專利名稱:在人類肝臟中特異表達(dá)的表達(dá)序列標(biāo)簽的制作方法
技術(shù)領(lǐng)域:
本發(fā)明涉及生物技術(shù)領(lǐng)域,尤其涉及一類在人類肝臟中特異表達(dá)的表達(dá)序列標(biāo)簽。
背景技術(shù):
肝臟是人體內(nèi)最大的消化腺。也是體內(nèi)新陳代謝的中心站。據(jù)估計(jì),在肝臟中發(fā)生的化學(xué)反應(yīng)有500種以上,實(shí)驗(yàn)證明,動物在完全摘除肝臟后即使給予相應(yīng)的治療,最多也只能生存50多個(gè)小時(shí)。這說明肝臟是維持生命活動的一個(gè)必不可少的重要器官。肝臟的血流量極為豐富,約占心輸出量的1/4。每分鐘進(jìn)入肝臟的血流量為1000-1200ml。肝臟的主要功能是進(jìn)行糖的分解、貯存糖原;參與蛋白質(zhì)、脂肪、維生素、激素的代謝;解毒;分泌膽汁;吞噬、防御機(jī)能;制造凝血因子;調(diào)節(jié)血容量及水電解質(zhì)平衡;產(chǎn)生熱量等。在胚胎時(shí)期肝臟還有造血功能。
肝臟疫病分為肝炎、肝硬化、脂肪肝、肝癌等。現(xiàn)代醫(yī)學(xué)實(shí)驗(yàn)證明,肝病病毒侵入人體后,并不直接引起肝細(xì)胞的損害,只是在肝細(xì)胞內(nèi)吸收營養(yǎng)賴以生存,并在肝細(xì)胞內(nèi)復(fù)制、繁殖。其復(fù)制病毒的“零部件”如表面抗原(HBsAg)、e抗原(HBeAg)釋放在肝細(xì)胞膜上,引起人體免疫系統(tǒng)對這些抗原物質(zhì)產(chǎn)生免疫反應(yīng),這種反應(yīng)造成肝細(xì)胞的損傷、壞死。免疫反應(yīng)的強(qiáng)弱決定于肝臟受損程度及臨床癥狀輕重。這場由病毒引發(fā)的、免疫系統(tǒng)對肝細(xì)胞的戰(zhàn)爭,使大約25%的患者的肝臟成為戰(zhàn)火連綿的戰(zhàn)場,肝臟的損傷由此加重。肝病的危害絕不僅僅限于肝臟本身,它還可以引起其它多種疾病。常見的有(1)糖尿??;(2)胰腺炎;(3)膽道感染;(4)功能性腎衰竭;(5)膽汗性腎?。?6)腎小球腎炎;(7)腎小管酸中毒;(8)溶血性貧血;(9)再生障礙性貧血;(10)心肌炎和心包炎;(11)結(jié)節(jié)性動脈炎;(12)消化性潰瘍;(13)自發(fā)性腹膜炎;(14)性激素代謝紊亂;(15)甲狀腺功能改變;(16)肝性骨病,等等。肝病不僅對患者的身體甚至生命造成危害,而且對患者心理上的打擊也是十分沉重的。無論是肝病患者還是病毒攜帶者,在生活、社交、求職、升學(xué)等方面都會受到嚴(yán)重影響。
生物基因組中可轉(zhuǎn)錄表達(dá)的序列(即基因)僅占總序列的3-5%,對這部分序列進(jìn)行測定,將直接導(dǎo)致新基因的發(fā)現(xiàn),并獲取基因組中與產(chǎn)業(yè)化關(guān)系最為密切的信息。20世紀(jì)80年代,高通量的自動測序的出現(xiàn),使從質(zhì)粒互補(bǔ)脫氧核糖核酸(Complementary DNA,簡稱cDNA)文庫隨機(jī)選取許多cDNA克隆和決定來自非載體兩端的幾百個(gè)堿基的DNA序列成為可能。這些短的DNA序列叫做“表達(dá)序列標(biāo)簽”(Expressed Sequence Tags,簡稱ESTs)。表達(dá)序列標(biāo)簽的概念最早是由Adams等在1992年提出來的(Nature,355,642-644)。1992年Sikela和Matsubara(Sikela,et al.Nucleic Acids Res.19,1837-1843;Matsubara,et al.Nature Genetics,2,173-179)針對獲得大量信使核糖核酸(mRNA)序列的迫切需要,提出大規(guī)?;パa(bǔ)脫氧核糖核酸(cDNA)測序的研究戰(zhàn)略。隨后Venter創(chuàng)立了大規(guī)模表達(dá)序列標(biāo)簽技術(shù)。其基本特征就是從以質(zhì)粒為載體,構(gòu)建完成的目的組織互補(bǔ)脫氧核糖核酸(Complementary DNA,簡稱cDNA)文庫中,隨機(jī)選擇許多cDNA克隆,利用質(zhì)粒上攜帶的通用引物對cDNA兩端進(jìn)行一輪脫氧核糖核酸序列測定,所獲得的來自3’端或5’端的幾百個(gè)堿基的非載體短脫氧核糖核酸(DNA)序列。簡而言之,表達(dá)序列標(biāo)簽是來自表達(dá)基因片段3’端或5’端的短脫氧核糖核酸序列,代表一個(gè)表達(dá)基因的部分轉(zhuǎn)錄片段。
表達(dá)序列標(biāo)簽可用于新基因克隆、人類基因組圖譜繪制、基因組序列編碼區(qū)的確定等。如果一個(gè)表達(dá)序列標(biāo)簽在基因組中只出現(xiàn)一次,那么它可以作為序列標(biāo)簽位點(diǎn)(STS)。由表達(dá)序列標(biāo)簽構(gòu)建的物理圖譜叫表達(dá)圖或轉(zhuǎn)錄圖(expression ortranscript map)。利用表達(dá)序列標(biāo)簽進(jìn)行基因圖制作,可以加快序列標(biāo)簽位點(diǎn)的制作和新基因的染色體定位。表達(dá)序列標(biāo)簽可以作為基因特異性探針,對組織特異性基因表達(dá)的研究具有重要的作用。表達(dá)序列標(biāo)簽還可以進(jìn)行新基因的遺傳進(jìn)化關(guān)系分析。表達(dá)序列標(biāo)簽可以對所有動植物的基因作為一種數(shù)據(jù)庫,通過不同的序列比較可以獲得保守序列片段,從而獲得基因的遺傳進(jìn)化圖譜。正因?yàn)楸磉_(dá)序列標(biāo)簽具有如此的優(yōu)越性,因此表達(dá)序列標(biāo)簽測序已經(jīng)成為許多基因組研究機(jī)構(gòu)的工作重點(diǎn)。
由于本發(fā)明人類肝臟特異表達(dá)基因與一些肝臟疾病相關(guān),因此,研究人類肝臟中特異表達(dá)的表達(dá)序列標(biāo)簽對探索肝臟疾病的發(fā)病機(jī)理及研制肝病的治療藥物具有重要意義。
發(fā)明內(nèi)容
本發(fā)明要解決的技術(shù)問題是提供一類在人類肝臟中特異表達(dá)的表達(dá)序列標(biāo)簽。
本發(fā)明要解決的技術(shù)問題通過如下技術(shù)方案實(shí)現(xiàn)本發(fā)明提供了一類分離出的在人類肝臟中特異表達(dá)的表達(dá)序列標(biāo)簽的序列,其包括(a)SEQ ID No.1~SEQ ID No.21所示的序列;(b)SEQ ID No.1~SEQ ID No.21所示的序列中每條序列的互補(bǔ)序列;(c)與SEQ ID No.1~SEQ ID No.21所示的序列中每條序列有至少70%同源性的序列,及(d)上述(a)~(c)中一條或數(shù)條的組合。
較佳地,所述序列包括具有SEQ ID No.1~SEQ ID No.21所示的序列。
本發(fā)明還提供了一種探針分子,所述的探針分子含有上述序列中約8-100個(gè)連續(xù)的核苷酸。
由本發(fā)明的在人類肝臟中特異表達(dá)的表達(dá)序列標(biāo)簽,可以方便的尋找出在人類肝臟中特異表達(dá)的相關(guān)基因,從而在研究肝臟疾病的致病機(jī)理以及開發(fā)治療肝臟疾病的藥物中發(fā)揮重要作用。
具體實(shí)施例方式
下面結(jié)合具體實(shí)施例,進(jìn)一步闡述本發(fā)明。應(yīng)理解,這些實(shí)施例僅用于說明本發(fā)明而不是限制本發(fā)明的范圍。下列實(shí)施例中未注明具體條件的實(shí)驗(yàn)方法,通常按照常規(guī)條件如Sambrook等人,分子克隆實(shí)驗(yàn)室手冊(New YorkCold Spring HarborLaboratory Press,1989)中所述的條件,或按照制造廠商所建議的條件。
實(shí)施例1人肝臟組織的mRNA的分離組織分離(Tissue isolation)肝臟來源于5個(gè)成年男性,在肝臟切除手術(shù)后,將肝臟組織立即置于液氮中冷凍保存。
mRNA的分離(mRNA isolation)取出肝臟組織,用研缽研碎,加入盛有裂解液的50ml管,充分振蕩后,再移入玻璃勻漿器內(nèi),勻漿后移至50ml新管,抽提總RNA(TRIzol Reagents,Gibco,NY,USA)。用甲醛變性膠電泳鑒定總RNA質(zhì)量。用帶Oligod(T)的纖維素柱分離總RNA中的mRNA,定量。
實(shí)施例2cDNA文庫的構(gòu)建(Constuction of cDNA library)以mRNA為模板,合成雙鏈cDNA。補(bǔ)平末端后,加含EcoRI切點(diǎn)的接頭。磷酸化EcoRI末端后,用XhoI限制性內(nèi)切酶消化1.5小時(shí),再進(jìn)行片斷分離。過柱篩選長度>500bp的片段,用酚-氯仿抽提,乙醇沉淀,無菌水溶解,連接至Uni-ZAP XR載體(Strategene,CA9203,USA),以ZAP-cDNA Gigapack III Gold Cloning Kit(Strategene,CA9203,USA)進(jìn)行包裝,宿主菌使用XL 1 Blue MRF’(Strategene,CA9203,USA)細(xì)菌。涂板并測定滴度。
實(shí)施例3測序及數(shù)據(jù)庫建立(Seqencing and Database Constructing)挑選文庫中有外源片段插入的克隆,擴(kuò)增后抽提質(zhì)粒(Qiagen Germany),用T3和T7作為3’和5’端的通用引物,采用終止物熒光標(biāo)記(Big-Dye,Perkin-Elmer,USA)的方法,在ABI 377測序儀(Perkin-Elmer,USA)上進(jìn)行EST大規(guī)模測序。測序結(jié)果用FACTURA軟件去除載體序列,傳輸?shù)絊UN Ultra 450Server上進(jìn)行下一步的處理。所有的序列信息再用GCG軟件包(Wisconsin group,USA)中的BLAST和FASTA軟件搜索已有的數(shù)據(jù)庫(Genebank+EMBL),將無同源性或同源性低于95%的序列視為新基因建立數(shù)據(jù)庫。
實(shí)施例4基因的全長克隆(Cloning of Full-length cDNA)在得到的新基因片段序列信息基礎(chǔ)上,進(jìn)行cDNA全長克隆,分兩階段進(jìn)行(1)“電子克隆”(Electronic Cloning)以新基因片段序列作為探針?biāo)褜bEST數(shù)據(jù)庫,將重疊序列>50bp,同源性在98%以上的表達(dá)序列標(biāo)簽(Expressed Sequence Tag,簡稱“EST”)序列認(rèn)為同一序列(Consensus Sequence),取出并用AUTOASSEMBLER軟件進(jìn)行連接,部分EST可以延伸探針序列。再用STRIDER軟件分析被延伸的序列是否具有完整的開放閱讀框架(OpenReading Frame,ORF),用BLAST搜尋Genbank或SwissProt以確定該序列的核苷酸和氨基酸水平上是否與其他物種有同源性,以幫助判別所得到的基因全長完整性如何。通過電子克隆的方法,通常可獲取人肝臟相關(guān)基因的全長序列。
(2)cDNA末端快速擴(kuò)增(Rapid Amplification of cDNA Ends,RACE)如果通過“電子克隆”方法仍未得到完整的cDNA全長,則在已有序列5’或3’端設(shè)計(jì)引物,在人類肝臟Marathon-Ready cDNA文庫(Clontech Lab,Inc,USA)中進(jìn)行長距離PCR反應(yīng)。然后對PCR產(chǎn)物克隆、測序。用AUTOASSEMBLER及STRIDER軟件分析被延長的序列有無完整的ORF,如無,重復(fù)上述過程直至獲得全長。
(3)RT-PCR對于5’和3’端的已知的序列,如果中間有一段間隙(gap)無法從已有的公共數(shù)據(jù)庫或自身數(shù)據(jù)庫獲得,可考慮采用RT-PCR的方法。在序列5,端設(shè)計(jì)引物,3’端引物采用Oligo-dT,在肝臟總RNA庫中進(jìn)行擴(kuò)增。然后對產(chǎn)物進(jìn)行克隆、測序。最后拼接便獲得全長。
通過組合使用上述3種方法,可獲得人肝臟相關(guān)蛋白的全長編碼序列。
序列表<110>上海人類基因組研究中心<120>在人類肝臟中特異表達(dá)的表達(dá)序列標(biāo)簽<130>NP-1963<160>21<210>1<211>3119<212>DNA<213>Homo sapiens<400>11 gaagctccac accagccatt acaaccctgc caatctcaag cacctgcctc tacagttggt61 acagatggca ttgtcccagt ctgttccctt ctcggccaca gagcttctcc tggcctctgc121 catcttctgc ctggtattct gggtgctcaa gggtttgagg cctcgggtcc ccaaaggcct181 gaaaagtcca ccagagccat ggggctggcc cttgctcggg catgtgctga ccctggggaa241 gaacccgcac ctggcactgt caaggatgag ccagcgctac ggggacgtcc tgcagatccg301 cattggctcc acgcccgtgc tggtgctgag ccgcctggac accatccggc aggccctggt361 gcggcagggc gacgatttca agggccggcc tgacctctac acctccaccc tcatcactga421 tggccagagc ttgaccttca gcacagactc tggaccggtg tgggctgccc gccggcgcct481 ggcccagaat gccctcaaca ccttctccat cgcctctgac ccagcttcct catcctcctg541 ctacctggag gagcatgtga gcaaggaggc taaggccctg atcagcaggt tgcaggagct601 gatggcaggg cctgggcact tcgaccctta caatcaggtg gtggtgtcag tggccaacgt661 cattggtgcc atgtgcttcg gacagcactt ccctgagagt agcgatgaga tgctcagcct721 cgtgaagaac actcatgagt tcgtggagac tgcctcctcc gggaaccccc tggacttctt781 ccccatcctt cgctacctgc ctaaccctgc cctgcagagg ttcaaggcct tcaaccagag841 gttcctgtgg ttcctgcaga aaacagtcca ggagcactat caggactttg acaagaacag901 tgtccgggac atcacgggtg ccctgttcaa gcacagcaag aaggggccta gagccagcgg961 caacctcatc ccacaggaga agattgtcaa ccttgtcaat gacatctttg gagcaggatt1021 tgacacagtc accacagcca tctcctggag cctcatgtac cttgtgacca agcctgagat1081 acagaggaag atccagaagg agctggacac tgtgattggc agggagcggc ggccccggct1141 ctctgacaga ccccagctgc cctacttgga ggccttcatc ctggagacct tccgacactc1201 ctccttcttg cccttcacca tcccccacag cacaacaagg gacacaacgc tgaatggctt1261 ctacatcccc aagaaatgct gtgtcttcgt aaaccagtgg caggtcaacc atgacccaga1321 gctgtgggag gacccctctg agttccggcc tgagcggttc ctcaccgccg atggcactgc1381 cattaacaag cccttgagtg agaagatgat gctgtttggc atgggcaagc gccggtgtat1441 cggggaagtc ctggccaagt gggagatctt cctcttcctg gccatcctgc tacagcaact1501 ggagttcagc gtgccgccgg gcgtgaaagt cgacctgacc cccatctacg ggctgaccat1561 gaagcacgcc cgctgtgaac atgtccaggc gcggcgcttc tccatcaatt gaagaagaca
1621 ccaccattct gaggccaggg agcgagtggg ggccagccac ggggactcag cccttgtttc1681 tcttcctttc tttttttaaa aaatagcagc tttagccaag tgcagggcct gtaatcccag1741 cattttggga ggccggggtt ggaggatcat ttgagcccag gaattggaaa gcagcctggc1801 caacatagtg ggaccctgtc tctacaaaaa aaaaatttgc caagagcctg agtgacagag1861 caagacccca tctcaaaaaa aaaacaaaca aacaaaaaaa aaaccatata tatacatata1921 tatatagcag ctttatggag atataattct tatgccatat aattcacctt cttttttttt1981 tttgtctgag acagaatctc agtctgtcac ccaggttgga gtgcagtggc gtgatctcag2041 ctcactgcaa cctccacctc gcaggttcaa gcaatcctcc cacttcagcc tcccaagcac2101 ctgggattac aagcatgagt cactacgcct ggctgatttt tgtagtttta gtggagatgg2161 ggtttcacca tgttggccag gcttgtctcg aactcctgac cccaagttat ccacctgcct2221 tggcttccca aagtcctggg attacaggtg tgagccacca catccagcct aacttacatt2281 cttaaagtgt cgaatgactt ctagtgtaga attgtgcaac catcaccaga attaatttta2341 ttattcttat tatttttgag acagagtctt actctgttgc caggctggag tgcagtggcg2401 cgatctcagc tcactacaac ctccgcctcc catgttcaag cgattctcct gcctcagcct2461 cccgagtagc tgggactata gatgcgccac catggccagc taatttttgt atttttagta2521 gagacgaggt ttcactgtgt tggccaggat ggtctccatc tcttgacctc gtgatccacc2581 cgcctcagcc tcccaaagtg ctgggattaa caggtatgaa ccaccgcgcc cagccttttt2641 gttttttttt ttttgagaca gagtcttcct ctgtctccta agctggagtg cagtggcatc2701 atctcagctc actgcaacct ctgcctccca ggttcaagtg cttctccagc ctcggcctcc2761 caagtagctg agactacagg cacacaccac cacgcctggc taatttttgt atttttggta2821 gagacgggtt tcaccatgtt ggtcagacta gtctcaaact cctgacctca agtgatctgc2881 ccgcctcgac ctctctcaaa atgctggcat tacaggtgtg agccacggtg cccggcccac2941 aattaatttt agaacatttt catcacccct aaaagaaacc ctgcacccat tagcagtccc3001 tccacatttc cccctagcct gcctcccctg cctcaccagc cctggcaact gctaatctac3061 tttctgtgtc tatggatttg ccttctctaa acatttcata taaatggaat tacacaatg<210>2<211>2877<212>DNA<213>Homo sapiens<400>21 gtggcatcct tccctttcta atcagagatt ttcttcctca gagattttgg cctagatttg61 caaaatgatg accacatctt tgatttgggg gattgctata gcagcatgct gttgtctatg121 gcttattctt ggaattagga gaaggcaaac gggtgaacca cctctagaga atggattaat181 tccatacctg ggctgtgctc tgcaatttgg tgccaatcct cttgagttcc tcagagcaaa241 tcaaaggaaa catggtcatg tttttacctg caaactaatg ggaaaatatg tccatttcat301 cacaaatccc ttgtcatacc ataaggtgtt gtgccacgga aaatattttg attggaaaaa361 atttcacttt gctacttctg cgaaggcatt tgggcacaga agcattgacc cgatggatgg421 aaataccact gaaaacataa acgacacttt catcaaaacc ctgcagggcc atgccttgaa481 ttccctcacg gaaagcatga tggaaaacct ccaacgtatc atgagacctc cagtctcctc541 taactcaaag accgctgcct gggtgacaga agggatgtat tctttctgct accgagtgat601 gtttgaagct gggtatttaa ctatctttgg cagagatctt acaaggcggg acacacagaa
661 agcacatatt ctaaacaatc ttgacaactt caagcaattc gacaaagtct ttccagccct721 ggtagcaggc ctccccattc acatgttcag gactgcgcac aatgcccggg agaaactggc781 agagagcttg aggcacgaga acctccaaaa gagggaaagc atctcagaac tgatcagcct841 gcgcatgttt ctcaatgaca ctttgtccac ctttgatgat ctggagaagg ccaagacaca901 cctcgtggtc ctctgggcat cgcaagcaaa caccattcca gcgactttct ggagtttatt961 tcaaatgatt aggaacccag aagcaatgaa agcagctact gaagaagtga aaagaacatt1021 agagaatgct ggtcaaaaag tcagcttgga aggcaatcct atttgtttga gtcaagcaga1081 actgaatgac ctgccagtat taaatagtat aatcaaggaa tcgctgaggc tttccagtgc1141 ctccctcaac atccggacag ctaaggagga tttcactttg caccttgagg acggttccta1201 caacatccga aaagatagca tcatagctcttt acccacag ttaatgcact tagatccaga1261 aatctaccca gaccctttga cttttaaata tgataggtat cttgatgaaa acgggaagac1321 aaagactacc ttctattgta atggactcaa gttaaagtat tactacatgc cctttggatc1381 gggagctaca atatgtcctg gaagattgtt cgctatccac gaaatcaagc aatttttgat1441 tctgatgctt tcttattttg aattggagct tatagagggc caagctaaat gtccaccttt1501 ggaccagtcc cgggcaggct tgggcatttt gccgccattg aatgatattg aatttaaata1561 taaattcaag catttgtgaa tacatggctg gaataagagg acactagatg atattacagg1621 actgcagaac accctcacca cacagtccct ttggacaaat gcatttagtg gtggtagaaa1681 tgattcacca ggtccaatgt tgttcaccag tgcttgcttg tgaatcttaa cattttggtg1741 acagtttcca gatgctatca cagactctgc tagtgaaaag aactagtttc taggagcaca1801 ataatttgtt ttcatttgta taagtccatg aatgttcata tagccaggga ttgaagttta1861 ttattttcaa aggaaaacac ctttatttta ttttttttca aaatgaagat acacattaca1921 gccaggtgtg gtagcaggca cctgtagtct tagctactcg agaggccaaa gaaggaggat1981 ggcttgagcc caggagttca agaccagcct ggacagctta gtgagatccc gtctccgaag2041 aaaagatatg tattctaatt ggcagattgt tttttcctaa ggaaactgct ttatttttat2101 aaaactgcct gacaattatg aaaaaatgtt caaattcacg ttctagtgaa actgcattat2161 ttgttgacta gatggtgggg ttcttcgggt gtgatcatat atcataaagg atatttcaaa2221 tgattatgat tagttatgtc ttttaataaa aaggaaatat ttttcaactt cttctatatc2281 caaaattcag ggctttaaac atgattatct tgatttccca aaaacactaa aggtggtttt2341 attttccctt catgttttaa cttattgttg ctgaaaactc tatgtccggc tttaactatc2401 ttctctatat ttttatttca ttcacattaa tgagaagagt tttctcagag attaaaaaag2461 gtagtttttc tgtcattgtt aaatacacat tatcactgaa aaaatgtagc ttttatgatg2521 tatgttttaa agttaaaact ggatggaaat agccatttgg aagctttggt tatgaaacat2581 gtggagtgta ttaagtgcag cttgacatta tgttttattt aaatgctttt tatcgctaaa2641 tgacttgcag atgaaaaaaa ctaaggtgac tcgagtgttt aaatgcctgt gtacaacaat2701 gctttgataa aatattttaa ggtatgagtt atcagctcta tgtcaattga tatttctgtg2761 tagtatttat atttaaatta tatttacctt tttgcttatt ttacaaatat taagaaaata2821 ttctaacatt tgataatttt gaaatgattc atctttcaga aataaaagta tgaatct<210>3<211>1057<212>DNA<213>Homo sapiens
<400>31 accagaagag atggagctgg acagagctgt gggggtcctg ggcgctgcca ccctgctgct61 ctctttcctg ggcatggcct gggctctcca ggcggcagac acctgtccag aggtgaagat121 ggtgggcctg gagggctctg acaagctcac cattctccga ggctgtccgg ggctgcctgg181 ggcccctggg cccaagggag aggcaggcac caatggaaag agaggagaac gtggcccccc241 tggacctcct gggaaggcag gaccacctgg gcccaacgga gcacctgggg agccccagcc301 gtgcctgaca ggcccgcgta cctgcaagga cctgctagac cgagggcact tcctgagcgg361 ctggcacacc atctacctgc ccgactgccg gcccctgact gtgctctgtg acatggacac421 ggacggaggg ggctggaccg ttttccagcg gagggtggat ggctctgtgg acttctaccg481 ggactgggcc acgtacaagc agggcttcgg cagtcggctg ggggagttct ggctggggaa541 tgacaacatc cacgccctga ccgcccaggg aaccagcgag ctccgtgtag acctggtgga601 ctttgaggac aactaccagt ttgctaagta cagatcattc aaggtggccg acgaggcgga661 gaagtacaat ctggtcctgg gggccttcgt ggagggcagt gcgggagatt ccctgacgtt721 ccacaacaac cagtccttct ccaccaaaga ccaggacaat gatcttaaca ccggaaattg781 tgctgtgatg tttcagggag cttggtggta caaaaactgc catgtgtcaa acctgaatgg841 tcgctacctc agggggactc atggcagctt tgcaaatggc atcaactgga agtcggggaa901 aggatacaat tatagctaca aggtgtcaga gatgaaggtg cgacctgcct agcccaggcc961 ggcctcaggg tcaggacgcc tccacacata gttggttggg gggtagggtt gggagcttgg1021 ccctacggtt tgtaaaagaa acacatgtcg tgattct<210>4<211>2912<212>DNA<213>Homo sapiens<400>41 aaaggagtct cggaggactg taagaagaat gcttcgaggc cgatccctct ctgtaacatc61 cctgggtggg cttccccagt gggaagtcga agaacttcct gtggaggagt tactgctctt121 tgaagttgct tgggaagtga ccaataaagt tggaggcatc tatactgtga ttcagacaaa181 ggccaaaaca acagcagatg aatggggaga gaactatttt ctgataggtc catattttga241 gcataatatg aagactcagg tggaacagtg tgaacctgta aatgatgctg tcagaagagc301 agtggacgca atgaataagc atggctgcca ggtgcatttt ggaagatggc tgatagaagg361 aagtccttat gtggtacttt ttgacatagg ctattcagct tggaatctgg acaggtggaa421 gggtgacctc tgggaagcat gcagtgtcgg cattccttat catgaccgag aagccaatga481 tatgctgata tttggatctt taactgcctg gttcttaaaa gaggtgacag atcatgcaga541 tggtaaatat gtcgttgccc aattccatga atggcaggct ggaattggac tgatcctttc601 tcgagccagg aaacttccta ttgccacaat atttacaacc cacgctacac tacttgggag661 gtatctctgt gcagcaaata ttgatttcta caaccatctt gataagttta acattgacaa721 agaggctggg gaaaggcaga tttaccaccg gtactgcatg gagcgagctt ccgttcattg781 cgctcacgtg ttcaccacgg tttctgaaat aacagcaata gaagctgaac atatgctgaa841 gagaaagcct gatgtagtta ctccaaacgg cttgaatgtt aagaaatttt cagcagtgca901 tgagtttcaa aatctacatg ccatgtacaa ggccagaatc caagattttg ttcgaggtca961 tttctatggt catctcgact ttgatcttga aaagactttg ttccttttca ttgctgggag
1021 gtatgagttt tcaaacaaag gagctgacat cttcctagaa tccttatcca ggctaaattt1081 cctgctgagg atgcataaaa gtgacatcac agtggtggtg tttttcatta tgcctgccaa1141 gacaaataat ttcaacgtgg aaaccctgaa aggacaagca gtgcgaaaac agctgtggga1201 tgttgcacat tctgtgaagg aaaagtttgg aaaaaaactc tatgatgcat tattaagagg1261 agaaattcct gacctgaacg atattttaga tcgagatgat ctaacaatta tgaaaagagc1321 catcttttca actcagcgac agtcattgcc cccagtgacc acgcacaaca tgattgatga1381 ctccaccgac cccatcctca gcaccattag acggattgga cttttcaaca accgcacaga1441 tagagtcaag gtgattttgc acccagagtt tctatcctcc accagtccct tactacccat1501 ggactatgaa gagtttgtta gaggttgtca tcttggagta tttccatcat actatgaacc1561 ctggggttat actccagctg aatgcactgt gatgggtatc cccagtgtga ccacgaatct1621 ctccgggttt ggctgtttca tgcaggagca cgtggctgat cctactgctt acggtattta1681 catcgttgac aggcggttcc gttctccaga tgattcttgc aatcagctga ctaagtttct1741 ctatggattt tgcaaacagt cacgccgcca aaggattatc cagaggaaca gaactgagag1801 gctctcagat cttctggatt ggagatactt aggcagatat taccagcatg ccagacacct1861 gacattaagc agagcttttc cagataaatt ccatgtggaa ctaacatcac caccaacgac1921 agaaggattt aaatatccca ggccttcctc agtaccacct tctccttcag ggtctcaggc1981 ctccagtcct cagagcagtg atgtggaaga tgaagtggag gatgagagat acgatgagga2041 agaggaggct gaaagggatc ggttaaatat caagtcacca ttttcactga gccacgttcc2101 tcatgggaag aaaaagctgc atggtgaata taagaactga attcatgtgc tgcatgaaga2161 gctaatttaa aaaagcaaag taagactaat tatttaaaat aaaaatgcca caaatttcat2221 tttctccttc taagtattac aatggagttt attctctgcc taaaaagtgg aagaaattga2281 gtgaatgata attttgtaat ttaggataag atccaagtta ttttccccaa ctcttgtttc2341 ccccataaag ttaggcatga ggaggagcac tcattaaagg cagaagacgg aaaagtgttt2401 ttaaaatggt gaatttaagt ggtaaggatt ttctcttact ctgtttattt ttaaatgatc2461 atcataatcc tttgcttact atttatgcag cttctctacc ccaccacaca aatttcccat2521 ttcccccccg aaaaccttga tcttacccat gaatgtgcac tacctacatt ttttaaatag2581 ctaggttttt actgattatt ttcatttttc acatgcatca gaaccatgat ttagatgtag2641 ttttacagag acaaaaatcc atgagtgaat agctatccta agtccatatt ttgatgcata2701 ttaatggaca tttatgtcac ttttgaaatc tagaattgat gttgtaatta atgcaagata2761 ttaccatgta catggtacca ccatcttact gtaacatttt tctattgttt aaatagaaag2821 cctttttaaa atttggtcaa tcttcataga tgataacttg taaaatccaa gtaaataaac2881 acattaatat ttaataactt aaaaaaaaaa aa<210>5<211>477<212>DNA<213>Homo sapiens<400>51 cctcagaaac attttattga caacagttcc caacagagtc tttggggtct ttaagtggca61 ggtgcagcgt ccacaggcag agtgagggct cctgaggaac ctcaccccaa attccctaac121 cggccgagga cgcgacccca ggcccctctc aggtgggcat ggcagtcccg gcagcacccc181 ctctgagcag cctgctgtgg ggaagaagcc gggccgggag cctccagtcg tggtgccagc
241 ccagctcatg ctccccgccc cgaggccccc agcctgtggg aagcccctgc ctgtaatgga301 cagctcgtga agacacagga acagtggtgg gggtgagggt ctaggaatga ggcagagggt361 ggctgagcac acacctgact ccctggaggg tcgcttcaaa gacatgggag gcgagggcac421 tggggaggct gggatgaaca accgactcca tgcacctcaa cgctctcatc aaagagg<210>6<211>1084<212>DNA<213>Homo sapiens<400>61 cagacagcag ggaacatcac cctcttcaga ctggagtcag tgggaacaga cccaagatgt61 tggggaggaa cacttggaag acctcagctt tctccttctt ggttgagcag atgtgggccc121 ctctctggag tcgttcgatg aggccagggc gatggtgttc tcagcgttcc tgtgcatggc181 aaaccagcaa taacactttg cacccactct ggacggtccc ggtctccgtg ccagggggca241 cccggcagtc tcctattaac atccagtgga gggacagcgt ctatgacccc cagctgaagc301 cactcagggt ctcctatgaa gcggcatcct gcctgtacat ctggaacact ggctacctct361 tccaggtgga atttgacgat gccaccgagg catcaggaat tagtggtggg cccttggaaa421 accactacag actgaagcaa tttcacttcc actggggagc agtgaacgag gggggctcag481 agcacacagt ggacggccac gcgtaccccg cagagctgca tttagttcac tggaattctg541 tgaaatacca aaattacaag gaagctgtcg tgggagagaa tggtttggct gtgataggcg601 tgtttttaaa gctcggggcc catcatcaga cgctgcagag gctggtggac atcttgccgg661 aaataaaaca taaggacgcg cgggcggcca tgcgcccctt cgacccctcc actctgctgc721 ccacctgctg ggattactgg acctacgcgg gctcgctcac caccccgccg ctgaccgagt781 cggtcacctg gatcatccag aaggagcccg ttgaagtggc cccaagccag ctctctgcat841 ttcgtactct cctgttttct gcacttggtg aagaggagaa gatgatggtg aacaactatc901 gcccacttca acccttgatg aaccggaagg tctgggcgtc cttccaggcc actaatgagg961 gcacaaggtc ctagagacat taggtccaca tgaatagcag aactgacttt gaaggaagga1021 agcgttgttt cccaagtttc acaatgtgat tgtacatgac ttctgaaatt aaaaagagag1081 catg<210>7<211>1346<212>DNA<213>Homo sapiens<400>71 cgggatgggg aagaggagca ttgaggaccg tgttcaagag gaagctcact gccttgtgga61 ggagttgaga aaaaccaagg cttcaccctg tgatcccact ttcatcctgg gctgtgctcc121 ctgcaatgtg atctgctccg ttgttttcca gaaacgattt gattataaag atcagaattt181 tctcaccctg atgaaaagat tcaatgaaaa cttcaggatt ctgaactccc catggatcca241 ggtctgcaat aatttccctc tactcattga ttgtttccca ggaactcaca acaaagtgct
301 taaaaatgtt gctcttacac gaagttacat tagggagaaa gtaaaagaac accaagcatc361 actggatgtt aacaatcctc gggactttat cgattgcttc ctgatcaaaa tggagcagga421 aaaggacaac caaaagtcag aattcactat tgaaaacttg gtaatcactg cagctgactt481 acttggagct gggacagaga caacaagcac aaccctgaga tatgctctcc ttctcctgct541 gaagcaccca gaggtcacag ctaaagtcca ggaagagatt gaacgtgtcg ttggcagaaa601 ccggagcccc tgcatgcagg acaggggcca catgccctac acagatgctg tggtgcacga661 ggtccagaga tacatcgacc tcatccccac cagcctgccc catgcagtga cctgtgacat721 taaattcaga aactacctca ttcccaaggg cacaaccata ttaacttccc tcacttctgt781 gctacatgac aacaaagaat ttcccaaccc agagatgttt gaccctcgtc actttctgga841 tgaaggtgga aattttaaga aaagtaacta cttcatgcct ttctcagcag gaaaacggat901 ttgtgtggga gagggcctgg cccgcatgga gctgttttta ttcctgacct tcattttaca961 gaactttaac ctgaaatctc tgattgaccc aaaggacctt gacacaactc ctgttgtcaa1021 tggatttgct tctgtcccgc ccttctatca gctgtgcttc attcctgtct gaagaagcac1081 agatggtctg gctgctcctg tgctgtccct gcagctctct ttcctctggt ccaaatttca1141 ctatctgtga tgcttcttct gacccgtcat ctcacatttt cccttccccc aagatctagt1201 gaacattcag cctccattaa aaaagtttca ctgtgcaaat atatctgcta ttccccatac1261 tctataatag ttacattgag tgccacataa tgctgatact tgtctaatgt tgagttatta1321 acatattatt attaaatagg gaattc<210>8<211>1576<212>DNA<213>Homo sapiens<400>81 gtccttgtgc tctgtctctc atgtttgctt ctcctttcac tctggagaca gagctctggg61 agaggaaaac tccctcctgg ccccactcct ctcccagtga ttggaaatat cctacagata121 ggtattaagg acatcagcaa atccttaacc aatctctcaa aggtctatgg ccctgtgttc181 actctgtatt ttggcctgaa acccatagtg gtgctgcatg gatatgaagc agtgaaggaa241 gccctgattg atcttggaga ggagttttct ggaagaggca ttttcccact ggctgaaaga301 gctaacagag gatttggaat tgttttcagc aatggaaaga aatggaagga gatccggcgt361 ttctccctca tgacgctgcg gaattttggg atggggaaga ggagcattga ggaccgtgtt421 caagaggaag cccgctgcct tgtggaggag ttgagaaaaa ccaaggcctc accctgtgat481 cccactttca tcctgggctg tgctccctgc aatgtgatct gctccattat tttccataaa541 cgttttgatt ataaagatca gcaatttctt aacttaatgg aaaagttgaa tgaaaacatc601 aagattttga gcagcccctg gatccagatc tgcaataatt tttctcctat cattgattac661 ttcccgggaa ctcacaacaa attacttaaa aacgttgctt ttatgaaaag ttatattttg721 gaaaaagtaa aagaacacca agaatcaatg gacatgaaca accctcagga ctttattgat781 tgcttcctga tgaaaatgga gaaggaaaag cacaaccaac catcagaatt tactattgaa841 agcttggaaa acactgcagt tgacttgttt ggagctggga cagagacgac aagcacaacc901 ctgagatatg ctctccttct cctgctgaag cacccagagg tcacagctaa agtccaggaa961 gagattgaac gtgtgattgg cagaaaccgg agcccctgca tgcaagacag gagccacatg1021 ccctacacag atgctgtggt gcacgaggtc cagagatgca ttgaccttct ccccaccagc
1081 ctgccccatg cagtgacctg tgacattaaa ttcagaaact atctcattcc caagggcaca1141 accatattaa tttccctgac ttctgtgcta catgacaaca aagaatttcc caacccagag1201 atgtttgacc ctcatcactt tctggatgaa ggtgacaatt ttaagaaaag taaatacttc1261 atgcctttct cagcaggaaa acggatttgt gtgggagaag ccctggccgg catggagctg1321 tttttattcc tgacctccat tttacagaac tttaacctga aatctctggt tgacccaaag1381 aaccttgaca ccactccagt tgtcaatgga tttgcctctg tgccgccctt ctaccagctg1441 tgcttcattc ctgtctgaag aagagcagat ggcctggctg ctgctcagtc cctgcagctc1501 tctttcctct ggggcgatta tccatctttg ctacattaca gaaatggaga tgctgctgag1561 atgagaaagg gaattc<210>9<211>2823<212>DNA<213>Homo sapiens<400>91 ggcaggtgct tgttactgtt aatgaaagca gatttaaagc aacaccacca tcactggagt61 atttttagtt atatacgatt gagactacca agcatgttgc tcttattcag tgtaatccta121 atctcatggg tatccactgt tgggggagaa ggaacacttt gtgattttcc aaaaatacac181 catggatttc tgtatgatga agaagattat aacccttttt cccaagttcc tacaggggaa241 gttttctatt actcctgtga atataatttt gtgtctcctt caaaatcctt ttggactcgc301 ataacatgca cagaagaagg atggtcacca acaccgaagt gtctcagaat gtgttccttt361 ccttttgtga aaaatggtca ttctgaatct tcaggactaa tacatctgga aggtgatact421 gtacaaatta tttgcaacac aggatacagc cttcaaaaca atgagaaaaa catttcgtgt481 gtagaacggg gctggtccac tcctcccata tgcagcttca ctaaaggaga atgtcatgtt541 ccaattttag aagccaatgt agatgctcag ccaaaaaaag aaagctacaa agttggagac601 gtgttgaaat tctcctgcag aaaaaatctt ataagagttg gatcagactc agttcaatgt661 taccaatttg ggtggtcacc taactttcca acatgcaaag gacaagtacg atcatgtggt721 ccacctcctc aactctccaa tggtgaagtt aaggagataa gaaaagagga atatggacac781 aatgaagtag tggaatatga ttgcaatcct aattttataa taaacgggcc taagaaaata841 caatgtgtgg atggagaatg gacaacttta cccacttgtg ttgaacaagt gaaaacatgt901 ggatacatac ctgaactcga gtacggttat gttcagccgt ctgtccctcc ctatcaacat961 ggagtttcag tcgaggtgaa ttgcagaaat gaatatgcaa tgattggaaa taacatgatt1021 acctgtatta atggaatatg gacagagctt cctatgtgtg ttgcaacaca ccaacttaag1081 aggtgcaaaa tagcaggagt taatataaaa acattactca agctatctgg gaaagaattt1141 aatcataatt ctagaatacg ttacagatgt tcagacatct tcagatacag gcactcagtc1201 tgtataaacg ggaaatggaa tcctgaagta gactgcacag aaaaaaggga acaattctgc1261 ccaccgccac ctcagatacc taatgctcag aatatgacaa ccacagtgaa ttatcaggat1321 ggagaaaaag tagctgttct ctgtaaagaa aactatctac ttccagaagc aaaagaaatt1381 gtatgtaaag atggacgatg gcaatcatta ccacgctgtg ttgagtctac tgcatattgt1441 gggccccctc catctattaa caatggagat accacctcat tcccattatc agtatatcct1501 ccagggtcaa cagtgacgta ccgttgccag tccttctata aactccaggg ctctgtaact1561 gtaacatgca gaaataaaca gtggtcagaa ccaccaagat gcctagatcc atgtgtggta
1621 tctgaagaaa acatgaacaa aaataacata cagttaaaat ggagaaacga tggaaaactc1681 tatgcaaaaa caggggatgc tgttgaattc cagtgtaaat tcccacataa agcgatgata1741 tcatcaccac catttcgagc aatctgtcag gaagggaaat ttgaatatcc tatatgtgaa1801 tgaagcaagc ataattttcc tgaatatatt cttcaaacat ccatctacgc taaaagtagc1861 cattatgtag ccaattctgt agttacttct tttattcttt caggtgttgt ttaactcagt1921 tttatttaga actctggatt tttagagctt tagaaatttg taagctgaga gaacaatgtt1981 tcacttaata ggagggtgtc ttagtccata ttacattgtt ataacagagt atcacagact2041 ggataacttc taaccaatag tttatttgtt tcataaatct aaaagctgag aagtccaaga2101 tggtggggct gcctctggtg agggtcttct cgaagcatca taatatgctg gaaggcatca2161 caacatggtg gaagggatca cgtggcaaaa gagcatgtac atgggagtga gagaaaaaga2221 gagagagaga cagagtggcg ggggccgggg aggagcgcaa actcatcctt tataaagaca2281 ccactcctga gataacaatc caatcccatg ataatgacat taatccattc aagaagatag2341 agctctcgtg acttaatcac cttctaaaga tctcacctga caacactgtt gcattggcag2401 ttaagtttcc acgtaaactt tcggggacac attcaaacca caggagaaac tcaaattgtt2461 cctgggcaaa tcacaacatg gggaatttta ttcataaatg tccacagaaa cagtaaatgt2521 tctcgcttca gaacttaatt catctaatcc ctcctgtttg tctcaaatta taggataact2581 ttgaaacttt ctgaattaac gttatttaaa aggaaatgta gatgttattt tagtctctat2641 cttcaggtta ttatcactta aaaacctgcg aaagctgtca acttttgtgg ttgtagcaag2701 tattaataaa tatttataaa tcctctaatg taagtctagc tacctatcca atactaaata2761 ccccttaaag tattaaatgc actatctgct gtaaacggaa aaaaaaaaaa aaaaaaaaaa2821 aaa<210>10<211>991<212>DNA<213>Homo sapiens<400>101 atggatccca aatatcagcg tgtagagcta aatgatggtc atttcatgcc cgtattggga61 tttggcacct atgcacctcc agaggttccg aggaacagag ctgtagaggt caccaaatta121 gcaatagaag ctggcttccg ccatattgat tctgcttatt tatacaataa tgaggagcag181 gttggactgg ccatccgaag caagattgca gatggcagtg tgaagagaga agacatattc241 tacacttcaa agctttggtg cactttcttt caaccacaga tggtccaacc agccttggaa301 agctcactga aaaaacttca actggactat gttgacctct atcttcttca tttcccaatg361 gctctcaagc caggtgagac gccactacca aaagatgaaa atggaaaagt aatattcgac421 acagtggatc tctgtgccac atgggaggtc atggagaagt gtaaggatgc aggattggcc481 aagtccatcg gggtgtcaaa cttcaactgc aggcagctgg agatgatcct caacaagcca541 ggactcaagt acaagcctgt ctgcaaccag gtagaatgtc atccttacct caaccagagc601 aaactgctgg atttctgcaa gtcaaaagac attgttctgg ttgcccacag tgctctggga661 acccaacgac ataaactatg ggtggaccca aactccccag ttcttttgga ggacccagtt721 ctttgtgcct tagcaaagaa acacaaacga accccagccc tgattgccct gcgctaccag781 ctgcagcgtg gggttgtggt cctggccaag agctacaatg agcagcggat cagagagaac841 atccaggttt ttgaattcca gttgacatca gaggatatga aagttctaga tggtctaaac
901 agaaattatc gatatgttgt catggatttt gttatggacc atcctgatta tccattttca961 gatgaatatt agcatagagg gtgttgcacg a<210>11<211>1938<212>DNA<213>Homo sapiens<400>111 cgccaggtgg tggctcagag gaggacacag tcgctgtggg caggtggtca gggcgcagga61 gggaatgagc tgtggatttt tagtaatcta caacaatcag gcagttccag gacacaggga121 agtgagtgtg aacagccaat ggacccggag ccgagagcct gggcaggcgt aggctggact181 atggacgccc tgcaaccctg ccaggctggg aaggggaggc ttgatcctga gcgcgtgtta241 ggaaggagat gcccaggttc aggtgtatcg tgcatttttt ttccacagtg cagaaatgac301 atttctggtt ggtcttgaat gtctgctctg gccaagccac ctcctctcat gctagctaac361 caagtggcac gtgtgcccac gcaggccgtt ctaaggaaca ctgtaattgt ctacacaatt421 ttctctcaaa tactccgtcc tggaagcgtc tggttggcag aagagggaag gcaggagggt481 ggcagcgtcc cggctgagtc ctcttgcaca tgggagctgg agtccagcca ggctccagag541 cggctccggc tggcaaggga cctgaacagg aagatgagac tcgaggtttt ctgcatgcct601 ggaagtgcac atgctcatct acagctttct tggaagaaga aagaaacaaa aactgagatt661 tagaacacca ggtctgtttc cactggcggc cactcttggg cactggagac cagcaagagc721 tttgttttta aaaggctctt ccatggcaga tattcgcaga ggcatcaggg ctacacttaa781 atgaagggct ccggctggca cctgaggagc ggcgtgaccc cgagggccca gggagctgcc841 cggctggcct aggcaggcag ccgcaccatg gccagcacgg ccgtgcagct tctgggcttc901 ctgctcagct tcctgggcat ggtgggcacg ttgatcacca ccatcctgcc gcactggcgg961 aggacagcgc acgtgggcac caacatcctc acggccgtgt cctacctgaa agggctctgg1021 atggagtgtg tgtggcacag cacaggcatc taccagtgcc agatctaccg atccctgctg1081 gcgctgcccc aagacctcca ggctgcccgc gccctcatgg tcatctcctg cctgctctcg1141 ggcatagcct gcgcctgcgc cgtcatcggg atgaagtgca cgcgctgcgc caagggcaca1201 cccgccaaga ccacctttgc catcctcggc ggcaccctct tcatcctggc cggcctcctg1261 tgcatggtgg ccgtctcctg gaccaccaac gacgtggtgc agaacttcta caacccgctg1321 ctgcccagcg gcatgaagtt tgagattggc caggccctgt acctgggctt catctcctcg1381 tccctctcgc tcattggtgg caccctgctt tgcctgtcct gccaggacga ggcaccctac1441 aggccctacc aggccccgcc cagggccacc acgaccactg caaacaccgc acctgcctac1501 cagccaccag ctgcctacaa agacaatcgg gccccctcag tgacctcggc cacgcacagc1561 gggtacaggc tgaacgacta cgtgtgagtc cccacagcct gcttctcccc tgggctgctg1621 tgggctgggt ccccggcggg actgtcaatg gaggcagggg ttccagcaca aagtttactt1681 ctgggcaatt tttgtatcca aggaaataat gtgaatgcga ggaaatgtct ttagagcaca1741 gggacagagg gggaaataag aggaggagaa agctctctat accaaagact gaaaaaaaaa1801 atcctgtctg tttttgtatt tattatatat atttatgtgg gtgatttgat aacaagttta1861 atataaagtg acttgggagt ttggtcagtg gggttggttt gtgatccagg aataaacctt1921 gcggatgtgg ctgtttat
<210>12<211>5413<212>DNA<213>Homo sapiens<400>121 gaagagggat agggccagca aggcagggat cgaacgagtg tctggcagcc gggagcccag61 cgaagagagc gagcaagctt aggaaaacga gcgaagtaaa gggagtaggg gagactgaga121 ctgaccggta gccaggcagg cggacggacg cacgcccgga cagactgagc aggcgccgga181 gaaccactca caggttcccc ccgcctttcc ctttgaaagc taggattttg cctttcccgt241 ggcgcccgag agagaatgct ggactctgcc gacttcagcg caagctaaga tttctcagct301 agggacaaac gatcagccca atcctgagaa ggggggaacc aagcaccccg tccccatccc361 cctcccctcc cccgactaaa ctcgggcgcc aaacccagcc cttctctaac caccctactt421 cctcctctcc tttctagcat ggtggctgta tggacagtct gacagaacag agactgacat481 ctcccaatct gccggccccc cacctggaac actacagtgt tctgcattgc accatgaccc541 tggatgtgca aactgtagtc gtttttgccg tgattgtagt cctcctgctt gtcaatgtca601 tactcatgtt tttcctggga acgcgctgaa tggagtccag ccacctgagc tgtcgcgaac661 tctcgctttg atttcatccc gagagccacc gagaaaaaaa aaaaatcaca gacagagaca721 gggaaagaga gagaaagaac aagctttctt actcaggggg gaaaacgttt tgagcttcaa781 catggcctcg ctgtgatatg tatgacgttg ctgatcactg gagattccat cgttagtgct841 gaggcagtat gggatcacgt caccatggcc aaccgggagt tggcatttaa agctggcgac901 gtcatcaaag tcttggatgc ttccaacaag gattggtggt ggggccagat cgacgatgag961 gagggatggt ttcctgccag ctttgtgagg ctctgggtga accaggagga tgaggtggag1021 gaggggccca gcgatgtgca gaacggacac ctggacccca attcagactg cctctgtctg1081 gggcggccac tacagaaccg ggaccagatg cgggccaatg tcatcaatga gataatgagc1141 actgagcgtc actacatcaa gcacctcaag gatatttgtg agggctatct gaagcagtgc1201 cggaagagaa gggacatgtt cagtgacgag caactgaagg taatctttgg gaacattgaa1261 gatatctaca gatttcagat gggctttgtg agagacctgg agaaacagta taacaatgat1321 gacccccacc tcagcgagat aggaccctgc ttcctagagc accaagatgg attctggata1381 tactctgagt attgtaacaa ccacctggat gcttgcatgg agctctccaa actgatgaag1441 gacagccgct accagcactt ctttgaggcc tgtcgcctct tgcagcagat gattgacatt1501 gctatcgatg gtttcctttt gactccagtg cagaagatct gcaagtatcc cttacagttg1561 gctgagctcc taaagtatac tgcccaagac cacagtgact acaggtatgt ggcagctgct1621 ttggctgtca tgagaaatgt gactcagcag atcaacgaac gcaagcgacg tttagagaat1681 attgacaaga ttgctcagtg gcaggcttct gtcctagact gggagggcga ggacatccta1741 gacaggagct cggagctgat ctacactggg gagatggcct ggatctacca gccctacggc1801 cgcaaccagc agcgggtctt cttcctgttt gaccaccaga tggtcctctg caagaaggac1861 ctaatccgga gagacatcct gtactacaaa ggccgcattg acatggataa atatgaggta1921 gttgacattg aggatggcag agatgatgac ttcaatgtca gcatgaagaa tgcctttaag1981 cttcacaaca aggagactga ggagatacat ctgttctttg ccaagaagct ggaggaaaaa2041 atacgctggc tcagggcttt cagagaagag aggaaaatgg tacaggaaga tgaaaaaatt2101 ggctttgaaa tttctgaaaa ccagaagagg caggctgcaa tgactgtgag aaaagtccct2161 aagcaaaaag gtgtcaactc tgcccgctca gttcctcctt cctacccacc accgcaggac
2221 ccgttaaacc acggccagta cctggtcccc gacggcatcg ctcagtcgca ggtctttgag2281 ttcaccaaac ccaagcgcag ccagtcacca ttctggcaaa acttcagcag gttaaccccc2341 ttcaaaaaat gatacctaca gggaggcaga taattttaaa ataaagtaaa taaaattata2401 tttatagatg gacctttttt cggagaagca ctgttgaaat ttatacacac acacacacac2461 agagaccctt gagtacacat acacacacac acacacagac acacacacac acacacacac2521 acacacacac acagagagat aaggaacaaa agtgttttct gttgttttgg ggaagtgaaa2581 tatgtggttg gtaggaagag gtaccaatga cttccaaaca tgtgattccg tcttaaaagt2641 tttccatttt taccctgtcc cccttccctt tgctttcaga agttgacatt tctattcatt2701 gcttttcttg ttaagataat ctctttactc ccctgtgagt gattcactgc cttgtcatta2761 ttacgataga tgtgtttgta ttgttttttt tctgatgata ctgatgttga tgaattttta2821 attttatttg atgtggtaga gttgggaggt ttcagggttt tttcccctct tttactttcc2881 attgaggaag ggaatgagct cctttctcct ctccttcagc caatcattat caaatgttcc2941 ttcagccctg cagttgcccc aaataacctt ttttcagcat cctctgtcct cagtcatgcc3001 agtctggaca tgctctgttg tgccctgtga caaaactgct cagtattcct attgctttta3061 ctgtgtttta ggtactgtga agggatcaaa aaaccaaaca gaagcaaggg agtatcagac3121 tatgatgatg ctggagtgga cttctgttca gggaacattt tgcattcagg ctgtttcttc3181 tatcactggg gtttcccatg ttgcagcact tctgggtcgt tgcaattttg catctaggag3241 ttagtttgat cgagttattc tcttttttca agtcactttt gttataggtc tccccctagg3301 cctgtctctc ccttagccca aaagatctga actggaagca gaggttgaga ttctgcctcc3361 caggagaggg atttacctgc cccctagtac cagataggtt tagggcagtg atctctacag3421 caatcagttc agtgtcctgg ttgtccctgc tcccatttac agatgtttgg gcagcattga3481 tagaagtatg gaggggttca agacagagcc cacctgatca agatcatcag ctaccttcaa3541 attattgacc tggacagggt ccaagtctga tagtaacctt ttacaagaaa gaacagggat3601 gggaatggaa agagatagcc ttgatccaca gtattgtacc tgcattttct accaccctaa3661 aattgtgtga gacttctccc attgttaaca gattgcatgg acaatcttcc ctggcttctt3721 tctttccctc tctctttctt ctttctcctg ccatcctagc acaggaggat ttttggtatt3781 gatatagtta aagctgttct ggcactcaaa gaaggccgtg tttccaacat cctctcatcc3841 caggacattt ggggcaagtg agttaggggc ccaggggcaa ttttccctct gaataacgtg3901 tctgaggcag ggatgctacc ctcaggctcg cttttggcca gctttttgct tgggaaaatc3961 taacttcttt cacaaggagg caggcttcct atggatgttg gagtacctgt ttttcctcca4021 cacatagccc ttttcatgga tagaccttga acaacaaaaa gggtataagg gaataaggat4081 gaactctgct gtgaagagca agccactgta gtgaggaatg tggagactgg gagtctgtcc4141 taaaccccat gggagaagac ttcatcatga caggacttca gcttaccaag cagcagccat4201 agctgtgtgg aggcttcagc atagctagca tgtttactgc tctatgcctc ctgatccaga4261 ccaggcattg cccagcctgg gaatcttttc tttgtgggaa tcaaattaca agctatttaa4321 gtttatattc catcacaacc aagtcagact tgtattataa gtcaaggatg agcctgatct4381 ggggagaggg ccggggctcg ggactggcca ccactgttca gcacatgacc taactacgta4441 agcctctttg gcaagggtcc tggtgcccag cacccaggct aaaatatcct gtctggcaga4501 gtgttttggt agctatgcag gcctcccttc agtgtacctc tttttccaac ttctcactcc4561 tccttactag gcttggcctt gacatgcttc ttcgagggtt ggcagcacac cgggagggga4621 tgcttggaca agtttctggg cctacatttc ttgactaggc cctctcattt cctccctcct4681 tggggcttct gcccagggct ccaggatcag ggatattact tctcaacccg cacttctcct4741 ctactgaacc cactggcatc acctgatgcc actaatttgt gaacaacaag aaatcatttc4801 cccattggtt ggagtattcc ctcagcctat agcatcaaag cagaccagtg gccaacagcc
4861 ccaaggggag cccaattaaa tacctgggtt cagtatccta acctgttatg tcctgacagc4921 aatggtaacc ccagtaattc tgtaatgttg taatttccgc atggccctga gctccctttt4981 cctcaactca gtgaggccag gatttgctct ccaaaaggct ttgctagtgt gttcaatggg5041 acctgctgtg gggagtccta agacagacat ctaattattc tctctttttc cccccctctc5101 tatgtgtata tttctaatgg atctataaga acagcaacaa gagagttcta acaattctag5161 tgtgaagcca aatagtgatc ttttagtgct ttggggatgg ggtgggctgg ggtggatgga5221 tgggcaacag tgactttgat tacccttgct gctctgcatt tgccagttta ttcttttgtt5281 tcttttatct gactgactct gtcaaacaag tgtcaaagtt gtgtgttaaa aaatgtttaa5341 caaaaaaaaa tgttgtaatg acacaaagcc ttatgaaaat atttatggag ttcaataaaa5401 gaagtaaaaa gac<210>13<211>2935<212>DNA<213>Homo sapiens<400>131 gaagatgctc cctggagcct ggctgctctg gacctccctc ctgctcctgg ccaggcctgc61 ccagccctgt cccatgggtt gtgactgctt cgtccaggag gtgttctgct cagatgagga121 gcttgccacc gtcccgctgg acatcccgcc atatacgaaa aacatcatct ttgtggagac181 ctcgttcacc acattggaaa ccagagcttt tggcagtaac cccaacttga ccaaggtggt241 cttcctcaac actcagctct gccagtttag gccggatgcc tttggggggc tgcccaggct301 ggaggacctg gaggtcacag gcagtagctt cttgaacctc agcaccaaca tcttctccaa361 cctgacctcg ctgggcaagc tcaccctcaa cttcaacatg ctggaggctc tgcccgaggg421 tcttttccag cacctggctg ccctggagtc cctccacctg caggggaacc agctccaggc481 cctgcccagg aggctcttcc agcctctgac ccatctgaag acactcaacc tggcccagaa541 cctcctggcc cagctcccgg aggagctgtt ccacccactc accagcctgc agaccctgaa601 gctgagcaac aacgcgctct ctggtctccc ccagggtgtg tttggcaaac tgggcagcct661 gcaggagctc ttcctggaca gcaacaacat ctcggagctg ccccctcagg tgttctccca721 gctcttctgc ctagagaggc tgtggctgca acgcaacgcc atcacgcacc tgccgctctc781 catctttgcc tccctgggta atctgacctt tctgagcttg cagtggaaca tgcttcgggt841 cctgcctgcc ggcctctttg cccacacccc atgcctggtt ggcctgtctc tgacccataa901 ccagctggag actgtcgctg agggcacctt tgcccacctg tccaacctgc gttccctcat961 gctctcatac aatgccatta cccacctccc agctggcatc ttcagagacc tggaggagtt1021 ggtcaaactc tacctgggca gcaacaacct tacggcgctg cacccagccc tcttccagaa1081 cctgtccaag ctggagctgc tcagcctctc caagaaccag ctgaccacac ttccggaggg1141 catcttcgac accaactaca acctgttcaa cctggccctg cacggtaacc cctggcagtg1201 cgactgccac ctggcctacc tcttcaactg gctgcagcag tacaccgatc ggctcctgaa1261 catccagacc tactgcgctg gccctgccta cctcaaaggc caggtggtgc ccgccttgaa1321 tgagaagcag ctggtgtgtc ccgtcacccg ggaccacttg ggcttccagg tcacgtggcc1381 ggacgaaagc aaggcagggg gcagctggga tctggctgtg caggaaaggg cagcccggag1441 ccagtgcacc tacagcaacc ccgagggcac cgtggtgctc gcctgtgacc aggcccagtg1501 tcgctggctg aacgtccagc tctctcctcg gcagggctcc ctgggactgc agtacaatgc
1561 tagtcaggag tgggacctga ggtcgagctg cggttctctg cggctcacca tgtctatcga1621 ggctcgggca gcagggccct agtagcagcg catacaggag ctggggaagg gggcctctgg1681 ggcctgacca ggcgacaggt aggggcggag gggagctgag tctccgaagc cttggctttt1741 cacatgcaag ggacagggtt acatccccaa ggtgaggggg tggagtctgg tctgctccac1801 taaccagggt ctcctcctcc tcttccttca tcgcttctcc tggagtgtgc ggcctaataa1861 ggccatcctt atgccttgca aagcaccctc aaaagctgca ccacagcctg gagaataaaa1921 tatcctcagc cctgatgcct ccccattatg taacacccaa ccgctctcac ctacaccctg1981 aggtctattc actgcatccc agtgatacaa agtggaggcc actgccttct gacatctggc2041 tcaaaagccc agtgtctgtt tccatttatt tccctggaat ttcatttaaa attggtatag2101 agaaaaaaag gatgtgacag aagcagagat gaccagaaag cacaggggca gggttctgac2161 tggcgtgtgg gagaccctgt ggccggcacc cacctccaca cgaggactaa gctctgattt2221 ttttatcttg cccaaattcc tacctaaggg gtctagggag tcgcgcctta caaatcataa2281 attctcatca gatgggtttt atttgaccct gtatatcatg acttattttt aatctgacta2341 tggcataaca ttacaagacg aggcaaaaat atttaacccc caaatatatt tccttgccct2401 accttgaact tgccctgcag agtctcttgt gaggagaatc cacatcctat aaagaagccc2461 ctttcccctt tgttttcctt cctttctttc cagtccagga gatcatcaac taagagccag2521 gcaccccttt taagtcgata agaaacagtt tacaacctgc tctctctctc tctgaagtct2581 gctgagagct tcccctgcac aataaaactt ggcctccacg atcctttatc ttaacctgaa2641 cattcctttc cattgatccc aggtcttcag ctaagctcaa ccaattgtca accagaaaat2701 gtttaaattt acctacagcc tggaagcacc cacccccgct gcttcgagtt gtcctgcctt2761 tctgaactca accaatgtat ttcttaaatg tatttgattg atgcctcatt cctccctaaa2821 atgtataaaa ccaagctgta cctcgaccac cttgggcaca tgttcccagg ccctcctgag2881 gtctgtgtca cgggccatgg ccactcatat ttggctcaga ataaatctct tcaaa<210>14<211>1720<212>DNA<213>Homo sapiens<400>141 aggcagaaca ggatcaggaa gcgatcaaac ctaccaaggc agtctcactt ctcaatgact61 ggactgtgtg ggtactctgc tccagacatg cgtggcctca gactcatcat gataccagtt121 gagctgctac tttgctacct cctgctgcac cctgtggatg ccacttcata tggaaagcag181 acaaatgtct tgatgcactt tcccttgtcc ttggaatccc agacaccctc ctcagacccc241 ttgtcctgcc aatttctgca cccaaagtca ctgcctggtt tcagccacat ggcccctcta301 cccaagttct tggtaagcct ggctctaagg aatgccctgg aggaagctgg ttgtcaggct361 gatgtttggg ctctacagct acagctctac cgccagggtg gtgtgaatgc tacacaggtc421 ctcatccagc atcttcgagg gctccagaaa ggcagaagca cagagaggaa cgtgtcagtg481 gaagccctgg cctctgctct gcagctgtta gccagggagc agcaaagcac aggaagggtc541 gggcgctccc tcccgacaga ggactgtgag aatgagaagg agcaagctgt gcacaatgta601 gtccagctgc tgccaggagt gggaaccttc tacaacctgg gcacagcttt gtattatgct661 actcaaaact gcctgggcaa ggccagggaa cgaggccgag atggggccat agatctggga721 tatgaccttc tgatgaccat ggctgggatg tcaggggggc ctatgggtct agcgatcagt
781 gctgcactta aacctgcatt aaggtctggg gttcagcagt tgatccagta ttaccaagat841 cagaaagacg caaacatctc tcagccggag accaccaagg agggtttgag ggccatctca901 gatgtgagtg acttggaaga aacaactact ctggcttctt tcatatcaga agtagtaagt961 tcagctccct actgggggtg ggccataatc aagagctatg acttagatcc tggggctggg1021 agtcttgaga tataaaagaa tgtggtaacc acagaattaa taactgtact accctgacaa1081 gctatataca tgtcttcaaa attttaatct gatttatcca ggaggaaggc tgtacagtaa1141 aacgtaagaa cgtaaatgtt tgggtgttga agtcacaggg tttggtttcg aatctaggct1201 ccacttgtta gagcctcggt gatcactgaa tagtaacttc tttcttgaac taagatcagt1261 tttgaagttt ctaaaggaga tagaatgatt ttaacctcaa tgagttgccc tgtaaattta1321 aaatgataca atgaatctaa aatgcttatc acagtacttt caataaatag ctattagcca1381 ggtgcggtgg ctcacgcctg taatcccagc actgtgagag gctgaggcgg gatgatcacc1441 tgaggtcagg agttcaagat cagcctgggc aacatggcga aaccccgtct ctacaataaa1501 tacaaaaaat tatcctggcg gagttatgca cgcttgtagt cccaactacc tgggaggctg1561 aggcgggaga atcacctgag cctgggaggt cgaggctgca gcgagccgag atcgcgccgc1621 tgcattccag cctgggtgac agagcgagac catgtctcaa aaaataaaaa taaaaaaaaa1681 ttgttttcac aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa<210>15<211>3014<212>DNA<213>Homo sapiens<400>151 caaaccgcta cggcgtttga aagtgtccgg gttgcttagg atccctacag gtagcgcctc61 tggatacatg cgtggtctgc tgacccagag agaaacgaaa gcagaactgt ttggcgggag121 atcatgtcag ccgtggtagc tcagacgctg catgtttttg gtcttcgatc ccacgtggcc181 aacaatatct tctacttcga tgaacagatc attatatttc cttcaggaaa tcactgtgtg241 aagtacaatg tggatcagaa atggcaaaaa ttcattccag gctcagagaa gagtcagggc301 atgttggcct tgtccatcag tcccaatcgg cggtacctcg ctatctctga gactgtgcaa361 gaaaaacctg ccatcaccat ttatgaattg tcatccatcc cttgccggaa gcgcaaagtt421 cttaataatt ttgacttcca agttcagaaa tttattagca tggctttttc tccagactcc481 aaatacctat tggctcagac gtcacctcca gagtcaaatc ttgtctactg gctgtgggaa541 aaacagaaag taatggccat tgttagaatc gacactcaga acaaccctgt ctaccaggtg601 agcttcagtc cacaggataa cactcaggtg tgtgtcactg gaaatgggat gtttaagctt661 ctccgttttg ctgagggaac cctgaagcaa accagctttc agaggggaga accccaaaac721 tatctagctc acacctgggt ggctgatgac aagattgtcg ttggcactga cacaggcaaa781 ctcttcctct ttgaatctgg agatcagcgt tgggagacca gcataatggt caaggaacct841 accaatggct caaagagcct ggatgtcatt caggaatcag agagcctgat tgaatttcca901 ccagtcagtt ctccactccc ttcctatgaa cagatggtgg cggccagtag ccatagccag961 atgtccatgc cccaggtgtt tgccattgca gcctattcaa agggatttgc ctgttctgct1021 gggccaggga gagttctgct gtttgagaag atggaagaaa aggattttta ccgtgagagc1081 agagaaatca ggattcctgt ggacccgcag agcaatgatc caagtcagtc tgacaaacag1141 gacgttctct gcctgtgctt cagcccctca gaggaaactc tggttgccag caccagtaag
1201 aaccaactct acagcatcac catgtccctg acagagatca gcaaggggga gcctgctcac1261 tttgagtatt tgatgtatcc attgcactca gcacccatca ccggtctagc tacctgcatc1321 cgcaaacccc ttatagccac ctgttctctg gatcgatcca tccgcctttg gaattatgaa1381 acaaacaccc tggaactatt taaggaatac caagaagagg catattccat cagccttcat1441 ccatctggac acttcattgt agtagggttt gctgacaaac tacgcctcat gaatctactc1501 attgatgata tacgttcttt caaagaatac tctgttagag gatgcggaga gtgttccttt1561 agcaatggag gtcacctgtt tgctgcagtc aatggaaatg tgattcacgt ttacaccacc1621 acgagcctag agaacatctc aagcctgaaa ggacacacag ggaagattcg ctcaattgtg1681 tggaatgcag atgatagcaa actgatttct ggtggcacag atggtgctgt gtatgaatgg1741 aatctgtcca caggaaagag agagacagaa tgcgtgctca agtcttgcag ctacaactgt1801 gttactgtct cccccgatgc caaaattatc tttgctgttg gatcagacca caccctcaag1861 gagattgcag attccttgat ccttcgagag atatcggcgt ttgatgtcac ctacaccgcc1921 attgtcatct cacattctgg acgcatgatg tttgtgggca cctcggtggg aaccattcgt1981 gccatgaagt accctctgcc tctgcagaag gaattcaatg agtaccaggc ccatgccggt2041 cctatcacca aggtgagcag gaccctctcc ccaggaaccc agtcccacac ctgcctgcta2101 cgtgccttgt tcatcccttc aacctcccaa tgtcttttct ctctccttct tctctcttat2161 ttattcatcc atcattcatt gaatcaccat ctattgacta tgaatatact ctttgtttaa2221 actacttcca ggaatttagc ctaggaaatc atcagagata cacctaaaaa tgtatgtaca2281 acgttttcac cataatatta tgcataataa ggggccgttt ggtggatgcc gtagctgccg2341 tgagtgtggg ctgcacttga ccacagctgc ctcctcctcc agagaatgcc ccagactgaa2401 aggagccata gccctgaaga ttggccccta cctctccctg agggtacaaa aggccacccc2461 aggggcaata ccatgagtac acatttgtaa attgtccttc cattcaccct tctcataaag2521 tagtatctat gttcaacagt caaaatgtgg aagcaaccaa gcatccatcg acagacgaat2581 gcataagcaa aagatggtat atctatacaa tggaacaata ccctgcctaa aaaggaaggg2641 aattctgcaa tgtgctacca catggatgaa ccttgaggat gttatgctaa attaaataag2701 gccaaccaca aaaagataag tacagtgtga ttccactttt aggagatact tagagcagtc2761 agaatcacaa agacagagtg gtggttggca ggggctgcag gaagggggaa tgaggaatga2821 ttgtttcata ggtatagagt tttggtttta caagacaaaa ggattatggg ggtagttggt2881 ggcaatggct gcacaacatt acaaatgtat ttaataacat gaactgtaca cttgaaaatg2941 gttaagatag caaattttac agaatatgta ttttacgaca attttaaaaa tgaaataaaa3001 aagaattatc ttgc<210>16<211>2087<212>DNA<213>Homo sapiens<400>161 ctcccaggtg cctggcagag agtcctcacc agccccctgc cggatgtctg gctggcatct61 gaggggactg aacatggcaa gaagcaaaac agcagcacaa gaaaccagtt tcttcatctg121 aaaccgagca ggctctactc cagaacagaa cccacagtcc caggcgctgg gccttcttct181 taagttggga aatcactcat ccccaggaga aaaaaagagc aaaagcttcc agtactgggg241 atgtggggag aggtttttta aaaatatcag cccaatatat gggaaaatat gggatgcagg
301 catccccagg tgtcaagcgt ccagatccgt agacacactg ggacgatggt gatcagtatc361 actccctctg actcatcggc cctacagaga agacaccatg ctggtgcaca gtcggtgcca421 aacccgcgtt tgtaaatgaa taagtgttgc tgccctggtg gaagcccagc tcatgtggag481 gaagccagct tgcagagaga gcaagaacag agccagcaca cacattggag caaaggcaag541 ggcagatgga aagttctggc ggcatcatgc caaggctccc atccgaggcc tccctgaacc601 ccactctctc ggcgccacct tggatgctgc gggctggtac attccccact tgcaaaactc661 tgtggggctg ggttcctctc ttttctttcc aaatatccca ggaagtggat ggttttatcc721 aaattcagca gacgagtaaa aagagtcttc gggaggtgca atagctttct aggaatgagg781 atattcttca aggaaaatga accccacact aggcctggcc atttttctgg ctgttctcct841 cacggtgaaa ggtcttctaa agccgagctt ctcaccaagg aattataaag ctttgagcga901 ggtccaagga tggaagcaaa ggatggcagc caaggagctt gcaaggcaga acatggactt961 aggctttaag ctgctcaaga agctggcctt ttacaaccct ggcaggaaca tcttcctatc1021 ccccttgagc atctctacag ctttctccat gctgtgcctg ggtgcccagg acagcaccct1081 ggacgagatc aagcaggggt tcaacttcag aaagatgcca gaaaaagatc ttcatgaggg1141 cttccattac atcatccacg agctgaccca gaagacccag gacctcaaac tgagcattgg1201 gaacacgctg ttcattgacc agaggctgca gccacagcgt aagtttttgg aagatgccaa1261 gaacttttac agtgccgaaa ccatccttac caactttcag aatttggaaa tggctcagaa1321 gcagatcaat gactttatca gtcaaaaaac ccatgggaaa attaacaacc tgatcgagaa1381 tatagacccc ggcactgtga tgcttcttgc aaattatatt ttctttcgag ccaggtggaa1441 acatgagttt gatccaaatg taactaaaga ggaagatttc tttctggaga aaaacagttc1501 agtcaaggtg cccatgatgt tccgtagtgg catataccaa gttggctatg acgataagct1561 ctcttgcacc atcctggaaa taccctacca gaaaaatatc acagccatct tcatccttcc1621 tgatgagggc aagctgaagc acttggagaa gggattgcag gtggacactt tctccagatg1681 gaaaacatta ctgtcacgca gggtcgtaga cgtgtctgta cccagactcc acatgacggg1741 caccttcgac ctgaagaaga ctctctccta cataggtgtc tccaaaatct ttgaggaaca1801 tggtgatctc accaagatcg cccctcatcg cagcctgaaa gtgggcgagg ctgtgcacaa1861 ggctgagctg aagatggatg agaggggtac ggaaggggcc gctggcaccg gagcacagact921 tctgcccatg gagacaccac tcgtcgtcaa gatagacaaa ccctatctgc tgctgattta1981 cagcgagaaa ataccttccg tgctcttcct gggaaagatt gttaacccta ttggaaaata2041 aaggagaatt cctgcttgcc aaaaaaaaaa aaaaaaaaaa aaaaaaa<210>17<211>2090<212>DNA<213>Homo sapiens<400>171 ttcggcacga gtaagaccag gatgtctctg aaatggacgt cagtctttct gctgatacag61 ctcagttgtt actttagctc tggaagctgt ggaaaggtgc tagtgtggcc cacagaatac121 agccattgga taaatatgaa gacaatcctg gaagagcttg ttcagagggg tcatgaggtg181 actgtgttga catcttcggc ttctactctt gtcaatgcca gtaaatcatc tgctattaaa241 ttagaagttt atcctacatc tttaactaaa aatgatttgg aagattctct tctgaaaatt301 ctcgatagat ggatatatgg tgtttcaaaa aatacatttt ggtcatattt ttcacaatta
361 caagaattgt gttgggaata ttatgactac agtaacaagc tctgtaaaga tgcagttttg421 aataagaaac ttatgatgaa actacaagag tcaagtttg atgtcattct ggcagatgcc481 cttaatccct gtggtgagct actggctgaa ctatttaaca taccctttct gtacagtctt541 cgattctctg ttggctacac atttgagaag aatggtggag gatttctgtt ccctccttcc601 tatgtacctg ttgttatgtc agaattaagt gatcaaatga ttttcatgga gaggataaaa661 aatatgatac atatgcttta ttttgacttt tggtttcaaa tttatgatct gaagaagtgg721 gaccagtttt atagtgaagt tctaggaaga cccactacat tatttgagac aatggggaaa781 gctgaaatgt ggctcattcg aacctattgg gattttgaat ttcctcgccc attcttacca841 aatgttgatt ttgttggagg acttcactgt aaaccagcca aacccctgcc taaggaaatg901 gaagagtttg tgcagagctc tggagaaaat ggtattgtgg tgttttctct ggggtcgatg961 atcagtaaca tgtcagaaga aagtgccaac atgattgcat cagcccttgc ccagatccca1021 caaaaggttc tatggagatt tgatggcaag aagccaaata cattaggttc caatactcga1081 ctgtacaagt ggttacccca gaatgacctt cttggtcatc ccaaaaccaa agcttttata1141 actcatggtg gaaccaatgg catctatgag gcgatctacc atgggatccc tatggtgggc1201 attcccttgt ttgcggatca acatgataac attgctcaca tgaaagccaa gggagcagcc1261 ctcagtgtgg acatcaggac catgtcaagt agagatttgc tcaatgcatt gaagtcagtc1321 attaatgacc ctgtctataa agagaatgtc atgaaattat caagaattca tcatgaccaa1381 ccaatgaagc ccctggatcg agcagtcttc tggattgagt ttgtcatgcg ccacaaagga1441 gccaagcacc ttcgagtcgc agctcacaac ctcacctgga tccagtacca ctctttggat1501 gtgatagcat tcctgctggc ctgcgtggca actgtgatat ttatcatcac aaaattttgc1561 ctgttttgtt tccgaaagct tgccaaaaca ggaaagaaga agaaaagaga ttagttatat1621 caaaagcctg aagtggaatg actgaaagat gggactcctc ctttatttca gcatggaggg1681 ttttaaatgg aggatttcct ttttcctgtg acaaaacatc ttttcacaac ttaccttgtt1741 aagacaaaat ttattttcca gggatttaat acgtacttta gttggaatta ttctatgtca1801 atgattttta agctatgaaa aatacaatgg ggggaaggat agcatttgga gatataccta1861 atgttaaatg acgagttact ggatgcagca cgcaacatgg cacatgtgta tacatatgta1921 gctaaccctt cgttgtgcac atgtacccta aaacttaaag tataatttaa aaaaagcaaa1981 aaaaaaaaat accaactctt ttttttaaac caggaaggaa aatgtgaaca tggaaacaac2041 ttctagtatt ggatctgaaa ataaagtgtc atccaagcca taaaaaaaaa<210>18<211>2324<212>DNA<213>Homo sapiens<400>181 attcatggct ggaatgatgg tgggaggcaa cctatatggc catttgtcag acaggaaacc61 attatcatcg cccaaccatg tctccactga ttgtgacgag ggacttgagg tgcccattgc121 catccaccag catcacgtct tctggtatct ctcctgaaac cctgaatgaa aatggcctcc181 atctgcatcc atgttgctgc agaagacatg atttcattct tttttgtggc tacatagtat241 tccagtctac cattggtggg cattgaggtt attccatgcc tttgctactg tgaatagtgc301 ttcaatgaac atgtttggga gaaagttcgt gctcagatgg tcttacctcc agctcgccat361 tgtaggcacc tgtgcggcct ttgctcccac catcctcgta tactgctccc tgcgcttctt
421 ggctggggct gctacattta gcatcattgt aaatactgtt ttgttaattg tagagtggat481 aactcaccaa ttctgtgcca tggcattgac attgacactt tgtgctgcta gtattggaca541 tataaccctg ggaggcctgg cttttgtcat tcgagaccag tgcatcctcc agttggtgat601 gtctgcacca tgctttgtct tctttctgtt ctcaaggtgg ctggcagagt ctgctcggtg661 gctcattatc aacaacaaac cagaagaggg cttaaaggaa cttacaaaag ctgcacacag721 gaatggaatg aagaatgctg aagacatcct aaccatggag gttttgaaat ccaccatgaa781 gcaagaactg gaggcagcac agaaaaagca ttctctttgt gaattgctcc gcatacccaa841 catatgtaaa agaatctgtt tcctgtcctt tgtgaggtct gctggagttt gctggaggtc901 cactccagat cctgtttgct tgggtatcac cagcggaggt tgcagaacag caaagattcc961 tgcctgctcc ttcctctgga agcttcattt tagaggagca cctgcctgat gccagccaga1021 gctctcctgt atgaagtgtc tgttgacccc tgctgggaag tgtctcccag tcaggaggca1081 caggtgttag tgacccactt aaggaggcag tctatccctt agcagagctc aagcactgtg1141 ctgagagatc cactgctctc ttcagagctg gcaagcaaga atgtttaagt ccactgaagc1201 tgcacccaca gccacccctt ccccaaagtg ctctgtccca ggtgatggga gttttatcta1261 taagcccttg actggggctg ctgcctttct ctcagagatg ccctgcccag tgaggaggaa1321 tctagagagg cagtctggcc acagttgctt tgcagcactg cagtaagttc cacacagttt1381 gaacttccca atggcttcct taacactgtg aggggaaaac tgcctacaca agcctcagta1441 atggtggaca ttcctctccc accaaggttg atcatcccag ttcgacctca gactgatgtg1501 ctggcagtga gaatttcaag ccagtggttc ttagcttgct gggctccatg ggagtgggac1561 ctgctgagcg agaccacttg gctttctggc atcagcccct tctccaggag agtgaatggt1621 tctgtctccc cctggtagca ttggcacaca agggaatctc ctggtctgcg tgttgcaaaa1681 actatgggaa aagcataatt tctgggctgg atagcacagt ccctatggct tccttgggta1741 ggtgaggaag ttccctggcc ctttggactt cctgggtgag gtgatgcccc accctgcttc1801 agcttaccct ccgtgggctg cacccaccca ctgtctaacc agtcccagtg agatgaaccg1861 ggtacctcag ttggaaatgc agaaatcact caccttccgc attgctctcg ctgggagctg1921 cagaccagag ctcttcctat tcggccatct tgccagctgt ctctatcgac tacctcttat1981 tccaaaaaat aaaaccataa tgaagttaga caccattaaa tatacataat ataaaaatag2041 gttttcttat tctaatctag atttgctaca caagaccatc tacagaatga atgccatgaa2101 tatacaatct gtacccaata agttgtacat tttagtaaac attcctgatt gtaagggtgg2161 caaatgggaa ttttggcttc ttagatcttt actgtgagtt tgactgatat cagtacattt2221 ttatttttaa ttgtatattt tcattactgt gaattttttt gcagtgattt ttgatgccat2281 gtggctacat tggttttaga atactaataa aatccattgc tttt<210>19<211>1925<212>DNA<213>Homo sapiens<400>191 ccccacagtg agaggaagga aggcaacagt cgccagcagc cgatgtgaag accggactcc61 gtgcgcccct cgccgcctct gcctggccac atcgatgttg tgtccgccgc ctgctcgccc121 ggatcacgat gaacgcgcag ctgaccatgg aagcgatcgg cgagctgcac ggggtgagcc181 atgagccggt gcccgcccct gccgacctgc tgggcggcag cccccacgcg cgcagctccg
241 tggcgcaccg cggcagccac ctgccccccg cgcacccgcg ctccatgggc atggcgtccc301 tgctggacgg cggcagcggc ggcggagatt accaccacca ccaccgggcc cctgagcaca361 gcctggccgg ccccctgcat cccaccatga ccatggcctg cgagactccc ccaggtatga421 gcatgcccac cacctacacc accttgaccc ctctgcagcc gctgcctccc atctccacag481 tctcggacaa gttcccccac catcaccacc accaccatca ccaccaccac ccgcaccacc541 accagcgcct ggcgggcaac gtgagcggta gcttcacgct catgcgggat gagcgcgggc601 tggcctccat gaataacctc tataccccct accacaagga cgtggccggc atgggccaga661 gcctctcgcc cctctccagc tccggtctgg gcagcatcca caactcccag caagggctcc721 cccactatgc ccacccgggg gccgccatgc ccaccgacaa gatgctcacc cccaacggct781 tcgaagccca ccacccggcc atgctcggcc gccacgggga gcagcacctc acgcccacct841 cggccggcat ggtgcccatc aacggccttc ctccgcacca tccccacgcc cacctgaacg901 cccagggcca cgggcaactc ctgggcacag cccgggagcc caacccttcg gtgaccggcg961 cgcaggtcag caatggaagt aattcagggc agatggaaga gatcaatacc aaagaggtgg1021 cgcagcgtat caccaccgag ctcaagcgct acagcatccc acaggccatc ttcgcgcaga1081 gggtgctctg ccgctcccag gggaccctct cggacctgct gcgcaacccc aaaccctgga1141 gcaaactcaa atccggccgg gagaccttcc ggaggatgtg gaagtggctg caggagccgg1201 agttccagcg catgtccgcg ctccgcttag cagcatgcaa aaggaaagaa caagaacatg1261 ggaaggatag aggcaacaca cccaaaaagc ccaggttggt cttcacagat gtccagcgtc1321 gaactctaca tgcaatattc aaggaaaata agcgtccatc caaagaattg caaatcacca1381 tttcccagca gctggggttg gagctgagca ctgtcagcaa cttcttcatg aacgcaagaa1441 ggaggagtct ggacaagtgg caggacgagg gcagctccaa ttcaggcaac tcatcttctt1501 catcaagcac ttgtaccaaa gcatgaagga agaaccacaa actaaaacct cggtggaaaa1561 gctttaaatt aaaaaaaatt tttaaaagac caggacctca agatagcagg tttatactta1621 gaaatatttg aagaaaaaaa agcgttattt atagtccaaa gaaaccaaag acttagctca1681 cctgcattct gactttgttt ggagacacac acttcagcag ggcggcgact tggcaagaca1741 aatgatgagc aggaaaacac cactggatct cacaccttca atccatgacc atcctcgctg1801 tgcttggctg tttagtggtt tggagcatag tgattttgag ccattgagcg gacatctttt1861 aagatcgaac tttctcatct gttctaccat gccacgaagg tgtatggtgt ctcagtacta1921 ccacc<210>20<211>3605<212>DNA<213>Homo sapiens<400>201 ggtaaatatg tgttcattaa ctgagattaa ccttccctga gttttctcac accaaggtga61 ggaccatgtc cctgtttcca tcactccctc tecttctcct gagtatggtg gcagcgtctt121 actcagaaac tgtgacctgt gaggatgccc aaaagacctg ccctgcagtg attgcctgta181 gctctccagg catcaacggc ttcccaggca aagatgggcg tgatggcacc aagggagaaa241 agggggaacc aggccaaggg ctcagaggct tacagggccc ccctggaaag ttggggcctc301 caggaaatcc agggccttct gggtcaccag gaccaaaggg ccaaaaagga gaccctggaa361 aaagtccgga tggtgatagt agcctggctg cctcagaaag aaaagctctg caaacagaaa
421 tggcacgtat caaaaagtgg ctgaccttct ctctgggcaa acaagttggg aacaagttct481 tcctgaccaa tggtgaaata atgacctttg aaaaagtgaa ggccttgtgt gtcaagttcc541 aggcctctgt ggccaccccc aggaatgctg cagagaatgg agccattcag aatctcatca601 aggaggaagc cttcctgggc atcactgatg agaagacaga agggcagttt gtggatctga661 caggaaatag actgacctac acaaactgga acgagggtga acccaacaat gctggttctg721 atgaagattg tgtattgcta ctgaaaaatg gccagtggaa tgacgtcccc tgctccacct781 cccatctggc cgtctgtgag ttccctatct gaagggtcat atcactcagg ccctccttgt841 ctttttactg caacccacag gcccacagta tgcttgaaaa gataaattat atcaatttcc901 tcatatccag tattgttcct tttgtgggca atcactaaaa atgatcacta acagcaccaa961 caaagcaata atagtagtag tagtagttag cagcagcagt agtagtcatg ctaattatat1021 aatattttta atatatacta tgaggcccta tcttttgcat cctacattaa ttatctagtt1081 taattaatct gtaatgcttt cgatagtgtt aacttgctgc agtatgaaaa taagacggat1141 ttatttttcc atttacaaca aacacctgtg ctctgttgag ccttcctttc tgtttgggta1201 gagggctccc ctaatgacat caccacagtt taataccaca gctttttacc aagtttcagg1261 tattaagaaa atctattttg taactttctc tatgaactct gttttctttc taatgagata1321 ttaaaccatg taaagaacat aaataacaaa tctcaagcaa acagcttcac aaattctcac1381 acacatacat acctatatac tcactttcta gattaagata tgggacattt ttgactccct1441 agaagccccg ttataactcc tcctagtact aactcctagg aaaatactat tctgacctcc1501 atgactgcac agtaatttcg tctgtttata aacattgtat agttggaatc atattgtgtg1561 taatgttgta tgtcttgctt actcagaatt aagtctgtga gattcattca tgtcatgtgt1621 acaaaagttt catccttttc attgccatgt agggttccct tatattaata ttcctcagtt1681 catccattct attgttaata ggcacttaag tggcttccaa tttttggcca tgaggaagag1741 aacccacgaa cattcctgga cttgtctttt ggtggacatg gtgcactaat ttcactacct1801 atccaggagt ggaactggta gaggatgagg aaagcatgta ttcagcttta gtagatatta1861 ccagttttcc taagtgattg tatgaattta tgctcctacc ggcaatgtgt ggcagtccta1921 gatgctctat gtgcttgtaa aaagtcaatg ttttcagttc tcttgatttt cattattcct1981 gtggatgtaa agtgatattt ccccatggtt ttaatctgta tttccccaac atgtaataag2041 gttgaacact tttttatatg cttattgggc acttgggtat cttcttctgt gaagtacccg2101 ttcacatttt tgtattttgt ttaaattagt tagccaatat ttttcttact gatttttaag2161 ttatttttac attctgaata tgtccttttt aatgtgtatt acaaatattt tgctagtttt2221 tgacttgctc ctaatgttga attttgatga acaaaatttc ctaattttga gaaagtctta2281 tttattcata ttttctttca aaattagtgc tttttgtgtc atgtttaaga aatttttgcc2341 catcccaaaa tcataagata tttttcatga ttttgaaacc atgaagagat ttttcatgat2401 tttgaaatca tgaagatatt tttccatttt tttctaatag ttttattaat aaacattcta2461 tctattcctg gtagaataga tatccacttg agacagcact atgtaggaaa gaccattttt2521 cctccactga actagggtgg tgcatttttg taagttaggt aactgtatgt gtgtgtgtct2581 gtttctgggc tgtctattct agtctatttg ttgatgcttg tgtcaaacag tacactatct2641 taattattgt acatttatag ttgtaactgt agtccagctt tgttcttctt caagtcaaga2701 tttccatata aatattagaa acagtttctc aatttctaca aaatcctgat gaggtttcta2761 ctgggaccac attgagtcta tcaatcaact tatgcagaac tggcaactta ctactgaatc2821 tctaatcaat gttcatcatg tatcgcttca tttaactagg atttctctaa cttaattgct2881 atgttttgag atttttagtt taaaaacctt gtatatcttg ttttggtggt tttagtgatt2941 ttaataatat attttaaata ttttttcttt tctattgttg tacacagaaa tacagttaag3001 ttttgtgtgt agtcttacga tgtttagtaa cctcaataag tttatttctt aaatctagta
3061 atttgtagat tcctctggat tttgtatatg catagtcatg taagctgaaa atatggcaat3121 acttgcttct tcccaattgc tttacctttt ttcttacctt attgcactgg ttagcaaccc3181 caatacagag accaccagag caggtataga ctcctgaaag acaatataat gaagtgctcc3241 agtcaggcct atctaaactg gattcacagc tctgtcactt aattgctaca tgatctagag3301 ccagttactt tgtgtttcag ccatgtattt gcagctgaga gaaaataatc attcttattt3361 catgaaaatt gtggggatga tgaaataagt taacaccttt aaagtgtgta gtaaagtatc3421 aggatactat attttaggtc ttaatacaca cagttatgcc gctagataca tgctttttaa3481 tgagataatg tgatattata cataacacat atcgattttt aaaaattaaa tcaaccttgc3541 tttgatggaa taaactccat ttagtcacaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa3601 aaaaa<210>21<211>544<212>DNA<213>Homo sapiens<220>
<221>misc_feature<222>(507)..(507)<223>n is a,c,g,or t<220>
<221>misc_feature<222>(511)..(511)<223>n is a,c,g,or t<220>
<221>misc_feature<222>(519)..(519)<223>n is a,c,g,or t<400>211 gtgctgcctc cagttctttt ttcatggtgg atttcaaaat ctccagggtt agggtgtctc61 tggcattctt cattccactc ctgtgtgcag cttttctaag ttcctttaag ccttcctctg121 gtttattgtt gataatgagc caccgagcag actctagcag ccaacttgag gtcagaaaga181 tcacaaagta tggtacagac accaccagct ggaggatatg ccagtctcga atggcaaaag241 ccaggcctgc cagggtcata aatgcaatac cagaagggca cattcccaat gtaattccca301 tggcctggaa tctgtgtgtt gcccactcgg ctattaacat aatagtattt gttatgaggc361 tcattgcagc aatcccagac aagaagcgta gtgagcagta aatgaggaag gtgggagcca421 aggctgcaca ggtgccaaca atggcaacct tgaggtaaca ccatctgagc acgaaccttc
481 tcccaaacct ttctgataaa tgaccgncta ngatgcctnc caccatcatt ccagccatga541 atac
權(quán)利要求
1.一類分離出的在人類肝臟中特異表達(dá)的表達(dá)序列標(biāo)簽的序列,其包括(a)SEQ IDNo.1~SEQ ID No.21所示的序列;(b)SEQ ID No.1~SEQ ID No.21所示的序列中每條序列的互補(bǔ)序列;(c)與SEQ ID No.1~SEQ ID No.21所示的序列中每條序列有至少70%同源性的序列,及(d)上述(a)~(c)中一條或數(shù)條的組合。
2.根據(jù)權(quán)利要求1所述的一類分離出的在人類肝臟中特異表達(dá)的表達(dá)序列標(biāo)簽的序列,其特征在于所述序列包括具有SEQ ID No.1~SEQ ID No.21所示的序列。
3.一種探針分子,其特征在于所述的探針分子含有權(quán)利要求1中所述的序列中約8-100個(gè)連續(xù)的核苷酸。
全文摘要
本發(fā)明公開了一類新的在人類肝臟中特異表達(dá)的表達(dá)序列標(biāo)簽的序列。利用本發(fā)明的在人類肝臟中特異表達(dá)的表達(dá)序列標(biāo)簽,可以方便的尋找出在人類肝臟中特異表達(dá)的相關(guān)基因,從而在研究肝臟疾病的致病機(jī)理以及開發(fā)治療肝臟疾病的藥物中發(fā)揮重要作用。
文檔編號C12Q1/68GK1928082SQ200510029538
公開日2007年3月14日 申請日期2005年9月9日 優(yōu)先權(quán)日2005年9月9日
發(fā)明者黃健, 韓澤廣 申請人:上海人類基因組研究中心