CCGCCT CCCCAAGTCAGCAGTCCTAGCCCCAAACCAGCCCAGAGCAGGGTCTCTCTAAAGGGGACTTGAGGGCCTGAGCA- GGAAAG ACTGGCCCTCTAGCTTCTACCCTTTGTCCCTGTAGCCTATACAGTTTAGAATATTTATTTGTTAATTTTATTAA- AATGCT TTAAAAAAA SEQ. ID NO. 30 SEQ. ID NO. 75 CTCGCTTTTCGGTTGCCGTTGTCTTTTTTCCTTGACTCGGAAATGTCCGGTCGTGGTAAGCAGGGTGGCAAGGC- GCGCGC MSGRGKQGGKARAKAKSRSS CAAGGCTAAGTCGCGCTCGTCGCGCGCGGGGCTGCAGTTCCCCGTGGGCCGCGTGCACCGGTTGCTCCGCAAGG- GCAACT RAGLQFPVGRVHRLLRKGNY ATTCGGAGCGCGTGGGCGCCGGCGCCCCGGTCTATCTGGCCGCGGTGCTCGAGTACTTGACTGCCGAGATCCTG- GAGCTT SERVGAGAPVYLAAVLEYLT GCCGGCAACGCGGCGCGCGACAACAAGAAGACGCGCATCATCCCGCGCCACCTGCAGCTGGCCATCCGCAACGA- CGAGGA AEILELAGNAARDNKKTRII GCTCAACAAGCTGCTGGGCCGCGTGACCATCGCGCAGGGTGGCGTCCTGCCCAACATCCAGGCCGTACTGCTGC- CCAAGA PRHLQLAIRNDEELNKLLGR AGACGGAGAGCCACCACAAGGCCAAGGGCAAGTGAGGCCGCCCGCCGCCCCCGGGGCCCCTTTGATGGACATAA- AGGCTC VTIAQGGVLPNIQAVLLPKK TTTTCAGAGC TESHHKAKGK CACCTA SEQ. ID NO. 31 SEQ. ID NO. 76 ATGTCTGGCCGTGGTAAAGGTGGAAAAGGTTTGGGTAAGGGAGGAGCTAAGCGTCATCGCAAGGTTTTGCGCGA- TAACAT MSGRGKGGKGLGKGGAKRHR CCAGGGCATCACTAAGCCAGCTATCCGGCGCCTTGCTCGTCGCGGCGGTGTCAAGCGAATTTCTGGCCTTATCT- ATGAGG KVLRDNIQGITKPAIRRLAR AGACTCGTGGTGTTCTGAAGGTGTTCCTGGAGAACGTGATTCGTGACGCTGTCACTTACACAGAGCACGCCAAA- CGCAAG RGGVKRISGLIYEETRGVLK ACCGTGACAGCAATGGATGTGGTCTACGCGCTGAAGCGACAGGGACGCACTCTTTACGGCTTCGGTGGCTAAGG- CTCCTG VFLENVIRDAVTYTEHAKRK CTTGCTGCACTCTTATTTTCATTTTCAACCAAAGGCCCTTTTCAGGGCCGCCCA TVTAMDVVYALKRQGRTLYG FGG SEQ. ID NO. 32 SEQ. ID NO. 77 GCCTCCACAGATATCAAAAGAAACCTGAAGAGCCTACAAAAAAAAAAGAGATAAAGACAAAATTCAAGAAAACA- CACACA MLFEQGQQALELPECTMQKA TACATAATTGTGGTCACCTGGAGCCTGGGGGCCGGCCCAGCTCTCTCAGGATTCAGCAGACATTGGAGGTGGCA- GTGAAG AYYENPGLFGGYGYSKTTDT GATACAGTGGTAGTCAATGTTATTTGAGCAGGGTCAGCAGGCCCTGGAGCTTCCTGAGTGCACAATGCAGAAGG- CTGCTT YGYSTPHQPYPPPAAASSLD ACTATGAAAACCCAGGACTGTTTGGAGGCTATGGCTACAGCAAAACTACGGACACTTACGGCTACAGCACCCCC- CACCAG TDYPGSACSIQSSAPLRAPA CCCTACCCACCCCCTGCTGCTGCCAGCTCCCTGGACACTGACTATCCAGGTTCTGCCTGCTCCATCCAGAGCTC- TGCCCC HKGAELNGSCMRPGTGNSQG TCTGAGAGCCCCAGCCCACAAAGGAGCTGAACTCAATGGCAGCTGCATGCGGCCGGGCACTGGGAACAGCCAGG- GTGGGG GGGGSQPPGLNSEQQPPQPP GTGGTGGCAGCCAGCCTCCTGGTCTGAACTCAGAGCAGCAGCCACCACAACCCCCTCCTCCACCACCGACCCTG- CCCCCA PPPPTLPPSSPTNPGGGVPA TCTTCACCCACCAATCCTGGAGGTGGAGTGCCTGCCAAGAAGCCCAAAGGTGGGCCCAATGCTTCTAGCTCCTC- AGCCAC KKPKGGPNASSSSATISKQI CATCAGCAAGCAGATCTTCCCCTGGATGAAAGAGTCTCGACAGAACTCCAAGCAGAAGAACAGCTGTGCCACTG- CAGGAG FPWMKESRQNSKQKNSCATA AGAGCTGCGAGGACAAGAGCCCGCCAGGCCCAGCATCCAAGCGGGTACGCACGGCATACACGAGCGCGCAGCTG- GTGGAA GESCEDKSPPGPASKRVRTA TTGGAAAAGGAATTCCACTTCAACCGCTACTTGTGCCGGCCGCGCCGCGTGGAGATGGCCAACCTGCTGAATCT- CACGGA YTSAQLVELEKEFHFNRYLC ACGCCAGATCAAGATCTGGTTCCAGAACCGGCGCATGAAGTACAAGAAGGACCAGAAGGCCAAGGGCATCCTGC- ACTCGC RPRRVEMANLLNLTERQIKI CGGCTAGCCAGTCCCCTGAGCGCAGCCCACCGCTCGGCGGCGCCGCTGGCCACGTGGCCTACTCCGGCCAGCTG- CCGCCA WFQNRRMKYKKDQKAKGILH GTGCCCGGCCTGGCCTACGACGCGCCCTCGCCGCCTGCTTTCGCCAAATCACAGCCCAATATGTACGGCCTGGC- CGCCTA SPASQSPERSPPLGGAAGHV CACGGCGCCACTCAGCAGCTGCCTGCCACAACAGAAGCGCTACGCAGCGCCGGAGTTCGAGCCCCATCCCATGG- CGAGCA AYSGQLPPVPGLAYDAPSPP ACGGCGGCGGCTTCGCCAGCGCCAACTTGCAGGGCAGCCCGGTGTACGTGGGCGGCAACTTCGTCGAGTCCATG- GCGCCC AFAKSQPNMYGLAAYTAPLS GCGTCCGGGCCTGTCTTCAACCTGGGCCACCTCTCGCACCCGTCGTCGGCCAGCGTGGACTACAGTTGCGCCGC- GCAGAT SCLPQQKRYAAPEFEPHPMA TCCAGGCAACCACCACCATGGACCTTGCGACCCTCATCCCACCTACACAGATCTCTCGGCCCACCACTCGTCTC- AGGGAC SNGGGFASANLQGSPVYVGG GACTGCCGGAGGCTCCCAAACTGACGCATCTGTAGCGGCCGCCGCCAGCCCGAACTCGCGGCAAAATTACCTCT- CTTGCT NFVESMAPASGPVFNLGHLS GTAGTGGTGGGGTAGAGGGTGGGGCCCGCGGGGCAGTTCGGGAACCCCCTTCCCCGCTCTTGCCCTGCCGCCGC- CTCCCG HPSSASVDYSCAAQIPGNHH GGTCTCAGGCCTCCAGCGGCGGAGGCGCAGGCGACCGGGCCTCCCCTCCATGGGCGTCCTTTGGGTGACTCGCC- ATAAAT HGPCDPHPTYTDLSAHHSSQ CAGCCGCAAGGATCCTTCCCTGTAAATTTGACAGTGCCACATACTGCGGACCAAGGGACTCCAATCTGGTAATG- GTGTCC GRLPEAPKLTHL CAAAGGTAAGTCTGAGACCCATCAGCGGCGCGCCCTGCAGAGGGACCAGAGCTTGGAGAGTCTTGGGCCTGGCC- CGCGTC TAGCTTAGTTTCAGAGACCTTAATTTATATTCTCCTTCCTGTGCCGTAAGGATTGCATCGGACTAAACTATCTG-

TATTTA TTATTTGAAGCGAGTCATTTCGTTCCCTGATTATTTATCCTTGTCTGAATGTATTTATGTGTATATTTGTAGAT- TTATCC AGCCGAGCTTAGGAATTCGCTTCCAGGCCGTGGGGGCCACATTTCACCTCCTTAGTCCCCCTGGTCTGAACTAG- TTGAGA GAGTAGTTTTGAACAGTCGTAACCGTGGCTGGTGTTTGTAGTTGACATAAAGGATTAAGACCGCAAATTGTCCT- TCATGG GTAGAGTCAGGAAGCCCGGTGGCGTGGCACAACACACTTTGGTCATTTCTCAAAAACCACAGTCCTCACCACAG- TTTATT GATTTCAAATTGTCTGGTACTATTGGAACAAATATTTAGAATAAAAAAATTTCCCAGTCAAAAAAAAAAAAAAA- AAAAA SEQ. ID NO. 33 SEQ. ID NO. 78 CCAGCCCTGAGATTCCCAGGTGTTTCCATTCGGTGATCAGCACTGAACACAGAACTCACCATGGAGTTTGGACT- GAGCTG MEFGLSWVFLVAILKGVQCE GGTTTTCCTTGTTGCTATTTTAAAAGGTGTCCAGTGTGAAGTGCAGCTGGTGGAGTCTGGGGGAGTCGTGGTAC- AGCCTG VQLVESGGVVVQPGGSLRLS GGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTTGATGACTATGCCATGCACTGGGTCCGTCAA- GCTCCG CAASGFTFDDYAMHWVRQAP GGGAAGGGTCTGGAGTGGGTCTCCCTTATTAGTTGGGATGGTGGTAGCACCTACTATGCAGACTCTGTGAAGGG- TCGATT GKGLEWVSLISWDGGSTYYA CACCATCTCCAGAGACAATAGTAAAAATTCCTTGTATCTGCAAATGAACAGTCTGAGAGCTGAGGACACCGCCT- TGTATT DSVKGRFTISRDNSKNSLYL ACTGTGCAACCCGGGGGGGTTATTCCACCGCCGGCTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCC- TCAGCC QMNSLRAEDTALYYCATRGG TCCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGG- CTGCCT YSTAGFDYWGQGTLVTVSSA GGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCT- TCCCGG STKGPSVFPLAPSSKSTSGG CTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAG- ACCTAC TAALGCLVKDYFPEPVTVSW ATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATCTTGTGACAAAAC- TCACAC NSGALTSGVHTFPAVLQSSG ATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACA- CCCTCA LYSLSSVVTVPSSSLGTQTY TGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAAC- TGGTAC ICNVNHKPSNTKVDKKVEPK GTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGT- CAGCGT SCDKTHTCPPCPAPELLGGP CCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAG- CCCCCA SVFLFPPKPKDTLMISRTPE TCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGAT- GAGCTG VTCVVVDVSHEDPEVKFNWY ACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAG- CAATGG VDGVEVHNAKTKPREEQYNS GCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGC- TCACCG TYRVVSVLTVLHQDWLNGKE TGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTAC- ACGCAG YKCKVSNKALPAPIEKTISK AAGAGCCTCTCCCTGTCTCCGGGTAAATGAGTGCGACGGCCGGCAAGCCCCCGCTCCCCGGGCTCTCGCGGTCG- CACGAG AKGQPREPQVYTLPPSRDEL GATGCTTGGCACGTACCCCGTGTACATACTTCCCGGGCGCCCAGCATGGAAATAAAGCACCCAGCGCTGCCCTG- GGCCCC TKNQVSLTCLVKGFYPSDIA TGCGAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA- AAAAAA VEWESNGQPENNYKTTPPVL AAAAAAAAAAAAAAAAAAAAAA DSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQ KSLSLSPGK SEQ. ID NO. 34 SEQ. ID NO. 79 GAGGGAACCATGGAAACCCCAGCGCAGCTTCTCTTCCTCCTGCTACTCTGGCTCCCAGATATCACCGGAGAAAT- TGTGTT METPAQLLFLLLLWLPDITG GACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGAGAAAGAGCCGCCCTCTCATGCAGGGCCAGTCAGAGTG- TTAACA EIVLTQSPGTLSLSPGERAA GCAAGTACTTAGCCTGGTACCAGCAGAAGCCTGGCCAGGCTCCCAGGCTCCTCATGTATGCTGCATCCATCAGG- GCCACT LSCRASQSVNSKYLAWYQQK GGCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAATCTGA- GGACTT PGQAPRLLMYAASIRATGIP TGCACTGTATTTCTGTCAGCAATATGGTACTTCACCTCTCACTTTCGGCGGAGGGACCAAGGTGGAGATCAAAC- GAACTG DRFSGSGSGTDFTLTISRLE TGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGC- CTGCTG SEDFALYFCQQYGTSPLTFG AATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGA- GAGTGT GGTKVEIKRTVAAPSVFIFP CACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGA- AACACA PSDEQLKSGTASVVCLLNNF AAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT- TAGAGG YPREAKVQWKVDNALQSGNS GAGAAGTGCCCCCACCTGCTCCTCAGTTCCAGCCTGACCCCCTCCCATCCTTTGGCCTCTGACCCTTTTTCCAC- AGGGGA QESVTEQDSKDSTYSLSSTL CCTACCCCTATTGCGGTCCTCCAGCTCATCTTTCACCTCACCCCCCTCCTCCTCCTTGGCTTTAATTATGCTAA- TGTTGG TLSKADYEKHKVYACEVTHQ AGGAGAATGAATAAATAAAGTGAATCTTTGCACCTAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA- AAAAAA GLSSPVTKSFNRGEC AAAAAAAAAAAAAAA SEQ. ID NO. 35 SEQ. ID NO. 80 ACGCGGGGGGCCCGCTCTCGGCGAGCCCGAGCCGCCGCCGGCCCCGCGGCGGAGATGAGCAGGTCCGCGACGCT- GCTGCT MSRSATLLLCLLGCHVWKAV GTGCCTGCTGGGCTGCCACGTCTGGAAGGCGGTGACCAAGACGCTGCGGGAGCCCGGCGCCGGAGCCCAAGAGG- TGACGT TKTLREPGAGAQEVTLKVHIS TAAAGGTGCACATCAGCGACGCCAGCACCCACCAGCCCGTAGCAGATGCGCTCATCGAGATCTTCACCAACCAG- GCCTCC DASTHQPVADALIEIFTNQAS ATAGCCTCTGGCACCTCGGGGACTGATGGCGTCGCCTTTATCAAGTTCCAGTATAAGCTGGGCAGTCAGTTGAT- TGTCAC IASGTSGTDGVAFIKFQYKLG CGCCTCGAAGCATGCCTACGTGCCAAACTCTGCCCCATGGAAGCCAATCCGGTTACCTGTATTTTCCTCTCTGA- GCCTTG SQLIVTASKHAYVPNSAPWKP GCCTGCTTCCAGAACGCTCTGCCACTCTAATGGTATATGAAGATGTCGTCCAAATAGTATCAGGATTCCAAGGT- GCCCGG IRLPVFSSLSLGLLPERSATL CCACAGCCTCGCGTTCATTTCCAGAGAAGGGCTCTGAGGTTGCCTGAGAACACCAGCTACAGTGACCTGACCGC- GTTTCT MVYEDVVQIVSGFQGARPQPR CACGGCCGCCAGCTCCCCTTCGGAGGTGGACAGTTTTCCTTATTTGCGAGGATTAGACGGAAATGGAACAGGAA- ACAGCA VHFQRRALRLPENTSYSDLTA CCAGGCATGACCTGACCCCAGTCACAGCCGTCAGCGTCCACTTGCTGAGCAGTAATGGAACGCCGGTGCTGGTG- GATGGT FLTAASSPSEVDSFPYLRGLD CCCATCTATGTCACTGTGCCCCTGGCCACGCAGAGCAGCCTGAGGCACAATGCCTATGTCGCGGCGTGGCGGTT- TGACCA GNGTGNSTRHDLTPVTAVSVH GAAGCTGGGAACGTGGCTGAAGAGCGGTCTGGGTCTTGTGCACCAGGAAGGCAGCCAGCTGACGTGGACATACA- TTGCCC LLSSNGTPVLVDGPIYVTVPL CCCAGTTGGGGTACTGGGTGGCCGCCATGTCCCCTCCCATCCCAGGTCCCGTTGTAACACAGGACATTACCACG- TATCAC ATQSSLRHNAYVAAWRFDQKL ACGGTGTTTCTTTTGGCCATTTTAGGAGGAATGGCTTTCATACTTTTGGTTTTGCTGTGTCTCCTTTTATATTA- TTGCAG GTWLKSGLGLVHQEGSQLTWT GAGGAAGTGCTTGAAACCTCGTCAGCACCACAGAAAACTGCAGCTCCCTGCAGGACTGGAGAGTTCCAAAAGAG- ACCAGT YIAPQLGYWVAAMSPPIPGPV CCACGTCCATGTCACACATTAACTTGCTGTTTTCACGCCGAGCGTCAGAATTCCCTGGCCCGCTGTCCGTCACC- AGCCAC VTQDITTYHTVFLLAILGGMA GGCCGCCCCGAGGCCCCCGGCACGAAGGAACTGATGAGTGGAGTCCATTTGGAAATGATGTCTCCGGGCGGCGA- AGGGGA FILLVLLCLLLYYCRRKCLKP CCTGCACACCCCCATGCTCAAGCTCTCCTACAGCACCTCCCAGGAATTTAGCTCCCGGGAGGAGCTCCTCTCTT- GCAAGG RQHHRKLQLPAGLESSKRDQS AAGAGGATAAAAGCCAGATCTCCTTTGATAACCTCACTCCAAGTGGGACGCTGGGGAAAGACTACCATAAGTCA- GTGGAG TSMSHINLLFSRRASEFPGPL GTTTTTCCCTTAAAGGCAAGAAAATCTATGGAAAGAGAAGGCTACGAGTCCTCGGGCAATGATGACTACAGGGG- TAGTTA SVTSHGRPEAPGTKELMSGVH CAACACCGTGCTCTCACAGCCTTTATTTGAAAAGCAGGACAGAGAAGGTCCAGCCTCCACGGGAAGCAAACTCA- CCATTC LEMMSPGGEGDLHTPMLKLSY AGGAACATCTGTACCCCGCGCCTTCATCACCTGAGAAAGAACAGCTGCTGGACCGCAGACCCACTGAATGTATG- ATGTCG STSQEFSSREELLSCKEEDKS CGATCAGTAGATCACCTCGAGAGACCTACGTCCTTCCCACGGCCCGGCCAGTTAATCTGCTGCAGTTCTGTCGA- CCAGGT QISFDNLTPSGTLGKDYHKSV CAATGACAGCGTTTACAGGAAAGTACTGCCTGCCTTGGTCATCCCGGCTCATTATATGAAACTCCCCGGGGACC- ACTCCT EVFPLKARKSMEREGYESSGN ATGTCAGCCAGCCCCTCGTCGTCCCGGCTGATCAGCAGCTTGAGATAGAAAGACTACAGGCTGAGCTGTCCAAT- CCCCAT DDYRGSYNTVLSQPLFEKQDR GCCGGGATCTTCCCACACCCGTCCTCACAGATCCAGCCCCAGCCCCTGTCTTCCCAGGCCATCTCTCAGCAGCA- CCTGCA EGPASTGSKLTIQEHLYPAPS GGATGCGGGCACCCGGGAGTGGAGCCCTCAGAACGCATCCATGTCGGAGTCTCTCTCCATCCCAGCTTCCCTGA- ACGACG SPEKEQLLDRRPTECMMSRSV CGGCTTTGGCTCAGATGAACAGTGAGGTGCAGCTCCTGACTGAAAAGGCCCTGATGGAGCTTGGGGGTGGGAAG- CCGCTT DHLERPTSFPRPGQLICCSSV CCGCACCCCCGGGCGTGGTTCGTCTCCTTGGATGGCAGGTCCAACGCTCACGTTAGACATTCATACATTGATCT- CCAAAG DQVNDSVYRKVLPALVIPAHY AGCTGGAAGGAACGGAAGTAATGATGCCAGTTTGGACTCTGGCGTAGATATGAATGAACCAAAATCAGCCCGGA- AGGGAA MKLPGDHSYVSQPLVVPADQQ GGGGAGATGCTTTGTCTCTGCAGCAGAACTACCCGCCCGTCCAAGAGCACCAGCAGAAAGAGCCTCGAGCCCCA- GACAGC LEIERLQAELSNPHAGIFPHP ACGGCCTACACGCAGCTCGTGTACCTGGATGACGTGGAACAGAGTGGTAGCGAATGTGGGACCACGGTCTGTAC- CCCCGA SSQIQPQPLSSQAISQQHLQD GGACAGTGCCCTGCGATGCTTGTTGGAGGGGTCGAGTCGGAGAAGTGGTGGCCAGCTGCCCAGCCTGCAGGAGG- AGACGA AGTREWSPQNASMSESLSIPA CCAGACGGACTGCGGATGCCCCCTCGGAGCCAGCAGCCAGCCCCCACCAGAGAAGATCTGCCCACGAGGAAGAG- GAAGAC SLNDAALAQMNSEVQLLTEKA GATGATGATGATGACCAAGGAGAAGACAAGAAAAGCCCCTGGCAGAAACGGGAGGAGAGGCCCCTGATGGCGTT- TAACAT LMELGGGKPLPHPRAWFVSLD TAAATGAGCTATCGCAGACCCACCTGACTGTGGAATATAAAATTGCCAAATATCCTTTCTCATGGAAGCGCGTA- CCCGTT GRSNAHVRHSYIDLQRAGRNG CGTGGAGGAAACGGAACGGCAGCCCAGCCGTGGGACGGACGTGGACGTTTACTGCATTCCTGTTTGCCGTGTAA- ATGTTA SNDASLDSGVDMNEPKSARKG GAAAGGAATTAAAGTTATTACTCGGAATAAAGGATGACTTTGGCGGATGTCGCCCCTGCAAGGAGGTGGCTGAA- AGTGGT RGDALSLQQNYPPVQEHQQKE GTCCAGATGTCCTTCCGAGGACTCGGCGTATCCGCCACCAGGGACATTAAGAAACCGCACGTGATGTCGCTATG- CTCTAA PRAPDSTAYTQLVYLDDVEQS CGATCACCTCAGTTCTCCCTCGGATTCTGGGAACAGATGAAACTTTTTGCATCGCTTGAGTCATTTTTATCACA- ATAATC GSECGTTVCTPEDSALRCLLE CTACTGTGAAGCTGTCGTTGAGAACTTAGGTTGGCACGTAGCGTCTCAAGGTATGCGTTCTCTCAAAGGAAAGC- TATGCA GSSRRSGGQLPSLQEETTRRT TCGCTGCTTCTTTGTCTGATTTTGCTTAGATTTTGCTTTGGTTAGGTTGCGTTTTGGGGTTTGCCTTTTTTTGT- TGTCGC ADAPSEPAASPHQRRSAHEEE TTAAATGCAATTTGGTTGTAAAGATTTGATTCCTTTGTGTTCATCTGTTCCGCTTCTCAGCGGTCCATCTCAGC- GTCTCC EDDDDDDQGEDKKSPWQKREE CTTCAGGAACCGCTGAGTGTCCTCTCTTAACATCCAAGCCTTTTAATGAAATCGTACTGAAATCTGTATCAGCT- AAGAGT RPLMAFNIK CCTCCAATCCTGGTCCCATTAACTCCAAGTGCCTTTTTGTCAGTGACAACAGACAGTCCCTCGCTTTTTGTTGT- TGTTGG TTTTCTTAACCCCTTTAATGGAACTGCCTGGATTTTATACAGTTATTAAAGGATGTCTCTTTTGCTTTAAACTG- CATGCT GCCAAGTGCCATTTGGGGTCAGCATCCTCGTTTCAACACAGTGTGCTCTCTAGTTATCATGTGTAACGTGGGTT- CTGTTT AGCGAAGATAGACTAGAGGACACGTTAGAGATGCCCTTCCCTGCTCCATCCCTGTGGCACCATTATGGTTTTTT- GGCTGT TTGTATATACGGTTACGTATTAACTCTGGAATCCTATGGGCTCATCTTGCTCACCCAATGTGGGAGTCTGGTTT- GAGCAA GCGAGCTGAATGTGACTATTAAAAAAAATTTAAAAAAAAAAAAGAAAATCTTATGTACTATCCAAAAGTGCCAG- AATGAC TCTTCTGTGCATTCTTCTTAAAGAGCTGCTTGGTTATCCAAAAATGAAAATTCAAAATAAACTCTGAAAAAAAA- AAAAAA AAAAAA SEQ. ID NO. 36 SEQ. ID NO. 81 CGTCACTTCCTGTTGCCTTAGGGGAACGTGGCTTTCCCTGCAGAGCCGGTGTCTCCGCCTGCGTCCCTGCTGCA- GCAACC MDSALSDPHNGSAEAGGPTNS GGAGCTGGAGTCGGATCCCGAACGCACCCTCGCCATGGACTCGGCCCTCAGCGATCCGCATAACGGCAGTGCCG- AGGCAG TTRPPSTPEGIALAYGSLLLM GCGGCCCCACCAACAGCACTACGCGGCCGCCTTCCACGCCCGAGGGCATCGCGCTGGCCTACGGCAGCCTCCTG- CTCATG ALLPIFFGALRSVRCARGKNA GCGCTGCTGCCCATCTTCTTCGGCGCCCTGCGCTCCGTACGCTGCGCCCGCGGCAAGAATGCTTCAGACATGCC- TGAAAC SDMPETITSRDAARFPIIASC AATCACCAGCCGGGATGCCGCCCGCTTCCCCATCATCGCCAGCTGCACACTCTTGGGGCTCTACCTCTTTTTCA- AAATAT TLLGLYLFFKIFSQEYINLLL TCTCCCAGGAGTACATCAACCTCCTGCTGTCCATGTATTTCTTCGTGCTGGGAATCCTGGCCCTGTCCCACACC- ATCAGC SMYFFVLGILALSHTISPFMN CCCTTCATGAATAAGTTTTTTCCAGCCAGCTTTCCAAATCGACAGTACCAGCTGCTCTTCACACAGGGTTCTGG- GGAAAA KFFPASFPNRQYQLLFTQGSG CAAGGAAGAGATCATCAATTATGAATTTGACACCAAGGACCTGGTGTGCCTGGGCCTGAGCAGCATCGTTGGCG- TCTGGT ENKEEIINYEFDTKDLVCLGL ACCTGCTGAGGAAGCACTGGATTGCCAACAACCTTTTTGGCCTGGCCTTCTCCCTTAATGGAGTAGAGCTCCTG- CACCTC SSIVGVWYLLRKHWIANNLFG AACAATGTCAGCACTGGCTGCATCCTGCTGGGCGGACTCTTCATCTACGATGTCTTCTGGGTATTTGGCACCAA- TGTGAT LAFSLNGVELLHLNNVSTGCI GGTGACAGTGGCCAAGTCCTTCGAGGCACCAATAAAATTGGTGTTTCCCCAGGATCTGCTGGAGAAAGGCCTCG- AAGCAA LLGGLFIYDVFWVFGTNVMVT ACAACTTTGCCATGCTGGGACTTGGAGATGTCGTCATTCCAGGGATCTTCATTGCCTTGCTGCTGCGCTTTGAC- ATCAGC VAKSFEAPIKLVFPQDLLEKG TTGAAGAAGAATACCCACACCTACTTCTACACCAGCTTTGCAGCCTACATCTTCGGCCTGGGCCTTACCATCTT- CATCAT LEANNFAMLGLGDVVIPGIFI GCACATCTTCAAGCATGCTCAGCCTGCCCTCCTATACCTGGTCCCCGCCTGCATCGGTTTTCCTGTCCTGGTGG- CGCTGG ALLLRFDISLKKNTHTYFYTS CCAAGGGAGAAGTGACAGAGATGTTCAGCTACGAGTCCTCGGCGGAAATCCTGCCTCATACCCCGAGGCTCACC- CACTTC FAAYIFGLGLTIFIMHIFKHA CCCACAGTCTCGGGCTCCCCAGCCAGCCTGGCCGACTCCATGCAGCAGAAGCTAGCTGGCCCTCGCCGCCGGCG- CCCGCA QPALLYLVPACIGFPVLVALA GAATCCCAGCGCCATGTAATGCCCAGCGGGTGCCCACCTGCCCGCTTCCCCCTACTGCCCCGGGGCCCAAGTTA- TGAGGA KGEVTEMFSYESSAEILPHTP GTCAAATCCTAAGGATCCAGCGGCAGTGACAGAATCCAAAGAGGGAACAGAGGCATCAGCATCGAAGGGGCTGG- AGAAGA RLTHFPTVSGSPASLADSMQQ AAGAGAAATGATGCAGCTGGTGCCCGAGCCTCTCAGGGCCAGACCAGACAGATGGGGGCTGGGCCCACACAGGC- GTGCAC KLAGPRRRRPQNPSAM CGGTAGAGGGCACAGGAGGCCAAGGGCAGCTCCAGGACAGGGCAGGGGGCAGCAGGATACCTCCAGCCAGGCCT- CTGTGG CCTCTGTTTCCTTCTCCCTTTCTTGGCCCTCCTCTGCTCCTCCCCACACCCTGCAGGCAAAAGAAACCCCCAGC- TTCCCC CCTCCCCGGGAGCCAGGTGGGAAAAGTGGGTGTGATTTTTAGATTTTGTATTGTGGACTGATTTTGCCTCACAT- TAAAAA CTCATCCCATGGCCAGGGCGGGCCACTGTGCTCCTGGAAAAAAAAAA SEQ. ID NO. 37 STAR clone: TGCCTCAGTCTCTCACTGTGCCTTATGCCCCTCAGCTGAATTCTTTCTTCTGAGCAGGCAGGAATTGAGGTTGC- TGCAGA CGTGTATGCATTTGCCACCAGTAACATACTTTGGTGCCACATGACTAGGATATGTTCTCTAGTGCTAACATGTT- CGTTTA CAGTTCTTAGGACTCCCTGATAGAAAAAAACACAAAAAAAAACACAAAAAAACCCAACCA SEQ. ID NO. 38 SEQ. ID NO. 82 GTTGGGAAAGAGCAGCCTGGGCGGCAGGGGCGGTGGCTGGAGCTCGGTAAAGCTCGTGGGACCCCATTGGGGGA- ATTTGA MVCGSPGGMLLLRAGLLALAA TCCAAGGAAGCGGTGATTGCCGGGGGAGGAGAAGCTCCCAGATCCTTGTGTCCACTTGCAGCGGGGGAGGCGGA- GACGGC LCLLRVPGARAAACEPVRIPL GGAGCGGGCCTTTTGGCGTCCACTGCGCGGCTGCACCCTGCCCCATCCTGCCGGGATCATGGTCTGCGGCAGCC- CGGGAG CKSLPWNMTKMPNHLHHSTQA

GGATGCTGCTGCTGCGGGCCGGGCTGCTTGCCCTGGCTGCTCTCTGCCTGCTCCGGGTGCCCGGGGCTCGGGCT- GCAGCC NAILAIEQFEGLLGTHCSPDL TGTGAGCCCGTCCGCATCCCCCTGTGCAAGTCCCTGCCCTGGAACATGACTAAGATGCCCAACCACCTGCACCA- CAGCAC LFFLCAMYAPICTIDFQHEPI TCAGGCCAACGCCATCCTGGCCATCGAGCAGTTCGAAGGTCTGCTGGGCACCCACTGCAGCCCCGATCTGCTCT- TCTTCC KPCKSVCERARQGCEPILIKY TCTGTGCCATGTACGCGCCCATCTGCACCATTGACTTCCAGCACGAGCCCATCAAGCCCTGTAAGTCTGTGTGC- GAGCGG RHSWPENLACEELPVYDRGVC GCCCGGCAGGGCTGTGAGCCCATACTCATCAAGTACCGCCACTCGTGGCCGGAGAACCTGGCCTGCGAGGAGCT- GCCAGT ISPEAIVTADGADFPMDSSNG GTACGACAGGGGCGTGTGCATCTCTCCCGAGGCCATCGTTACTGCGGACGGAGCTGATTTTCCTATGGATTCTA- GTAACG NCRGASSERCKCKPIRATQKT GAAACTGTAGAGGGGCAAGCAGTGAACGCTGTAAATGTAAGCCTATTAGAGCTACACAGAAGACCTATTTCCGG- AACAAT YFRNNYNYVIRAKVKEIKTKC TACAACTATGTCATTCGGGCTAAAGTTAAAGAGATAAAGACTAAGTGCCATGATGTGACTGCAGTAGTGGAGGT- GAAGGA HDVTAVVEVKEILKSSLVNIP GATTCTAAAGTCCTCTCTGGTAAACATTCCACGGGACACTGTCAACCTCTATACCAGCTCTGGCTGCCTCTGCC- CTCCAC RDTVNLYTSSGCLCPPLNVNE TTAATGTTAATGAGGAATATATCATCATGGGCTATGAAGATGAGGAACGTTCCAGATTACTCTTGGTGGAAGGC- TCTATA EYIIMGYEDEERSRLLLVEGS GCTGAGAAGTGGAAGGATCGACTCGGTAAAAAAGTTAAGCGCTGGGATATGAAGCTTCGTCATCTTGGACTCAG- TAAAAG IAEKWKDRLGKKVKRWDMKLR TGATTCTAGCAATAGTGATTCCACTCAGAGTCAGAAGTCTGGCAGGAACTCGAACCCCCGGCAAGCACGCAACT- AAATCC HLGLSKSDSSNSDSTQSQKSG CGAAATACAAAAAGTAACACAGTGGACTTCCTATTAAGACTTACTTGCATTGCTGGACTAGCAAAGGAAAATTG- CACTAT RNSNPRQARN TGCACATCATATTCTATTGTTTACTATAAAAATCATGTGATAACTGATTATTACTTCTGTTTCTCTTTTGGTTT- CTGCTT CTCTCTTCTCTCAACCCCTTTGTAATGGTTTGGGGGCAGACTCTTAAGTATATTGTGAGTTTTCTATTTCACTA- ATCATG AGAAAAACTGTTCTTTTGCAATAATAATAAATTAAACATGCTGTTACCAGAGCCTCTTTGCTGGAGTCTCCAGA- TGTTAA TTTACTTTCTGCACCCCAATTGGGAATGCAATATTGGATGAAAAGAGAGGTTTCTGGTATTCACAGAAAGCTAG- ATATGC CTTAAAACATACTCTGCCGATCTAATTACAGCCTTATTTTTGTATGCCTTTTGGGCATTCTCCTCATGCTTAGA- AAGTTC CAAATGTTTATAAAGGTAAAATGGCAGTTTGAAGTCAAATGTCACATAGGCAAAGCAATCAAGCACCAGGAAGT- GTTTAT GAGGAAACAACACCCAAGATGAATTATTTTTGAGACTGTCAGGAAGTAAAATAAATAGGAGCTTAAGAAAGAAC- ATTTTG CCTGATTGAGAAGCACAACTGAAACCAGTAGCCGCTGGGGTGTTAATGGTAGCATTCTTCTTTTGGCAATACAT- TTGATT TGTTCATGAATATATTAATCAGCATTAGAGAAATGAATTATAACTAGACATCTGCTGTTATCACCATAGTTTTG- TTTAAT TTGCTTCCTTTTAAATAAACCCATTGGTGAAAGTCCCAAAAAAAAAAAAAAAAAAAAA ATACCAGGGAGACTGGCATTGACGAGAACTCAGGTGGAGGCTTGAGAAGGCCGAAAGGGCCCCTGACCTGCCTG- GCTTCC TTAGCTTGCCCCTCAGCTTTGCAAAGAGCCACCCTAGGCCCCAGCTGACCGCATGGGTGTGAGCCAGCTTGAGA- ACACTA ACTACTCAATAAAAGCGAAGGTGGACAAAAAAAAAAAAAAAAAAAAA SEQ. ID NO. 39 SEQ, ID NO. 83 ACTGAAAGCTCCGGTGCCAGACCCCACCCCCGGCCCCGGCCCGGGACCCCCTCCCCTCCCGGGATCCCCCGGGG- TTCCCA MKTSPRRPLILKRRRLPLPVQ CCCCGCCCGCACCGCCGGGGACCCGGCCGGTCCGGCGCGAGCCCCCGTCCGGGGCCCTGGCTCGGCCCCCAGGT- TGGAGG NAPSETSEEEPKRSPAQQESN AGCCCGGAGCCCGCCTTCGGAGCTACGGCCTAACGGCGGCGGCGACTGCAGTCTGGAGGGTCCACACTTGTGAT- TCTCAA QAEASKEVAESNSCKFPAGIK TGGAGAGTGAAAACGCAGATTCATAATGAAAACTAGCCCCCGTCGGCCACTGATTCTCAAAAGACGGAGGCTGC- CCCTTC IINHPTMPNTQVVAIPNNANI CTGTTCAAAATGCCCCAAGTGAAACATCAGAGGAGGAACCTAAGAGATCCCCTGCCCAACAGGAGTCTAATCAA- GCAGAG HSIITALTAKGKESGSSGPNK GCCTCCAAGGAAGTGGCAGAGTCCAACTCTTGCAAGTTTCCAGCTGGGATCAAGATTATTAACCACCCCACCAT- GCCCAA FILISCGGAPTQPPGLRPQTQ CACGCAAGTAGTGGCCATCCCCAACAATGCTAATATTCACAGCATCATCACAGCACTGACTGCCAAGGGAAAAG- AGAGTG TSYDAKRTEVTLETLGPKPAA GCAGTAGTGGGCCCAACAAATTCATCCTCATCAGCTGTGGGGGAGCCCCAACTCAGCCTCCAGGACTCCGGCCT- CAAACC RDVNLPRPPGALCEQKRETCA CAAACCAGCTATGATGCCAAAAGGACAGAAGTGACCCTGGAGACCTTGGGACCAAAACCTGCAGCTAGGGATGT- GAATCT DGEAAGCTINNSLSNIQWLRK TCCTAGACCACCTGGAGCCCTTTGCGAGCAGAAACGGGAGACCTGTGCAGATGGTGAGGCAGCAGGCTGCACTA- TCAACA MSSDGLGSRSIKQEMEEKENC ATAGCCTATCCAACATCCAGTGGCTTCGAAAGATGAGTTCTGATGGACTGGGCTCCCGCAGCATCAAGCAAGAG- ATGGAG HLEQRQVKVEEPSRPSASWQN GAAAAGGAGAATTGTCACCTGGAGCAGCGACAGGTTAAGGTTGAGGAGCCTTCGAGACCATCAGCGTCCTGGCA- GAACTC SVSERPPYSYMAMIQFAINST TGTGTCTGAGCGGCCACCCTACTCTTACATGGCCATGATACAATTCGCCATCAACAGCACTGAGAGGAAGCGCA- TGACTT ERKRMTLKDIYTWIEDHFPYF TGAAAGACATCTATACGTGGATTGAGGACCACTTTCCCTACTTTAAGCACATTGCCAAGCCAGGCTGGAAGAAC- TCCATC KHIAKPGWKNSIRHNLSLHDM CGCCACAACCTTTCCCTGCACGACATGTTTGTCCGGGAGACGTCTGCCAATGGCAAGGTCTCCTTCTGGACCAT- TCACCC FVRETSANGKVSFWTIHPSAN CAGTGCCAACCGCTACTTGACATTGGACCAGGTGTTTAAGCAGCAGAAACGACCGAATCCAGAGCTCCGCCGGA- ACATGA RYLTLDQVFKQQKRPNPELRR CCATCAAAACCGAACTCCCCCTGGGCGCACGGCGGAAGATGAAGCCACTGCTACCACGGGTCAGCTCATACCTG- GTACCT NMTIKTELPLGARRKMKPLLP ATCCAGTTCCCGGTGAACCAGTCACTGGTGTTGCAGCCCTCGGTGAAGGTGCCATTGCCCCTGGCGGCTTCCCT- CATGAG RVSSYLVPIQFPVNQSLVLQP CTCAGAGCTTGCCCGCCATAGCAAGCGAGTCCGCATTGCCCCCAAGGTGCTGCTAGCTGAGGAGGGGATAGCTC- CTCTTT SVKVPLPLAASLMSSELARHS CTTCTGCAGGACCAGGGAAAGAGGAGAAACTCCTGTTTGGAGAAGGGTTTTCTCCTTTGCTTCCAGTTCAGACT- ATCAAG KRVRIAPKVLLAEEGIAPLSS GAGGAAGAAATCCAGCCTGGGGAGGAAATGCCACACTTAGCGAGACCCATCAAAGTGGAGAGCCCTCCCTTGGA- AGAGTG AGPGKEEKLLFGEGFSPLLPV GCCCTCCCCGGCCCCATCTTTCAAAGAGGAATCATCTCACTCCTGGGAGGATTCGTCCCAATCTCCCACCCCAA- GACCCA QTIKEEEIQPGEEMPHLARPI AGAAGTCCTACAGTGGGCTTAGGTCCCCAACCCGGTGTGTCTCGGAAATGCTTGTGATTCAACACAGGGAGAGG- AGGGAG KVESPPLEEWPSPAPSFKEES AGGAGCCGGTCTCGGAGGAAACAGCATCTACTGCCTCCCTGTGTGGATGAGCCGGAGCTGCTCTTCTCAGAGGG- GCCCAG SHSWEDSSQSPTPRPKKSYSG TACTTCCCGCTGGGCCGCAGAGCTCCCGTTCCCAGCAGACTCCTCTGACCCTGCCTCCCAGCTCAGCTACTCCC- AGGAAG LRSPTRCVSEMLVIQHRERRE TGGGAGGACCTTTTAAGACACCCATTAAGGAAACGCTGCCCATCTCCTCCACCCCGAGCAAATCTGTCCTCCCC- AGAACC RSRSRRKQHLLPPCVDEPELL CCTGAATCCTGGAGGCTCACGCCCCCAGCCAAAGTAGGGGGACTGGATTTCAGCCCAGTACAAACCTCCCAGGG- TGCCTC FSEGPSTSRWAAELPFPADSS TGACCCCTTGCCTGACCCCCTGGGGCTGATGGATCTCAGCACCACTCCCTTGCAAAGTGCTCCCCCCCTTGAAT- CACCGC DPASQLSYSQEVGGPFKTPIK AAAGGCTCCTCAGTTCAGAACCCTTAGACCTCATCTCCGTCCCCTTTGGCAACTCTTCTCCCTCAGATATAGAC- GTCCCC ETLPISSTPSKSVLPRTPESW AAGCCAGGCTCCCCGGAGCCACAGGTTTCTGGCCTTGCAGCCAATCGTTCTCTGACAGAAGGCCTGGTCCTGGA- CACAAT RLTPPAKVGGLDFSPVQTSQG GAATGACAGCCTCAGCAAGATCCTGCTGGACATCAGCTTTCCTGGCCTGGACGAGGACCCACTGGGCCCTGACA- ACATCA ASDPLPDPLGLMDLSTTPLQS ACTGGTCCCAGTTTATTCCTGAGCTACAGTAGAGCCCTGCCCTTGCCCCTGTGCTCAAGCTGTCCACCATCCCG- GGCACT APPLESPQRLLSSEPLDLISV CCAAGGCTCAGTGCACCCCAAGCCTCTGAGTGAGGACAGCAGGCAGGGACTGTTCTGCTCCTCATAGCTCCCTG- CTGCCT PFGNSSPSDIDVPKPGSPEPQ GATTATGCAAAAGTAGCAGTCACACCCTAGCCACTGCTGGGACCTTGTGTTCCCCAAGAGTATCTGATTCCTCT- GCTGTC VSGLAANRSLTEGLVLDTMND CCTGCCAGGAGCTGAAGGGTGGGAACAACAAAGGCAATGGTGAAAAGAGATTAGGAACCCCCCAGCCTGTTTCC- ATTCTC SLSKILLDISFPGLDEDPLGP TGCCCAGCAGTCTCTTACCTTCCCTGATCTTTGCAGGGTGGTCCGTGTAAATAGTATAAATTCTCCAAATTATC- CTCTAA DNINWSQFIPELQ TTATAAATGTAAGCTTATTTCCTTAGATCATTATCCAGAGACTGCCAGAAGGTGGGTAGGATGACCTGGGGTTT- CAATTG ACTTCTGTTCCTTGCTTTTAGTTTTGATAGAAGGGAAGACCTGCAGTGCACGGTTTCTTCCAGGCTGAGGTACC- TGGATC TTGGGTTCTTCACTGCAGGGACCCAGACAAGTGGATCTGCTTGCCAGAGTCCTTTTTGCCCCTCCCTGCCACCT- CCCCGT GTTTCCAAGTCAGCTTTCCTGCAAGAAGAAATCCTGGTTAAAAAAGTCTTTTGTATTGGGTCAGGAGTTGAATT- TGGGGT GGGAGGATGGATGCAACTGAAGCAGAGTGTGGGTGCCCAGATGTGCGCTATTAGATGTTTCTCTGATAATGTCC- CCAATC ATACCAGGGAGACTGGCATTGACGAGAACTCAGGTGGAGGCTTGAGAAGGCCGAAAGGGCCCCTGACCTGCCTG- GCTTCC TTAGCTTGCCCCTCAGCTTTGCAAAGAGCCACCCTAGGCCCCAGCTGACCGCATGGGTGTGAGCCAGCTTGAGA- ACACTA ACTACTCAATAAAAGCGAAGGTGGACAAAAAAAAAAAAAAAAAAAAA SEQ. ID NO. 40 SEQ. ID NO. 84 GTCGAGGCTGCGGCGCGTGGGGAGCGGGCGGAGCGGGGGCGGGGGCCGAGCGCGGGGCACCCGGGGGCCTCCTG- TATAGG MGSCSGRCALVVLCAFQLVAA CGGGCACCATGGGCTCCTGCTCCGGCCGCTGCGCGCTCGTCGTCCTCTGCGCTTTTCAGCTGGTCGCCGCCCTG- GAGAGG LERQVFDFLGYQWAPILANFV CAGGTGTTTGACTTCCTGGGCTACCAGTGGGCGCCCATCCTGGCCAACTTTGTCCACATCATCATCGTCATCCT- GGGACT HIIIVILGLFGTIQYRLRYVM CTTCGGCACCATCCAGTACCGGCTGCGCTATGTCATGGTGTACACGCTGTGGGCAGCCGTCTGGGTCACCTGGA- ACGTCT VYTLWAAVWVTWNVFIICFYL TCATCATCTGCTTCTACCTGGAAGTCGGTGGCCTCTTAAAGGACAGCGAGCTACTGACCTTCAGCCTCTCCCGG- CATCGC EVGGLLKDSELLTFSLSRHRS TCCTGGTGGCGTGAGCGCTGGCCAGGCTGTCTGCATGAGGAGGTGCCAGCAGTGGGCCTCGGGGCCCCCCATGG- CCAGGC WWRERWPGCLHEEVPAVGLGA CCTGGTGTCAGGTGCTGGCTGTGCCCTGGAGCCCAGCTATGTGGAGGCCCTACACAGTTGCCTGCAGATCCTGA- TCGCGC PHGQALVSGAGCALEPSYVEA TTCTGGGCTTTGTCTGTGGCTGCCAGGTGGTCAGCGTGTTTACGGATGAAGAGGACAGCTTTGATTTCATTGGT- GGATTT LHSCLQILIALLGFVCGCQVV GATCCATTTCCTCTCTACCATGTCAATGAAAAGCCATCCAGTCTCTTGTCCAAGCAGGTGTACTTGCCTGCGTA- AGTGAG SVFTDEEDSFDFIGGFDPFPL GAAACAGCTGACCCTGCTCCTGTGGCCTCCAGCCTCAGCGACCGACCAGTGACAATGACAGGAGCTCCCAGGCC- TTGGGA YHVNEKPSSLLSKQVYLPA CGCGCCCCCACCCAGCACCCCCCAGGCGGCCGGCAGCACCTGCCCTGGGTTCTAAGTACTGGACACCAGCCAGG- GCGGCA GGGCAGTGCCACGGCTGGCTGCAGCGTCAAGAGAGTTTGTAATTTCCTTTCTCTTAAAAAAAAAAAAGAAAAGA- AAACAT ACAAAAGAAAAGGCAAAACCCCACATGCCCACCTCCTCTGGCAACATGGGGGTCACAGCTCTGCCCCCAGGCTG- TCGTCT CGTCGAGGAGCCCCTCCCTCAGGTGCCAACCTGGGGCTGCTGGACCCTCGGGCTGCAAGCACTGCTGCTGGGAT- GCAGCC TCCCCAGGAAGTCAATGTGAGGCCCGAGACCCCTCAAGCGGTGAGGGCCCCTGTTGAACATGGAGGGTTCCTAA- CCCCAA ACTCGTGCCAGAAGAACCCCCACCCCACCCAGGAGCTGAGGCTGATGGAGCCCTAGGGTGGGGGCTGGGCTTGA- CCAGGA ACAGCAGAGCCAGGCCCCAAGGCATAGGGCAGGGCACATGGTGGTGACGAGCAGGCAGTACTCTTGTAAAGGGG- GCTCTT GGGCAAACAGTCCCAAAGGCTCCCCCAGGTATCATCAAGTTGGTAAATAAACAGGAACATGGCCCAAAAAAAAA- AAAAAAA SEQ. ID NO. 41 STAR clone: AAAAAATAAGTATATCTGTCNAGAATCNTATTTATGTGAGATGTGTCAATACTGGTCTTGCGTTATTTCGGCTA- CTTGAA AATAAGTTAAAAAAGATAGTGTTTGGTTCCAAAAAGGAAAAGTCAGCCTCTCCTGCNTGAGTGGGAGCTGCAAC- CTTTTA GAATTGATAATCACAAACCCCTCAGACCCAAAGTGGAATAAAGAAAAATATGTAACATTAGGCATTGATGGAAA- AGGACT AGATCCTAGTGTAAGCATCCTAATAAAAGGAGAGGTTCACAA SEQ. ID NO. 42 SEQ. ID NO. 85 GCAGCCAGATCTGCTGGGACACCTTTCCCAAGGAAGAGCCCGTTGCACTGGGCTTTGAAGGATAAGCAGGAGCT- TGTTAC MCVSSSSSSHDEAPVLNDKHL TCAGGCAGAGGAAGAAAGAGCATCCCAGGCGGGGGGAGCAGCATATGCAAAGGCACGAAGGGGCCCCAGGAGCC- TAGGGA DVPDIIITPPTPTGMMLPRDL GTCTGGGGAAGTGTGAGCACTTTGGAGAGTGGAGGCTGGAGCGCTGTGGAGAGTGGGGGCTGGTGGCCGGGAAT- GAAGCT GSTVWLDETGSCPDDGEIDP GCAGCTGGCTGGGCCACATGGTAAAGGCTGACAACTGGACCCAGAGGCCAACTAGCCTATGATCAGCATTTCCC- AAAATC EA TGTTTCCCGACTCATGGTTCTGTGAGATGTGACAAGGGCTCCTTTTTCATTCCTGAGACGCCGGTTTTCATCTG- TGATGC GGGGACAGCTGCGCTCCTTGCTGCGAGGCGTCAGGACCCAGGTGATAGTGAAGGGAGGGTGGCGCCCGCGGTTC- CCGGCG GCCACTGATGCCTGTCTCTCTGTCGTGTGTACGTGCGTGTGTGCTCCACGCCTGGCTTCTCAGGCTTTCAAATG- TGTGTC AGCAGCAGCAGCAGCAGCCACGACGAGGCCCCCGTCCTGAACGACAAGCACCTGGACGTGCCCGACATCATCAT- CACGCC CCCCACCCCCACGGGCATGATGCTGCCGAGGGACTTGGGGAGCACAGTCTGGCTGGATGAGACAGGGTCGTGCC- CAGATG ATGGAGAAATCGACCCAGAAGCCTGAGGAGGTGTCCTGGGTTTGGCTGGCTGGCTCCTGCTCCAGCGGCCCGGC- TTCAGG TGTCCGGGGGCGTGGCTGCCTGGAGCAGGTGTGCTGAATACCCTGGATGGGAACTGAGCGAACCCGGGCCTCCG- CTCAGA GAGACGTGGCAGGACCAGCGAGGAATCCAGCCTGTCCACTTCCAGAACAGTGTTTCCCAGGCCCCGCTGAGTGG- ACCGGA CCTCTGACACCTCCAGGTTCTTGCTGACTCCGGCCTGGTGAAAGGGAGCGCCATGGTCCTGGCTGTTGGGGTCC- CAGGGA GAGGCTCTCTTCTGGACAAACACACCCTCCCAGCCCCCAGGGCTGTGCAAACACATGCCCCTCCCATAAGCACC- AACAAG AACTTCTTGCAGGTGGAGTGGCTGTTTTTTATAAGTTGTTTTACAGATACGGAAACAGTCCAAAATGGGATTTA- TAATTT CTTTTTTGCATTATAAATAAAGATCCTCTGTAACAAAAAAAAAAAAAAAAAAAAAAAAAAA SEQ. ID NO. 43 SEQ. ID NO. 86 GCGAAGTGAAGGGTGGCCCAGGTGGGGCCAGGCTGACTGAATGTATCTCCTAGCTATGGACTAAATAATACATG- GGGGGA MDTMMLNVRNLFEQLVRRVE AATAAACAAGTATTCATGAGGGTGAAAATGTGACCCAGCAGGAAAATTACAACTATTTTCAATTGACGTTGAAT- AGGATG ILSEGNEVQFIQLAKDFEDF AGTCATGGAATTTAAGTGATTTACTGAAGATTATACTACTGGTAGATAGAAGAGCTAAAGAAAGATGGATACTA- TGATGC RKKWQRTDHELGKYKDLLMK TGAATGTGCGGAATCTGTTTGAGCAGCTTGTGCGCCGGGTGGAGATTCTCAGTGAAGGAAATGAAGTCCAATTT- ATCCAG AETERSALDVKLKHARNQVD TTGGCGAAGGACTTTGAGGATTTCCGTAAAAAGTGGCAGAGGACTGACCATGAGCTGGGGAAATACAAGGATCT- TTTGAT VEIKRRQRAEADCEKLERQI GAAAGCAGAGACTGAGCGAAGTGCTCTGGATGTTAAGCTGAAGCATGCACGTAATCAGGTGGATGTAGAGATCA- AACGGA QLIREMLMCDTSGSIQLSEE GACAGAGAGCTGAGGCTGACTGCGAAAAGCTGGAACGACAGATTCAGCTGATTCGAGAGATGCTCATGTGTGAC- ACATCT QKSALAFLNRGQPSSSNAGN GGCAGCATTCAACTAAGCGAGGAGCAAAAATCAGCTCTGGCTTTTCTCAACAGAGGCCAACCATCCAGCAGCAA- TGCTGG KRLSTIDESGSILSDISFDK GAACAAAAGACTATCAACCATTGATGAATCTGGTTCCATTTTATCAGATATCAGCTTTGACAAGACTGATGAAT- CACTGG TDESLDWDSSLVKTFKLKKR ATTGGGACTCTTCTTTGGTGAAGACTTTCAAACTGAAGAAGAGAGAAAAGAGGCGCTCTACTAGCCGACAGTTT- GTTGAT EKRRSTSRQFVDGPPGPVKK GGTCCCCCTGGACCTGTAAAGAAAACTCGTTCCATTGGCTCTGCAGTAGACCAGGGGAATGAATCCATAGTTGC- AAAAAC TRSIGSAVDQGNESIVAKTT TACAGTGACTGTTCCCAATGATGGCGGGCCCATCGAAGCTGTGTCCACTATTGAGACTGTGCCATATTGGACCA- GGAGCC VTVPNDGGPIEAVSTIETVP GAAGGAAAACAGGTACTTTACAACCTTGGAACAGTGACTCCACCCTGAACAGCAGGCAGCTGGAGCCAAGAACT- GAGACA YWTRSRRKTGTLQPWNSDST GACAGTGTGGGCACGCCACAGAGTAATGGAGGGATGCGCCTGCATGACTTTGTTTCTAAGACGGTTATTAAACC- TGAATC LNSRQLEPRTETDSVGTPQS CTGTGTTCCATGTGGAAAGCGGATAAAATTTGGCAAATTATCTCTGAAGTGTCGAGACTGTCGTGTGGTCTCTC-

ATCCAG NGGMRLHDFVSKTVIKPESC AATGTCGGGACCGCTGTCCCCTTCCCTGCATTCCTACCCTGATAGGAACACCTGTCAAGATTGGAGAGGGAATG- CTGGCA VPCGKRIKFGKLSLKCRDCR GACTTTGTGTCCCAGACTTCTCCAATGATCCCCTCCATTGTTGTGCATTGTGTAAATGAGATTGAGCAAAGAGG- TCTGAC VVSHPECRDRCPLPCIPTLI TGAGACAGGCCTGTATAGGATCTCTGGCTGTGACCGCACAGTAAAAGAGCTGAAAGAGAAATTCCTCAGAGTGA- AAACTG GTPVKIGEGMLADFVSQTSP TACCCCTCCTCAGCAAAGTGGATGATATCCATGCTATCTGTAGCCTTCTAAAAGACTTTCTTCGAAACCTCAAA- GAACCT MIPSIVVHCVNEIEQRGLTE CTTCTGACCTTTCGCCTTAACAGAGCCTTTATGGAAGCAGCAGAAATCACAGATGAAGACAACAGCATAGCTGC- CATGTA TGLYRISGCDRTVKELKEKF CCAAGCTGTTGGTGAACTGCCCCAGGCCAACAGGGACACATTAGCTTTCCTCATGATTCACTTGCAGAGAGTGG- CTCAGA LRVKTVPLLSKVDDIHAICS GTCCACATACTAAAATGGATGTTGCCAATCTGGCTAAAGTCTTTGGCCCTACAATAGTGGCCCATGCTGTGCCC- AATCCA LLKDFLRNLKEPLLTFRLNR GACCCAGTGACAATGTTACAGGACATCAAGCGTCAACCCAAGGTGGTTGAGCGCCTGCTTTCCTTGCCTCTGGA- GTATTG AFMEAAEITDEDNSIAAMYQ GAGTCAGTTCATGATGGTGGAGCAAGAGAACATTGACCCCCTACATGTCATTGAAAACTCAAATGCCTTTTCAA- CACCAC AVGELPQANRDTLAFLMIHL AGACACCAGATATTAAAGTGAGTTTACTGGGACCTGTGACCACTCCTGAACATCAGCTTCTCAAGACTCCTTCA- TCTAGT QRVAQSPHTKMDVANLAKVF TCCCTGTCACAGAGAGTCCGTTCCACCCTCACCAAGAACACTCCTAGATTTGGGAGCAAAAGCAAGTCTGCCAC- TAACCT GPTIVAHAVPNPDPVTMLQD AGGACGACAAGGCAACTTTTTTGCTTCTCCAATGCTCAAGTGAAGTCACATCTGCCTGTTACTTCCCAGCATTG- ACTGAC IKRQPKVVERLLSLPLEYWS TATAAGAAAGGACACATCTGTACTCTGCTCTGCAGCCTCCTGTACTCATTACTACTTTTAGCATTCTCCAGGCT- TTTACT QFMMVEQENIDPLHVIENSN CAAGTTTAATTGTGCATGAGGGTTTTATTAAAACTATATATATCTCCCCTTCCTTCTCCTCAAGTCACATAATA- TCAGCA AFSTPQTPDIKVSLLGPVTT CTTTGTGCTGGTCATTGTTGGGAGCTTTTAGATGAGACATCTTTCCAGGGGTAGAAGGGTTAGTATGGAATTGG- TTGTGA PEHQLLKTPSSSSLSQRVRS TTCTTTTTGGGGAAGGGGGTTATTGTTCCTTTGGCTTAAAGCCAAATGCTGCTCATAGAATGATCTTTCTCTAG- TTTCAT TLTKNTPRFGSKSKSATNLG TTAGAACTGATTTCCGTGAGACAATGACAGAAACCCTACCTATCTGATAAGATTAGCTTGTCTCAGGGTGGGAA- GTGGGA RQGNFFASPMLK GGGCAGGGCAAAGAAAGGATTAGACCAGAGGATTTAGGATGCCTCCTTCTAAGAACCAGAAGTTCTCATTCCCC- ATTATG AACTGAGCTATAATATGGAGCTTTCATAAAAATGGGATGCATTGAGGACAGAACTAGTGATGGGAGTATGCGTA- GCTTTG ATTTGGATGATTAGGTCTTTAATAGTGTTGAGTGGCACAACCTTGTAAATGTGAAAGTACAACTCGTATTTATC- TCTGAT GTGCCGCTGGCTGAACTTTGGGTTCATTTGGGGTCAAAGCCAGTTTTTCTTTTAAAATTGAATTCATTCTGATG- CTTGGC CCCCATACCCCCAACCTTGTCCAGTGGAGCCCAACTTCTAAAGGTCAATATATCATCCTTTGGCATCCCAACTA- ACAATA AAGAGTAGGCTATAAGGGAAGATTGTCAATATTTTGTGGTAAGAAAAGCTACAGTCATTTTTTCTTTGCACTTT- GGATGC TGAAATTTTTCCCATGGAACATAGCCACATCTAGATAGATGTGAGCTTTTTCTTCTGTTAAAATTATTCTTAAT- GTCTGT AAAAACGATTTTCTTCTGTAGAATGTTTGACTTCGTATTGACCCTTATCTGTAAAACACCTATTTGGGATAATA- TTTGGA AAAAAAGTAAATAGCTTTTTCAAAATGAAAAAAAAAA SEQ. ID NO. 44 SEQ. ID NO. 87 AGGCGCTAGAGGCGGGGGCGCCGGGAGGCGCGGGCTTTGCTCCTGGGGTCTCGGCCTTGGCCGGCTGGACCTGA- CCCTAG MTDLNDNICKRYIKMITNIV GGCGGCTTGCGCAGCTGTCGGGACGTGACTGCGTTCAGCCGCGTCGGGCGTGCTTCCCAGACTTGCCCAAGTTC- GGGTGC ILSLIICISLAFWIISMTAS CCTAGCTGCCCCTTTGCAGCCGCTGGCCTACCCGGCCCGCGGGTGAGAAGGTTGCGACGGGAGGTGGGTGGAAC- TCGCCA TYYGNLRPISPWRWLFSVVV GCGCCGGGACCGCGGATTGGCTGCCTCGGCTTTCTCTTTTCCCCGTGGGCTCCGGCGTGAGGCGCTGAAGCGGC- CGGCAG PVLIVSNGLKKKSLDHSGAL CCGGCGACCGGCCCTCACCGTCCGCCGGGTTGCGCTCTGCTTTTGCGGTGAGGCGTTGACCACGCCCATATGAA- TTGGAG GGLVVGFILTIANFSFFTSL CTCTCCGCCAGTAGGAGTTTCCGGAAGGAGTTTGAATTTTTGTGATTTTTATGCTTGTTTGGTCGGTGGAATAT- GTTGGG LMFFLSSSKLTKWKGEVKKR ATTTATGTTTGCCTCTGAACAAGTGTCTTGCTCACATCGTAAATGACTTTCTCTCCGAAACGCTAAATATTCTT- TCCCGC LDSEYKEGGQRNWVQVFCNG AGGAGCTCATATCCTTATTTTCCATGACAGATCTTAACGACAATATATGCAAAAGATATATAAAGATGATAACT- AATATA AVPTELALLYMIENGPGEIP GTTATACTGAGCCTGATCATTTGCATTTCGTTAGCTTTCTGGATTATATCAATGACTGCAAGCACCTATTATGG- TAACTT VDFSKQYSASWMCLSLLAAL ACGACCTATTTCTCCGTGGCGTTGGCTGTTTTCTGTTGTTGTTCCTGTTCTGATCGTCTCTAATGGCCTTAAAA- AGAAAA ACSAGDTWASEVGPVLSKSS GTCTAGATCACAGTGGGGCTCTAGGAGGGCTAGTCGTTGGATTTATCCTAACCATTGCAAATTTCAGCTTTTTT- ACCTCT PRLITTWEKVPVGTNGGVTV TTGCTGATGTTTTTCTTGTCTTCTTCGAAACTCACTAAATGGAAGGGAGAAGTGAAGAAGCGTCTAGATTCAGA- ATATAA VGLVSSLLGGTFVGIAYFLT GGAAGGTGGGCAAAGGAATTGGGTTCAGGTGTTCTGTAATGGAGCTGTACCCACAGAACTGGCCCTGCTGTACA- TGATAG QLIFVNDLDISAPQWPIIAF AAAATGGCCCCGGGGAAATCCCAGTCGATTTTTCCAAGCAGTACTCCGCTTCCTGGATGTGTTTGTCTCTCTTG- GCTGCA GGLAGLLGSIVDSYLGATMQ CTGGCCTGCTCTGCTGGAGACACATGGGCTTCAGAAGTTGGCCCAGTTCTGAGTAAAAGTTCTCCAAGACTGAT- AACAAC YTGLDESTGMVVNSPTNKAR CTGGGAGAAAGTTCCAGTTGGTACCAATGGAGGAGTTACAGTGGTGGGCCTTGTCTCCAGTCTCCTTGGTGGTA- CCTTTG HIAGKPILDNNAVNLFSSVL TGGGCATTGCATACTTCCTCACACAGCTGATTTTTGTGAATGATTTAGACATTTCTGCCCCGCAGTGGCCAATT- ATTGCA IALLLPTAAWGFWPRG TTTGGTGGTTTAGCTGGATTACTAGGATCAATTGTGGACTCATACTTAGGGGCTACAATGCAGTATACTGGGTT- GGATGA AAGCACTGGCATGGTGGTCAACAGCCCAACAAATAAGGCAAGGCACATAGCAGGGAAACCCATTCTTGATAACA- ACGCAG TGAATCTGTTTTCTTCTGTTCTTATTGCCCTCTTGCTCCCAACTGCTGCTTGGGGTTTTTGGCCCAGGGGGTGA- ACTTTA TTTCATTTCCACAGGTTGAAACTGGTGAGTCCAGCTAAATTTGCAATTCCAACTTTCATCCTAAGAATAATAAC- TGTAAT GGCAAAGCGGAAATGCCAGTTCCTCCTGTATTCCATTGAGATGGGATTTCACATTTTCCTCTCATCAACTCCCC- TGTAAT AGCTAGCGTCTTTCTAGTGAAAGAGAAGAATTCCTAGAACTTATGCATTTTTTTCCTGCTGAATGGAAGTCTTG- AGCAAT GAAGCTATATTGTCCCTACATATTACTATATATTGAACTGAAAGTTCTTACATAATCAATGTCAAGTTTTGTCT- TATTTT GTTTTGTTTGTTTAAACCAGTGTAGGAAATAAAAGTGATGATATTTAAAATAGTTCTCAGTTGAAGCAGAGAAA- TGCCAC TGTGCTAGTTGCCCAAATGTTGTATCTATTTTAAATAGTTTAAGCTGATGTGTATGGGAGCCTAAACAAGTGTA- GTATCC TGAACTTCTCCCATTAATTGCTATTCACAATTGGGAAAAGTGTGGAGATTGGTTCCTAGTGAGTTTTGTGGCCT- ACTCCA CATTTGTTCTTCCTTCCTCAGGGTTAGTGATGAAAAAAAGTAAATATCTTTTTCATATGTCCATTAGAATGTAT- GAAAAA AATCATTTTAACTAAAAGCAAAAGAATTTTATCTTATATCTAAAAAATATATAACTTACTATATGTTTCAGTTG- CTCTCT GAACAAAAATTATCTTCAATTTAATATGTGGAATGTGTTTTCTAGCTTTCTTTGAATTATGTATGGCAACCTGG- TTTAGC ACTGGCATCCTGAACAGTTAAGAGTCACTGGGAAATTATTGTATTTCTTTATAAATTTACTGTCATATCAATTG- CTGGAA AATGCTATGATTTTTCTATTATTACCTTCTAAGTTGTATTCTCTCTTACACTGTAGCCTCAACTAAGGCAATTC- TGCTAT GTTTGTTCTTCACTATGATTTACTGTGTGCCAAAGGAGTTTTGACAGGGTACAGAGTATTTTACTAAAAGTATT- TTTAAA TGTTTCTCATGTGATTTCTGTACCTTCTTCCTCCTGCCCCTTTTGCTTTTTTAAAGAAACTGGGGAAGGATTTA- TGAATA CACCACCACCAGAGTGGATAATGCTTAGAATTCTTTATTGGTGGCCCTACTATGGTGATGATCTAGAACTGACT- TACTTC AGGACAGAAGAAAAAACAATCACACCCTTAACCTTTAAGCCAGTTAGATCAGGGGGTTGCAACAATTGGGTTAA- ACTTTG GGTATACATTGGAAGCACCAGGGCATGTTTGCTTTTTTTGTTTATGTGTTTGTTTTTTGAGACAGAGTCTCACA- CTGTGG CCCAGGCTGGACTCCAGCACAGTGGCATGATCTCAGCTCCGCCTCCTGGGTTCACGTGATTCTCATGCCTCAGC- CTCCCA AGTAGCTGGGATCACAGGCGTGCACCATCACGCCCGGCTAATTTTTGTATTTTCAGTAGAGACAGGGTTTCGCC- ACGTTG GCTAGGCTGGTCTCGAACTCCTGACCTCAAGTGATCTGCCCATCTCAGCCTCCCAAAGATCTATTACAAGATGT- GAGCCA CTGTGCCCAGCCACCAGGGCATGTTTTTAAAAAAGTACTGATGTCTGGGTTTCACACTGCAAAATTCTGATTTA- TCTGAT CTAAGGTACAGCCTGGATATTGAGACTTTTTAAAGCTCTGACTGTACATTGAATCATCATGTAAGGAGTTTTTA- AAACAT TGTTGCCAGGGCCCCTTTCTAGACCAAGTTAGTCAGAATGTTGGACAATGAGGCCCATGCATGGGTATTTTTAC- AAAGCT CTCTGGGAGATTCTAATGCTTAACCAAATTGAGAAGCACTGAATAAGAATATCCTGGGCCGGGCGCACTGGCTC- ATGCCT GTAATCCCAGCATTTTGGAAGGCCGAGGCGGGTGGATCACTTGAGGTCAGGAGTTCGAGACCAGCCTGGCCAAC- ATGGTG AAACACCGTCTCTACTAAAAATACAAAAAATTAGGTGTGGTGGTGCGTGCCTGTATTCCCAGCCACTCAGGAGG- CTGAGG CAGGAGAATCGCTGGAACCTGGGATGTGGAGGTTGCAGTGAGCCAAGATTGCACCACTGTACTCCAGCCTGGGC- AACAGA GGGAGACTCCATCTAGACTCCATCTCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAGAATATTCT- AAGCAC TAGAACTACATAAGAATGTCCTAAAGCACTGTATCTAAGCACTTGAAAAGAATGGGACTTTTCGGTTTTAGGGA- GATAAC TATTAGCAACCACACAATATGTTATCTTTATGGATGAATAACTTCTGGTAATGACACAGTGTCTTACAGCTACA- TCATTT ATAAAATCATGTGTCAGTTTTCACACAGCCTGCACATCGTTCTGACATGCCCTTTTTTTCCCTGGAGATTTATC- CTCATG ACATACAAGGGGACAAAAATATTTATTGGGACTGTCTTTGAATTTAGTAGAATCACTGTATCATTAACAGTTTG- GGGAAG TACTGCTTTGCAGTCCTTTATTTGAAAACTTAGGTCTAGCTGTGTTTTGCATCAAAATTTTTGAGCTATTCAAA- AACTAA TAGGATCTGTGTAAAATATTTCACTCAAAACTACTAAAAAAAAGTCTGGGATGGCAGCTCATTATCAAATATAC- TCCTAT TTTTGTGGTGATTTATGAACATCCCCACTAAGTATAACTAAAGATCATAAAGAGCCTCAGATCAAGTTTGGTCA- GGTTTT GTCACCAAGCTTTGTAAATAAACTGGTTTTCATAGCTTTTTGGAGATGAGAATTGAGGATAAGAAATTGTGTCT- CTGTCC TTTTTTTTTTTTTTTGTTAAGTCTTACATGTATTTTACTGTAACATCTTTTGAATTGGATATTTAACTAATTCA- ACATAT TTTTCCTCTTTGCAGAATGGGCAGTTCATGTTAAAATCACTTTTCATGGAAAGAGCTCTATGTAACAGCATAAT- AAAACT GCCTACCTAGCAGCATAAA SEQ. ID NO. 45 STAR clone: CNGGACACATCAAACTGCTTATCCAGGNACCACTAGAAGTGAATCTCTTCTTGAGTATTCCATACTGCTGCCCC- TGCTAT TCACTTGGGGTCCCAGTCAGTTGTTACTATATATTTGTCATCTATTGTGAGAGTCGTGATATCACCTTCCACAT- CAGTGA TACTGAGAAGGAACAAATCTGCCAAAGATGCTTCACAGTTAGTTGTTACCTTTTTAAGAAGACTGTGCTTGAAA- ATTATG GTAAAACACATTTAGAAGAAGGATGTGCATTTTCACATCAGTCTATGAAGTATAACTTGACATTTAAATTAAAA- TGCTGT TCTTCAAAATCGA SEQ. ID NO. 46 STAR clone: GTTCCCGACTAGCTGCCCNTGCACATTATCTTCATTTTCCTGGAATTTGATACAGAGAGCAATTTATAGCCNAT- TGATAG CTTATGCTGTTTCAATGTAAATTCGTGGTAAATAACTTAGGAACTGCCTCTTCTTTTTCTTTGAAAACCTACTT- ATAACT GTTGCTAATAAGAATGTGTATTGTTCAGGACAACTTGTCTCCATACAGTTGGGTTGTAACCCTCATGCTTGGCC- CAAATA AACTCTCTACTTATATCAGTA SEQ. ID NO. 47 STAR clone: CTAGGGGTCCTGACGGTTCTCTGGCTCCAAGTCTGGCCCCTCAACCTCCCTGGTCATCAGTGGGCTCCAGGCTG- AGGATG AGGCTGATTACTACTGTGCAGCATGGGATGACAGCCTGAAAGGTCCTGCGTTCGGAGGAGGCACCCACCTGACC- GTCCTC GGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCACCCTCCTCTGAGGAGCTTCAAGCCAACAAGGCCAC- ACTGGT GTGTCTCGTAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCCTGGAAGGCAGATGGCAGCCCCGTCAAGGTGG- GAGTGG AGACCACCAAACCCTCCAAACAAAGCAACAACAAGTATGCGGCCAGCAGCTACCTGAGCCTGACGCCCGAGCAG- TGGAAG TCCCACAGAAGCTACAGCTGCCGGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTGCAGAATG- CTCTTA GGCCCCCGACCCTCACCCCACCCACAGGGGCCTGGAGCTGCAGGTTCCCAGGGGAGGGGTCTCTGCCCCCATCC- CAAGTC ATCCAGCCCTTCTCAATAAATATCCTCATCGTCAACGA SEQ. ID NO. 48 SEQ. ID NO. 88 GGTAGTTGGTTGTGGGCACTGGGTTAGAGGTATCACGTGGGGGCACTTTCGTCTTAGCTTTTGGACAAGACGCA- GGCGCA MAQSRDGGNPFAEPSELDNP ACCCACGGCTGCTGCGGGGATCCTTGTGGCCCTTCCGGTCGGTGGAACCAATCCGTGCACAGAGAAGCGGGGCG- AACTGA FQDPAVIQHRPSRQYATLDV GGCGAGTGAAGTGGACTCTGAGGGCTACCGCTACCGCCACTGCTGCGGCAGGGGCGTGGAGGGCAGAGGGCCGC- GGAGGC YNPFETREPPPAYEPPAPAP CGCAGTTGCAAACATGGCTCAGAGCAGAGACGGCGGAAACCCGTTCGCCGAGCCCAGCGAGCTTGACAACCCCT- TTCAGG LPPPSAPSLQPSRKLSPTEP ACCCAGCTGTGATCCAGCACCGACCCAGCCGGCAGTATGCCACGCTTGACGTCTACAACCCTTTTGAGACCCGG- GAGCCA KNYGSYSTQASAAAATAELL CCACCAGCCTATGAGCCTCCAGCCCCTGCCCCATTGCCTCCACCCTCAGCTCCCTCCTTGCAGCCCTCGAGAAA- GCTCAG KKQEELNRKAEELDRREREL CCCCACAGAACCTAAGAACTATGGCTCATACAGCACTCAGGCCTCAGCTGCAGCAGCCACAGCTGAGCTGCTGA- AGAAAC QHAALGGTATRQNNWPPLPS AGGAGGAGCTCAACCGGAAGGCAGAGGAGTTGGACCGAAGGGAGCGAGAGCTGCAGCATGCTGCCCTGGGGGGC- ACAGCT FCPVQPCFFQDISMEIPQEF ACTCGACAGAACAATTGGCCCCCTCTACCTTCTTTTTGTCCAGTTCAGCCCTGCTTTTTCCAGGACATCTCCAT- GGAGAT QKTVSTMYYLWMCSTLALLL CCCCCAAGAATTTCAGAAGACTGTATCCACCATGTACTACCTCTGGATGTGCAGCACGCTGGCTCTTCTCCTGA- ACTTCC NFLACLASFCVETNNGAGFG TCGCCTGCCTGGCCAGCTTCTGTGTGGAAACCAACAATGGCGCAGGCTTTGGGCTTTCTATCCTCTGGGTCCTC- CTTTTC LSILWVLLFTPCSFVCWYRP ACTCCCTGCTCCTTTGTCTGCTGGTACCGCCCCATGTATAAGGCTTTCCGGAGTGACAGTTCATTCAATTTCTT- CGTTTT MYKAFRSDSSFNFFVFFFIF CTTCTTCATTTTCTTCGTCCAGGATGTGCTCTTTGTCCTCCAGGCCATTGGTATCCCAGGTTGGGGATTCAGTG- GCTGGA FVQDVLFVLQAIGIPGWGFS TCTCTGCTCTGGTGGTGCCGAAGGGCAACACAGCAGTATCCGTGCTCATGCTGCTGGTCGCCCTGCTCTTCACT- GGCATT GWISALVVPKGNTAVSVLML GCTGTGCTAGGAATTGTCATGCTGAAACGGATCCACTCCTTATACCGCCGCACAGGTGCCAGCTTTCAGAAGGC- CCAGCA LVALLFTGIAVLGIVMLKRI AGAATTTGCTGCTGGTGTCTTCTCCAACCCTGCGGTGCGAACCGCAGCTGCCAATGCAGCCGCTGGGGCTGCTG- AAAATG HSLYRRTGASFQKAQQEFAA CCTTCCGGGCCCCGTGACCCCTGACTGGGATGCCCTGGCCCTGCTACTTGAGGGAGCTGACTTAGCTCCCGTCC- CTAAGG GVFSNPAVRTAAANAAAGAA TCTCTGGGACTTGGAGAGACATCACTAACTGATGGCTCCTCCGTAGTGCTCCCAATCCTATGGCCATGACTGCT- GAACCT ENAFRAP GACAGGCGTGTGGGGAGTTCACTGTGACCTAGTCCCCCCATCAGGCCACACTGCTGCCACCTCTCACACGCCCC- AACCCA

GCTTCCCTCTGCTGTGCCACGGCTGTTGCTTCGGTTATTTAAATAAAAAGAAAGTGGAACTGGAACTGACAAAA- AAAAAA AAAAAAAAAAAAAA SEQ. ID NO. 49 STAR clone: CTGCAAGAACTANTCATTCNAGGTCACCAGANAGGAGCCCTGACCCNTCGCTGCCCAGCCTGTCCTTGTGTCGT- CTTTTT ACGGGAGACGACTGGATCATGGGGGCGGATTTTCCCCTTGCTGTTCTCATGATAGTGAGTTCTCATGAGATCTG- GTTGTT TAAAAGTGTATAGCACTTCCTGCTTCACTCTCTCCCACTCCACCATGTGAAGAAGGTGCCTTTGCCCTTCCGCC- ACGACT GTGTTTCCTGAGGCCTCCCCAGCCATGCTTCCTGTACAGCCTGCAGAACTGTGAGTTAATTAAACCTCTTTTCT- TCATAA AGAACA SEQ. ID NO. 50 SEQ. ID NO. 89 TCAAGATTAAACGACAAGGACAGACATGGCTCAGCGGATGACAACACAGCTGCTGCTCCTTCTAGTGTGGGTGG- CTGTAG MAQRMTTQLLLLLVWVAVVG TAGGGGAGGCTCAGACAAGGATTGCATGGGCCAGGACTGAGCTTCTCAATGTCTGCATGAACGCCAAGCACCAC- AAGGAA EAQTRIAWARTELLNVCMNA AAGCCAGGCCCCGAGGACAAGTTGCATGAGCAGTGTCGACCCTGGAGGAAGAATGCCTGCTGTTCTACCAACAC- CAGCCA KHHKEKPGPEDKLHEQCRPW GGAAGCCCATAAGGATGTTTCCTACCTATATAGATTCAACTGGAACCACTGTGGAGAGATGGCACCTGCCTGCA- AACGGC RKNACCSTNTSQEAHKDVSY ATTTCATCCAGGACACCTGCCTCTACGAGTGCTCCCCCAACTTGGGGCCCTGGATCCAGCAGGTGGATCAGAGC- TGGCGC LYRFNWNHCGEMAPACKRHF AAAGAGCGGGTACTGAACGTGCCCCTGTGCAAAGAGGACTGTGAGCAATGGTGGGAAGATTGTCGCACCTCCTA- CACCTG IQDTCLYECSPNLGPWIQQV CAAGAGCAACTGGCACAAGGGCTGGAACTGGACTTCAGGGTTTAACAAGTGCGCAGTGGGAGCTGCCTGCCAAC- CTTTCC DQSWRKERVLNVPLCKEDCE ATTTCTACTTCCCCACACCCACTGTTCTGTGCAATGAAATCTGGACTCACTCCTACAAGGTCAGCAACTACAGC- CGAGGG QWWEDCRTSYTCKSNWHKGW AGTGGCCGCTGCATCCAGATGTGGTTCGACCCAGCCCAGGGCAACCCCAATGAGGAGGTGGCGAGGTTCTATGC- TGCAGC NWTSGFNKCAVGAACQPFHF CATGAGTGGGGCTGGGCCCTGGGCAGCCTGGCCTTTCCTGCTTAGCCTGGCCCTAATGCTGCTGTGGCTGCTCA- GCTGAC YFPTPTVLCNEIWTHSYKVS CTCCTTTTACCTTCTGATACCTGGAAATCCCTGCCCTGTTCAGCCCCACAGCTCCCAACTATTTGGTTCCTGCT- CCATGG NYSRGSGRCIQMWFDPAQGN TCGGGCCTCTGACAGCCACTTTGAATAAACCAGACACCGCACATGTGTCTTGAGAATTATTTGG PNEEVARFYAAAMSGAGPWA AWPFLLSLALMLLWLLS 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 TTTTCCCAGTCACGACGTTGTAAAACGACGGCCAGTGAATTCTAATACGACTCACTATAGGGAGATGGAGAAAA- AAATCA CTGGACGCGTGGCGCGCCATTAATTAATGCGGCCGCTAGCTCGAGTGATAATAAGCGGATGAATGGCTGCAGGC- ATGCAA GCTTGGCGTAATCATGGTCATAGCTGTTTCCTGTGTGAAATTGTTATCCGCTCACAATTCCACACAACATACGA- GCCGGA AGCATAAAGTGTAAAGCCTGGGGTGCCTAATGAGTGAGCTAACTCACATTAATTGCGTTGCGCTCACTGCCCGC- TTTCCA GTCGGGAAACCTGTCGTGCCAGCTGCATTAATGAATCGGCCAACGCGCGGGGAGAGGCGGTTTGCGTATTGGGC- GCTCTT CCGCTTCCTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGCTGCGGCGAGCGGTATCAGCTCACTCAAAGGCG- GTAATA CGGTTATCCACAGAATCAGGGGATAACGCAGGAAAGAACATGTGAGCAAAAGGCCAGCAAAAGGCCAGGAACCG- TAAAAA GGCCGCGTTGCTGGCGTTTTTCCATAGGCTCCGCCCCCCTGACGAGCATCACAAAAATCGACGCTCAAGTCAGA- GGTGGC GAAACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGGAAGCTCCCTCGTGCGCTCTCCTGTTCCGACC- CTGCCG CTTACCGGATACCTGTCCGCCTTTCTCCCTTCGGGAAGCGTGGCGCTTTCTCAATGCTCACGCTGTAGGTATCT- CAGTTC GGTGTAGGTCGTTCGCTCCAAGCTGGGCTGTGTGCACGAACCCCCCGTTCAGCCCGACCGCTGCGCCTTATCCG- GTAACT ATCGTCTTGAGTCCAACCCGGTAAGACACGACTTATCGCCACTGGCAGCAGCCACTGGTAACAGGATTAGCAGA- GCGAGG TATGTAGGCGGTGCTACAGAGTTCTTGAAGTGGTGGCCTAACTACGGCTACACTAGAAGGACAGTATTTGGTAT- CTGCGC TCTGCTGAAGCCAGTTACCTTCGGAAAAAGAGTTGGTAGCTCTTGATCCGGCAAACAAACCACCGCTGGTAGCG- GTGGTT TTTTTGTTTGCAAGCAGCAGATTACGCGCAGAAAAAAAGGATCTCAAGAAGATCCTTTGATCTTTTCTACGGGG- TCTGAC GCTCAGTGGAACGAAAACTCACGTTAAGGGATTTTGGTCATGAGATTATCAAAAAGGATCTTCACCTAGATCCT- TTTAAA TTAAAAATGAAGTTTTAAATCAATCTAAAGTATATATGAGTAAACTTGGTCTGACAGTTACCAATGCTTAATCA- GTGAGG CACCTATCTCAGCGATCTGTCTATTTCGTTCATCCATAGTTGCCTGACTCCCCGTCGTGTAGATAACTACGATA- CGGGAG GGCTTACCATCTGGCCCCAGTGCTGCAATGATACCGCGAGACCCACGCTCACCGGCTCCAGATTTATCAGCAAT- AAACCA GCCAGCCGGAAGGGCCGAGCGCAGAAGTGGTCCTGCAACTTTATCCGCCTCCATCCAGTCTATTAATTGTTGCC- GGGAAG CTAGAGTAAGTAGTTCGCCAGTTAATAGTTTGCGCAACGTTGTTGCCATTGCTACAGGCATCGTGGTGTCACGC- TCGTCG TTTGGTATGGCTTCATTCAGCTCCGGTTCCCAACGATCAAGGCGAGTTACATGATCCCCCATGTTGTGCAAAAA- AGCGGT TAGCTCCTTCGGTCCTCCGATCGTTGTCAGAAGTAAGTTGGCCGCAGTGTTATCACTCATGGTTATGGCAGCAC- TGCATA ATTCTCTTACTGTCATGCCATCCGTAAGATGCTTTTCTGTGACTGGTGAGTACTCAACCAAGTCATTCTGAGAA- TAGTGT ATGCGGCGACCGAGTTGCTCTTGCCCGGCGTCAATACGGGATAATACCGCGCCACATAGCAGAACTTTAAAAGT- GCTCAT CATTGGAAAACGTTCTTCGGGGCGAAAACTCTCAAGGATCTTACCGCTGTTGAGATCCAGTTCGATGTAACCCA- CTCGTG CACCCAACTGATCTTCAGCATCTTTTACTTTCACCAGCGTTTCTGGGTGAGCAAAAACAGGAAGGCAAAATGCC- GCAAAA AAGGGAATAAGGGCGACACGGAAATGTTGAATACTCATACTCTTCCTTTTTCAATATTATTGAAGCATTTATCA- GGGTTA TTGTCTCATGAGCGGATACATATTTGAATGTATTTAGAAAAATAAACAAATAGGGGTTCCGCGCACATTTCCCC- GAAAAG TGCCACCTGACGTCTAAGAAACCATTATTATCATGACATTAACCTATAAAAATAGGCGTATCACGAGGCCCTTT- CGTCTC GCGCGTTTCGGTGATGACGGTGAAAACCTCTGACACATGCAGCTCCCGGAGACGGTCACAGCTTGTCTGTAAGC- GGATGC CGGGAGCAGACAAGCCCGTCAGGGCGCGTCAGCGGGTGTTGGCGGGTGTCGGGGCTGGCTTAACTATGCGGCAT- CAGAGC AGATTGTACTGAGAGTGCACCATATGCGGTGTGAAATACCGCACAGATGCGTAAGGAGAAAATACCGCATCAGG- CGCCAT TCGCCATTCAGGCTGCGCAACTGTTGGGAAGGGCGATCGGTGCGGGCCTCTTCGCTATTACGCCAGCTGGCGAA- AGGGGG ATGTGCTGCAAGGCGATTAAGTTGGGTAACGCCAGGG SEQ. ID NO. 100 TTTTCCCAGTCACGACGTTGTAAAACGACGGCCAGTGAATTCAATTAACCCTCACTAAAGGGAGACTTGTTCCA- AATGTG TTAGGcgCGCCGCATGCGTCGACGGATCCTGAGAACTTCAGGCTCCTGGGCAACGTGCTGGTTATTGTGCTGTC- TCATCA TTTTGGCAAAGAATTCACTCCTCAGGTGCAGGCTGCCTATCAGAAGGTGGTGGCTGGTGTGGCCAATGCCCTGG- CTCACA AATACCACTGAGATCTTTTTCCCTCTGCCAAAAATTATGGGGACATCATGAAGCCCCTTGAGCATCTGACTTCT- GGCTAA TAAAGGAAATTTATTTTCATTGCAAAAAAAAAAAGCGGCCGCTCTTCTATAGTGTCACCTAAATGGCCCAGCGG- CCGAGC TTGGCGTAATCATGGTCATAGCTGTTTCCTGTGTGAAATTGTTATCCGCTCACAATTCCACACAACATACGAGC- CGGAAG CATAAAGTGTAAAGCCTGGGGTGCCTAATGAGTGAGCTAACTCACATTAATTGCGTTGCGCTCACTGCCCGCTT- TCCAGT CGGGAAACCTGTCGTGCCAGCTGCATTAATGAATCGGCCAACGCGCGGGGAGAGGCGGTTTGCGTATTGGGCGC- TCTTCC GCTTCCTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGCTGCGGCGAGCGGTATCAGCTCACTCAAAGGCGGT- AATACG GTTATCCACAGAATCAGGGGATAACGCAGGAAAGAACATGTGAGCAAAAGGCCAGCAAAAGGCCAGGAACCGTA- AAAAGG CCGCGTTGCTGGCGTTTTTCCATAGGCTCCGCCCCCCTGACGAGCATCACAAAAATCGACGCTCAAGTCAGAGG- TGGCGA AACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGGAAGCTCCCTCGTGCGCTCTCCTGTTCCGACCCT- GCCGCT TACCGGATACCTGTCCGCCTTTCTCCCTTCGGGAAGCGTGGCGCTTTCTCAAAGCTCACGCTGTAGGTATCTCA- GTTCGG TGTAGGTCGTTCGCTCCAAGCTGGGCTGTGTGCACGAACCCCCCGTTCAGCCCGACCGCTGCGCCTTATCCGGT- AACTAT CGTCTTGAGTCCAACCCGGTAAGACACGACTTATCGCCACTGGCAGCAGCCACTGGTAACAGGATTAGCAGAGC- GAGGTA TGTAGGCGGTGCTACAGAGTTCTTGAAGTGGTGGCCTAACTACGGCTACACTAGAAGAACAGTATTTGGTATCT- GCGCTC TGCTGAAGCCAGTTACCTTCGGAAAAAGAGTTGGTAGCTCTTGATCCGGCAAACAAACCACCGCTGGTAGCGGT- GGTTTT TTTGTTTGCAAGCAGCAGATTACGCGCAGAAAAAAAGGATCTCAAGAAGATCCTTTGATCTTTTCTACGGGGTC- TGACGC TCAGTGGAACGAAAACTCACGTTAAGGGATTTTGGTCATGAGATTATCAAAAAGGATCTTCACCTAGATCCTTT- TAAATT AAAAATGAAGTTTTAAATCAATCTAAAGTATATATGAGTAAACTTGGTCTGACAGTTACCAATGCTTAATCAGT- GAGGCA CCTATCTCAGCGATCTGTCTATTTCGTTCATCCATAGTTGCCTGACTCCCCGTCGTGTAGATAACTACGATACG- GGAGGG CTTACCATCTGGCCCCAGTGCTGCAATGATACCGCGAGACCCACGCTCACCGGCTCCAGATTTATCAGCAATAA- ACCAGC CAGCCGGAAGGGCCGAGCGCAGAAGTGGTCCTGCAACTTTATCCGCCTCCATCCAGTCTATTAATTGTTGCCGG- GAAGCT AGAGTAAGTAGTTCGCCAGTTAATAGTTTGCGCAACGTTGTTGCCATTGCTACAGGCATCGTGGTGTCACGCTC- GTCGTT TGGTATGGCTTCATTCAGCTCCGGTTCCCAACGATCAAGGCGAGTTACATGATCCCCCATGTTGTGCAAAAAAG- CGGTTA GCTCCTTCGGTCCTCCGATCGTTGTCAGAAGTAAGTTGGCCGCAGTGTTATCACTCATGGTTATGGCAGCACTG- CATAAT TCTCTTACTGTCATGCCATCCGTAAGATGCTTTTCTGTGACTGGTGAGTACTCAACCAAGTCATTCTGAGAATA- GTGTAT GCGGCGACCGAGTTGCTCTTGCCCGGCGTCAATACGGGATAATACCGCGCCACATAGCAGAACTTTAAAAGTGC- TCATCA TTGGAAAACGTTCTTCGGGGCGAAAACTCTCAAGGATCTTACCGCTGTTGAGATCCAGTTCGATGTAACCCACT- CGTGCA CCCAACTGATCTTCAGCATCTTTTACTTTCACCAGCGTTTCTGGGTGAGCAAAAACAGGAAGGCAAAATGCCGC- AAAAAA GGGAATAAGGGCGACACGGAAATGTTGAATACTCATACTCTTCCTTTTTCAATATTATTGAAGCATTTATCAGG- GTTATT GTCTCATGAGCGGATACATATTTGAATGTATTTAGAAAAATAAACAAATAGGGGTTCCGCGCACATTTCCCCGA- AAAGTG CCACCTGACGTCTAAGAAACCATTATTATCATGACATTAACCTATAAAAATAGGCGTATCACGAGGCCCTTTCG- TCTCGC GCGTTTCGGTGATGACGGTGAAAACCTCTGACACATGCAGCTCCCGGAGACGGTCACAGCTTGTCTGTAAGCGG- ATGCCG GGAGCAGACAAGCCCGTCAGGGCGCGTCAGCGGGTGTTGGCGGGTGTCGGGGCTGGCTTAACTATGCGGCATCA- GAGCAG ATTGTACTGAGAGTGCACCATATGCGGTGTGAAATACCGCACAGATGCGTAAGGAGAAAATACCGCATCAGGCG- CCATTC GCCATTCAGGCTGCGCAACTGTTGGGAAGGGCGATCGGTGCGGGCCTCTTCGCTATTACGCCAGCTGGCGAAAG- GGGGAT GTGCTGCAAGGCGATTAAGTTGGGTAACGCCAGGG SEQ. ID NO. 101 TCGCGCGTTTCGGTGATGACGGTGAAAACCTCTGACACATGCAGCTCCCGGAGACGGTCACAGCTTGTCTGTAA- GCGGAT GCCGGGAGCAGACAAGCCCGTCAGGGCGCGTCAGCGGGTGTTGGCGGGTGTCGGGGCTGGCTTAACTATGCGGC- ATCAGA GCAGATTGTACTGAGAGTGCACCATATGCGGTGTGAAATACCGCACAGATGCGTAAGGAGAAAATACCGCATCA- GGCGCC ATTCGCCATTCAGGCTGCGCAACTGTTGGGAAGGGCGATCGGTGCGGGCCTCTTCGCTATTACGCCAGCTGGCG- AAAGGG GGATGTGCTGCAAGGCGATTAAGTTGGGTAACGCCAGGGTTTTCCCAGTCACGACGTTGTAAAACGACGGCCAG- TGCCAA GCTTTTCCAAAAAACTACCGTTGTTATAGGTGTCTCTTGAACACCTATAACAACGGTAGTGGATCCCGCGTCCT- TTCCAC AAGATATATAAACCCAAGAAATCGAAATACTTTCAAGTTACGGTAAGCATATGATAGTCCATTTTAAAACATAA- TTTTAA AACTGCAAACTACCCAAGAAATTATTACTTTCTACGTCACGTATTTTGTACTAATATCTTTGTGTTTACAGTCA- AATTAA TTCTAATTATCTCTCTAACAGCCTTGTATCGTATATGCAAATATGAAGGAATCATGGGAAATAGGCCCTCTTCC- TGCCCG ACCTTGGCGCGCGCTCGGCGCGCGGTCACGCTCCGTCACGTGGTGCGTTTTGCCTGCGCGTCTTTCCACTGGGG- AATTCA TGCTTCTCCTCCCTTTAGTGAGGGTAATTCTCTCTCTCTCCCTATAGTGAGTCGTATTAATTCCTTCTCTTCTA- TAGTGT CACCTAAATCGTTGCAATTCGTAATCATGTCATAGCTGTTTCCTGTGTGAAATTGTTATCCGCTCACAATTCCA- CACAAC ATACGAGCCGGAAGCATAAAGTGTAAAGCCTGGGGTGCCTAATGAGTGAGCTAACTCACATTAATTGCGTTGCG- CTCACT GCCCGCTTTCCAGTCGGGAAACCTGTCGTGCCAGCTGCATTAATGAATCGGCCAACGCGCGGGGAGAGGCGGTT- TGCGTA TTGGGCGCTCTTCCGCTTCCTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGCTGCGGCGAGCGGTATCAGCT- CACTCA AAGGCGGTAATACGGTTATCCACAGAATCAGGGGATAACGCAGGAAAGAACATGTGAGCAAAAGGCCAGCAAAA- GGCCAG

GAACCGTAAAAAGGCCGCGTTGCTGGCGTTTTTCCATAGGCTCCGCCCCCCTGACGAGCATCACAAAAATCGAC- GCTCAA GTCAGAGGTGGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGGAAGCTCCCTCGTGCGCTCT- CCTGTT CCGACCCTGCCGCTTACCGGATACCTGTCCGCCTTTCTCCCTTCGGGAAGCGTGGCGCTTTCTCATAGCTCACG- CTGTAG GTATCTCAGTTCGGTGTAGGTCGTTCGCTCCAAGCTGGGCTGTGTGCACGAACCCCCCGTTCAGCCCGACCGCT- GCGCCT TATCCGGTAACTATCGTCTTGAGTCCAACCCGGTAAGACACGACTTATCGCCACTGGCAGCAGCCACTGGTAAC- AGGATT AGCAGAGCGAGGTATGTAGGCGGTGCTACAGAGTTCTTGAAGTGGTGGCCTAACTACGGCTACACTAGAAGAAC- AGTATT TGGTATCTGCGCTCTGCTGAAGCCAGTTACCTTCGGAAAAAGAGTTGGTAGCTCTTGATCCGGCAAAAAAACCA- CCGCTG GTAGCGGTGGTTTTTTTGTTTGCAAGCAGCAGATTACGCGCAGAAAAAAAGGATCTCAAGAAGATCCTTTGATC- TTTTCT ACGGGGTCTGACGCTCAGTGGAACGAAAACTCACGTTAAGGGATTTTGGTCATGAGATTATCAAAAAGGATCTT- CACCTA GATCCTTTTAAATTAAAAATGAAGTTTTAAATCAATCTAAAGTATATATGAGTAAACTTGGTCTGACAGTTACC- AATGCT TAATCAGTGAGGCACCTATCTCAGCGATCTGTCTATTTCGTTCATCCATAGTTGCCTGACTCCCCGTCGTGTAG- ATAACT ACGATACGGGAGGGCTTACCATCTGGCCCCAGTGCTGCAATGATACCGCGAGACCCACGCTCACCGGCTCCAGA- TTTATC AGCAATAAACCAGCCAGCCGGAAGGGCCGAGCGCAGAAGTGGTCCTGCAACTTTATCCGCCTCCATCCAGTCTA- TTAATT GTTGCCGGGAAGCTAGAGTAAGTAGTTCGCCAGTTAATAGTTTGCGCAACGTTGTTGCCATTGCTACAGGCATC- GTGGTG TCACGCTCGTCGTTTGGTATGGCTTCATTCAGCTCCGGTTCCCAACGATCAAGGCGAGTTACATGATCCCCCAT- GTTGTG CAAAAAAGCGGTTAGCTCCTTCGGTCCTCCGATCGTTGTCAGAAGTAAGTTGGCCGCAGTGTTATCACTCATGG- TTATGG CAGCACTGCATAATTCTCTTACTGTCATGCCATCCGTAAGATGCTTTTCTGTGACTGGTGAGTACTCAACCAAG- TCATTC TGAGAATAGTGTATGCGGCGACCGAGTTGCTCTTGCCCGGCGTCAATACGGGATAATACCGCGCCACATAGCAG- AACTTT AAAAGTGCTCATCATTGGAAAACGTTCTTCGGGGCGAAAACTCTCAAGGATCTTACCGCTGTTGAGATCCAGTT- CGATGT AACCCACTCGTGCACCCAACTGATCTTCAGCATCTTTTACTTTCACCAGCGTTTCTGGGTGAGCAAAAACAGGA- AGGCAA AATGCCGCAAAAAAGGGAATAAGGGCGACACGGAAATGTTGAATACTCATACTCTTCCTTTTTCAATATTATTG- AAGCAT TTATCAGGGTTATTGTCTCATGAGCGGATACATATTTGAATGTATTTAGAAAAATAAACAAATAGGGGTTCCGC- GCACAT TTCCCCGAAAAGTGCCACCTATTGGTGTGGAAAGTCCCCAGGCTCCCCAGCAGGCAGAAGTATGCAAAGCATGC- ATCTCA ATTAGTCAGCAACCAGGTGTGGAAAGTCCCCAGGCTCCCCAGCAGGCAGAAGTATGCAAAGCATGCATCTCAAT- TAGTCA GCAACCATAGTCCCGCCCCTAACTCCGCCCATCCCGCCCCTAACTCCGCCCAGTTCCGCCCATTCTCCGCCCCA- TGGCTG ACTAATTTTTTTTATTTATGCAGAGGCCGAGGCCGCCTCGGCCTCTGAGCTATTCCAGAAGTAGTGAGGAGGCT- TTTTTG GAGGCCTAGGCTTTTGCAAAAAGCTAGCTTGCATGCCTGCAGGTCGGCCGCCACGACCGGTGCCGCCACCATCC- CCTGAC CCACGCCCCTGACCCCTCACAAGGAGACGACCTTCCATGACCGAGTACAAGCCCACGGTGCGCCTCGCCACCCG- CGACGA CGTCCCCCGGGCCGTACGCACCCTCGCCGCCGCGTTCGCCGACTACCCCGCCACGCGCCACACCGTCGACCCGG- ACCGCC ACATCGAGCGGGTCACCGAGCTGCAAGAACTCTTCCTCACGCGCGTCGGGCTCGACATCGGCAAGGTGTGGGTC- GCGGAC GACGGCGCCGCGGTGGCGGTCTGGACCACGCCGGAGAGCGTCGAAGCGGGGGCGGTGTTCGCCGAGATCGGCCC- GCGCAT GGCCGAGTTGAGCGGTTCCCGGCTGGCCGCGCAGCAACAGATGGAAGGCCTCCTGGCGCCGCACCGGCCCAAGG- AGCCCG CGTGGTTCCTGGCCACCGTCGGCGTCTCGCCCGACCACCAGGGCAAGGGTCTGGGCAGCGCCGTCGTGCTCCCC- GGAGTG GAGGCGGCCGAGCGCGCCGGGGTGCCCGCCTTCCTGGAGACCTCCGCGCCCCGCAACCTCCCCTTCTACGAGCG- GCTCGG CTTCACCGTCACCGCCGACGTCGAGGTGCCCGAAGGACCGCGCACCTGGTGCATGACCCGCAAGCCCGGTGCCT- GACGCC CGCCCCACGACCCGCAGCGCCCGACCGAAAGGAGCGCACGACCCCATGGCTCCGACCGAAGCCACCCGGGGCGG- CCCCGC CGACCCCGCACCCGCCCCCGAGGCCCACCGACTCTAGAGGATCATAATCAGCCATACCACATTTGTAGAGGTTT- TACTTG CTTTAAAAAACCTCCCACACCTCCCCCTGAACCTGAAACATAAAATGAATGCAATTGTTGTTGTTAACTTGTTT- ATTGCA GCTTATAATGGTTACAAATAAAGCAATAGCATCACAAATTTCACAAATAAAGCATTTTTTTCACTGCAATCTAA- GAAACC ATTATTATCATGACATTAACCTATAAAAATAGGCGTATCACGAGGCCCTTTCGTC 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 ccctaatgcctccaacaataactgttgactttttattttcagtcagagaagcctggcaaccaagaactgttttt- ttggtg MKILILGIFLFLCSTPAWAK gtttacgagaacttaactgaattggaaaatatttgctttaatgaaacaatttactcttgtgcaacactaaattg- tgtcaa EKHYYIGIIETTWDYASDHG tcaagcaaataaggaagaaagtcttatttataaaattgcctgctcctgattttacttcatttcttctcaggctc- caagaa EKKLISVDTEHSNIYLQNGP ggggaaaaaaatgaagattttgatacttggtatttttctgtttttatgtagtaccccagcctgggcgaaagaaa- agcatt DRIGRLYKKALYLQYTDETF attacattggaattattgaaacgacttgggattatgcctctgaccatggggaaaagaaacttatttctgttgac- acggaa RTTIEKPVWLGFLGPIIKAE cattccaatatctatcttcaaaatggcccagatagaattgggagactatataagaaggccctttatcttcagta- cacaga TGDKVYVHLKNLASRPYTFH tgaaacctttaggacaactatagaaaaaccggtctggcttgggtttttaggccctattatcaaagctgaaactg- gagata SHGITYYKEHEGAIYPDNTT aagtttatgtacacttaaaaaaccttgcctctaggccctacacctttcattcacatggaataacttactataag- gaacat DFQRADDKVYPGEQYTYMLL gagggggccatctaccctgataacaccacagattttcaaagagcagatgacaaagtatatccaggagagcagta- tacata ATEEQSPGEGDGNCVTRIYH catgttgcttgccactgaagaacaaagtcctggggaaggagatggcaattgtgtgactaggatttaccattccc- acattg SHIDAPKDIASGLIGPLIIC atgctccaaaagatattgcctcaggactcatcggacctttaataatctgtaaaaaagattctctagataaagaa- aaagaa KKDSLDKEKEKHIDREFVVM aaacatattgaccgagaatttgtggtgatgttttctgtggtggatgaaaatttcagctggtacctagaagacaa- cattaa FSVVDENFSWYLEDNIKTYC aacctactgctcagaaccagagaaagttgacaaagacaacgaagacttccaggagagtaacagaatgtattctg- tgaatg SEPEKVDKDNEDFQESNRMY gatacacttttggaagtctcccaggactctccatgtgtgctgaagacagagtaaaatggtacctttttggtatg- ggtaat SVNGYTFGSLPGLSMCAEDR gaagttgatgtgcacgcagctttctttcacgggcaagcactgactaacaagaactaccgtattgacacaatcaa- cctctt VKWYLFGMGNEVDVHAAFFH tcctgctaccctgtttgatgcttatatggtggcccagaaccctggagaatggatgctcagctgtcagaatctaa- accatc GQALTNKNYRIDTINLFPAT tgaaagccggtttgcaagcctttttccaggtccaggagtgtaacaagtcttcatcaaaggataatatccgtggg- aagcat LFDAYMVAQNPGEWMLSCQN gttagacactactacattgccgctgaggaaatcatctggaactatgctccctctggtatagacatcttcactaa- agaaaa LNHLKAGLQAFFQVQECNKS cttaacagcacctggaagtgactcagcggtgttttttgaacaaggtaccacaagaattggaggctcttataaaa- agctgg SSKDNIRGKHVRHYYIAAEE tttatcgtgagtacacagatgcctccttcacaaatcgaaaggagagaggccctgaagaagagcatcttggcatc- ctgggt IIWNYAPSGIDIFTKENLTA cctgtcatttgggcagaggtgggagacaccatcagagtaaccttccataacaaaggagcatatcccctcagtat- tgagcc PGSDSAVFFEQGTTRIGGSY gattggggtgagattcaataagaacaacgagggcacatactattccccaaattacaacccccagagcagaagtg- tgcctc KKLVYREYTDASFTNRKERG cttcagcctcccatgtggcacccacagaaacattcacctatgaatggactgtccccaaagaagtaggacccact- aatgca PEEEHLGILGPVIWAEVGDT gatcctgtgtgtctagctaagatgtattattctgctgtggatcccactaaagatatattcactgggcttattgg- gccaat IRVTFHNKGAYPLSIEPIGV gaaaatatgcaagaaaggaagtttacatgcaaatgggagacagaaagatgtagacaaggaattctatttgtttc- ctacag RFNKNNEGTYYSPNYNPQSR tatttgatgagaatgagagtttactcctggaagataatattagaatgtttacaactgcacctgatcaggtggat- aaggaa SVPPSASHVAPTETFTYEWT gatgaagactttcaggaatctaataaaatgcactccatgaatggattcatgtatgggaatcagccgggtctcac- tatgtg VPKEVGPTNADPVCLAKMYY caaaggagattcggtcgtgtggtacttattcagcgccggaaatgaggccgatgtacatggaatatacttttcag- gaaaca SAVDPTKDIFTGLIGPMKIC catatctgtggagaggagaacggagagacacagcaaacctcttccctcaaacaagtcttacgctccacatgtgg- cctgac KKGSLHANGRQKDVDKEFYL acagaggggacttttaatgttgaatgccttacaactgatcattacacaggcggcatgaagcaaaaatatactgt- gaacca FPTVFDENESLLLEDNIRMF atgcaggcggcagtctgaggattccaccttctacctgggagagaggacatactatatcgcagcagtggaggtgg- aatggg TTAPDQVDKEDEDFQESNKM attattccccacaaagggagtgggaaaaggagctgcatcatttacaagagcagaatgtttcaaatgcattttta- gataag HSMNGFMYGNQPGLTMCKGD ggagagttttacataggctcaaagtacaagaaagttgtgtatcggcagtatactgatagcacattccgtgttcc- agtgga SVVWYLFSAGNEADVHGIYF gagaaaagctgaagaagaacatctgggaattctaggtccacaacttcatgcagatgttggagacaaagtcaaaa- ttatct SGNTYLWRGERRDTANLFPQ ttaaaaacatggccacaaggccctactcaatacatgcccatggggtacaaacagagagttctacagttactcca- acatta TSLTLHMWPDTEGTFNVECL ccaggtgaaactctcacttacgtatggaaaatcccagaaagatctggagctggaacagaggattctgcttgtat- tccatg TTDHYTGGMKQKYTVNQCRR ggcttattattcaactgtggatcaagttaaggacctctacagtggattaattggccccctgattgtttgtcgaa- gacctt QSEDSTFYLGERTYYIAAVE acttgaaagtattcaatcccagaaggaaactggaatttgcccttctgtttctagtttttgatgagaatgaatct- tggtac VEWDYSPQREWEKELHHLQE ttagatgacaacatcaaaacatactctgatcaccccgagaaagtaaacaaagatgatgaggaattcatagaaag- caataa QNVSNAFLDKGEFYIGSKYK aatgcatgctattaatggaagaatgtttggaaacctacaaggcctcacaatgcacgtgggagatgaagtcaact- ggtatc KVVYRQYTDSTFRVPVERKA tgatgggaatgggcaatgaaatagacttacacactgtacattttcacggccatagcttccaatacaagcacagg- ggagtt EEEHLGILGPQLHADVGDKV tatagttctgatgtctttgacattttccctggaacataccaaaccctagaaatgtttccaagaacacctggaat- ttggtt KIIFKNMATRPYSIHAHGVQ actccactgccatgtgaccgaccacattcatgctggaatggaaaccacttacaccgttctacaaaatgaagaca- ccaaat TESSTVTPTLPGETLTYVWK ctggctgaatgaaataaattggtgataagtggaaaaaagagaaaaaccaatgattcataacaatgtatgtgaaa- gtgtaa IPERSGAGTEDSACIPWAYY aatagaatgttactttggaatgactataaacattaaaagaagactggaagcatacaactttgtacatttgtggg- ggaaaa STVDQVKDLYSGLIGPLIVC ctattaattttttgcaaatggaaagatcaacagactatataatgatacatgactgacacttgtacactaggtaa- taaaac RRPYLKVFNPRRKLEFALLF tgattcatacagtctaatgatatcaccgctgttagggttttataaaactgcatttaaaaaaagatctatgacca- gatatt LVFDENESWYLDDNIKTYSD ctcctgggtgctcctcaaaggaacactattaaggttcattgaaatgttttcaatcattgccttcccattgatcc- ttctaa HPEKVNKDDEEFIESNKMHA catgctgttgacatcacacctaatattcagagggaatgggcaaggtatgagggaaggaaataaaaaataaaata- aataaa INGRMFGNLQGLTMHVGDEV atagaatgacacaaatttgagttttgtgaacccctgaacagatggtcttaaggacgttatctggaactggagaa- aagcag NWYLMGMGNEIDLHTVHFHG agttgagagacaattctatagattaaatcctggtaaggacaaacattgccattagaagaaaagcttcaaaatag- acctgt HSFQYKHRGVYSSDVFDIFP ggcagatgtcacatgagtagaatttctgcccagccttaactgcattcagaggataatatcaatgaactaaactt- gaacta GTYQTLEMFPRTPGIWLLHC aaaattttttaaacaaaaagttataaatgaagacacatggttgtgaatacaatgatgtatttctttattttcac- atacac HVTDHIHAGMETTYTVLQNE tctagctaaaagagcaagagtacacatcaacaaaaatggaaacaaggctttggctgaaaaaaacatgcatttga- caaatc DTKSG atgttaatagctagacaagaagaaagttagctttgtaaacttctacttcatttgattcagagaaacagagcatg- agtttt cttaaaagtaacaagaaaa 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

REFERENCES

[0495] Jemal A, Murray T, Ward E, Samuels A, Tiwari R C, Ghafoor A, Feuer E J and Thun M J. Cancer statistics, 2005. CA Cancer J Clin 2005; 55:10-30. [0496] Menon U, Skates S J, Lewis S, Rosenthal A N, Rufford B, Sibley K, Macdonald N, Dawnay A, Jeyarajah A, Bast R C Jr, Oram D and Jacobs I J. Prospective study using the risk of ovarian cancer algorithm to screen for ovarian cancer. J Clin Oncol. 2005 Nov. 1; 23(31):7919-26. [0497] Bonome T, Lee J Y, Park D C, Radonovich M, Pise-Masison C, Brady J, Gardner G J, Hao K, Wong W H, Barrett J C, Lu K H, Sood A K, Gershenson D M, Mok S C and Birrer M J. Expression profiling of serous low malignancy potential, low grade, and high grade tumors of the ovary. Cancer Res 2005; 65:10602-10612. [0498] Chambers, A. and Vanderhyden, B. Ovarian Cancer Biomarkers in Urine. Clin Cancer Res 2006; 12(2):323-327. [0499] Berek et al. Cancer Medicine. 5th ed. London: B.C. Decker, Inc.; 2000. p. 1687-1720. [0500] Bristow R.E. Surgical standards in the management of ovarian cancer. Curr Opin Oncol 2000; 12:474-480. [0501] Brown E, Stewart M, Rye T, Al-Nafussi A, Williams A R, Bradburn M, Smyth J and Gabra H. Carcinosarcoma of the ovary: 19 years of prospective data from a single center. Cancer 2004; 100:2148-2153. [0502] Shih, L-M and Kurman, R J. Molecular Pathogenesis of Ovarian Borderline Tumors: New Insights and Old Challenges. Clin Cancer Res 2005; 11(20):7273-7279. [0503] Seidman J D, Russell P, Kurman R J. Surface epithelial tumors of the ovary. In: Kurman R J, editor. Blaustein's pathologyo f the female genital tract. 5th ed. New York: Springer-Verlag; 2002. pp. 791-904. [0504] Mor G, Visintin I, Lai Y, Zhao H, Schwartz P, Rutherford T, Yue L, Bray-Ward P and Ward D C Serum protein markers for early detection of ovarian cancer. P NA S 2005; 102:7677-7682. [0505] Kozak K R, Amneus M W, Pusey S M, Su F, Luong M N, Luong S A, Reddy S T and Farias-Eisner R. Identification of biomarkers for ovarian cancer using strong anion-exchange ProteinChips: potential use in diagnosis and prognosis. P NA S 2003; 100:12343-12348. [0506] McIntosh M W, Drescher C, Karlan B, Scholler N, Urban N, Hellstrom K E and Hellstrom I. Gynecol Oncol. 2004 October; 95(1):9-15. [0507] Woolas R P, Xu F J, Jacobs I J, Yu Y H, Daly L, Berchuck A, Soper J T, Clarke-Pearson D L, Oram D H and Bast R C Jr. Elevation of multiple serum markers in patients with stage I ovarian cancer. J Natl Cancer Inst. 1993 Nov. 3; 85(21):1748-51. [0508] Schorge J O, Drake R D, Lee H, Skates S J, Rajanbabu R, Miller D S, Kim J H, Cramer D W, Berkowitz R S and Mok S C. Osteopontin as an adjunct to CA125 in detecting recurrent ovarian cancer. Clin. Cancer Res. 10; 3474-3478. [0509] Gorelik E, Landsittel D P, Marrangoni A M, Modugno F, Velikokhatnaya L, Winans M T, Bigbee W L, Herberman R B and Lokshin A E. 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Microbiol. Mol Biol Rev. 2003 December; 67(4):657-85. [0520] Brummelkamp T R, Bernards R and Agami R. A system for stable expression of short interfering RNAs in mammalian cells. Science 2002. 296: 550-553. [0521] Elbashir S M, Harborth J, Lendeckel W, Yalcin A, Weber K, and Tuschl T. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 2001. 411: 494-498. [0522] Hannon G J. RNA interference. Nature 2002. 418: 244-251. [0523] Leamon C P and Low P S. Folate-mediated targeting: from diagnostics to drug and gene delivery. Drug Discov Today 2001. 6: 44-51. [0524] Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983. 65: 55-63. [0525] Provencher D M, Lounis H, Champoux L, Tetrault M, Manderson E N, Wang J C, Eydoux P, Savoie R, Tonin P N and Mes-Masson A M. Characterization of four novel epithelial ovarian cancer cell lines. 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Sequence CWU 1

2561114DNAHomo 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 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 282421261DNAHomo sapiens 42gcagccagat ctgctgggac acctttccca aggaagagcc cgttgcactg ggctttgaag 60gataagcagg agcttgttac tcaggcagag gaagaaagag catcccaggc ggggggagca 120gcatatgcaa aggcacgaag gggccccagg agcctaggga gtctggggaa gtgtgagcac 180tttggagagt ggaggctgga gcgctgtgga gagtgggggc tggtggccgg gaatgaagct 240gcagctggct gggccacatg gtaaaggctg acaactggac ccagaggcca actagcctat 300gatcagcatt tcccaaaatc tgtttcccga ctcatggttc tgtgagatgt gacaagggct 360cctttttcat tcctgagacg ccggttttca tctgtgatgc ggggacagct gcgctccttg 420ctgcgaggcg tcaggaccca ggtgatagtg aagggagggt ggcgcccgcg gttcccggcg 480gccactgatg cctgtctctc tgtcgtgtgt acgtgcgtgt gtgctccacg cctggcttct 540caggctttca aatgtgtgtc agcagcagca gcagcagcca cgacgaggcc cccgtcctga 600acgacaagca cctggacgtg cccgacatca tcatcacgcc ccccaccccc acgggcatga 660tgctgccgag ggacttgggg agcacagtct ggctggatga gacagggtcg tgcccagatg 720atggagaaat cgacccagaa gcctgaggag gtgtcctggg tttggctggc tggctcctgc 780tccagcggcc cggcttcagg tgtccggggg cgtggctgcc tggagcaggt gtgctgaata 840ccctggatgg gaactgagcg aacccgggcc tccgctcaga gagacgtggc aggaccagcg 900aggaatccag cctgtccact tccagaacag tgtttcccag gccccgctga gtggaccgga 960cctctgacac ctccaggttc ttgctgactc cggcctggtg aaagggagcg ccatggtcct 1020ggctgttggg gtcccaggga gaggctctct tctggacaaa cacaccctcc cagcccccag 1080ggctgtgcaa acacatgccc ctcccataag caccaacaag aacttcttgc aggtggagtg 1140gctgtttttt ataagttgtt ttacagatac ggaaacagtc caaaatggga tttataattt 1200cttttttgca ttataaataa agatcctctg taacaaaaaa aaaaaaaaaa aaaaaaaaaa 1260a 1261433237DNAHomo 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 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 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 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 Lys1 5 10 15Met Glu Val Asp Gln Leu Lys Lys Glu Val Thr Leu Glu Arg Met Leu 20 25 30Val Ser Lys Cys Cys Glu Glu Val Arg Asp Tyr Val Glu Glu Arg Ser 35 40 45Gly Glu Asp Pro Leu Val Lys Gly Ile Pro Glu Asp Lys Asn Pro Phe 50 55 60Lys Glu Leu Lys Gly Gly Cys Val Ile Ser65 7052413PRTHomo sapiens 52Met Val Glu Arg Cys Ser Arg Gln Gly Cys Thr Ile Thr Met Ala Tyr1 5 10 15Ile Asp Tyr Asn Met Ile Val Ala Phe Met Leu Gly Asn Tyr Ile Asn 20 25 30Leu Arg Glu Ser Ser Thr Glu Pro Asn Asp Ser Leu Trp Phe Ser Leu 35 40 45Gln Lys Lys Asn Asp Thr Thr Glu Ile Glu Thr Leu Leu Leu Asn Thr 50 55 60Ala Pro Lys Ile Ile Asp Glu Gln Leu Val Cys Arg Leu Ser Lys Thr65 70 75 80Asp Ile Phe Ile Ile Cys Arg Asp Asn Lys Ile Tyr Leu Asp Lys Met 85 90 95Ile Thr Arg Asn Leu Lys Leu Arg Phe Tyr Gly His Arg Gln Tyr Leu 100 105 110Glu Cys Glu Val Phe Arg Val Glu Gly Ile Lys Asp Asn Leu Asp Asp 115 120 125Ile Lys Arg Ile Ile Lys Ala Arg Glu His Arg Asn Arg Leu Leu Ala 130 135 140Asp Ile Arg Asp Tyr Arg Pro Tyr Ala Asp Leu Val Ser Glu Ile Arg145 150 155 160Ile Leu Leu Val Gly Pro Val Gly Ser Gly Lys Ser Ser Phe Phe Asn 165 170 175Ser Val Lys Ser Ile Phe His Gly His Val Thr Gly Gln Ala Val Val 180 185 190Gly Ser Asp Thr Thr Ser Ile Thr Glu Arg Tyr Arg Ile Tyr Ser Val 195 200 205Lys Asp Gly Lys Asn Gly Lys Ser Leu Pro Phe Met Leu Cys Asp Thr 210 215 220Met Gly Leu Asp Gly Ala Glu Gly Ala Gly Leu Cys Met Asp Asp Ile225 230 235 240Pro His Ile Leu Lys Gly Cys Met Pro Asp Arg Tyr Gln Phe Asn Ser 245 250 255Arg Lys Pro Ile Thr Pro Glu His Ser Thr Phe Ile Thr Ser Pro Ser 260 265 270Leu Lys Asp Arg Ile His Cys Val Ala Tyr Val Leu Asp Ile Asn Ser 275 280 285Ile Asp Asn Leu Tyr Ser Lys Met Leu Ala Lys Val Lys Gln Val His 290 295 300Lys Glu Val Leu Asn Cys Gly Ile Ala Tyr Val Ala Leu Leu Thr Lys305 310 315 320Val Asp Asp Cys Ser Glu Val Leu Gln Asp Asn Phe Leu Asn Met Ser 325 330 335Arg Ser Met Thr Ser Gln Ser Arg Val Met Asn Val His Lys Met Leu 340 345 350Gly Ile Pro Ile Ser Asn Ile Leu Met Val Gly Asn Tyr Ala Ser Asp 355 360 365Leu Glu Leu Asp Pro Met Lys Asp Ile Leu Ile Leu Ser Ala Leu Arg 370 375 380Gln Met Leu Arg Ala Ala Asp Asp Phe Leu Glu Asp Leu Pro Leu Glu385 390 395 400Glu Thr Gly Ala Ile Glu Arg Ala Leu Gln Pro Cys Ile 405 41053328PRTHomo sapiens 53 Met Ser Ser Tyr Leu Glu Tyr Val Ser Cys Ser Ser Ser Gly Gly Val1 5 10 15Gly Gly Asp Val Leu Ser Leu Ala Pro Lys Phe Cys Arg Ser Asp Ala 20 25 30Arg Pro Val Ala Leu Gln Pro Ala Phe Pro Leu Gly Asn Gly Asp Gly 35 40 45Ala Phe Val Ser Cys Leu Pro Leu Ala Ala Ala Arg Pro Ser Pro Ser 50 55 60Pro Pro Ala Ala Pro Ala Arg Pro Ser Val Pro Pro Pro Ala Ala Pro65 70 75 80Gln Tyr Ala Gln Cys Thr Leu Glu Gly Ala Tyr Glu Pro Gly Ala Ala 85 90 95Pro Ala Ala Ala Ala Gly Gly Ala Asp Tyr Gly Phe Leu Gly Ser Gly 100 105 110Pro Ala Tyr Asp Phe Pro Gly Val Leu Gly Arg Ala Ala Asp Asp Gly 115 120 125Gly Ser His Val His Tyr Ala Thr Ser Ala Val Phe Ser Gly Gly Gly 130 135 140Ser Phe Leu Leu Ser Gly Gln Val Asp Tyr Ala Ala Phe Gly Glu Pro145 150 155 160Gly Pro Phe Pro Ala Cys Leu Lys Ala Ser Ala Asp Gly His Pro Gly 165 170 175Ala Phe Gln Thr Ala Ser Pro Ala Pro Gly Thr Tyr Pro Lys Ser Val 180 185 190Ser Pro Ala Ser Gly Leu Pro Ala Ala Phe Ser Thr Phe Glu Trp Met 195 200 205Lys Val Lys Arg Asn Ala Ser Lys Lys Gly Lys Leu Ala Glu Tyr Gly 210 215 220Ala Ala Ser Pro Ser Ser Ala Ile Arg Thr Asn Phe Ser Thr Lys Gln225 230 235 240Leu Thr Glu Leu Glu Lys Glu Phe His Phe Asn Lys Tyr Leu Thr Arg 245 250 255Ala Arg Arg Ile Glu Ile Ala Asn Cys Leu His Leu Asn Asp Thr Gln 260 265 270Val Lys Ile Trp Phe Gln Asn Arg Arg Met Lys Gln Lys Lys Arg Glu 275 280 285Arg Glu Gly Leu Leu Ala Thr Ala Ile Pro Val Ala Pro Leu Gln Leu 290 295 300Pro Leu Ser Gly Thr Thr Pro Thr Lys Phe Ile Lys Asn Pro Gly Ser305 310 315 320Pro Ser Gln Ser Gln Glu Pro Ser 32554107PRTHomo sapiens 54Met Ala Asn Glu Val Gln Asp Leu Leu Ser Pro Arg Lys Gly Gly His1 5 10 15Pro Pro Ala Val Lys Ala Gly Gly Met Arg Ile Ser Lys Lys Gln Glu 20 25 30Ile Gly Thr Leu Glu Arg His Thr Lys Lys Thr Gly Phe Glu Lys Thr 35 40 45Ser Ala Ile Ala Asn Val Ala Lys Ile Gln Thr Leu Asp Ala Leu Asn 50 55 60Asp Thr Leu Glu Lys Leu Asn Tyr Lys Phe Pro Ala Thr Val His Met65 70 75 80Ala His Gln Lys Pro Thr Pro Ala Leu Glu Lys Val Val Pro Leu Lys 85 90 95Arg Ile Tyr Ile Ile Gln Gln Pro Arg Lys Cys 100 10555478PRTHomo sapiens 55Met Ser Thr Asn Gly Asp Asp His Gln Val Lys Asp Ser Leu Glu Gln1 5 10 15Leu Arg Cys His Phe Thr Trp Glu Leu Ser Ile Asp Asp Asp Glu Met 20 25 30Pro Asp Leu Glu Asn Arg Val Leu Asp Gln Ile Glu Phe Leu Asp Thr 35 40 45Lys Tyr Ser Val Gly Ile His Asn Leu Leu Ala Tyr Val Lys His Leu 50 55 60Lys Gly Gln Asn Glu Glu Ala Leu Lys Ser Leu Lys Glu Ala Glu Asn65 70 75 80Leu Met Gln Glu Glu His Asp Asn Gln Ala Asn Val Arg Ser Leu Val 85 90 95Thr Trp Gly Asn Phe Ala Trp Met Tyr Tyr His Met Gly Arg Leu Ala 100 105 110Glu Ala Gln Thr Tyr Leu Asp Lys Val Glu Asn Ile Cys Lys Lys Leu 115 120 125Ser Asn Pro Phe Arg Tyr Arg Met Glu Cys Pro Glu Ile Asp Cys Glu 130 135 140Glu Gly Trp Ala Leu Leu Lys Cys Gly Gly Lys Asn Tyr Glu Arg Ala145 150 155 160Lys Ala Cys Phe Glu Lys Val Leu Glu Val Asp Pro Glu Asn Pro Glu 165 170 175Ser Ser Ala Gly Tyr Ala Ile Ser Ala Tyr Arg Leu Asp Gly Phe Lys 180 185 190Leu Ala Thr Lys Asn His Lys Pro Phe Ser Leu Leu Pro Leu Arg Gln 195 200 205Ala Val Arg Leu Asn Pro Asp Asn Gly Tyr Ile Lys Val Leu Leu Ala 210 215 220Leu Lys Leu Gln Asp Glu Gly Gln Glu Ala Glu Gly Glu Lys Tyr Ile225 230 235 240Glu Glu Ala Leu Ala Asn Met Ser Ser Gln Thr Tyr Val Phe Arg Tyr 245 250 255Ala Ala Lys Phe Tyr Arg Arg Lys Gly Ser Val Asp Lys Ala Leu Glu 260 265 270Leu Leu Lys Lys Ala Leu Gln Glu Thr Pro Thr Ser Val Leu Leu His 275 280 285His Gln Ile Gly Leu Cys Tyr Lys Ala Gln Met Ile Gln Ile Lys Glu 290 295 300Ala Thr Lys Gly Gln Pro Arg Gly Gln Asn Arg Glu Lys Leu Asp Lys305 310 315 320Met Ile Arg Ser Ala Ile Phe His Phe Glu Ser Ala Val Glu Lys Lys 325 330 335Pro Thr Phe Glu Val Ala His Leu Asp Leu Ala Arg Met Tyr Ile Glu 340 345 350Ala Gly Asn His Arg Lys Ala Glu Glu Asn Phe Gln Lys Leu Leu Cys 355 360 365Met Lys Pro Val Val Glu Glu Thr Met Gln Asp Ile His Phe His Tyr 370 375 380Gly Arg Phe Gln Glu Phe Gln Lys Lys Ser Asp Val Asn Ala Ile Ile385 390 395 400His Tyr Leu Lys Ala Ile Lys Ile Glu Gln Ala Ser Leu Thr Arg Asp 405 410 415Lys Ser Ile Asn Ser Leu Lys Lys Leu Val Leu Arg Lys Leu Arg Arg 420 425 430Lys Ala Leu Asp Leu Glu Ser Leu Ser Leu Leu Gly Phe Val Tyr Lys 435 440 445Leu Glu Gly Asn Met Asn Glu Ala Leu Glu Tyr Tyr Glu Arg Ala Leu 450 455 460Arg Leu Ala Ala Asp Phe Glu Asn Ser Val Arg Gln Gly Pro465 470 475561020PRTHomo sapiens 56Met Gln Ser Cys Ala Arg Ala Trp Gly Leu Arg Leu Gly Arg Gly Val1 5 10 15Gly Gly Gly Arg Arg Leu Ala Gly Gly Ser Gly Pro Cys Trp Ala Pro 20 25 30Arg Ser Arg Asp Ser Ser Ser Gly Gly Gly Asp Ser Ala Ala Ala Gly 35 40 45Ala Ser Arg Leu Leu Glu Arg Leu Leu Pro Arg His Asp Asp Phe Ala 50 55 60Arg Arg His Ile Gly Pro Gly Asp Lys Asp Gln Arg Glu Met Leu Gln65 70 75 80Thr Leu Gly Leu Ala Ser Ile Asp Glu Leu Ile Glu Lys Thr Val Pro 85 90 95Ala Asn Ile Arg Leu Lys Arg Pro Leu Lys Met Glu Asp Pro Val Cys 100 105 110Glu Asn Glu Ile Leu Ala Thr Leu His Ala Ile Ser Ser Lys Asn Gln 115 120 125Ile Trp Arg Ser Tyr Ile Gly Met Gly Tyr Tyr Asn Cys Ser Val Pro 130 135 140Gln Thr Ile Leu Arg Asn Leu Leu Glu Asn Ser Gly Trp Ile Thr Gln145 150 155 160Tyr Thr Pro Tyr Gln Pro Glu Val Ser Gln Gly Arg Leu Glu Ser Leu 165 170 175Leu Asn Tyr Gln Thr Met Val Cys Asp Ile Thr Gly Leu Asp Met Ala 180 185 190Asn Ala Ser Leu Leu Asp Glu Gly Thr Ala Ala Ala Glu Ala Leu Gln 195 200 205Leu Cys Tyr Arg His Asn Lys Arg Arg Lys Phe Leu Val Asp Pro Arg 210 215 220Cys His Pro Gln Thr Ile Ala Val Val Gln Thr Arg Ala Lys Tyr Thr225 230 235 240Gly Val Leu Thr Glu Leu Lys Leu Pro Cys Glu Met Asp Phe Ser Gly 245 250 255Lys Asp Val Ser Gly Val Leu Phe Gln Tyr Pro Asp Thr Glu Gly Lys 260 265 270Val Glu Asp Phe Thr Glu Leu Val Glu Arg Ala His Gln Ser Gly Ser 275 280 285Leu Ala Cys Cys Ala Thr Asp Leu Leu Ala Leu Cys Ile Leu Arg Pro 290 295 300Pro Gly Glu Phe Gly Val Asp Ile Ala Leu Gly Ser Ser Gln Arg Phe305 310 315 320Gly Val Pro Leu Gly Tyr Gly Gly Pro His Ala Ala Phe Phe Ala Val 325 330 335Arg Glu Ser Leu Val Arg Met Met Pro Gly Arg Met Val Gly Val Thr 340 345 350Arg Asp Ala Thr Gly Lys Glu Val Tyr Arg Leu Ala Leu Gln Thr Arg 355 360 365Glu Gln His Ile Arg Arg Asp Lys Ala Thr Ser Asn Ile Cys Thr Ala 370 375 380Gln Ala Leu Leu Ala Asn Met Ala Ala Met Phe Arg Ile Tyr His Gly385 390 395 400Ser His Gly Leu Glu His Ile Ala Arg Arg Val His Asn Ala Thr Leu 405 410 415Ile Leu Ser Glu Gly Leu Lys Arg Ala Gly His Gln Leu Gln His Asp 420 425 430Leu Phe Phe Asp Thr Leu Lys Ile His Cys Gly Cys Ser Val Lys Glu 435 440 445Val Leu Gly Arg Ala Ala Gln Arg Gln Ile Asn Phe Arg Leu Phe Glu 450 455 460Asp Gly Thr Leu Gly Ile Ser Leu Asp Glu Thr Val Asn Glu Lys Asp465 470 475 480Leu Asp Asp Leu Leu Trp Ile Phe Gly Cys Glu Ser Ser Ala Glu Leu 485 490 495Val Ala Glu Ser Met Gly Glu Glu Cys Arg Gly Ile Pro Gly Ser Val 500 505 510Phe Lys Arg Thr Ser Pro Phe Leu Thr His Gln Val Phe Asn Ser Tyr 515 520 525His Ser Glu Thr Asn Ile Val Arg Tyr Met Lys Lys Leu Glu Asn Lys 530 535 540Asp Ile Ser Leu Val His Ser Met Ile Pro Leu Gly Ser Cys Thr Met545 550 555 560Lys Leu Asn Ser Ser Ser Glu Leu Ala Pro Ile Thr Trp Lys Glu Phe 565 570 575Ala Asn Ile His Pro Phe Val Pro Leu Asp Gln Ala Gln Gly Tyr Gln 580 585 590Gln Leu Phe Arg Glu Leu Glu Lys Asp Leu Cys Glu Leu Thr Gly Tyr 595 600 605Asp Gln Val Cys Phe Gln Pro Asn Ser Gly Ala Gln Gly Glu Tyr Ala 610 615 620Gly Leu Ala Thr Ile Arg Ala Tyr Leu Asn Gln Lys Gly Glu Gly His625 630 635 640Arg Thr Val Cys Leu Ile Pro Lys Ser Ala His Gly Thr Asn Pro Ala 645 650 655Ser Ala His Met Ala Gly Met Lys Ile Gln Pro Val Glu Val Asp Lys 660 665 670Tyr Gly Asn Ile Asp Ala Val His Leu Lys Ala Met Val Asp Lys His 675 680 685Lys Glu Asn Leu Ala Ala Ile Met Ile Thr Tyr Pro Ser Thr Asn Gly 690 695 700Val Phe Glu Glu Asn Ile Ser Asp Val Cys Asp Leu Ile His Gln His705 710 715 720Gly Gly Gln Val Tyr Leu Asp Gly Ala Asn Met Asn Ala Gln Val Gly 725 730 735Ile Cys Arg Pro Gly Asp Phe Gly Ser Asp Val Ser His Leu Asn Leu 740 745 750His Lys Thr Phe Cys Ile Pro His Gly Gly Gly Gly Pro Gly Met Gly 755 760 765Pro Ile Gly Val Lys Lys His Leu Ala Pro Phe Leu Pro Asn His Pro 770 775 780Val Ile Ser Leu Lys Arg Asn Glu Asp Ala Cys Pro Val Gly Thr Val785 790 795 800Ser Ala Ala Pro Trp Gly Ser Ser Ser Ile Leu Pro Ile Ser Trp Ala 805 810 815Tyr Ile Lys Met Met Gly Gly Lys Gly Leu Lys Gln Ala Thr Glu Thr 820 825 830Ala Ile Leu Asn Ala Asn Tyr Met Ala Lys Arg Leu Glu Thr His Tyr 835 840 845Arg Ile Leu Phe Arg Gly Ala Arg Gly Tyr Val Gly His Glu Phe Ile 850 855 860Leu Asp Thr Arg Pro Phe Lys Lys Ser Ala Asn Ile Glu Ala Val Asp865 870 875 880Val Ala Lys Arg Leu Gln Asp Tyr Gly Phe His Ala Pro Thr Met Ser 885 890 895Trp Pro Val Ala Gly Thr Leu Met Val Glu Pro Thr Glu Ser Glu Asp 900 905 910Lys Ala Glu Leu Asp Arg Phe Cys Asp Ala Met Ile Ser Ile Arg Gln 915 920 925Glu Ile Ala Asp Ile Glu Glu Gly Arg Ile Asp Pro Arg Val Asn Pro 930 935 940Leu Lys Met Ser Pro His Ser Leu Thr Cys Val Thr Ser Ser His Trp945 950 955 960Asp Arg Pro Tyr Ser Arg Glu Val Ala Ala Phe Pro Leu Pro Phe Met 965 970 975Lys Pro Glu Asn Lys Phe Trp Pro Thr Ile Ala Arg Ile Asp Asp Ile 980 985 990Tyr Gly Asp Gln His Leu Val Cys Thr Cys Pro Pro Met Glu Val Tyr 995 1000

1005Glu Ser Pro Phe Ser Glu Gln Lys Arg Ala Ser Ser 1010 1015 102057513PRTHomo sapiens 57Met Ile Arg Thr Pro Leu Ser Ala Ser Ala His Arg Leu Leu Leu Pro1 5 10 15Gly Ser Arg Gly Arg Pro Pro Arg Asn Met Gln Pro Thr Gly Arg Glu 20 25 30Gly Ser Arg Ala Leu Ser Arg Arg Tyr Leu Arg Arg Leu Leu Leu Leu 35 40 45Leu Leu Leu Leu Leu Leu Arg Gln Pro Val Thr Arg Ala Glu Thr Thr 50 55 60Pro Gly Ala Pro Arg Ala Leu Ser Thr Leu Gly Ser Pro Ser Leu Phe65 70 75 80Thr Thr Pro Gly Val Pro Ser Ala Leu Thr Thr Pro Gly Leu Thr Thr 85 90 95Pro Gly Thr Pro Lys Thr Leu Asp Leu Arg Gly Arg Ala Gln Ala Leu 100 105 110Met Arg Ser Phe Pro Leu Val Asp Gly His Asn Asp Leu Pro Gln Val 115 120 125Leu Arg Gln Arg Tyr Lys Asn Val Leu Gln Asp Val Asn Leu Arg Asn 130 135 140Phe Ser His Gly Gln Thr Ser Leu Asp Arg Leu Arg Asp Gly Leu Val145 150 155 160Gly Ala Gln Phe Trp Ser Ala Ser Val Ser Cys Gln Ser Gln Asp Gln 165 170 175Thr Ala Val Arg Leu Ala Leu Glu Gln Ile Asp Leu Ile His Arg Met 180 185 190Cys Ala Ser Tyr Ser Glu Leu Glu Leu Val Thr Ser Ala Glu Gly Leu 195 200 205Asn Ser Ser Gln Lys Leu Ala Cys Leu Ile Gly Val Glu Gly Gly His 210 215 220Ser Leu Asp Ser Ser Leu Ser Val Leu Arg Ser Phe Tyr Val Leu Gly225 230 235 240Val Arg Tyr Leu Thr Leu Thr Phe Thr Cys Ser Thr Pro Trp Ala Glu 245 250 255Ser Ser Thr Lys Phe Arg His His Met Tyr Thr Asn Val Ser Gly Leu 260 265 270Thr Ser Phe Gly Glu Lys Val Val Glu Glu Leu Asn Arg Leu Gly Met 275 280 285Met Ile Asp Leu Ser Tyr Ala Ser Asp Thr Leu Ile Arg Arg Val Leu 290 295 300Glu Val Ser Gln Ala Pro Val Ile Phe Ser His Ser Ala Ala Arg Ala305 310 315 320Val Cys Asp Asn Leu Leu Asn Val Pro Asp Asp Ile Leu Gln Leu Leu 325 330 335Lys Lys Asn Gly Gly Ile Val Met Val Thr Leu Ser Met Gly Val Leu 340 345 350Gln Cys Asn Leu Leu Ala Asn Val Ser Thr Val Ala Asp His Phe Asp 355 360 365His Ile Arg Ala Val Ile Gly Ser Glu Phe Ile Gly Ile Gly Gly Asn 370 375 380Tyr Asp Gly Thr Gly Arg Phe Pro Gln Gly Leu Glu Asp Val Ser Thr385 390 395 400Tyr Pro Val Leu Ile Glu Glu Leu Leu Ser Arg Ser Trp Ser Glu Glu 405 410 415Glu Leu Gln Gly Val Leu Arg Gly Asn Leu Leu Arg Val Phe Arg Gln 420 425 430Val Glu Lys Val Arg Glu Glu Ser Arg Ala Gln Ser Pro Val Glu Ala 435 440 445Glu Phe Pro Tyr Gly Gln Leu Ser Thr Ser Cys His Ser His Leu Val 450 455 460Pro Gln Asn Gly His Gln Ala Thr His Leu Glu Val Thr Lys Gln Pro465 470 475 480Thr Asn Arg Val Pro Trp Arg Ser Ser Asn Ala Ser Pro Tyr Leu Val 485 490 495Pro Gly Leu Val Ala Ala Ala Thr Ile Pro Thr Phe Thr Gln Trp Leu 500 505 510Cys 58174PRTHomo sapiens 58Met Leu Arg Thr Glu Ser Cys Arg Pro Arg Ser Pro Ala Gly Gln Val1 5 10 15Ala Ala Ala Ser Pro Leu Leu Leu Leu Leu Leu Leu Leu Ala Trp Cys 20 25 30Ala Gly Ala Cys Arg Gly Ala Pro Ile Leu Pro Gln Gly Leu Gln Pro 35 40 45Glu Gln Gln Leu Gln Leu Trp Asn Glu Ile Asp Asp Thr Cys Ser Ser 50 55 60Phe Leu Ser Ile Asp Ser Gln Pro Gln Ala Ser Asn Ala Leu Glu Glu65 70 75 80Leu Cys Phe Met Ile Met Gly Met Leu Pro Lys Pro Gln Glu Gln Asp 85 90 95Glu Lys Asp Asn Thr Lys Arg Phe Leu Phe His Tyr Ser Lys Thr Gln 100 105 110Lys Leu Gly Lys Ser Asn Val Val Ser Ser Val Val His Pro Leu Leu 115 120 125Gln Leu Val Pro His Leu His Glu Arg Arg Met Lys Arg Phe Arg Val 130 135 140Asp Glu Glu Phe Gln Ser Pro Phe Ala Ser Gln Ser Arg Gly Tyr Phe145 150 155 160Leu Phe Arg Pro Arg Asn Gly Arg Arg Ser Ala Gly Phe Ile 165 17059431PRTHomo sapiens 59Met His Val Arg Ser Leu Arg Ala Ala Ala Pro His Ser Phe Val Ala1 5 10 15Leu Trp Ala Pro Leu Phe Leu Leu Arg Ser Ala Leu Ala Asp Phe Ser 20 25 30Leu Asp Asn Glu Val His Ser Ser Phe Ile His Arg Arg Leu Arg Ser 35 40 45Gln Glu Arg Arg Glu Met Gln Arg Glu Ile Leu Ser Ile Leu Gly Leu 50 55 60Pro His Arg Pro Arg Pro His Leu Gln Gly Lys His Asn Ser Ala Pro65 70 75 80Met Phe Met Leu Asp Leu Tyr Asn Ala Met Ala Val Glu Glu Gly Gly 85 90 95Gly Pro Gly Gly Gln Gly Phe Ser Tyr Pro Tyr Lys Ala Val Phe Ser 100 105 110Thr Gln Gly Pro Pro Leu Ala Ser Leu Gln Asp Ser His Phe Leu Thr 115 120 125Asp Ala Asp Met Val Met Ser Phe Val Asn Leu Val Glu His Asp Lys 130 135 140Glu Phe Phe His Pro Arg Tyr His His Arg Glu Phe Arg Phe Asp Leu145 150 155 160Ser Lys Ile Pro Glu Gly Glu Ala Val Thr Ala Ala Glu Phe Arg Ile 165 170 175Tyr Lys Asp Tyr Ile Arg Glu Arg Phe Asp Asn Glu Thr Phe Arg Ile 180 185 190Ser Val Tyr Gln Val Leu Gln Glu His Leu Gly Arg Glu Ser Asp Leu 195 200 205Phe Leu Leu Asp Ser Arg Thr Leu Trp Ala Ser Glu Glu Gly Trp Leu 210 215 220Val Phe Asp Ile Thr Ala Thr Ser Asn His Trp Val Val Asn Pro Arg225 230 235 240His Asn Leu Gly Leu Gln Leu Ser Val Glu Thr Leu Asp Gly Gln Ser 245 250 255Ile Asn Pro Lys Leu Ala Gly Leu Ile Gly Arg His Gly Pro Gln Asn 260 265 270Lys Gln Pro Phe Met Val Ala Phe Phe Lys Ala Thr Glu Val His Phe 275 280 285Arg Ser Ile Arg Ser Thr Gly Ser Lys Gln Arg Ser Gln Asn Arg Ser 290 295 300Lys Thr Pro Lys Asn Gln Glu Ala Leu Arg Met Ala Asn Val Ala Glu305 310 315 320Asn Ser Ser Ser Asp Gln Arg Gln Ala Cys Lys Lys His Glu Leu Tyr 325 330 335Val Ser Phe Arg Asp Leu Gly Trp Gln Asp Trp Ile Ile Ala Pro Glu 340 345 350Gly Tyr Ala Ala Tyr Tyr Cys Glu Gly Glu Cys Ala Phe Pro Leu Asn 355 360 365Ser Tyr Met Asn Ala Thr Asn His Ala Ile Val Gln Thr Leu Val His 370 375 380Phe Ile Asn Pro Glu Thr Val Pro Lys Pro Cys Cys Ala Pro Thr Gln385 390 395 400Leu Asn Ala Ile Ser Val Leu Tyr Phe Asp Asp Ser Ser Asn Val Ile 405 410 415Leu Lys Lys Tyr Arg Asn Met Val Val Arg Ala Cys Gly Cys His 420 425 43060212PRTHomo sapiens 60Met Lys Pro Pro Ser Ser Ile Gln Thr Ser Glu Phe Asp Ser Ser Asp1 5 10 15Glu Glu Pro Ile Glu Asp Glu Gln Thr Pro Ile His Ile Ser Trp Leu 20 25 30Ser Leu Ser Arg Val Asn Cys Ser Gln Phe Leu Gly Leu Cys Ala Leu 35 40 45Pro Gly Cys Lys Phe Lys Asp Val Arg Arg Asn Val Gln Lys Asp Thr 50 55 60Glu Glu Leu Lys Ser Cys Gly Ile Gln Asp Ile Phe Val Phe Cys Thr65 70 75 80Arg Gly Glu Leu Ser Lys Tyr Arg Val Pro Asn Leu Leu Asp Leu Tyr 85 90 95Gln Gln Cys Gly Ile Ile Thr His His His Pro Ile Ala Asp Gly Gly 100 105 110Thr Pro Asp Ile Ala Ser Cys Cys Glu Ile Met Glu Glu Leu Thr Thr 115 120 125Cys Leu Lys Asn Tyr Arg Lys Thr Leu Ile His Cys Tyr Gly Gly Leu 130 135 140Gly Arg Ser Cys Leu Val Ala Ala Cys Leu Leu Leu Tyr Leu Ser Asp145 150 155 160Thr Ile Ser Pro Glu Gln Ala Ile Asp Ser Leu Arg Asp Leu Arg Gly 165 170 175Ser Gly Ala Ile Gln Thr Ile Lys Gln Tyr Asn Tyr Leu His Glu Phe 180 185 190Arg Asp Lys Leu Ala Ala His Leu Ser Ser Arg Asp Ser Gln Ser Arg 195 200 205Ser Val Ser Arg 2106179PRTHomo sapiens 61Met Ser His Lys Gln Ile Tyr Tyr Ser Asp Lys Tyr Asp Asp Glu Glu1 5 10 15Phe Glu Tyr Arg His Val Met Leu Pro Lys Asp Ile Ala Lys Leu Val 20 25 30Pro Lys Thr His Leu Met Ser Glu Ser Glu Trp Arg Asn Leu Gly Val 35 40 45Gln Gln Ser Gln Gly Trp Val His Tyr Met Ile His Glu Pro Glu Pro 50 55 60His Ile Leu Leu Phe Arg Arg Pro Leu Pro Lys Lys Pro Lys Lys65 70 7562509PRTHomo sapiens 62Met Glu Arg Arg Arg Leu Trp Gly Ser Ile Gln Ser Arg Tyr Ile Ser1 5 10 15Met Ser Val Trp Thr Ser Pro Arg Arg Leu Val Glu Leu Ala Gly Gln 20 25 30Ser Leu Leu Lys Asp Glu Ala Leu Ala Ile Ala Ala Leu Glu Leu Leu 35 40 45Pro Arg Glu Leu Phe Pro Pro Leu Phe Met Ala Ala Phe Asp Gly Arg 50 55 60His Ser Gln Thr Leu Lys Ala Met Val Gln Ala Trp Pro Phe Thr Cys65 70 75 80Leu Pro Leu Gly Val Leu Met Lys Gly Gln His Leu His Leu Glu Thr 85 90 95Phe Lys Ala Val Leu Asp Gly Leu Asp Val Leu Leu Ala Gln Glu Val 100 105 110Arg Pro Arg Arg Trp Lys Leu Gln Val Leu Asp Leu Arg Lys Asn Ser 115 120 125His Gln Asp Phe Trp Thr Val Trp Ser Gly Asn Arg Ala Ser Leu Tyr 130 135 140Ser Phe Pro Glu Pro Glu Ala Ala Gln Pro Met Thr Lys Lys Arg Lys145 150 155 160Val Asp Gly Leu Ser Thr Glu Ala Glu Gln Pro Phe Ile Pro Val Glu 165 170 175Val Leu Val Asp Leu Phe Leu Lys Glu Gly Ala Cys Asp Glu Leu Phe 180 185 190Ser Tyr Leu Ile Glu Lys Val Lys Arg Lys Lys Asn Val Leu Arg Leu 195 200 205Cys Cys Lys Lys Leu Lys Ile Phe Ala Met Pro Met Gln Asp Ile Lys 210 215 220Met Ile Leu Lys Met Val Gln Leu Asp Ser Ile Glu Asp Leu Glu Val225 230 235 240Thr Cys Thr Trp Lys Leu Pro Thr Leu Ala Lys Phe Ser Pro Tyr Leu 245 250 255Gly Gln Met Ile Asn Leu Arg Arg Leu Leu Leu Ser His Ile His Ala 260 265 270Ser Ser Tyr Ile Ser Pro Glu Lys Glu Glu Gln Tyr Ile Ala Gln Phe 275 280 285Thr Ser Gln Phe Leu Ser Leu Gln Cys Leu Gln Ala Leu Tyr Val Asp 290 295 300Ser Leu Phe Phe Leu Arg Gly Arg Leu Asp Gln Leu Leu Arg His Val305 310 315 320Met Asn Pro Leu Glu Thr Leu Ser Ile Thr Asn Cys Arg Leu Ser Glu 325 330 335Gly Asp Val Met His Leu Ser Gln Ser Pro Ser Val Ser Gln Leu Ser 340 345 350Val Leu Ser Leu Ser Gly Val Met Leu Thr Asp Val Ser Pro Glu Pro 355 360 365Leu Gln Ala Leu Leu Glu Arg Ala Ser Ala Thr Leu Gln Asp Leu Val 370 375 380Phe Asp Glu Cys Gly Ile Thr Asp Asp Gln Leu Leu Ala Leu Leu Pro385 390 395 400Ser Leu Ser His Cys Ser Gln Leu Thr Thr Leu Ser Phe Tyr Gly Asn 405 410 415Ser Ile Ser Ile Ser Ala Leu Gln Ser Leu Leu Gln His Leu Ile Gly 420 425 430Leu Ser Asn Leu Thr His Val Leu Tyr Pro Val Pro Leu Glu Ser Tyr 435 440 445Glu Asp Ile His Gly Thr Leu His Leu Glu Arg Leu Ala Tyr Leu His 450 455 460Ala Arg Leu Arg Glu Leu Leu Cys Glu Leu Gly Arg Pro Ser Met Val465 470 475 480Trp Leu Ser Ala Asn Pro Cys Pro His Cys Gly Asp Arg Thr Phe Tyr 485 490 495Asp Pro Glu Pro Ile Leu Cys Pro Cys Phe Met Pro Asn 500 50563165PRTHomo sapiens 63Met Gly Trp Asp Leu Thr Val Lys Met Leu Ala Gly Asn Glu Phe Gln1 5 10 15Val Ser Leu Ser Ser Ser Met Ser Val Ser Glu Leu Lys Ala Gln Ile 20 25 30Thr Gln Lys Ile Gly Val His Ala Phe Gln Gln Arg Leu Ala Val His 35 40 45Pro Ser Gly Val Ala Leu Gln Asp Arg Val Pro Leu Ala Ser Gln Gly 50 55 60Leu Gly Pro Gly Ser Thr Val Leu Leu Val Val Asp Lys Cys Asp Glu65 70 75 80Pro Leu Ser Ile Leu Val Arg Asn Asn Lys Gly Arg Ser Ser Thr Tyr 85 90 95Glu Val Arg Leu Thr Gln Thr Val Ala His Leu Lys Gln Gln Val Ser 100 105 110Gly Leu Glu Gly Val Gln Asp Asp Leu Phe Trp Leu Thr Phe Glu Gly 115 120 125Lys Pro Leu Glu Asp Gln Leu Pro Leu Gly Glu Tyr Gly Leu Lys Pro 130 135 140Leu Ser Thr Val Phe Met Asn Leu Arg Leu Arg Gly Gly Gly Thr Glu145 150 155 160Pro Gly Gly Arg Ser 16564363PRTHomo sapiens 64Met Arg Trp Val Arg His Asp Ala Pro Ala Arg Arg Gly Gln Leu Arg1 5 10 15Arg Leu Leu Glu His Val Arg Leu Pro Leu Leu Ala Pro Ala Tyr Phe 20 25 30Leu Glu Lys Val Glu Ala Asp Glu Leu Leu Gln Ala Cys Gly Glu Cys 35 40 45Arg Pro Leu Leu Leu Glu Ala Arg Ala Cys Phe Ile Leu Gly Arg Glu 50 55 60Ala Gly Ala Leu Arg Thr Arg Pro Arg Arg Phe Met Asp Leu Ala Glu65 70 75 80Val Ile Val Val Ile Gly Gly Cys Asp Arg Lys Gly Leu Leu Lys Leu 85 90 95Pro Phe Ala Asp Ala Tyr His Pro Glu Ser Gln Arg Trp Thr Pro Leu 100 105 110Pro Ser Leu Pro Gly Tyr Thr Arg Ser Glu Phe Ala Ala Cys Ala Leu 115 120 125Arg Asn Asp Val Tyr Val Ser Gly Gly His Ile Asn Ser His Asp Val 130 135 140Trp Met Phe Ser Ser His Leu His Thr Trp Ile Lys Val Ala Ser Leu145 150 155 160His Lys Gly Arg Trp Arg His Lys Met Ala Val Val Gln Gly Gln Leu 165 170 175Phe Ala Val Gly Gly Phe Asp Gly Leu Arg Arg Leu His Ser Val Glu 180 185 190Arg Tyr Asp Pro Phe Ser Asn Thr Trp Ala Ala Ala Ala Pro Leu Pro 195 200 205Glu Ala Val Ser Ser Ala Ala Val Ala Ser Cys Ala Gly Lys Leu Phe 210 215 220Val Ile Gly Gly Ala Arg Gln Gly Gly Val Asn Thr Asp Lys Val Gln225 230 235 240Cys Phe Asp Pro Lys Glu Asp Arg Trp Ser Leu Arg Ser Pro Ala Pro 245 250 255Phe Ser Gln Arg Cys Leu Glu Ala Val Ser Leu Glu Asp Thr Ile Tyr 260 265 270Val Met Gly Gly Leu Met Ser Lys Ile Phe Thr Tyr Asp Pro Gly Thr 275 280 285Asp Val Trp Gly Glu Ala Ala Val Leu Pro Ser Pro Val Glu Ser Cys 290 295 300Gly Val Thr Val Cys Asp Gly Lys Val His Ile Leu Gly Gly Arg Asp305 310 315 320Asp Arg Gly Glu Ser Thr Asp Lys Val Phe Thr Phe Asp Pro Ser Ser 325 330 335Gly Gln Val Glu Val Gln Pro Ser Leu Gln Arg Cys Thr Ser Ser His 340 345 350Gly Cys Val Thr Ile Ile Gln Ser Leu Gly Arg

355 36065282PRTHomo sapiens 65Met Ala Ser Leu Gly Gln Ile Leu Phe Trp Ser Ile Ile Ser Ile Ile1 5 10 15Ile Ile Leu Ala Gly Ala Ile Ala Leu Ile Ile Gly Phe Gly Ile Ser 20 25 30Gly Arg His Ser Ile Thr Val Thr Thr Val Ala Ser Ala Gly Asn Ile 35 40 45Gly Glu Asp Gly Ile Gln Ser Cys Thr Phe Glu Pro Asp Ile Lys Leu 50 55 60Ser Asp Ile Val Ile Gln Trp Leu Lys Glu Gly Val Leu Gly Leu Val65 70 75 80His Glu Phe Lys Glu Gly Lys Asp Glu Leu Ser Glu Gln Asp Glu Met 85 90 95Phe Arg Gly Arg Thr Ala Val Phe Ala Asp Gln Val Ile Val Gly Asn 100 105 110Ala Ser Leu Arg Leu Lys Asn Val Gln Leu Thr Asp Ala Gly Thr Tyr 115 120 125Lys Cys Tyr Ile Ile Thr Ser Lys Gly Lys Gly Asn Ala Asn Leu Glu 130 135 140Tyr Lys Thr Gly Ala Phe Ser Met Pro Glu Val Asn Val Asp Tyr Asn145 150 155 160Ala Ser Ser Glu Thr Leu Arg Cys Glu Ala Pro Arg Trp Phe Pro Gln 165 170 175Pro Thr Val Val Trp Ala Ser Gln Val Asp Gln Gly Ala Asn Phe Ser 180 185 190Glu Val Ser Asn Thr Ser Phe Glu Leu Asn Ser Glu Asn Val Thr Met 195 200 205Lys Val Val Ser Val Leu Tyr Asn Val Thr Ile Asn Asn Thr Tyr Ser 210 215 220Cys Met Ile Glu Asn Asp Ile Ala Lys Ala Thr Gly Asp Ile Lys Val225 230 235 240Thr Glu Ser Glu Ile Lys Arg Arg Ser His Leu Gln Leu Leu Asn Ser 245 250 255Lys Ala Ser Leu Cys Val Ser Ser Phe Phe Ala Ile Ser Trp Ala Leu 260 265 270Leu Pro Leu Ser Pro Tyr Leu Met Leu Lys 275 28066890PRTHomo sapiens 66Met Ser Gln Gly Ile Leu Ser Pro Pro Ala Gly Leu Leu Ser Asp Asp1 5 10 15Asp Val Val Val Ser Pro Met Phe Glu Ser Thr Ala Ala Asp Leu Gly 20 25 30Ser Val Val Arg Lys Asn Leu Leu Ser Asp Cys Ser Val Val Ser Thr 35 40 45Ser Leu Glu Asp Lys Gln Gln Val Pro Ser Glu Asp Ser Met Glu Lys 50 55 60Val Lys Val Tyr Leu Arg Val Arg Pro Leu Leu Pro Ser Glu Leu Glu65 70 75 80Arg Gln Glu Asp Gln Gly Cys Val Arg Ile Glu Asn Val Glu Thr Leu 85 90 95Val Leu Gln Ala Pro Lys Asp Ser Phe Ala Leu Lys Ser Asn Glu Arg 100 105 110Gly Ile Gly Gln Ala Thr His Arg Phe Thr Phe Ser Gln Ile Phe Gly 115 120 125Pro Glu Val Gly Gln Ala Ser Phe Phe Asn Leu Thr Val Lys Glu Met 130 135 140Val Lys Asp Val Leu Lys Gly Gln Asn Trp Leu Ile Tyr Thr Tyr Gly145 150 155 160Val Thr Asn Ser Gly Lys Thr His Thr Ile Gln Gly Thr Ile Lys Asp 165 170 175Gly Gly Ile Leu Pro Arg Ser Leu Ala Leu Ile Phe Asn Ser Leu Gln 180 185 190Gly Gln Leu His Pro Thr Pro Asp Leu Lys Pro Leu Leu Ser Asn Glu 195 200 205Val Ile Trp Leu Asp Ser Lys Gln Ile Arg Gln Glu Glu Met Lys Lys 210 215 220Leu Ser Leu Leu Asn Gly Gly Leu Gln Glu Glu Glu Leu Ser Thr Ser225 230 235 240Leu Lys Arg Ser Val Tyr Ile Glu Ser Arg Ile Gly Thr Ser Thr Ser 245 250 255Phe Asp Ser Gly Ile Ala Gly Leu Ser Ser Ile Ser Gln Cys Thr Ser 260 265 270Ser Ser Gln Leu Asp Glu Thr Ser His Arg Trp Ala Gln Pro Asp Thr 275 280 285Ala Pro Leu Pro Val Pro Ala Asn Ile Arg Phe Ser Ile Trp Ile Ser 290 295 300Phe Phe Glu Ile Tyr Asn Glu Leu Leu Tyr Asp Leu Leu Glu Pro Pro305 310 315 320Ser Gln Gln Arg Lys Arg Gln Thr Leu Arg Leu Cys Glu Asp Gln Asn 325 330 335Gly Asn Pro Tyr Val Lys Asp Leu Asn Trp Ile His Val Gln Asp Ala 340 345 350Glu Glu Ala Trp Lys Leu Leu Lys Val Gly Arg Lys Asn Gln Ser Phe 355 360 365Ala Ser Thr His Leu Asn Gln Asn Ser Ser Arg Ser His Ser Ile Phe 370 375 380Ser Ile Arg Ile Leu His Leu Gln Gly Glu Gly Asp Ile Val Pro Lys385 390 395 400Ile Ser Glu Leu Ser Leu Cys Asp Leu Ala Gly Ser Glu Arg Cys Lys 405 410 415Asp Gln Lys Ser Gly Glu Arg Leu Lys Glu Ala Gly Asn Ile Asn Thr 420 425 430Ser Leu His Thr Leu Gly Arg Cys Ile Ala Ala Leu Arg Gln Asn Gln 435 440 445Gln Asn Arg Ser Lys Gln Asn Leu Val Pro Phe Arg Asp Ser Lys Leu 450 455 460Thr Arg Val Phe Gln Gly Phe Phe Thr Gly Arg Gly Arg Ser Cys Met465 470 475 480Ile Val Asn Val Asn Pro Cys Ala Ser Thr Tyr Asp Glu Thr Leu His 485 490 495Val Ala Lys Phe Ser Ala Ile Ala Ser Gln Leu Val His Ala Pro Pro 500 505 510Met Gln Leu Gly Phe Pro Ser Leu His Ser Phe Ile Lys Glu His Ser 515 520 525Leu Gln Val Ser Pro Ser Leu Glu Lys Gly Ala Lys Ala Asp Thr Gly 530 535 540Leu Asp Asp Asp Ile Glu Asn Glu Ala Asp Ile Ser Met Tyr Gly Lys545 550 555 560Glu Glu Leu Leu Gln Val Val Glu Ala Met Lys Thr Leu Leu Leu Lys 565 570 575Glu Arg Gln Glu Lys Leu Gln Leu Glu Met His Leu Arg Asp Glu Ile 580 585 590Cys Asn Glu Met Val Glu Gln Met Gln Gln Arg Glu Gln Trp Cys Ser 595 600 605Glu His Leu Asp Thr Gln Lys Glu Leu Leu Glu Glu Met Tyr Glu Glu 610 615 620Lys Leu Asn Ile Leu Lys Glu Ser Leu Thr Ser Phe Tyr Gln Glu Glu625 630 635 640Ile Gln Glu Arg Asp Glu Lys Ile Glu Glu Leu Glu Ala Leu Leu Gln 645 650 655Glu Ala Arg Gln Gln Ser Val Ala His Gln Gln Ser Gly Ser Glu Leu 660 665 670Ala Leu Arg Arg Ser Gln Arg Leu Ala Ala Ser Ala Ser Thr Gln Gln 675 680 685Leu Gln Glu Val Lys Ala Lys Leu Gln Gln Cys Lys Ala Glu Leu Asn 690 695 700Ser Thr Thr Glu Glu Leu His Lys Tyr Gln Lys Met Leu Glu Pro Pro705 710 715 720Pro Ser Ala Lys Pro Phe Thr Ile Asp Val Asp Lys Lys Leu Glu Glu 725 730 735Gly Gln Lys Asn Ile Arg Leu Leu Arg Thr Glu Leu Gln Lys Leu Gly 740 745 750Glu Ser Leu Gln Ser Ala Glu Arg Ala Cys Cys His Ser Thr Gly Ala 755 760 765Gly Lys Leu Arg Gln Ala Leu Thr Thr Cys Asp Asp Ile Leu Ile Lys 770 775 780Gln Asp Gln Thr Leu Ala Glu Leu Gln Asn Asn Met Val Leu Val Lys785 790 795 800Leu Asp Leu Arg Lys Lys Ala Ala Cys Ile Ala Glu Gln Tyr His Thr 805 810 815Val Leu Lys Leu Gln Gly Gln Val Ser Ala Lys Lys Arg Leu Gly Thr 820 825 830Asn Gln Glu Asn Gln Gln Pro Asn Gln Gln Pro Pro Gly Lys Lys Pro 835 840 845Phe Leu Arg Asn Leu Leu Pro Arg Thr Pro Thr Cys Gln Ser Ser Thr 850 855 860Asp Cys Ser Pro Tyr Ala Arg Ile Leu Arg Ser Arg Arg Ser Pro Leu865 870 875 880Leu Lys Ser Gly Pro Phe Gly Lys Lys Tyr 885 89067235PRTHomo sapiens 67Met Phe Ile Trp Thr Ser Gly Arg Thr Ser Ser Ser Tyr Arg His Asp1 5 10 15Glu Lys Arg Asn Ile Tyr Gln Lys Ile Arg Asp His Asp Leu Leu Asp 20 25 30Lys Arg Lys Thr Val Thr Ala Leu Lys Ala Gly Glu Asp Arg Ala Ile 35 40 45Leu Leu Gly Leu Ala Met Met Val Cys Ser Ile Met Met Tyr Phe Leu 50 55 60Leu Gly Ile Thr Leu Leu Arg Ser Tyr Met Gln Ser Val Trp Thr Glu65 70 75 80Glu Ser Gln Cys Thr Leu Leu Asn Ala Ser Ile Thr Glu Thr Phe Asn 85 90 95Cys Ser Phe Ser Cys Gly Pro Asp Cys Trp Lys Leu Ser Gln Tyr Pro 100 105 110Cys Leu Gln Val Tyr Val Asn Leu Thr Ser Ser Gly Glu Lys Leu Leu 115 120 125Leu Tyr His Thr Glu Glu Thr Ile Lys Ile Asn Gln Lys Cys Ser Tyr 130 135 140Ile Pro Lys Cys Gly Lys Asn Phe Glu Glu Ser Met Ser Leu Val Asn145 150 155 160Val Val Met Glu Asn Phe Arg Lys Tyr Gln His Phe Ser Cys Tyr Ser 165 170 175Asp Pro Glu Gly Asn Gln Lys Ser Val Ile Leu Thr Lys Leu Tyr Ser 180 185 190Ser Asn Val Leu Phe His Ser Leu Phe Trp Pro Thr Cys Met Met Ala 195 200 205Gly Gly Val Ala Ile Val Ala Met Val Lys Leu Thr Gln Tyr Leu Ser 210 215 220Leu Leu Cys Glu Arg Ile Gln Arg Ile Asn Arg225 230 2356898PRTHomo sapiens 68Met Asn Gln Thr Ala Ile Leu Ile Cys Cys Leu Ile Phe Leu Thr Leu1 5 10 15Ser Gly Ile Gln Gly Val Pro Leu Ser Arg Thr Val Arg Cys Thr Cys 20 25 30Ile Ser Ile Ser Asn Gln Pro Val Asn Pro Arg Ser Leu Glu Lys Leu 35 40 45Glu Ile Ile Pro Ala Ser Gln Phe Cys Pro Arg Val Glu Ile Ile Ala 50 55 60Thr Met Lys Lys Lys Gly Glu Lys Arg Cys Leu Asn Pro Glu Ser Lys65 70 75 80Ala Ile Lys Asn Leu Leu Lys Ala Val Ser Lys Glu Met Ser Lys Arg 85 90 95Ser Pro69467PRTHomo sapiens 69Met Ala Ala Leu Thr Ile Ala Thr Gly Thr Gly Asn Trp Phe Ser Ala1 5 10 15Leu Ala Leu Gly Val Thr Leu Leu Lys Cys Leu Leu Ile Pro Thr Tyr 20 25 30His Ser Thr Asp Phe Glu Val His Arg Asn Trp Leu Ala Ile Thr His 35 40 45Ser Leu Pro Ile Ser Gln Trp Tyr Tyr Glu Ala Thr Ser Glu Trp Thr 50 55 60Leu Asp Tyr Pro Pro Phe Phe Ala Trp Phe Glu Tyr Ile Leu Ser His65 70 75 80Val Ala Lys Tyr Phe Asp Gln Glu Met Leu Asn Val His Asn Leu Asn 85 90 95Tyr Ser Ser Ser Arg Thr Leu Leu Phe Gln Arg Phe Ser Val Ile Phe 100 105 110Met Asp Val Leu Phe Val Tyr Ala Val Arg Glu Cys Cys Lys Cys Ile 115 120 125Asp Gly Lys Lys Val Gly Lys Glu Leu Thr Glu Lys Pro Lys Phe Ile 130 135 140Leu Ser Val Leu Leu Leu Trp Asn Phe Gly Leu Leu Ile Val Asp His145 150 155 160Ile His Phe Gln Tyr Asn Gly Phe Leu Phe Gly Leu Met Leu Leu Ser 165 170 175Ile Ala Arg Leu Phe Gln Lys Arg His Met Glu Gly Ala Phe Leu Phe 180 185 190Ala Val Leu Leu His Phe Lys His Ile Tyr Leu Tyr Val Ala Pro Ala 195 200 205Tyr Gly Val Tyr Leu Leu Arg Ser Tyr Cys Phe Thr Ala Asn Lys Pro 210 215 220Asp Gly Ser Ile Arg Trp Lys Ser Phe Ser Phe Val Arg Val Ile Ser225 230 235 240Leu Gly Leu Val Val Phe Leu Val Ser Ala Leu Ser Leu Gly Pro Phe 245 250 255Leu Ala Leu Asn Gln Leu Pro Gln Val Phe Ser Arg Leu Phe Pro Phe 260 265 270Lys Arg Gly Leu Cys His Ala Tyr Trp Ala Pro Asn Phe Trp Ala Leu 275 280 285Tyr Asn Ala Leu Asp Lys Val Leu Ser Val Ile Gly Leu Lys Leu Lys 290 295 300Phe Leu Asp Pro Asn Asn Ile Pro Lys Ala Ser Met Thr Ser Gly Leu305 310 315 320Val Gln Gln Phe Gln His Thr Val Leu Pro Ser Val Thr Pro Leu Ala 325 330 335Thr Leu Ile Cys Thr Leu Ile Ala Ile Leu Pro Ser Ile Phe Cys Leu 340 345 350Trp Phe Lys Pro Gln Gly Pro Arg Gly Phe Leu Arg Cys Leu Thr Leu 355 360 365Cys Ala Leu Ser Ser Phe Met Phe Gly Trp His Val His Glu Lys Ala 370 375 380Ile Leu Leu Ala Ile Leu Pro Met Ser Leu Leu Ser Val Gly Lys Ala385 390 395 400Gly Asp Ala Ser Ile Phe Leu Ile Leu Thr Thr Thr Gly His Tyr Ser 405 410 415Leu Phe Pro Leu Leu Phe Thr Ala Pro Glu Leu Pro Ile Lys Ile Leu 420 425 430Leu Met Leu Leu Phe Thr Ile Tyr Ser Ile Ser Ser Leu Lys Thr Leu 435 440 445Phe Arg Arg Ser Phe Thr Leu Val Ala Gln Ala Gly Val Gln Trp His 450 455 460Asp Leu Ser4657084PRTHomo sapiens 70Met Asp Asp Asp Ala Ala Pro Arg Val Glu Gly Val Pro Val Ala Val1 5 10 15His Lys His Ala Leu His Asp Gly Leu Arg Gln Val Ala Gly Pro Gly 20 25 30Ala Ala Ala Ala His Leu Pro Arg Trp Pro Pro Pro Gln Leu Ala Ala 35 40 45Ser Arg Arg Glu Ala Pro Pro Leu Ser Gln Arg Pro His Arg Thr Gln 50 55 60Gly Ala Gly Ser Pro Pro Glu Thr Asn Glu Lys Leu Thr Asn Pro Gln65 70 75 80Val Lys Glu Lys71156PRTHomo sapiens 71Met Glu Pro Ala Ala Gly Ser Ser Met Glu Pro Ser Ala Asp Trp Leu1 5 10 15Ala Thr Ala Ala Ala Arg Gly Arg Val Glu Glu Val Arg Ala Leu Leu 20 25 30Glu Ala Gly Ala Leu Pro Asn Ala Pro Asn Ser Tyr Gly Arg Arg Pro 35 40 45Ile Gln Val Met Met Met Gly Ser Ala Arg Val Ala Glu Leu Leu Leu 50 55 60Leu His Gly Ala Glu Pro Asn Cys Ala Asp Pro Ala Thr Leu Thr Arg65 70 75 80Pro Val His Asp Ala Ala Arg Glu Gly Phe Leu Asp Thr Leu Val Val 85 90 95Leu His Arg Ala Gly Ala Arg Leu Asp Val Arg Asp Ala Trp Gly Arg 100 105 110Leu Pro Val Asp Leu Ala Glu Glu Leu Gly His Arg Asp Val Ala Arg 115 120 125Tyr Leu Arg Ala Ala Ala Gly Gly Thr Arg Gly Ser Asn His Ala Arg 130 135 140Ile Asp Ala Ala Glu Gly Pro Ser Asp Ile Pro Asp145 150 15572747PRTHomo sapiens 72Met Ser Gln Val Lys Ser Ser Tyr Ser Tyr Asp Ala Pro Ser Asp Phe1 5 10 15Ile Asn Phe Ser Ser Leu Asp Asp Glu Gly Asp Thr Gln Asn Ile Asp 20 25 30Ser Trp Phe Glu Glu Lys Ala Asn Leu Glu Asn Lys Leu Leu Gly Lys 35 40 45Asn Gly Thr Gly Gly Leu Phe Gln Gly Lys Thr Pro Leu Arg Lys Ala 50 55 60Asn Leu Gln Gln Ala Ile Val Thr Pro Leu Lys Pro Val Asp Asn Thr65 70 75 80Tyr Tyr Lys Glu Ala Glu Lys Glu Asn Leu Val Glu Gln Ser Ile Pro 85 90 95Ser Asn Ala Cys Ser Ser Leu Glu Val Glu Ala Ala Ile Ser Arg Lys 100 105 110Thr Pro Ala Gln Pro Gln Arg Arg Ser Leu Arg Leu Ser Ala Gln Lys 115 120 125Asp Leu Glu Gln Lys Glu Lys His His Val Lys Met Lys Ala Lys Arg 130 135 140Cys Ala Thr Pro Val Ile Ile Asp Glu Ile Leu Pro Ser Lys Lys Met145 150 155 160Lys Val Ser Asn Asn Lys Lys Lys Pro Glu Glu Glu Gly Ser Ala His 165 170 175Gln Asp Thr Ala Glu Lys Asn Ala Ser Ser Pro Glu Lys Ala Lys Gly 180 185 190Arg His Thr Val Pro Cys Met Pro Pro Ala Lys Gln Lys Phe Leu Lys 195 200 205Ser Thr Glu Glu Gln Glu Leu Glu Lys Ser Met Lys Met Gln Gln Glu 210 215 220Val Val Glu Met Arg Lys Lys Asn Glu Glu Phe Lys Lys Leu Ala Leu225 230 235 240Ala Gly Ile Gly Gln Pro Val

Lys Lys Ser Val Ser Gln Val Thr Lys 245 250 255Ser Val Asp Phe His Phe Arg Thr Asp Glu Arg Ile Lys Gln His Pro 260 265 270Lys Asn Gln Glu Glu Tyr Lys Glu Val Asn Phe Thr Ser Glu Leu Arg 275 280 285Lys His Pro Ser Ser Pro Ala Arg Val Thr Lys Gly Cys Thr Ile Val 290 295 300Lys Pro Phe Asn Leu Ser Gln Gly Lys Lys Arg Thr Phe Asp Glu Thr305 310 315 320Val Ser Thr Tyr Val Pro Leu Ala Gln Gln Val Glu Asp Phe His Lys 325 330 335Arg Thr Pro Asn Arg Tyr His Leu Arg Ser Lys Lys Asp Asp Ile Asn 340 345 350Leu Leu Pro Ser Lys Ser Ser Val Thr Lys Ile Cys Arg Asp Pro Gln 355 360 365Thr Pro Val Leu Gln Thr Lys His Arg Ala Arg Ala Val Thr Cys Lys 370 375 380Ser Thr Ala Glu Leu Glu Ala Glu Glu Leu Glu Lys Leu Gln Gln Tyr385 390 395 400Lys Phe Lys Ala Arg Glu Leu Asp Pro Arg Ile Leu Glu Gly Gly Pro 405 410 415Ile Leu Pro Lys Lys Pro Pro Val Lys Pro Pro Thr Glu Pro Ile Gly 420 425 430Phe Asp Leu Glu Ile Glu Lys Arg Ile Gln Glu Arg Glu Ser Lys Lys 435 440 445Lys Thr Glu Asp Glu His Phe Glu Phe His Ser Arg Pro Cys Pro Thr 450 455 460Lys Ile Leu Glu Asp Val Val Gly Val Pro Glu Lys Lys Val Leu Pro465 470 475 480Ile Thr Val Pro Lys Ser Pro Ala Phe Ala Leu Lys Asn Arg Ile Arg 485 490 495Met Pro Thr Lys Glu Asp Glu Glu Glu Asp Glu Pro Val Val Ile Lys 500 505 510Ala Gln Pro Val Pro His Tyr Gly Val Pro Phe Lys Pro Gln Ile Pro 515 520 525Glu Ala Arg Thr Val Glu Ile Cys Pro Phe Ser Phe Asp Ser Arg Asp 530 535 540Lys Glu Arg Gln Leu Gln Lys Glu Lys Lys Ile Lys Glu Leu Gln Lys545 550 555 560Gly Glu Val Pro Lys Phe Lys Ala Leu Pro Leu Pro His Phe Asp Thr 565 570 575Ile Asn Leu Pro Glu Lys Lys Val Lys Asn Val Thr Gln Ile Glu Pro 580 585 590Phe Cys Leu Glu Thr Asp Arg Arg Gly Ala Leu Lys Ala Gln Thr Trp 595 600 605Lys His Gln Leu Glu Glu Glu Leu Arg Gln Gln Lys Glu Ala Ala Cys 610 615 620Phe Lys Ala Arg Pro Asn Thr Val Ile Ser Gln Glu Pro Phe Val Pro625 630 635 640Lys Lys Glu Lys Lys Ser Val Ala Glu Gly Leu Ser Gly Ser Leu Val 645 650 655Gln Glu Pro Phe Gln Leu Ala Thr Glu Lys Arg Ala Lys Glu Arg Gln 660 665 670Glu Leu Glu Lys Arg Met Ala Glu Val Glu Ala Gln Lys Ala Gln Gln 675 680 685Leu Glu Glu Ala Arg Leu Gln Glu Glu Glu Gln Lys Lys Glu Glu Leu 690 695 700Ala Arg Leu Arg Arg Glu Leu Val His Lys Ala Asn Pro Ile Arg Lys705 710 715 720Tyr Gln Gly Leu Glu Ile Lys Ser Ser Asp Gln Pro Leu Thr Val Pro 725 730 735Val Ser Pro Lys Phe Ser Thr Arg Phe His Cys 740 74573179PRTHomo sapiens 73Met Ala Ser Gln Asn Arg Asp Pro Ala Ala Thr Ser Val Ala Ala Ala1 5 10 15Arg 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 45Gly Ile Ser Ala Phe Pro Glu Ser Asp Asn Leu Phe Lys Trp Val Gly 50 55 60Thr Ile His Gly Ala Ala Gly Thr Val Tyr Glu Asp Leu Arg Tyr Lys65 70 75 80Leu Ser Leu Glu Phe Pro Ser Gly Tyr Pro Tyr Asn Ala Pro Thr Val 85 90 95Lys Phe Leu Thr Pro Cys Tyr His Pro Asn Val Asp Thr Gln Gly Asn 100 105 110Ile Cys Leu Asp Ile Leu Lys Glu Lys Trp Ser Ala Leu Tyr Asp Val 115 120 125Arg Thr Ile Leu Leu Ser Ile Gln Ser Leu Leu Gly Glu Pro Asn Ile 130 135 140Asp Ser Pro Leu Asn Thr His Ala Ala Glu Leu Trp Lys Asn Pro Thr145 150 155 160Ala Phe Lys Lys Tyr Leu Gln Glu Thr Tyr Ser Lys Gln Val Thr Ser 165 170 175Gln Glu Pro 74138PRTHomo sapiens 74Met Pro Asn Phe Ser Gly Asn Trp Lys Ile Ile Arg Ser Glu Asn Phe1 5 10 15Glu Glu Leu Leu Lys Val Leu Gly Val Asn Val Met Leu Arg Lys Ile 20 25 30Ala Val Ala Ala Ala Ser Lys Pro Ala Val Glu Ile Lys Gln Glu Gly 35 40 45Asp Thr Phe Tyr Ile Lys Thr Ser Thr Thr Val Arg Thr Thr Glu Ile 50 55 60Asn Phe Lys Val Gly Glu Glu Phe Glu Glu Gln Thr Val Asp Gly Arg65 70 75 80Pro Cys Lys Ser Leu Val Lys Trp Glu Ser Glu Asn Lys Met Val Cys 85 90 95Glu Gln Lys Leu Leu Lys Gly Glu Gly Pro Lys Thr Ser Trp Thr Arg 100 105 110Glu Leu Thr Asn Asp Gly Glu Leu Ile Leu Thr Met Thr Ala Asp Asp 115 120 125Val Val Cys Thr Arg Val Tyr Val Arg Glu 130 13575130PRTHomo sapiens 75Met Ser Gly Arg Gly Lys Gln Gly Gly Lys Ala Arg Ala Lys Ala Lys1 5 10 15Ser Arg Ser Ser Arg Ala Gly Leu Gln Phe Pro Val Gly Arg Val His 20 25 30Arg Leu Leu Arg Lys Gly Asn Tyr Ser Glu Arg Val Gly Ala Gly Ala 35 40 45Pro Val Tyr Leu Ala Ala Val Leu Glu Tyr Leu Thr Ala Glu Ile Leu 50 55 60Glu Leu Ala Gly Asn Ala Ala Arg Asp Asn Lys Lys Thr Arg Ile Ile65 70 75 80Pro Arg His Leu Gln Leu Ala Ile Arg Asn Asp Glu Glu Leu Asn Lys 85 90 95Leu Leu Gly Arg Val Thr Ile Ala Gln Gly Gly Val Leu Pro Asn Ile 100 105 110Gln Ala Val Leu Leu Pro Lys Lys Thr Glu Ser His His Lys Ala Lys 115 120 125Gly Lys 13076103PRTHomo sapiens 76Met Ser Gly Arg Gly Lys Gly Gly Lys Gly Leu Gly Lys Gly Gly Ala1 5 10 15Lys Arg His Arg Lys Val Leu Arg Asp Asn Ile Gln Gly Ile Thr Lys 20 25 30Pro Ala Ile Arg Arg Leu Ala Arg Arg Gly Gly Val Lys Arg Ile Ser 35 40 45Gly Leu Ile Tyr Glu Glu Thr Arg Gly Val Leu Lys Val Phe Leu Glu 50 55 60Asn Val Ile Arg Asp Ala Val Thr Tyr Thr Glu His Ala Lys Arg Lys65 70 75 80Thr Val Thr Ala Met Asp Val Val Tyr Ala Leu Lys Arg Gln Gly Arg 85 90 95Thr Leu Tyr Gly Phe Gly Gly 10077432PRTHomo sapiens 77Met Leu Phe Glu Gln Gly Gln Gln Ala Leu Glu Leu Pro Glu Cys Thr1 5 10 15Met Gln Lys Ala Ala Tyr Tyr Glu Asn Pro Gly Leu Phe Gly Gly Tyr 20 25 30Gly Tyr Ser Lys Thr Thr Asp Thr Tyr Gly Tyr Ser Thr Pro His Gln 35 40 45Pro Tyr Pro Pro Pro Ala Ala Ala Ser Ser Leu Asp Thr Asp Tyr Pro 50 55 60Gly Ser Ala Cys Ser Ile Gln Ser Ser Ala Pro Leu Arg Ala Pro Ala65 70 75 80His Lys Gly Ala Glu Leu Asn Gly Ser Cys Met Arg Pro Gly Thr Gly 85 90 95Asn Ser Gln Gly Gly Gly Gly Gly Ser Gln Pro Pro Gly Leu Asn Ser 100 105 110Glu Gln Gln Pro Pro Gln Pro Pro Pro Pro Pro Pro Thr Leu Pro Pro 115 120 125Ser Ser Pro Thr Asn Pro Gly Gly Gly Val Pro Ala Lys Lys Pro Lys 130 135 140Gly Gly Pro Asn Ala Ser Ser Ser Ser Ala Thr Ile Ser Lys Gln Ile145 150 155 160Phe Pro Trp Met Lys Glu Ser Arg Gln Asn Ser Lys Gln Lys Asn Ser 165 170 175Cys Ala Thr Ala Gly Glu Ser Cys Glu Asp Lys Ser Pro Pro Gly Pro 180 185 190Ala Ser Lys Arg Val Arg Thr Ala Tyr Thr Ser Ala Gln Leu Val Glu 195 200 205Leu Glu Lys Glu Phe His Phe Asn Arg Tyr Leu Cys Arg Pro Arg Arg 210 215 220Val Glu Met Ala Asn Leu Leu Asn Leu Thr Glu Arg Gln Ile Lys Ile225 230 235 240Trp Phe Gln Asn Arg Arg Met Lys Tyr Lys Lys Asp Gln Lys Ala Lys 245 250 255Gly Ile Leu His Ser Pro Ala Ser Gln Ser Pro Glu Arg Ser Pro Pro 260 265 270Leu Gly Gly Ala Ala Gly His Val Ala Tyr Ser Gly Gln Leu Pro Pro 275 280 285Val Pro Gly Leu Ala Tyr Asp Ala Pro Ser Pro Pro Ala Phe Ala Lys 290 295 300Ser Gln Pro Asn Met Tyr Gly Leu Ala Ala Tyr Thr Ala Pro Leu Ser305 310 315 320Ser Cys Leu Pro Gln Gln Lys Arg Tyr Ala Ala Pro Glu Phe Glu Pro 325 330 335His Pro Met Ala Ser Asn Gly Gly Gly Phe Ala Ser Ala Asn Leu Gln 340 345 350Gly Ser Pro Val Tyr Val Gly Gly Asn Phe Val Glu Ser Met Ala Pro 355 360 365Ala Ser Gly Pro Val Phe Asn Leu Gly His Leu Ser His Pro Ser Ser 370 375 380Ala Ser Val Asp Tyr Ser Cys Ala Ala Gln Ile Pro Gly Asn His His385 390 395 400His Gly Pro Cys Asp Pro His Pro Thr Tyr Thr Asp Leu Ser Ala His 405 410 415His Ser Ser Gln Gly Arg Leu Pro Glu Ala Pro Lys Leu Thr His Leu 420 425 43078469PRTHomo sapiens 78Met Glu Phe Gly Leu Ser Trp Val Phe Leu Val Ala Ile Leu Lys Gly1 5 10 15Val Gln Cys Glu Val Gln Leu Val Glu Ser Gly Gly Val Val Val Gln 20 25 30Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe 35 40 45Asp Asp Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu 50 55 60Glu Trp Val Ser Leu Ile Ser Trp Asp Gly Gly Ser Thr Tyr Tyr Ala65 70 75 80Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn 85 90 95Ser Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu 100 105 110Tyr Tyr Cys Ala Thr Arg Gly Gly Tyr Ser Thr Ala Gly Phe Asp Tyr 115 120 125Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly 130 135 140Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly145 150 155 160Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val 165 170 175Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe 180 185 190Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val 195 200 205Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val 210 215 220Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys225 230 235 240Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu 245 250 255Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 260 265 270Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 275 280 285Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val 290 295 300Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser305 310 315 320Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu 325 330 335Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala 340 345 350Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro 355 360 365Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln 370 375 380Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala385 390 395 400Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 405 410 415Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu 420 425 430Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser 435 440 445Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser 450 455 460Leu Ser Pro Gly Lys46579235PRTHomo sapiens 79Met Glu Thr Pro Ala Gln Leu Leu Phe Leu Leu Leu Leu Trp Leu Pro1 5 10 15Asp Ile Thr Gly Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser 20 25 30Leu Ser Pro Gly Glu Arg Ala Ala Leu Ser Cys Arg Ala Ser Gln Ser 35 40 45Val Asn Ser Lys Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala 50 55 60Pro Arg Leu Leu Met Tyr Ala Ala Ser Ile Arg Ala Thr Gly Ile Pro65 70 75 80Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 85 90 95Ser Arg Leu Glu Ser Glu Asp Phe Ala Leu Tyr Phe Cys Gln Gln Tyr 100 105 110Gly Thr Ser Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 115 120 125Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 130 135 140Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe145 150 155 160Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 165 170 175Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 180 185 190Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 195 200 205Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 210 215 220Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys225 230 23580890PRTHomo sapiens 80Met Ser Arg Ser Ala Thr Leu Leu Leu Cys Leu Leu Gly Cys His Val1 5 10 15Trp Lys Ala Val Thr Lys Thr Leu Arg Glu Pro Gly Ala Gly Ala Gln 20 25 30Glu Val Thr Leu Lys Val His Ile Ser Asp Ala Ser Thr His Gln Pro 35 40 45Val Ala Asp Ala Leu Ile Glu Ile Phe Thr Asn Gln Ala Ser Ile Ala 50 55 60Ser Gly Thr Ser Gly Thr Asp Gly Val Ala Phe Ile Lys Phe Gln Tyr65 70 75 80Lys Leu Gly Ser Gln Leu Ile Val Thr Ala Ser Lys His Ala Tyr Val 85 90 95Pro Asn Ser Ala Pro Trp Lys Pro Ile Arg Leu Pro Val Phe Ser Ser 100 105 110Leu Ser Leu Gly Leu Leu Pro Glu Arg Ser Ala Thr Leu Met Val Tyr 115 120 125Glu Asp Val Val Gln Ile Val Ser Gly Phe Gln Gly Ala Arg Pro Gln 130 135 140Pro Arg Val His Phe Gln Arg Arg Ala Leu Arg Leu Pro Glu Asn Thr145 150 155 160Ser Tyr Ser Asp Leu Thr Ala Phe Leu Thr Ala Ala Ser Ser Pro Ser 165 170 175Glu Val Asp Ser Phe Pro Tyr Leu Arg Gly Leu Asp Gly Asn Gly Thr 180 185 190Gly Asn Ser Thr Arg His Asp Leu Thr Pro Val Thr Ala Val Ser Val 195 200 205His Leu Leu Ser Ser Asn Gly Thr Pro Val Leu Val Asp Gly Pro Ile 210 215 220Tyr Val Thr Val Pro Leu Ala Thr Gln Ser Ser Leu Arg His Asn Ala225 230 235 240Tyr Val Ala Ala Trp Arg Phe Asp Gln Lys Leu Gly Thr Trp Leu Lys 245 250 255Ser Gly Leu Gly Leu Val His Gln Glu Gly Ser Gln Leu Thr Trp Thr 260 265 270Tyr

Ile Ala Pro Gln Leu Gly Tyr Trp Val Ala Ala Met Ser Pro Pro 275 280 285Ile Pro Gly Pro Val Val Thr Gln Asp Ile Thr Thr Tyr His Thr Val 290 295 300Phe Leu Leu Ala Ile Leu Gly Gly Met Ala Phe Ile Leu Leu Val Leu305 310 315 320Leu Cys Leu Leu Leu Tyr Tyr Cys Arg Arg Lys Cys Leu Lys Pro Arg 325 330 335Gln His His Arg Lys Leu Gln Leu Pro Ala Gly Leu Glu Ser Ser Lys 340 345 350Arg Asp Gln Ser Thr Ser Met Ser His Ile Asn Leu Leu Phe Ser Arg 355 360 365Arg Ala Ser Glu Phe Pro Gly Pro Leu Ser Val Thr Ser His Gly Arg 370 375 380Pro Glu Ala Pro Gly Thr Lys Glu Leu Met Ser Gly Val His Leu Glu385 390 395 400Met Met Ser Pro Gly Gly Glu Gly Asp Leu His Thr Pro Met Leu Lys 405 410 415Leu Ser Tyr Ser Thr Ser Gln Glu Phe Ser Ser Arg Glu Glu Leu Leu 420 425 430Ser Cys Lys Glu Glu Asp Lys Ser Gln Ile Ser Phe Asp Asn Leu Thr 435 440 445Pro Ser Gly Thr Leu Gly Lys Asp Tyr His Lys Ser Val Glu Val Phe 450 455 460Pro Leu Lys Ala Arg Lys Ser Met Glu Arg Glu Gly Tyr Glu Ser Ser465 470 475 480Gly Asn Asp Asp Tyr Arg Gly Ser Tyr Asn Thr Val Leu Ser Gln Pro 485 490 495Leu Phe Glu Lys Gln Asp Arg Glu Gly Pro Ala Ser Thr Gly Ser Lys 500 505 510Leu Thr Ile Gln Glu His Leu Tyr Pro Ala Pro Ser Ser Pro Glu Lys 515 520 525Glu Gln Leu Leu Asp Arg Arg Pro Thr Glu Cys Met Met Ser Arg Ser 530 535 540Val Asp His Leu Glu Arg Pro Thr Ser Phe Pro Arg Pro Gly Gln Leu545 550 555 560Ile Cys Cys Ser Ser Val Asp Gln Val Asn Asp Ser Val Tyr Arg Lys 565 570 575Val Leu Pro Ala Leu Val Ile Pro Ala His Tyr Met Lys Leu Pro Gly 580 585 590Asp His Ser Tyr Val Ser Gln Pro Leu Val Val Pro Ala Asp Gln Gln 595 600 605Leu Glu Ile Glu Arg Leu Gln Ala Glu Leu Ser Asn Pro His Ala Gly 610 615 620Ile Phe Pro His Pro Ser Ser Gln Ile Gln Pro Gln Pro Leu Ser Ser625 630 635 640Gln Ala Ile Ser Gln Gln His Leu Gln Asp Ala Gly Thr Arg Glu Trp 645 650 655Ser Pro Gln Asn Ala Ser Met Ser Glu Ser Leu Ser Ile Pro Ala Ser 660 665 670Leu Asn Asp Ala Ala Leu Ala Gln Met Asn Ser Glu Val Gln Leu Leu 675 680 685Thr Glu Lys Ala Leu Met Glu Leu Gly Gly Gly Lys Pro Leu Pro His 690 695 700Pro Arg Ala Trp Phe Val Ser Leu Asp Gly Arg Ser Asn Ala His Val705 710 715 720Arg His Ser Tyr Ile Asp Leu Gln Arg Ala Gly Arg Asn Gly Ser Asn 725 730 735Asp Ala Ser Leu Asp Ser Gly Val Asp Met Asn Glu Pro Lys Ser Ala 740 745 750Arg Lys Gly Arg Gly Asp Ala Leu Ser Leu Gln Gln Asn Tyr Pro Pro 755 760 765Val Gln Glu His Gln Gln Lys Glu Pro Arg Ala Pro Asp Ser Thr Ala 770 775 780Tyr Thr Gln Leu Val Tyr Leu Asp Asp Val Glu Gln Ser Gly Ser Glu785 790 795 800Cys Gly Thr Thr Val Cys Thr Pro Glu Asp Ser Ala Leu Arg Cys Leu 805 810 815Leu Glu Gly Ser Ser Arg Arg Ser Gly Gly Gln Leu Pro Ser Leu Gln 820 825 830Glu Glu Thr Thr Arg Arg Thr Ala Asp Ala Pro Ser Glu Pro Ala Ala 835 840 845Ser Pro His Gln Arg Arg Ser Ala His Glu Glu Glu Glu Asp Asp Asp 850 855 860Asp Asp Asp Gln Gly Glu Asp Lys Lys Ser Pro Trp Gln Lys Arg Glu865 870 875 880Glu Arg Pro Leu Met Ala Phe Asn Ile Lys 885 89081394PRTHomo sapiens 81Met Asp Ser Ala Leu Ser Asp Pro His Asn Gly Ser Ala Glu Ala Gly1 5 10 15Gly Pro Thr Asn Ser Thr Thr Arg Pro Pro Ser Thr Pro Glu Gly Ile 20 25 30Ala Leu Ala Tyr Gly Ser Leu Leu Leu Met Ala Leu Leu Pro Ile Phe 35 40 45Phe Gly Ala Leu Arg Ser Val Arg Cys Ala Arg Gly Lys Asn Ala Ser 50 55 60Asp Met Pro Glu Thr Ile Thr Ser Arg Asp Ala Ala Arg Phe Pro Ile65 70 75 80Ile Ala Ser Cys Thr Leu Leu Gly Leu Tyr Leu Phe Phe Lys Ile Phe 85 90 95Ser Gln Glu Tyr Ile Asn Leu Leu Leu Ser Met Tyr Phe Phe Val Leu 100 105 110Gly Ile Leu Ala Leu Ser His Thr Ile Ser Pro Phe Met Asn Lys Phe 115 120 125Phe Pro Ala Ser Phe Pro Asn Arg Gln Tyr Gln Leu Leu Phe Thr Gln 130 135 140Gly Ser Gly Glu Asn Lys Glu Glu Ile Ile Asn Tyr Glu Phe Asp Thr145 150 155 160Lys Asp Leu Val Cys Leu Gly Leu Ser Ser Ile Val Gly Val Trp Tyr 165 170 175Leu Leu Arg Lys His Trp Ile Ala Asn Asn Leu Phe Gly Leu Ala Phe 180 185 190Ser Leu Asn Gly Val Glu Leu Leu His Leu Asn Asn Val Ser Thr Gly 195 200 205Cys Ile Leu Leu Gly Gly Leu Phe Ile Tyr Asp Val Phe Trp Val Phe 210 215 220Gly Thr Asn Val Met Val Thr Val Ala Lys Ser Phe Glu Ala Pro Ile225 230 235 240Lys Leu Val Phe Pro Gln Asp Leu Leu Glu Lys Gly Leu Glu Ala Asn 245 250 255Asn Phe Ala Met Leu Gly Leu Gly Asp Val Val Ile Pro Gly Ile Phe 260 265 270Ile Ala Leu Leu Leu Arg Phe Asp Ile Ser Leu Lys Lys Asn Thr His 275 280 285Thr Tyr Phe Tyr Thr Ser Phe Ala Ala Tyr Ile Phe Gly Leu Gly Leu 290 295 300Thr Ile Phe Ile Met His Ile Phe Lys His Ala Gln Pro Ala Leu Leu305 310 315 320Tyr Leu Val Pro Ala Cys Ile Gly Phe Pro Val Leu Val Ala Leu Ala 325 330 335Lys Gly Glu Val Thr Glu Met Phe Ser Tyr Glu Ser Ser Ala Glu Ile 340 345 350Leu Pro His Thr Pro Arg Leu Thr His Phe Pro Thr Val Ser Gly Ser 355 360 365Pro Ala Ser Leu Ala Asp Ser Met Gln Gln Lys Leu Ala Gly Pro Arg 370 375 380Arg Arg Arg Pro Gln Asn Pro Ser Ala Met385 39082325PRTHomo sapiens 82Met Val Cys Gly Ser Pro Gly Gly Met Leu Leu Leu Arg Ala Gly Leu1 5 10 15Leu Ala Leu Ala Ala Leu Cys Leu Leu Arg Val Pro Gly Ala Arg Ala 20 25 30Ala Ala Cys Glu Pro Val Arg Ile Pro Leu Cys Lys Ser Leu Pro Trp 35 40 45Asn Met Thr Lys Met Pro Asn His Leu His His Ser Thr Gln Ala Asn 50 55 60Ala Ile Leu Ala Ile Glu Gln Phe Glu Gly Leu Leu Gly Thr His Cys65 70 75 80Ser Pro Asp Leu Leu Phe Phe Leu Cys Ala Met Tyr Ala Pro Ile Cys 85 90 95Thr Ile Asp Phe Gln His Glu Pro Ile Lys Pro Cys Lys Ser Val Cys 100 105 110Glu Arg Ala Arg Gln Gly Cys Glu Pro Ile Leu Ile Lys Tyr Arg His 115 120 125Ser Trp Pro Glu Asn Leu Ala Cys Glu Glu Leu Pro Val Tyr Asp Arg 130 135 140Gly Val Cys Ile Ser Pro Glu Ala Ile Val Thr Ala Asp Gly Ala Asp145 150 155 160Phe Pro Met Asp Ser Ser Asn Gly Asn Cys Arg Gly Ala Ser Ser Glu 165 170 175Arg Cys Lys Cys Lys Pro Ile Arg Ala Thr Gln Lys Thr Tyr Phe Arg 180 185 190Asn Asn Tyr Asn Tyr Val Ile Arg Ala Lys Val Lys Glu Ile Lys Thr 195 200 205Lys Cys His Asp Val Thr Ala Val Val Glu Val Lys Glu Ile Leu Lys 210 215 220Ser Ser Leu Val Asn Ile Pro Arg Asp Thr Val Asn Leu Tyr Thr Ser225 230 235 240Ser Gly Cys Leu Cys Pro Pro Leu Asn Val Asn Glu Glu Tyr Ile Ile 245 250 255Met Gly Tyr Glu Asp Glu Glu Arg Ser Arg Leu Leu Leu Val Glu Gly 260 265 270Ser Ile Ala Glu Lys Trp Lys Asp Arg Leu Gly Lys Lys Val Lys Arg 275 280 285Trp Asp Met Lys Leu Arg His Leu Gly Leu Ser Lys Ser Asp Ser Ser 290 295 300Asn Ser Asp Ser Thr Gln Ser Gln Lys Ser Gly Arg Asn Ser Asn Pro305 310 315 320Arg Gln Ala Arg Asn 32583748PRTHomo sapiens 83Met Lys Thr Ser Pro Arg Arg Pro Leu Ile Leu Lys Arg Arg Arg Leu1 5 10 15Pro Leu Pro Val Gln Asn Ala Pro Ser Glu Thr Ser Glu Glu Glu Pro 20 25 30Lys Arg Ser Pro Ala Gln Gln Glu Ser Asn Gln Ala Glu Ala Ser Lys 35 40 45Glu Val Ala Glu Ser Asn Ser Cys Lys Phe Pro Ala Gly Ile Lys Ile 50 55 60Ile Asn His Pro Thr Met Pro Asn Thr Gln Val Val Ala Ile Pro Asn65 70 75 80Asn Ala Asn Ile His Ser Ile Ile Thr Ala Leu Thr Ala Lys Gly Lys 85 90 95Glu Ser Gly Ser Ser Gly Pro Asn Lys Phe Ile Leu Ile Ser Cys Gly 100 105 110Gly Ala Pro Thr Gln Pro Pro Gly Leu Arg Pro Gln Thr Gln Thr Ser 115 120 125Tyr Asp Ala Lys Arg Thr Glu Val Thr Leu Glu Thr Leu Gly Pro Lys 130 135 140Pro Ala Ala Arg Asp Val Asn Leu Pro Arg Pro Pro Gly Ala Leu Cys145 150 155 160Glu Gln Lys Arg Glu Thr Cys Ala Asp Gly Glu Ala Ala Gly Cys Thr 165 170 175Ile Asn Asn Ser Leu Ser Asn Ile Gln Trp Leu Arg Lys Met Ser Ser 180 185 190Asp Gly Leu Gly Ser Arg Ser Ile Lys Gln Glu Met Glu Glu Lys Glu 195 200 205Asn Cys His Leu Glu Gln Arg Gln Val Lys Val Glu Glu Pro Ser Arg 210 215 220Pro Ser Ala Ser Trp Gln Asn Ser Val Ser Glu Arg Pro Pro Tyr Ser225 230 235 240Tyr Met Ala Met Ile Gln Phe Ala Ile Asn Ser Thr Glu Arg Lys Arg 245 250 255Met Thr Leu Lys Asp Ile Tyr Thr Trp Ile Glu Asp His Phe Pro Tyr 260 265 270Phe Lys His Ile Ala Lys Pro Gly Trp Lys Asn Ser Ile Arg His Asn 275 280 285Leu Ser Leu His Asp Met Phe Val Arg Glu Thr Ser Ala Asn Gly Lys 290 295 300Val Ser Phe Trp Thr Ile His Pro Ser Ala Asn Arg Tyr Leu Thr Leu305 310 315 320Asp Gln Val Phe Lys Gln Gln Lys Arg Pro Asn Pro Glu Leu Arg Arg 325 330 335Asn Met Thr Ile Lys Thr Glu Leu Pro Leu Gly Ala Arg Arg Lys Met 340 345 350Lys Pro Leu Leu Pro Arg Val Ser Ser Tyr Leu Val Pro Ile Gln Phe 355 360 365Pro Val Asn Gln Ser Leu Val Leu Gln Pro Ser Val Lys Val Pro Leu 370 375 380Pro Leu Ala Ala Ser Leu Met Ser Ser Glu Leu Ala Arg His Ser Lys385 390 395 400Arg Val Arg Ile Ala Pro Lys Val Leu Leu Ala Glu Glu Gly Ile Ala 405 410 415Pro Leu Ser Ser Ala Gly Pro Gly Lys Glu Glu Lys Leu Leu Phe Gly 420 425 430Glu Gly Phe Ser Pro Leu Leu Pro Val Gln Thr Ile Lys Glu Glu Glu 435 440 445Ile Gln Pro Gly Glu Glu Met Pro His Leu Ala Arg Pro Ile Lys Val 450 455 460Glu Ser Pro Pro Leu Glu Glu Trp Pro Ser Pro Ala Pro Ser Phe Lys465 470 475 480Glu Glu Ser Ser His Ser Trp Glu Asp Ser Ser Gln Ser Pro Thr Pro 485 490 495Arg Pro Lys Lys Ser Tyr Ser Gly Leu Arg Ser Pro Thr Arg Cys Val 500 505 510Ser Glu Met Leu Val Ile Gln His Arg Glu Arg Arg Glu Arg Ser Arg 515 520 525Ser Arg Arg Lys Gln His Leu Leu Pro Pro Cys Val Asp Glu Pro Glu 530 535 540Leu Leu Phe Ser Glu Gly Pro Ser Thr Ser Arg Trp Ala Ala Glu Leu545 550 555 560Pro Phe Pro Ala Asp Ser Ser Asp Pro Ala Ser Gln Leu Ser Tyr Ser 565 570 575Gln Glu Val Gly Gly Pro Phe Lys Thr Pro Ile Lys Glu Thr Leu Pro 580 585 590Ile Ser Ser Thr Pro Ser Lys Ser Val Leu Pro Arg Thr Pro Glu Ser 595 600 605Trp Arg Leu Thr Pro Pro Ala Lys Val Gly Gly Leu Asp Phe Ser Pro 610 615 620Val Gln Thr Ser Gln Gly Ala Ser Asp Pro Leu Pro Asp Pro Leu Gly625 630 635 640Leu Met Asp Leu Ser Thr Thr Pro Leu Gln Ser Ala Pro Pro Leu Glu 645 650 655Ser Pro Gln Arg Leu Leu Ser Ser Glu Pro Leu Asp Leu Ile Ser Val 660 665 670Pro Phe Gly Asn Ser Ser Pro Ser Asp Ile Asp Val Pro Lys Pro Gly 675 680 685Ser Pro Glu Pro Gln Val Ser Gly Leu Ala Ala Asn Arg Ser Leu Thr 690 695 700Glu Gly Leu Val Leu Asp Thr Met Asn Asp Ser Leu Ser Lys Ile Leu705 710 715 720Leu Asp Ile Ser Phe Pro Gly Leu Asp Glu Asp Pro Leu Gly Pro Asp 725 730 735Asn Ile Asn Trp Ser Gln Phe Ile Pro Glu Leu Gln 740 74584208PRTHomo sapiens 84Met Gly Ser Cys Ser Gly Arg Cys Ala Leu Val Val Leu Cys Ala Phe1 5 10 15Gln Leu Val Ala Ala Leu Glu Arg Gln Val Phe Asp Phe Leu Gly Tyr 20 25 30Gln Trp Ala Pro Ile Leu Ala Asn Phe Val His Ile Ile Ile Val Ile 35 40 45Leu Gly Leu Phe Gly Thr Ile Gln Tyr Arg Leu Arg Tyr Val Met Val 50 55 60Tyr Thr Leu Trp Ala Ala Val Trp Val Thr Trp Asn Val Phe Ile Ile65 70 75 80Cys Phe Tyr Leu Glu Val Gly Gly Leu Leu Lys Asp Ser Glu Leu Leu 85 90 95Thr Phe Ser Leu Ser Arg His Arg Ser Trp Trp Arg Glu Arg Trp Pro 100 105 110Gly Cys Leu His Glu Glu Val Pro Ala Val Gly Leu Gly Ala Pro His 115 120 125Gly Gln Ala Leu Val Ser Gly Ala Gly Cys Ala Leu Glu Pro Ser Tyr 130 135 140Val Glu Ala Leu His Ser Cys Leu Gln Ile Leu Ile Ala Leu Leu Gly145 150 155 160Phe Val Cys Gly Cys Gln Val Val Ser Val Phe Thr Asp Glu Glu Asp 165 170 175Ser Phe Asp Phe Ile Gly Gly Phe Asp Pro Phe Pro Leu Tyr His Val 180 185 190Asn Glu Lys Pro Ser Ser Leu Leu Ser Lys Gln Val Tyr Leu Pro Ala 195 200 2058564PRTHomo sapiens 85Met Cys Val Ser Ser Ser Ser Ser Ser His Asp Glu Ala Pro Val Leu1 5 10 15Asn Asp Lys His Leu Asp Val Pro Asp Ile Ile Ile Thr Pro Pro Thr 20 25 30Pro Thr Gly Met Met Leu Pro Arg Asp Leu Gly Ser Thr Val Trp Leu 35 40 45Asp Glu Thr Gly Ser Cys Pro Asp Asp Gly Glu Ile Asp Pro Glu Ala 50 55 6086632PRTHomo sapiens 86Met Asp Thr Met Met Leu Asn Val Arg Asn Leu Phe Glu Gln Leu Val1 5 10 15Arg Arg Val Glu Ile Leu Ser Glu Gly Asn Glu Val Gln Phe Ile Gln 20 25 30Leu Ala Lys Asp Phe Glu Asp Phe Arg Lys Lys Trp Gln Arg Thr Asp 35 40 45His Glu Leu Gly Lys Tyr Lys Asp Leu Leu Met Lys Ala Glu Thr Glu 50 55 60Arg Ser Ala Leu Asp Val Lys Leu Lys His Ala Arg Asn Gln Val Asp65 70 75 80Val Glu Ile Lys Arg Arg Gln Arg Ala Glu Ala Asp Cys Glu Lys Leu 85 90 95Glu Arg Gln Ile Gln Leu Ile Arg Glu Met Leu Met Cys Asp Thr Ser

100 105 110Gly Ser Ile Gln Leu Ser Glu Glu Gln Lys Ser Ala Leu Ala Phe Leu 115 120 125Asn Arg Gly Gln Pro Ser Ser Ser Asn Ala Gly Asn Lys Arg Leu Ser 130 135 140Thr Ile Asp Glu Ser Gly Ser Ile Leu Ser Asp Ile Ser Phe Asp Lys145 150 155 160Thr Asp Glu Ser Leu Asp Trp Asp Ser Ser Leu Val Lys Thr Phe Lys 165 170 175Leu Lys Lys Arg Glu Lys Arg Arg Ser Thr Ser Arg Gln Phe Val Asp 180 185 190Gly Pro Pro Gly Pro Val Lys Lys Thr Arg Ser Ile Gly Ser Ala Val 195 200 205Asp Gln Gly Asn Glu Ser Ile Val Ala Lys Thr Thr Val Thr Val Pro 210 215 220Asn Asp Gly Gly Pro Ile Glu Ala Val Ser Thr Ile Glu Thr Val Pro225 230 235 240Tyr Trp Thr Arg Ser Arg Arg Lys Thr Gly Thr Leu Gln Pro Trp Asn 245 250 255Ser Asp Ser Thr Leu Asn Ser Arg Gln Leu Glu Pro Arg Thr Glu Thr 260 265 270Asp Ser Val Gly Thr Pro Gln Ser Asn Gly Gly Met Arg Leu His Asp 275 280 285Phe Val Ser Lys Thr Val Ile Lys Pro Glu Ser Cys Val Pro Cys Gly 290 295 300Lys Arg Ile Lys Phe Gly Lys Leu Ser Leu Lys Cys Arg Asp Cys Arg305 310 315 320Val Val Ser His Pro Glu Cys Arg Asp Arg Cys Pro Leu Pro Cys Ile 325 330 335Pro Thr Leu Ile Gly Thr Pro Val Lys Ile Gly Glu Gly Met Leu Ala 340 345 350Asp Phe Val Ser Gln Thr Ser Pro Met Ile Pro Ser Ile Val Val His 355 360 365Cys Val Asn Glu Ile Glu Gln Arg Gly Leu Thr Glu Thr Gly Leu Tyr 370 375 380Arg Ile Ser Gly Cys Asp Arg Thr Val Lys Glu Leu Lys Glu Lys Phe385 390 395 400Leu Arg Val Lys Thr Val Pro Leu Leu Ser Lys Val Asp Asp Ile His 405 410 415Ala Ile Cys Ser Leu Leu Lys Asp Phe Leu Arg Asn Leu Lys Glu Pro 420 425 430Leu Leu Thr Phe Arg Leu Asn Arg Ala Phe Met Glu Ala Ala Glu Ile 435 440 445Thr Asp Glu Asp Asn Ser Ile Ala Ala Met Tyr Gln Ala Val Gly Glu 450 455 460Leu Pro Gln Ala Asn Arg Asp Thr Leu Ala Phe Leu Met Ile His Leu465 470 475 480Gln Arg Val Ala Gln Ser Pro His Thr Lys Met Asp Val Ala Asn Leu 485 490 495Ala Lys Val Phe Gly Pro Thr Ile Val Ala His Ala Val Pro Asn Pro 500 505 510Asp Pro Val Thr Met Leu Gln Asp Ile Lys Arg Gln Pro Lys Val Val 515 520 525Glu Arg Leu Leu Ser Leu Pro Leu Glu Tyr Trp Ser Gln Phe Met Met 530 535 540Val Glu Gln Glu Asn Ile Asp Pro Leu His Val Ile Glu Asn Ser Asn545 550 555 560Ala Phe Ser Thr Pro Gln Thr Pro Asp Ile Lys Val Ser Leu Leu Gly 565 570 575Pro Val Thr Thr Pro Glu His Gln Leu Leu Lys Thr Pro Ser Ser Ser 580 585 590Ser Leu Ser Gln Arg Val Arg Ser Thr Leu Thr Lys Asn Thr Pro Arg 595 600 605Phe Gly Ser Lys Ser Lys Ser Ala Thr Asn Leu Gly Arg Gln Gly Asn 610 615 620Phe Phe Ala Ser Pro Met Leu Lys625 63087336PRTHomo sapiens 87Met Thr Asp Leu Asn Asp Asn Ile Cys Lys Arg Tyr Ile Lys Met Ile1 5 10 15Thr 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 45Ile Ser Pro Trp Arg Trp Leu Phe Ser Val Val Val Pro Val Leu Ile 50 55 60Val Ser Asn Gly Leu Lys Lys Lys Ser Leu Asp His Ser Gly Ala Leu65 70 75 80Gly Gly Leu Val Val Gly Phe Ile Leu Thr Ile Ala Asn Phe Ser Phe 85 90 95Phe Thr Ser Leu Leu Met Phe Phe Leu Ser Ser Ser Lys Leu Thr Lys 100 105 110Trp Lys Gly Glu Val Lys Lys Arg Leu Asp Ser Glu Tyr Lys Glu Gly 115 120 125Gly Gln Arg Asn Trp Val Gln Val Phe Cys Asn Gly Ala Val Pro Thr 130 135 140Glu Leu Ala Leu Leu Tyr Met Ile Glu Asn Gly Pro Gly Glu Ile Pro145 150 155 160Val Asp Phe Ser Lys Gln Tyr Ser Ala Ser Trp Met Cys Leu Ser Leu 165 170 175Leu Ala Ala Leu Ala Cys Ser Ala Gly Asp Thr Trp Ala Ser Glu Val 180 185 190Gly Pro Val Leu Ser Lys Ser Ser Pro Arg Leu Ile Thr Thr Trp Glu 195 200 205Lys Val Pro Val Gly Thr Asn Gly Gly Val Thr Val Val Gly Leu Val 210 215 220Ser Ser Leu Leu Gly Gly Thr Phe Val Gly Ile Ala Tyr Phe Leu Thr225 230 235 240Gln Leu Ile Phe Val Asn Asp Leu Asp Ile Ser Ala Pro Gln Trp Pro 245 250 255Ile Ile Ala Phe Gly Gly Leu Ala Gly Leu Leu Gly Ser Ile Val Asp 260 265 270Ser Tyr Leu Gly Ala Thr Met Gln Tyr Thr Gly Leu Asp Glu Ser Thr 275 280 285Gly Met Val Val Asn Ser Pro Thr Asn Lys Ala Arg His Ile Ala Gly 290 295 300Lys Pro Ile Leu Asp Asn Asn Ala Val Asn Leu Phe Ser Ser Val Leu305 310 315 320Ile Ala Leu Leu Leu Pro Thr Ala Ala Trp Gly Phe Trp Pro Arg Gly 325 330 33588347PRTHomo sapiens 88Met Ala Gln Ser Arg Asp Gly Gly Asn Pro Phe Ala Glu Pro Ser Glu1 5 10 15Leu Asp Asn Pro Phe Gln Asp Pro Ala Val Ile Gln His Arg Pro Ser 20 25 30Arg Gln Tyr Ala Thr Leu Asp Val Tyr Asn Pro Phe Glu Thr Arg Glu 35 40 45Pro Pro Pro Ala Tyr Glu Pro Pro Ala Pro Ala Pro Leu Pro Pro Pro 50 55 60Ser Ala Pro Ser Leu Gln Pro Ser Arg Lys Leu Ser Pro Thr Glu Pro65 70 75 80Lys Asn Tyr Gly Ser Tyr Ser Thr Gln Ala Ser Ala Ala Ala Ala Thr 85 90 95Ala Glu Leu Leu Lys Lys Gln Glu Glu Leu Asn Arg Lys Ala Glu Glu 100 105 110Leu Asp Arg Arg Glu Arg Glu Leu Gln His Ala Ala Leu Gly Gly Thr 115 120 125Ala Thr Arg Gln Asn Asn Trp Pro Pro Leu Pro Ser Phe Cys Pro Val 130 135 140Gln Pro Cys Phe Phe Gln Asp Ile Ser Met Glu Ile Pro Gln Glu Phe145 150 155 160Gln Lys Thr Val Ser Thr Met Tyr Tyr Leu Trp Met Cys Ser Thr Leu 165 170 175Ala Leu Leu Leu Asn Phe Leu Ala Cys Leu Ala Ser Phe Cys Val Glu 180 185 190Thr Asn Asn Gly Ala Gly Phe Gly Leu Ser Ile Leu Trp Val Leu Leu 195 200 205Phe Thr Pro Cys Ser Phe Val Cys Trp Tyr Arg Pro Met Tyr Lys Ala 210 215 220Phe Arg Ser Asp Ser Ser Phe Asn Phe Phe Val Phe Phe Phe Ile Phe225 230 235 240Phe Val Gln Asp Val Leu Phe Val Leu Gln Ala Ile Gly Ile Pro Gly 245 250 255Trp Gly Phe Ser Gly Trp Ile Ser Ala Leu Val Val Pro Lys Gly Asn 260 265 270Thr Ala Val Ser Val Leu Met Leu Leu Val Ala Leu Leu Phe Thr Gly 275 280 285Ile Ala Val Leu Gly Ile Val Met Leu Lys Arg Ile His Ser Leu Tyr 290 295 300Arg Arg Thr Gly Ala Ser Phe Gln Lys Ala Gln Gln Glu Phe Ala Ala305 310 315 320Gly Val Phe Ser Asn Pro Ala Val Arg Thr Ala Ala Ala Asn Ala Ala 325 330 335Ala Gly Ala Ala Glu Asn Ala Phe Arg Ala Pro 340 34589257PRTHomo sapiens 89Met Ala Gln Arg Met Thr Thr Gln Leu Leu Leu Leu Leu Val Trp Val1 5 10 15Ala Val Val Gly Glu Ala Gln Thr Arg Ile Ala Trp Ala Arg Thr Glu 20 25 30Leu Leu Asn Val Cys Met Asn Ala Lys His His Lys Glu Lys Pro Gly 35 40 45Pro Glu Asp Lys Leu His Glu Gln Cys Arg Pro Trp Arg Lys Asn Ala 50 55 60Cys Cys Ser Thr Asn Thr Ser Gln Glu Ala His Lys Asp Val Ser Tyr65 70 75 80Leu Tyr Arg Phe Asn Trp Asn His Cys Gly Glu Met Ala Pro Ala Cys 85 90 95Lys Arg His Phe Ile Gln Asp Thr Cys Leu Tyr Glu Cys Ser Pro Asn 100 105 110Leu Gly Pro Trp Ile Gln Gln Val Asp Gln Ser Trp Arg Lys Glu Arg 115 120 125Val Leu Asn Val Pro Leu Cys Lys Glu Asp Cys Glu Gln Trp Trp Glu 130 135 140Asp Cys Arg Thr Ser Tyr Thr Cys Lys Ser Asn Trp His Lys Gly Trp145 150 155 160Asn Trp Thr Ser Gly Phe Asn Lys Cys Ala Val Gly Ala Ala Cys Gln 165 170 175Pro Phe His Phe Tyr Phe Pro Thr Pro Thr Val Leu Cys Asn Glu Ile 180 185 190Trp Thr His Ser Tyr Lys Val Ser Asn Tyr Ser Arg Gly Ser Gly Arg 195 200 205Cys Ile Gln Met Trp Phe Asp Pro Ala Gln Gly Asn Pro Asn Glu Glu 210 215 220Val Ala Arg Phe Tyr Ala Ala Ala Met Ser Gly Ala Gly Pro Trp Ala225 230 235 240Ala Trp Pro Phe Leu Leu Ser Leu Ala Leu Met Leu Leu Trp Leu Leu 245 250 255 Ser9043DNAHomo sapiensmisc_featureoligonucleotide is biotinylated 90actgtactaa ccctgcggcc gctttttttt tttttttttt ttv 439147DNAHomo sapiens 91ggaattctaa tacgactcac tatagggaga cgaagacagt agacagg 479250DNAHomo sapiens 92cgcgcctgtc tactgtcttc gtctccctat agtgagtcgt attagaattc 509352DNAHomo sapiens 93ggaattctaa tacgactcac tatagggaga gcctgcacca acagttaaca gg 529455DNAHomo sapiens 94cgcgcctgtt aactgttggt gcaggctctc cctatagtga gtcgtattag aattc 559519DNAHomo sapiens 95gggagacgaa gacagtaga 199620DNAHomo sapiens 96gcctgcacca acagttaaca 209728DNAHomo sapiens 97ggaattctaa tacgactcac tataggga 289831DNAHomo sapiens 98cgcgtcccta tagtgagtcg tattagaatt c 31992757DNAHomo sapiens 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 27571002995DNAHomo sapiens 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 29951014455DNAHomo sapiens 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 445510252RNAHomo sapiensmisc_feature(1)..(52)control sequence undisclosed by Ambion (may vary in lenght) 102nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nn 5210319DNAHomo sapiens 103gtcaagaaac cacacttta 1910419DNAHomo sapiens 104gtgacatgga acccagcga 1910519DNAHomo sapiens 105accgtggctg ctcgataaa 1910619DNAHomo sapiens 106gccagagagc acagaaata 1910719DNAHomo sapiens 107gaggaatgcc tctaagaaa 1910819DNAHomo sapiens 108gggaacgaga agggcttct 1910919DNAHomo sapiens 109agctggagga atgagaatt 1911019DNAHomo sapiens 110agggccaaag ctttccata 1911119DNAHomo sapiens 111ggcaggctgt ccgcttaaa 1911219DNAHomo sapiens 112ggtccttagg cacccagat 1911319DNAHomo sapiens 113gcggagccca gggagaata 1911419DNAHomo sapiens 114gcccggattg atgacatat 1911519DNAHomo sapiens 115gtggaggctg agtttccat 1911619DNAHomo sapiens 116ggatgttaac ctgcgaaat 1911719DNAHomo sapiens 117ggtcagcagg gttcattta 1911819DNAHomo sapiens 118gcctcaggaa caagatgaa 1911919DNAHomo sapiens 119gcgcgagatc ctctccatt 1912019DNAHomo sapiens 120gcgccagagg agcgggaag 1912119DNAHomo sapiens 121gccgcccagt tcaatacaa 1912219DNAHomo sapiens 122gagcttacaa cctgcctta 1912319DNAHomo sapiens 123ggcgcccact acccaagaa 1912419DNAHomo sapiens 124gagtcaggga tgggtccat 1912519DNAHomo sapiens 125gggccagtct gtactcatt 1912619DNAHomo sapiens 126gggaattcca tctccatat 1912719DNAHomo sapiens 127ggcgcagatc acccagaag 1912819DNAHomo sapiens 128gagcatcctg gtgaggaat 1912919DNAHomo sapiens 129ggtgccacat gactaggat 1913019DNAHomo sapiens 130gctgcagacg tgtatgcat 1913119DNAHomo sapiens 131gcggaggcac tgggcttat 1913219DNAHomo sapiens 132gcccgcttac ttcctggag 1913319DNAHomo sapiens 133gctctgctca agttggata 1913419DNAHomo sapiens 134gctgctgcct tgcagtttg 1913519DNAHomo sapiens 135gcccttacct gatgctaaa 1913619DNAHomo sapiens 136ggcacctaca aatgttata 1913719DNAHomo sapiens 137gaggcctgga agctcctaa 1913819DNAHomo sapiens 138gcagcttcag gaggttaaa 1913919DNAHomo sapiens 139gccggacctc ttcatctta 1914019DNAHomo sapiens 140gcgtccatca cggaaacat 1914119DNAHomo sapiens 141gtcatcagga cgtccatta 1914219DNAHomo sapiens 142gacacgatct accctcaaa 1914319DNAHomo sapiens 143gggccatagg gaagcttga 1914419DNAHomo sapiens 144gcccacgtgt tgagatcaa 1914519DNAHomo sapiens 145gctcccactg attccacat 1914619DNAHomo sapiens 146gccagagagt aaaagggat 1914719DNAHomo sapiens 147ggcatatgga aggagcatt 1914819DNAHomo sapiens 148gtggtttggt tcagcagtt 1914919DNAHomo sapiens 149ggcctccagc cacgtaatt 1915019DNAHomo sapiens 150ggcgctgctg ccgctcatc 1915119DNAHomo sapiens 151gggctggaac tggacttca 1915219DNAHomo sapiens 152gcccataagg atgtttcct 1915323DNAHomo sapiens 153gcgtccgggc ctgtcttcaa cct 2315424DNAHomo sapiens 154gccccaccct ctaccccacc acta 2415522DNAHomo sapiens 155gagatcctga tcaaggtgca gg 2215621DNAHomo sapiens 156tgcacgctca cagcagtcag g 2115722DNAHomo sapiens 157aacatgacta agatgcccaa cc 2215823DNAHomo sapiens 158aatctccttc acctccacta ctg 2315922DNAHomo sapiens 159aagcatagcc ataggtgatt gg 2216023DNAHomo sapiens 160acaggtatca gacaagggag cag 2316121DNAHomo sapiens 161ttacgaccta tttctccgtg g 2116221DNAHomo sapiens 162aatgcaataa ttggccactg c 2116323DNAHomo sapiens 163acacatcaaa ctgcttatcc agg 2316422DNAHomo sapiens 164actgatgtga aaatgcacat cc 2216521DNAHomo sapiens 165atggctcata cagcactcag g 2116622DNAHomo sapiens 166gaactgtcac tccggaaagc ct 2216726DNAHomo sapiens 167tgaaggtcgg agtcaacgga tttggt 2616824DNAHomo sapiens 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 Pro1 5 10 15Ala Trp Ala Lys Glu Lys His Tyr Tyr Ile Gly Ile Ile Glu Thr Thr 20 25

30Trp Asp Tyr Ala Ser Asp His Gly Glu Lys Lys Leu Ile Ser Val Asp 35 40 45Thr Glu His Ser Asn Ile Tyr Leu Gln Asn Gly Pro Asp Arg Ile Gly 50 55 60Arg Leu Tyr Lys Lys Ala Leu Tyr Leu Gln Tyr Thr Asp Glu Thr Phe65 70 75 80Arg Thr Thr Ile Glu Lys Pro Val Trp Leu Gly Phe Leu Gly Pro Ile 85 90 95Ile Lys Ala Glu Thr Gly Asp Lys Val Tyr Val His Leu Lys Asn Leu 100 105 110Ala Ser Arg Pro Tyr Thr Phe His Ser His Gly Ile Thr Tyr Tyr Lys 115 120 125Glu His Glu Gly Ala Ile Tyr Pro Asp Asn Thr Thr Asp Phe Gln Arg 130 135 140Ala Asp Asp Lys Val Tyr Pro Gly Glu Gln Tyr Thr Tyr Met Leu Leu145 150 155 160Ala Thr Glu Glu Gln Ser Pro Gly Glu Gly Asp Gly Asn Cys Val Thr 165 170 175Arg Ile Tyr His Ser His Ile Asp Ala Pro Lys Asp Ile Ala Ser Gly 180 185 190Leu Ile Gly Pro Leu Ile Ile Cys Lys Lys Asp Ser Leu Asp Lys Glu 195 200 205Lys Glu Lys His Ile Asp Arg Glu Phe Val Val Met Phe Ser Val Val 210 215 220Asp Glu Asn Phe Ser Trp Tyr Leu Glu Asp Asn Ile Lys Thr Tyr Cys225 230 235 240Ser Glu Pro Glu Lys Val Asp Lys Asp Asn Glu Asp Phe Gln Glu Ser 245 250 255Asn Arg Met Tyr Ser Val Asn Gly Tyr Thr Phe Gly Ser Leu Pro Gly 260 265 270Leu Ser Met Cys Ala Glu Asp Arg Val Lys Trp Tyr Leu Phe Gly Met 275 280 285Gly Asn Glu Val Asp Val His Ala Ala Phe Phe His Gly Gln Ala Leu 290 295 300Thr Asn Lys Asn Tyr Arg Ile Asp Thr Ile Asn Leu Phe Pro Ala Thr305 310 315 320Leu Phe Asp Ala Tyr Met Val Ala Gln Asn Pro Gly Glu Trp Met Leu 325 330 335Ser Cys Gln Asn Leu Asn His Leu Lys Ala Gly Leu Gln Ala Phe Phe 340 345 350Gln Val Gln Glu Cys Asn Lys Ser Ser Ser Lys Asp Asn Ile Arg Gly 355 360 365Lys His Val Arg His Tyr Tyr Ile Ala Ala Glu Glu Ile Ile Trp Asn 370 375 380Tyr Ala Pro Ser Gly Ile Asp Ile Phe Thr Lys Glu Asn Leu Thr Ala385 390 395 400Pro Gly Ser Asp Ser Ala Val Phe Phe Glu Gln Gly Thr Thr Arg Ile 405 410 415Gly Gly Ser Tyr Lys Lys Leu Val Tyr Arg Glu Tyr Thr Asp Ala Ser 420 425 430Phe Thr Asn Arg Lys Glu Arg Gly Pro Glu Glu Glu His Leu Gly Ile 435 440 445Leu Gly Pro Val Ile Trp Ala Glu Val Gly Asp Thr Ile Arg Val Thr 450 455 460Phe His Asn Lys Gly Ala Tyr Pro Leu Ser Ile Glu Pro Ile Gly Val465 470 475 480Arg Phe Asn Lys Asn Asn Glu Gly Thr Tyr Tyr Ser Pro Asn Tyr Asn 485 490 495Pro Gln Ser Arg Ser Val Pro Pro Ser Ala Ser His Val Ala Pro Thr 500 505 510Glu Thr Phe Thr Tyr Glu Trp Thr Val Pro Lys Glu Val Gly Pro Thr 515 520 525Asn Ala Asp Pro Val Cys Leu Ala Lys Met Tyr Tyr Ser Ala Val Asp 530 535 540Pro Thr Lys Asp Ile Phe Thr Gly Leu Ile Gly Pro Met Lys Ile Cys545 550 555 560Lys Lys Gly Ser Leu His Ala Asn Gly Arg Gln Lys Asp Val Asp Lys 565 570 575Glu Phe Tyr Leu Phe Pro Thr Val Phe Asp Glu Asn Glu Ser Leu Leu 580 585 590Leu Glu Asp Asn Ile Arg Met Phe Thr Thr Ala Pro Asp Gln Val Asp 595 600 605Lys Glu Asp Glu Asp Phe Gln Glu Ser Asn Lys Met His Ser Met Asn 610 615 620Gly Phe Met Tyr Gly Asn Gln Pro Gly Leu Thr Met Cys Lys Gly Asp625 630 635 640Ser Val Val Trp Tyr Leu Phe Ser Ala Gly Asn Glu Ala Asp Val His 645 650 655Gly Ile Tyr Phe Ser Gly Asn Thr Tyr Leu Trp Arg Gly Glu Arg Arg 660 665 670Asp Thr Ala Asn Leu Phe Pro Gln Thr Ser Leu Thr Leu His Met Trp 675 680 685Pro Asp Thr Glu Gly Thr Phe Asn Val Glu Cys Leu Thr Thr Asp His 690 695 700Tyr Thr Gly Gly Met Lys Gln Lys Tyr Thr Val Asn Gln Cys Arg Arg705 710 715 720Gln Ser Glu Asp Ser Thr Phe Tyr Leu Gly Glu Arg Thr Tyr Tyr Ile 725 730 735Ala Ala Val Glu Val Glu Trp Asp Tyr Ser Pro Gln Arg Glu Trp Glu 740 745 750Lys Glu Leu His His Leu Gln Glu Gln Asn Val Ser Asn Ala Phe Leu 755 760 765Asp Lys Gly Glu Phe Tyr Ile Gly Ser Lys Tyr Lys Lys Val Val Tyr 770 775 780Arg Gln Tyr Thr Asp Ser Thr Phe Arg Val Pro Val Glu Arg Lys Ala785 790 795 800Glu Glu Glu His Leu Gly Ile Leu Gly Pro Gln Leu His Ala Asp Val 805 810 815Gly Asp Lys Val Lys Ile Ile Phe Lys Asn Met Ala Thr Arg Pro Tyr 820 825 830Ser Ile His Ala His Gly Val Gln Thr Glu Ser Ser Thr Val Thr Pro 835 840 845Thr Leu Pro Gly Glu Thr Leu Thr Tyr Val Trp Lys Ile Pro Glu Arg 850 855 860Ser Gly Ala Gly Thr Glu Asp Ser Ala Cys Ile Pro Trp Ala Tyr Tyr865 870 875 880Ser Thr Val Asp Gln Val Lys Asp Leu Tyr Ser Gly Leu Ile Gly Pro 885 890 895Leu Ile Val Cys Arg Arg Pro Tyr Leu Lys Val Phe Asn Pro Arg Arg 900 905 910Lys Leu Glu Phe Ala Leu Leu Phe Leu Val Phe Asp Glu Asn Glu Ser 915 920 925Trp Tyr Leu Asp Asp Asn Ile Lys Thr Tyr Ser Asp His Pro Glu Lys 930 935 940Val Asn Lys Asp Asp Glu Glu Phe Ile Glu Ser Asn Lys Met His Ala945 950 955 960Ile Asn Gly Arg Met Phe Gly Asn Leu Gln Gly Leu Thr Met His Val 965 970 975Gly Asp Glu Val Asn Trp Tyr Leu Met Gly Met Gly Asn Glu Ile Asp 980 985 990Leu His Thr Val His Phe His Gly His Ser Phe Gln Tyr Lys His Arg 995 1000 1005Gly Val Tyr Ser Ser Asp Val Phe Asp Ile Phe Pro Gly Thr Tyr 1010 1015 1020Gln Thr Leu Glu Met Phe Pro Arg Thr Pro Gly Ile Trp Leu Leu 1025 1030 1035His Cys His Val Thr Asp His Ile His Ala Gly Met Glu Thr Thr 1040 1045 1050Tyr Thr Val Leu Gln Asn Glu Asp Thr Lys Ser Gly 1055 1060 106517123DNAHomo sapiens 171gcttaaaaga gtcctcctgt ggc 2317223DNAHomo sapiens 172tggacattgt tcttaaagtg tgg 2317321DNAHomo sapiens 173aggttttatg gccaccgtca g 2117422DNAHomo sapiens 174atcctatacc gctcggttat gc 2217522DNAHomo sapiens 175gggcggcggc tctttcctcc tc 2217619DNAHomo sapiens 176gctagcggcc ccatactcg 1917724DNAHomo sapiens 177acactggatg ccctgaatga caca 2417820DNAHomo sapiens 178gctttggccc tttttgctaa 2017922DNAHomo sapiens 179cccacttctg tcttactgca tc 2218022DNAHomo sapiens 180catagtactc cagggcttat tc 2218123DNAHomo sapiens 181aacgattgcc cggattgatg aca 2318224DNAHomo sapiens 182tacttgaggc tggggtggga gatg 2418322DNAHomo sapiens 183cactacgcca ggcaccccca aa 2218418DNAHomo sapiens 184cgaggcgcac ggcagtct 1818524DNAHomo sapiens 185atccgttgct gcagctcgtt cctc 2418624DNAHomo sapiens 186accctgctga ccttcttcca ttcc 2418724DNAHomo sapiens 187tcggaggagg gctggctggt gttt 2418824DNAHomo sapiens 188cttgggcgtc ttggagcggt tctg 2418922DNAHomo sapiens 189agagcctatt gaagatgaac ag 2219023DNAHomo sapiens 190tgattgcccc ggatcctctt agg 2319120DNAHomo sapiens 191ggacaaatac gacgacgagg 2019219DNAHomo sapiens 192ggtttcttgg gtagtgggc 1919322DNAHomo sapiens 193ccccggagaa ggaagagcag ta 2219424DNAHomo sapiens 194cgaaagccgg cagttagtta ttga 2419524DNAHomo sapiens 195ggcgggcaac gaattccagg tgtc 2419624DNAHomo sapiens 196tcagaggttc gtcgcatttg tcca 2419722DNAHomo sapiens 197caacagtcat gatgtgtgga tg 2219822DNAHomo sapiens 198actgcacctt gtccgtgttg ac 2219920DNAHomo sapiens 199ccggctggct gctttgttta 2020024DNAHomo sapiens 200atgatcagca ggttcgttgg tagg 2420119DNAHomo sapiens 201atgccggaag tgaatgtgg 1920219DNAHomo sapiens 202ggtgactccg ccttttgat 1920320DNAHomo sapiens 203acattcgctt ctccatctgg 2020420DNAHomo sapiens 204tgtcacggaa gggaaccagg 2020520DNAHomo sapiens 205acgctgcctc tgggtcactt 2020623DNAHomo sapiens 206ttggcaaatc aatggcttgt aat 2320720DNAHomo sapiens 207atggcttggg tcatcaggac 2020823DNAHomo sapiens 208gtgtcactgg gcgtaagata ctg 2320924DNAHomo sapiens 209caccaaatca gctgctacta ctcc 2421024DNAHomo sapiens 210gataaacccc aaagcagaaa gatt 2421120DNAHomo sapiens 211cgagattccg tgggcgtagg 2021219DNAHomo sapiens 212tgagtgggag cttcgtagg 1921321DNAHomo sapiens 213tcagagtgga cgttggatta c 2121421DNAHomo sapiens 214tgcttgaaat gtaggagaac a 2121524DNAHomo sapiens 215gaggggcatc aatcacaccg agaa 2421622DNAHomo sapiens 216ccccaccgcc cacccattta gg 2221720DNAHomo sapiens 217gggggcacca gaggcagtaa 2021822DNAHomo sapiens 218ggttgtggcg ggggcagttg tg 2221922DNAHomo sapiens 219acagactcct gtactgcaaa cc 2222021DNAHomo sapiens 220taccggttcg tcctcttcct c 2122123DNAHomo sapiens 221gaagttcctc acgccctgct atc 2322224DNAHomo sapiens 222ctggctggtg acctgctttg agta 2422331DNAHomo sapiens 223taggcgcgcc tgacatacag caatgccagt t 3122436DNAHomo sapiens 224taagaatgcg gccgcgccac atcttgaaca ctttgc 3622524DNAHomo sapiens 225tggggaggag tttgaggagc agac 2422623DNAHomo sapiens 226gtgggacgga gggggcagtg aag 2322720DNAHomo sapiens 227gcaactattc ggagcgcgtg 2022820DNAHomo sapiens 228ccagcagctt gttgagctcc 2022921DNAHomo sapiens 229ggaggagcta agcgtcatcg c 2123019DNAHomo sapiens 230tcgcttcagc gcgtagacc 1923124DNAHomo sapiens 231tattagttgg gatggtggta gcac 2423222DNAHomo sapiens 232gagaattcga gtcgacgatg ac 2223323DNAHomo sapiens 233gaaattgtgt tgacgcagtc tcc 2323422DNAHomo sapiens 234aggcacacaa cagaggcagt tc 2223522DNAHomo sapiens 235gtacatcaac ctcctgctgt cc 2223622DNAHomo sapiens 236gacatctcca agtcccagca tg 2223723DNAHomo sapiens 237agtctctcac tgtgccttat gcc 2323820DNAHomo sapiens 238agtcctaaga actgtaaacg 2023921DNAHomo sapiens 239catctatacg tggattgagg a 2124021DNAHomo sapiens 240ataggtacca ggtatgagct g 2124123DNAHomo sapiens 241tgtccacatc atcatcgtca tcc 2324222DNAHomo sapiens 242tgtcactggt cggtcgctga gg 2224318DNAHomo sapiens 243catggggctt aagatgtc 1824420DNAHomo sapiens 244gtcgatttct ccatcatctg 2024520DNAHomo sapiens 245aagaggcgct ctactagccg 2024620DNAHomo sapiens 246ctttccacat ggaacacagg 2024723DNAHomo sapiens 247cattttcctg gaatttgata cag 2324823DNAHomo sapiens 248gtagagagtt tatttgggcc aag 2324921DNAHomo sapiens 249catctatggt aactacaatc g 2125022DNAHomo sapiens 250gtagaagtca ctgatcagac ac 2225124DNAHomo sapiens 251ctgcctgcca acctttccat ttct 2425223DNAHomo sapiens 252tgagcagcca cagcagcatt agg 2325321DNAHomo sapiens 253cacctgatca ggtggataag g 2125422DNAHomo sapiens 254tcccaggtag aaggtggaat cc 22255628DNAHomo sapiens 255aatcatatta gtgaagatta ggaagaagct ttaaaatccc aaggctagtg tgcattgcta 60gaattgttaa gagagagagc tcatatgaaa ttggttatcg tgggatattt aaaataaaac 120aaagaacagt ttactttcag gcaaaaagat gccagtaatc aatattgagg acctgacaga 180aaaggacaaa ttgaagatgg aagttgacca gctcaagaaa gaagtgacac tggaaagaat 240gctagtttcc aaatgttgtg aagaagtaag agattacgtt gaagaacgat ctggcgagga 300tccactggta aagggcatcc cagaggacaa aaatcccttc aaggagctca aaggaggctg 360tgtgatttca taatacaaac aaaaagaaaa aaaattaaac aaattcttgg aaatatctca 420aatgttaata acaatatgaa tttttctcat gcatactatt actactaagc atgtacgtga 480atttttaaat ttatagatgt aaacttttaa taaaaattgg ggtgtggtaa cccatcattc 540tatgtttttc ttaacatagc tggcacaggg tttaacacat aattgccaat aaatattgct 600taaagttctt taaaaagaac tatgtttt 6282562499DNAHomo sapiens 256gctgggcacc gttctgtttt ctttcttttc ttaatcctat ccaagtatgc agtacgctct 60tgggtcgtct catgagaccc aggggcatgt tggaaagaac tgagagaaag agcaacaaag 120cggcgagtgg tgtgagaggg cagcacgcgc tgtggggccc ttccagagaa atgtactgaa 180aaagtctacg caatgtctgg gatttgctaa acaatacctg gaaagcagac aggtcttttt 240gccattcctc caggacatcc accataagga aaggagaccc tggaccaaca ttctctaaga 300tgtttatatg gaccagtggc cggacctctt catcttatag acatgatgaa aaaagaaata 360tttaccagaa aatcagggac catgacctcc tggacaaaag gaaaacagtc acagcactga 420aggcaggaga ggaccgagct attctcctgg gactggctat gatggtgtgc tccatcatga 480tgtattttct gctgggaatc acactcctgc gctcatacat gcagagcgtg tggaccgaag 540agtctcaatg caccttgctg aatgcgtcca tcacggaaac atttaattgc tccttcagct 600gtggtccaga ctgctggaaa ctttctcagt acccctgcct ccaggtgtac gttaacctga 660cttcttccgg ggaaaagctc ctcctctacc acacagaaga gacaataaaa atcaatcaga 720agtgctccta tatacctaaa tgtggaaaaa attttgaaga atccatgtcc ctggtgaatg 780ttgtcatgga aaacttcagg aagtatcaac acttctcctg ctattctgac ccagaaggaa 840accagaagag tgttatccta acaaaactct acagttccaa cgtgctgttc cattcactct 900tctggccaac ctgtatgatg gctgggggtg tggcaattgt tgccatggtg aaacttacac 960agtacctctc cctactatgt gagaggatcc aacggatcaa tagataaatg caaaaatgga 1020taaaataatt tttgttaaag ctcaaatact gttttctttc attcttcacc aaagaacctt 1080aagtttgtaa cgtgcagtct gttatgagtt ccctaatata ttcttatatg tagagcaata 1140atgcaaaagc tgttctatat gcaaacatga tgtctttatt attcaggaga ataaataact 1200gttttgtgtt ggttggtggt tttcataatc ttatttctgt actggaacta gtactttctt 1260ctctcattcc gccaaaacag ggctcagtta ttcatttgcc aagcttcgtg gaggaatgta 1320ggtgacatca

atgtgataaa gtctgtgttc tgagttgtca gatctcttga agacaatatt 1380tttcatcact tattgtttac taaagctaca gccaaaaata tttttttttc ttattctaaa 1440ctgagcccta tagcaagtga agggaccaga tttcctaatt aaaggaagtt aggtactttt 1500cttgtatttt ttaccatatc actgtaaaga agaggggaaa cccagccagc tacttttttt 1560catcactttt tattcataac ttcagatttg taaaactaat ttccaaaata taagctgttt 1620tcattagcca gttctataat atcttcctgt gatttatgta gaaaatgaac acaccccttt 1680tccatttaag accctgctac tgtgtgaaga gatgatactt acaaggagtg tcattacctg 1740tgagctgact gaatgttggt aggtgctcca ttacaatcca ggaaagtctg tgttactgat 1800atttgtgtgg aaatctttat ttcacttcaa tttaaccatt agatggtaaa attaagatgc 1860tacttgttgg taaaaattgg tggactggtt tcaatgggta aatgtgttgt ggcaaattaa 1920tgtgttggaa tattgctctt tgtgaatttg tgcttaagtc aatgaatgtg tagtatctcc 1980ttctgacaag cattccctat tgggatttta aagctatgtg cacagaatat tagtctcttc 2040tacatgtttt atttttctat ttataattcc cttttttgtt gttatatttt atacacagaa 2100tagatctttt ttctaacaca tatttgaact gaataacaga cttaaagaaa gcctttgttc 2160acattgctat ttacttttgt gtttggggga aaatacgagg gattgatttt aaataaaaaa 2220cattccatct ttcatttaat atcaatatca aaagaagaag acaaacatct atctttctca 2280tctatattta agtacctttt tgtaatgtag tatcaaagtt ttttaggtaa tgcaaaattt 2340tacaaatcat ttgtggaatg aatggtaaaa ctaatctgat gaaatggaaa attattctgc 2400aatattgtaa ttcatagttt gacttttcat aagcaaataa atccctagga tgtaatcagg 2460acttcaaatg tgtaattaaa tttttttaaa aaaaatcta 2499

Claims

1-152. (canceled)

153. An antibody or antigen binding fragment capable of binding to a polypeptide having at least 80% sequence identity with SEQ ID NO.:70 and capable of impairing an activity of the polypeptide in ovarian cancer cells.

154. The antibody or antigen binding fragment of claim 153, wherein the polypeptide has a sequence identical to SEQ ID NO.:70.

155. The antibody or antigen binding fragment of claim 153, wherein the activity is ovarian cancer tumorigenesis.

156. The antibody or antigen binding fragment of claim 153, wherein the antibody is a polyclonal antibody.

157. The antibody or antigen binding fragment of claim 153, wherein the antibody is a monoclonal antibody.

158. The antibody or antigen binding fragment of claim 153, wherein the antibody is a chimeric antibody.

159. The antibody or antigen binding fragment of claim 153, wherein the antibody is a humanized antibody.

160. The antibody or antigen binding fragment of claim 153, wherein the antibody is a human antibody.

161. The antibody or antigen binding fragment of claim 153, wherein the antigen binding fragment is a FV, a Fab, a Fab' or a (Fab').sub.2.

162. The antibody or antigen binding fragment of claim 153, wherein said antibody has sub-nanomolar affinity for the polypeptide.

163. A pharmaceutical composition comprising: a. an antibody or antigen binding fragment capable of binding to a polypeptide having at least 80% sequence identity with SEQ ID NO.:70 and capable of impairing an activity of the polypeptide in ovarian cancer cells and; b. a pharmaceutically acceptable carrier.

164. The pharmaceutical composition of claim 163, wherein the polypeptide has a sequence identical to SEQ ID NO.:70.

165. The pharmaceutical composition of claim 163, wherein the activity is ovarian cancer tumorigenesis.

166. The pharmaceutical composition of claim 163, wherein the antibody is a polyclonal antibody.

167. The pharmaceutical composition of claim 163, wherein the antibody is a monoclonal antibody or an antigen binding fragment thereof.

168. The pharmaceutical composition of claim 163, wherein the antibody is a chimeric antibody.

169. The pharmaceutical composition of claim 163, wherein the antibody is a humanized antibody.

170. The pharmaceutical composition of claim 163, wherein the antibody is a human antibody.

171. The pharmaceutical composition of claim 163, wherein the antigen binding fragment is a FV, a Fab, a Fab' or a (Fab').sub.2.

172. The pharmaceutical composition of claim 163, wherein the antibody has sub-nanomolar affinity for the polypeptide.

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