專利名稱：人類肝臟中表達(dá)的表達(dá)序列標(biāo)簽c組的制作方法
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(dòng)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(shuō)明肝臟是維持生命活動(dòng)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(yíng)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(duì)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(chǎng)由病毒引發(fā)的、免疫系統(tǒng)對(duì)肝細(xì)胞的戰(zhàn)爭(zhēng)，使大約25％的患者的肝臟成為戰(zhàn)火連綿的戰(zhàn)場(chǎng)，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)膽汗性腎病；(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(dòng)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(duì)患者的身體甚至生命造成危害，而且對(duì)患者心理上的打擊也是十分沉重的。無(wú)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(huì)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(duì)這部分序列進(jìn)行測(cè)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(dòng)測(cè)序的出現(xiàn)，使從質(zhì)?；パa(bǔ)脫氧核糖核酸(Complementary DNA，簡(jiǎn)稱cDNA)文庫(kù)隨機(jī)選取許多cDNA克隆和決定來(lái)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(jiǎn)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(lái)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(duì)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(cè)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(jiǎn)稱cDNA)文庫(kù)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(duì)cDNA兩端進(jìn)行一輪脫氧核糖核酸序列測(cè)定，所獲得的來(lái)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(jiǎn)而言之，表達(dá)序列標(biāo)簽是來(lái)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(duì)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(duì)所有動(dòng)植物的基因作為一種數(shù)據(jù)庫(kù)，通過(guò)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(cè)序已經(jīng)成為許多基因組研究機(jī)構(gòu)的工作重點(diǎn)。
表達(dá)序列標(biāo)簽(EST)是一種快速有效揭示基因組容量的方法。ESTs在新基因的發(fā)現(xiàn)、基因作圖和基因組序列編碼區(qū)域的確定等方面起到重要作用。EST不僅為基因組遺傳圖譜的構(gòu)建提供了大量的分子標(biāo)記，而且來(lái)自不同組織和器官的EST也為基因的功能研究提供了有價(jià)值的信息。此外，EST計(jì)劃還為基因的鑒定提供了候選基因(candidantes)。
在本發(fā)明之前，還沒(méi)有出現(xiàn)涉及本發(fā)明的一類在人類肝臟中表達(dá)的表達(dá)序列標(biāo)簽的公開報(bào)道。

發(fā)明內(nèi)容
本發(fā)明要解決的技術(shù)問(wèn)題是提供一類在人類肝臟中表達(dá)的表達(dá)序列標(biāo)簽。
為了解決上述技術(shù)問(wèn)題，本發(fā)明通過(guò)如下技術(shù)方案實(shí)現(xiàn)在本發(fā)明的一個(gè)方面，提供了一類在人類肝臟中表達(dá)的表達(dá)序列標(biāo)簽的序列，其包括(a)SEQ ID No.1～SEQ ID No.63所示的序列；(b)SEQ ID No.1～SEQ ID No.63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.63所示的序列中每條序列有至少70％同源性的序列；(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.63所示的序列。
本發(fā)明還提供了一種探針?lè)肿?，所述的探針?lè)肿雍猩鲜鲂蛄兄屑s8-100個(gè)連續(xù)的核苷酸。
由本發(fā)明的一類在人類肝臟中表達(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(shuō)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(cè)(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(lái)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(kù)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(guò)柱篩選長(zhǎng)度＞500bp的片段，用酚-氯仿抽提，乙醇沉淀，無(wú)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 1Blue MRF’(Strategene，CA9203，USA)細(xì)菌。涂板并測(cè)定滴度。
實(shí)施例3測(cè)序及數(shù)據(jù)庫(kù)建立(Seqencing and Database Constructing)挑選文庫(kù)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(cè)序儀(Perkin-Elmer，USA)上進(jìn)行EST大規(guī)模測(cè)序。測(cè)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(kù)(Genebank+EMBL)，將無(wú)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(kù)。
實(shí)施例4基因的全長(zhǎng)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(zhǎng)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(kù)，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(jiǎn)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(zhǎng)完整性如何。通過(guò)電子克隆的方法，通?？色@取人肝臟相關(guān)基因的全長(zhǎng)序列。
(2)cDNA術(shù)端快速擴(kuò)增(Rapid Amplification of cDNA Ends，RACE)如果通過(guò)“電子克隆”方法仍未得到完整的cDNA全長(zhǎng)，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(kù)(Clontech Lab，Inc，USA)中進(jìn)行長(zhǎng)距離PCR反應(yīng)。然后對(duì)PCR產(chǎn)物克隆、測(cè)序。用AUTOASSEMBLER及STRIDER軟件分析被延長(zhǎng)的序列有無(wú)完整的ORF，如無(wú)，重復(fù)上述過(guò)程直至獲得全長(zhǎng)。
(3)RT-PCR對(duì)于5’和3’端的已知的序列，如果中間有一段間隙(gap)無(wú)法從已有的公共數(shù)據(jù)庫(kù)或自身數(shù)據(jù)庫(kù)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(kù)中進(jìn)行擴(kuò)增。然后對(duì)產(chǎn)物進(jìn)行克隆、測(cè)序。最后拼接便獲得全長(zhǎng)。
通過(guò)組合使用上述3種方法，可獲得人肝臟相關(guān)蛋白的全長(zhǎng)編碼序列。
序列表<110>上海人類基因組研究中心<120>人類肝臟中表達(dá)的表達(dá)序列標(biāo)簽C組<130>NP-10046<160>63<210>1<211>574<212>DNA<213>Homo sapiens<400>11 gtgggagata ggggaatata ctatcttcta gtcctttagt tccttttggg aatgtcataa61 ttagtttgtg cagacttctt gagggtatgg tatattagta tgatagagct atttggatat121 cagcccaaag gattggtagt ttagcaatac agggggaaga aaaaagaatc tttggtagca181 tccttcggac cactgaatca accttccctg ggacttctct acctctgggc tttgggttat241 atttggacca tctggagtta gttcttctgt tttaagtcta aagcatccta aatgagatgt301 ttcttatgct tctaaatata ctctttttaa ccatgttcca ttttgtgtgg acattgtaag361 ggtaatatat acagacttaa aaagaatatg cctatgaatt aggaagcttt aagcaatgga421 aaccatnttt cattcactgc cantccacta tgggtagcaa ttcttccnat ggnaattctg481 ttngttactt ccncagtaat aaggaagaat catcagtnca attggtgtaa ggtactttta541 atggaaacat atctatattc nccaacngta gggg<210>2<211>476<212>DNA<213>Homo sapiens<400>21 ttttaaacat taatttcaaa ctatttttat ttaacatttg gtattgttaa acaggtatag61 tattcaggac atacaccttc taccacaatt tctttaatta gggtacttta tattttatca121 aaaatgtgca tattaataga ttgtagttta gcctttgtca aaagacatgc aagtatttag181 tatttacatt aaaaggattg cctcagaaga aacattgaat tcataagccc tcttaaaaag241 tcaaaaatat gcataaagaa gactagtatt gatattttct gatattttag atatgattaa301 tattttggac ctccattggt ttccacacta tcatgcaaat ttccaacttg ctttaacaca361 acagttctat cagctgtatt agagggaata cacattttaa ttgctctttt tgaaaatatc421 accaggcagt tcagaatgtc tcatttattg agaatattgt gacaatcaaa gacctg<210>3
<211>486<212>DNA<213>Homo sapiens<400>31 tcattgctaa ggaagaactc cctctgctct tggaagattt tctactctac tgatcttatt61 ttattttatt ttatttttac ctgatgattg tcttaggcac cctccttaca taataaacca121 tcaagctaac ttgaacaggg aaactgagtc acactcaaac aatagctaag gtcaaaagtg181 tagtgaaagt agaaaaagtg gggaagggat aggtctaagt gagtgacaga tgggctgatt241 cagacagggc aataagcaca gggagatatg aagacaacta ccaaagcaag tggaagacaa301 ggttttcaac tttattgtat tgaaaaatac ttgtcacttg gttcagatgg caaatctaaa361 atgagcccac aatgattatg taataaatgc agaacgtacc acaacaaatc gagactaaca421 cagaaacaga agatgtgact ttgtgaatac aacgccgctc agcgcttcac tgctgatgta481 ggagtc<210>4<211>455<212>DNA<213>Homo sapiens<400>41 tgaccaaaga agcaggagaa acatccaatc tatatctttt cttcatgttc caattcagtc61 attgtttctt gaatgtttct cccaggaaga attaatttca ccaatgaaag cactggaggg121 aatggtgcct gaatatttaa aaaaatgaaa atctctctca tatgtggctt ttagtaacag181 gggaaacaaa gtaaaatgca cctcaagcaa gtgtgagang ggcgaggaag aaagcttttc241 agaaaggtgc attagcgctc acaacagcgc cctctgctgt ccaagtggtg gctgaagtga301 aggtggcttt catgctatca gaaaagccct tttcactaaa caaaattgat gttatctcct361 cttctaggct ctagagaggt cagaaaagga agagcaaaga attagcaata agtcagacag421 acagcagtga cctattggaa gaaaggaaag gttac<210>5<211>428<212>DNA<213>Homo sapiens<400>51 aaactgttat ggaaaaacat tttattacac atattcaact tgcttccaat gaaatgatta61 atttttctat ataattttca tgtataatgg cgtccaatgt ttgtcttccg ttttttttcc121 tttcaaaacc agccccaaaa agtaaaacaa aaattccatn gggtacagta tgtaatgcaa181 gttaacgaat gggnaataga tacatttgac tctgaaacga aaaaaggaca atcgtattgc241 catagaggct cttttcctgc attctgatcc tatccagcaa cggtcagctg agagggttta301 attttgcacc aataaaaata agcaccgtag ggtcgtgaga ctcctgggta aacacgtgcg361 ttagtggaca cgtgttgcaa agcacaaaag ggtacagtac tcngaggggg accaggtacn421 ggggttgt
<210>6<211>460<212>DNA<213>Homo sapiens<400>61 ttcaagattt taagattttc attttattaa aaatatagca acataatagc agcattgttt61 gataaatctt tactagtacc atttaaaagt agtcctactc acaaataacc accacctatg121 cagcatgttt atgtttacat tccaaactct tcccttgata atctaacact gttctattaa181 tctaatcatt aaggaggtaa ttttttaagc attaagttga tctacacagc tacacagtat241 actcaaattt catacttaaa tctattgtag aaatcagaaa ttctttagtt tattccccaa301 cagtgtgtta cctaccagta ccctcaaaat gggttgaaat caacctattc tttcagtgtg361 atttttatga atttatactt acatatggta gttaagaaat tatgtctagc anataanaat421 aaaccaagan tagaaggtac tactcctcca taccaatcct<210>7<211>411<212>DNA<213>Homo sapiens<400>71 ttttacatgg attctagaag tttattagtg acataaatat gaagttaatg gcatctttta61 taggcacaac aaaagaaaca aacgtattag aaggtatttg cataatcaga ccattttgag121 cctggtatgt tttccccagt aattggagca tccttagatg ccttaacaac aaggacagtt181 tctccatcct ttgctgcata catactttct aatactatct ctctccttcc actcccaatt241 cctaataaaa atctctgatt cacattaaaa acttattctg gcaagtctcc ctcttccacc301 tctactgctt tctatgttag tgacaaagtg ctattcatat aaaatnatac aaaaggcaag361 aaacatnaaa gttaaaagga aaccagtatg ggactgatgc cttcanacct c<210>8<211>476<212>DNA<213>Homo sapiens<400>81 tctggtagtg atttatatat atttattata gatttataat aaaataaaaa atgctattgg61 aattctatat ttacacatgc tccatttata tacacgcaaa caaatgtcaa tatcaatggt121 aaaattttag gattttaaag aggcacattt cctcctacct acccacttcc acatattcat181 tactctaaga tgagttttca taagcaacat ttagatttgt gaaggaaaaa aatgaatatt241 tctagtactt atcctctttc ctttcatgct tttgtttgag aaaggaagca gcacataaaa301 tctaaaacag aaactaaggc tgtaagacct tctgtaatac atgttcacac tcatgcatga361 gttgactgta ataggtcaga agatatttga gcaaagtaag cacttacatg tatatgcact421 gcntataagt gatactcctc agacacacac acacagacac acacactcat gtttcg
<210>9<211>610<212>DNA<213>Homo sapiens<400>91 agaaaattac attactttct ttctttgttt cacattacaa aatctttttt tctttacaca61 aatcacattt tattgcagga atatttcaag tgccatcaaa tatttataga agggttaaaa121 aaatagaagt ctctctaaag tggtccagac aaggctttgt atagaataaa tctttttttc181 cccatcttct agttttgatt taagtatttt gaatacattt tcttttccat tgacacttag241 tagcctaaga agcggtccga cgcacacaca tcatacacat gcaaatcaca cacacacaca301 cacacacaca cacacactcc ttcctcacct gaccctcagc ccacccccat acgctcacag361 ataactgggt atccacacta taaagaacaa ccaaacttag aagcagtgtc ttaagtcatg421 tttttcttaa gttagaaagg gtgaattagg atgctgaaga ctttaaaaaa aaatccatag481 ctttaataca cgttaagatg ctgaacactt taaaaaaatc cgtagcttta acacaattgc541 aactgtccaa aagcactttc atcggacttt ggttgcatgt gaccaggcca ggttttcnca601 tatataccat<210>10<211>467<212>DNA<213>Homo sapiens<400>101 ctgttgttct attttactaa atattagtta ttttccaaat aaattattgg caatgtatgt61 taacaaatat taagttgaca aagtaactta ttgaactatc accatatttt tattcttaat121 aaacttcatc aattacatgg tacatatatg ccattcaaga tcgacattct tttagaatac181 tacagagttg tttccacttt aaagcagaga aaattgaggc acaggatgat tcaatgattt241 gcccctgtcc tcctgccaat aaagggtcaa actggaatca gaagtcagct tttctgatgg301 aggctaactc ctgtaaaatc gcatgtggag aaaggactct tgtgtttgac agtctaaggg361 ccttttctgc ctaatctaag gtctgtttcc ctatatgcag gctgggaggg ggtgattgtg421 cagagggacc cttggagaac tgttacatta tgcaaacttg attatcc<210>11<211>503<212>DNA<213>Homo sapiens<400>111 ttttttttct aaaactacct ttattgtggt tggctcgaca taagatgccg ccatcagcag61 aattataaaa ctgtacagga ggcacaaaaa taggctgttt aacttagata atgaccctca121 tgtcttcaag ctttaaaaat gcacataaaa gttgtacaat ctggcagttt ataaaatata181 aagctaaaaa gaggattttg ggttccacaa agaagactgt atcacacaat taacacgtac241 taattaaaca attaaccatc cacacagaag acataatggc acagaattct taaaaatcac
301 ctaaaaatta acattttacc ccgaccaaat taatcaccct ttaataataa gactactgta361 aagcatccat cccatggaag gntacagtat cacttttcca gttttaaaat gggcaagggg421 tgttggtccn aaacaaatct gatgtggcct taagccagta ccattgtaac tggggtacat481 ttccgngtaa aaatttaatn att<210>12<211>558<212>DNA<213>Homo sapiens<400>121 aagagttttt ttttttttaa ttattccttc atattcaaac ttcacaaaca gtgtgaactt61 gtacaatacc tcggaaagtg aaacttacaa aaaaagtgct ggtaacattt aaaaaaaaaa121 acaacaaaaa ccccaaaaaa acaaacntca ttcttagcaa catcaattac tcttccacac181 aaaacagaaa ccttgtaaaa tttattttcg tatttttaag gcgtaatact tccgtataaa241 gtatatgcaa gagataaaac ttcacagtat tccaaaatgt cacaataata ataataatat301 aatagtataa tgaagcgcta cagttaattt ttcntttttt gaatgttttt ttttctgttt361 aaataacaaa tacaagtcac aggtaaatat acgtgagaaa aatacgaggc taatattaaa421 tggcngggta aggatactgg tcacngtaag aaaaaactgg cagggatgtg tgtaatttag481 nccatatttt aangcccctg gatagaaaag ggcggtatgc caagggtttt tccnaaccaa541 ttttnccggt tgggtggt<210>13<211>582<212>DNA<213>Homo sapiens<400>131 tttttttttt tttttttttt ttttgtttta tataagcttg tattcaaaat aaaccgatat61 tcattacact tacatatttg atagttacaa attataatgt acattataga tacttgcacc121 tacatatgca cataaactgg ctataacttc tttaataatg agattgcctc cgtagagtaa181 atgacacaat aaatgttcaa ctattttgaa tggttgctat ttccatttta tggtcagtaa241 tatgtcttca ttgttttgaa aatgtaggca tttgaaatta agtagtctac agcattcatc301 tgtagtaagt gctaagtatg ttatacatga acaaaaacac ttataaaagc atcttatgca361 ttcctttgaa acaggtgaaa aataacagac ataacttgct ttaaaaagtc ataaaatagc421 tgcttttcta ctgataacat ttttgctttt agcatttcag atgagtattt ttcatatgga481 gaatttataa atgtacagga aacatgttca tttaccaata tttatagacc acataatttt541 gtttgcataa taagtgtaat tgtagatncc attaccatgc ca<210>14<211>617<212>DNA<213>Homo sapiens
<400>141 tacatatttg gtttaccttt agccagttct gtccactctg tctggcaata atttttgctt61 tacattttta tctccagctc tacatgaact aactgaaagt aaaatggtcc agaatttctt121 gtttctgatc agtaattcac atattgatga tgtctgtgta tcctggtatg acttttctga181 tttttaatta taatttttaa ttttaattaa tttttgttta gatagtttat ccctttctaa241 gtaccttgct ttttaaaaag tgtaaacata ttttgcaaca gtcacaccac ttctgcctta301 ttagtaactg tgaaacaaag gacctgcact acgtaaatgc atattagtga atgtgagtaa361 aaggtacaac aatgtctact gggatgagca aataatgata aaccgtctag gcaaatattt421 atcaactttt tattctacat tcaatttaaa aaaataacat tttagtgacc aactaaggaa481 tagccaacan aaattgcacg caaaaagtaa catgaaataa gacattgtgc ataattttgt541 ggaaataatg ctaacgagna aaataggcat accccagctt accctatgnt ttcccttaag601 gtcctttggc ttnattt<210>15<211>660<212>DNA<213>Homo sapiens<400>151 taatttcttt ttctgaggaa caaaattggc catttaaata aagttctttt ctagtgagta61 aagaggtttc tcagagccag aaatcactga aaagagagtc tgtcgaccct gcccatggaa121 aagcccagag atttctctaa ccacttcttg ccaaacttcc tagttttgtg attggatgtt181 tcttggttta gcattgtttg gtgctgaata cattttgcaa ttcttttgtt ctctgcccta241 gagcttccat taccctggac ttcaactcat taccaaatta aagaattctt ttagaagatt301 tcttttaaga gtcaggtcac aacagaaagg gcgccctcct gttctcctaa atctcaaggg361 catctcaggt tgtgtctgct cttacgttgc accttccttt tgttcccttt taatgcagca421 gcacactggg ctatagcaga ggcagacctg atttgattat ctgatacctt ttccacaaaa481 atcatatatc ccctgcttcc aggcccnact aatccaaata acatcttcta gaacaacagg541 ggaaagctcc cagaaagggg tngaaaancc tgtgacttcc tggccagatc caccttgctn601 cctgtcttcc taggggtcna ggtgttggag natgtggagg agccccanca agggagnacc<210>16<211>544<212>DNA<213>Homo sapiens<400>161 atttcataaa gctactttta atatattaac atttattgct cttgagttca aagtatatct61 tattctagcc accaaaacat ttagaaaata gaaaaaaagg taaaaactaa tttttttatc121 tcttatattt cagacactta atacccttac cccattcact gaatccaatt tcattgctat181 ttccttgttt tgtccttttg agtggttcgg gatctgcttc aaatgacaaa gagatgtgag241 taatagggtt caacgtcttt cttattttca gatttaaagc tcttcaatga tgtagctcaa301 aatgaaagtt ctttcaatcc aacaactttg cagagatgct gatccctctc ccaggtgaat361 cctggccagg cctttctnac aaatcctggg gatancctgg ggccagtata gagttcaagg
421 gcagaccaga ctnggggagg ggttcctgan ggacctggaa ccagcatcca ccagcacagt481 cagaattgaa ccccatgtga atccttgtna aaggactggg ccctgaactg gttaganacc541 gtta<210>17<211>543<212>DNA<213>Homo sapiens<400>171 tttaacaatt tatagtcctt ttaatagttt tttttttttt ttcataatac tactgagggg61 aattgttaga tgtattatgt aaggcattct taatttagtt attaaagtta catttttaat121 atttttaaac cttttgtaaa tgctggctta attagaaaat gtttacagaa aagtaaaaaa181 attctagtaa tatgggaaat ccttgtaagc agcatggttt cagaaaaatc tcaagatgat241 ttatttcacc aaatgagtat tttttaaaac taggaactcc ccaaccaaaa acacagactt301 gaataatatt tgtgttatta cctttattgt acattgagca agcacccttg tatagaggaa361 atgcctcttt cctcatctat aatatctata gtatttaggg cctggatgta agagtgtttt421 tattttacna atagttaatg tattaaatat taagttagtt tccctgattt cccttatttg481 gttggcganc atacggggag naattggaaa ggcctatttc caaagaanct atggcactnt541 ttt<210>18<211>590<212>DNA<213>Homo sapiens<400>181 ttaatatttt aaaagcttat tgaatcacaa gcattttttt attttactgt aaaaacatca61 tctttatcag ggagggggga aagtacaaaa ttatgtccct gatatgattc aaccatgtaa121 aatgatgtac atttatgaac gacgactaga agtgaacatg aataactgaa aacaaacagt181 gtgatgcaag tgaatttttg gagggtgaga tggtcattat attgttcttc gagcaattaa241 atattttatt ttcttcccaa aacaatgtcc acaagggggc agacagaaga tgacaaataa301 aaccatttaa taaaaacctc agctgaaaag ctaataactc cagaatgcag gttgaaagca361 agcttaaagg tcatctaggc tggggtcagt agctcacgcc tgcaatccca acaccctggg421 aggcccaggt gagaggaccg ctcgagcccn ggaggtaaag gccgcagcga gctatgaccg481 cgccactgca caccagcctg tgccacaaag taganttcgt cccaaaaaaa aaaaatcctc541 ctagtcntct agtccatntc cccccctggn caagaaggac ngaggcccca<210>19<211>463<212>DNA<213>Homo sapiens<400>19
1 naggtttgaa cngactgtag tantntgtaa atgtgaattt tacaaagcgc tttacaatta61 atgatcacat ccttttgtnt gtcatggatt tccactgtct gaaacggctc tgagcacgct121 tgaagccctc ggtttccctg ttcgcttttg aatgtttcag ttttagttat tgatacaatg181 tcagccatgg ctaaaaagta acagtcttga ctctaccgag taacagcaca aaaacaggag241 tgagggctca ggaaaacaaa acaaaggctt cctccttaaa aaaaagacaa nnaaaaaaag301 ctaagcanct gtgggcttga aatctaactc agtnggtact gttgaaacct tccttttaca361 gcacaggaaa atttattttt taacagtcgt gagttacagt actttaaccc ctaaacagac421 tctttaaaac aaccgtctcc cttttttaaa aggtctcttt ttt<210>20<211>610<212>DNA<213>Homo sapiens<400>201 tttcccaaga ggcagggtgg ctttatttga cattagaaac ccatttaaaa cggcaggtaa61 gagcatgaac aaaagcaaag tttagttcct cgaatgcctg cttttgtaat gcaggtggat121 ctggctctag tctttaaggt tattaattgg aatgaatgcc ccaaggtgct cttagtttct181 ctgtgaagca ttttatatgg gagctctggg gtgactctgg gtccacagtc atgttcacaa241 gccatctctt ccgcagangt gccctgcctt gaaggctgtt ggctgggtcc ccagatattc301 tcagggcaag atctgttgtg ttataaccac ctgccatctg ttggtgcaaa ttttctggat361 tctagatgat gaatcacttt acttctcctg ctgttccttc tggctgccaa gactaattta421 cctattggac tttatgaggg aatatactag agtaacctat catgaaggtt tgtccccatg481 caaagttcct actccatcac tagaaaaggt gggcnagagc ttcccttagc atctccagag541 ggtgggatga agagccagca gtaacaatgt gggatcccca ncttggggtc cctttgcana601 aaaagccaan<210>21<211>543<212>DNA<213>Homo sapiens<400>211 tttttgggag ggggtgccca gcagacacgt tttaatttta ttgcggaagt gatggaagtg61 gttcatcact tacaggttaa ctacacattt gaggtgaatt ttagaccaca gaaacaggaa121 gtagtaaaca tctgtgatga aactttgata cttcaagatg cttgtcttag ggaccaacat181 tctctcagac tagcagatta tttccatggt gaatgagtct tcttattaat ggtgtgtgaa241 ctatatacat gatgactgaa agcagctcat aagataaaat tcatcacctt ttctgaggca301 ctgaggctga gtaaatattg actcacccca gcctctctac tttaaggtga acagatgtgg361 attggctgga gcagaactgt ttgcccctgt ggactcacca tagttatttt catcccccaa421 gtcaggttct taaatcggcc cagtgttgac agaaaaaaaa tgcctcctct cccgggggaa481 caggnataaa cactgggtat aaaaattaaa aggncttatt ctgggacttg ccagcttcan541 ttt
<210>22<211>596<212>DNA<213>Homo sapiens<400>221 ttttttcttc agctccactt gagtaattaa gtgatcatat tgttttcact ttataaaaat61 actattaaga tttgcatctt aatagtatta agatttgcat cttaatagta ttaagattta121 catcttaata gtattaaggt ttccatattt ctacaaaata aatttgtagt ttcatactgt181 ttcctggctc ctctgtggaa tcaggtcatt taaggctact ctgctgttaa aaatgatgtc241 ttaattttta aaagatattc cagattctac tgttactttc ttatttactc ctcacatctc301 agagctggtc atcttcagca aaataatcca aaataatgaa caatcttatc cattttactt361 acaacagaat tcactgaaaa actaaaggaa aatgcactac caggacactg agaagaatat421 gatgcatttc tttatgatgt aaattgaaag cagctggaag ttagctatgt aatgaactcc481 cggaacaaat acatgagcaa ttgagtcnca acgatgtcac ctttacagag tccccataaa541 gttttctcta catgtcatct gcggtcnata caacaggagc gcggccactg agaagg<210>23<211>547<212>DNA<213>Homo sapiens<400>231 tacaagtaac attttactga ggaactggct acatttttct tgttgtaaaa tgaaaacgtt61 tactggaaac atgaaccaca gtgcatgaaa aataaatcag tggataatgc atagagatca121 ctcacttctt catcttctag gaaagcaaag ctggtggcag ggaaatagga aaaagagcag181 ttctctttat cggagtgaaa agaatgagaa cagaagaacc cgcagcctag taggaagagc241 tctcatcatc ctgatttggt ttggaaggct ttacaaaatt ccaagggcat ttccagacta301 gatatttgcc cacaaagtcc tgaccattct caactcattg acccttcttg aaaacagtgt361 tccttcacca atccagtcat ctctgtttta tctgttcatg caacctgtga ctagcaagaa421 tgaatgaaat ccaccataat catgaagttt agcccagagc ttcagtctct tcttggatat481 atggtgcatg tcctctgncc ttcctttggt agaacccatt taaaagggag ncatctagac541 ggtatcc<210>24<211>373<212>DNA<213>Homo sapiens<400>241 ttctgggggt ttattttacc atttacctct gacaggatgg ctgaagagga atcatcctgg61 gagttggtta taatattatt tatttaaaaa tatttatcat ttattaagta cttcttaggt121 gacaagaacc ataagagctt tccatacatt gtttcattca atacttacac aattctaatg181 ttatcnccat ttttcagata ggaaaatgaa gttaatcaga tgttgagctt agatttgaat
241 cgaggactat ttaatgccaa agcttaagat tctttaagtc acacacacac agacacacac301 acacacacac acacgacgtn gtttaaattt gngtttccaa ggaaaaagaa aacatgaact361 atagaaaaga aaa<210>25<211>603<212>DNA<213>Homo sapiens<400>251 tagaaaataa aaactttatt tttttcaagt ttataagata gttcccatta catataacat61 tacggtcacg gattctacag ccacaaatgc ccgcagtcac ataaatatat ccaatccaat121 caatgccttt tcctgctaac agaggcatct gaagttcaga gggagagtcg cattttgagt181 agaagtcgtc cttaatggga gggctcctgt cagtgcatta ggaactagcc aaggagcctt241 gcttgccaga gctgtctgac tcagaggaga ggaagggaca gatggcctgc tgactggggc301 tgaggcagaa cttagatttt ctctcttgtg gtttaagata ttttagaatc tcggaattca361 gatcctatag tgtgaatatc tggggagttc taacttctgg gatgaaaaag gaaaccaatt421 tagtggtaag aaatagaagc ctgcttaaga gggaccctaa ctgcctcctt gaggagtaag481 gagtcagagg aagaccccta agctcaccat tccctggccc agaccattgc tctaccccat541 actcctctcc cctgtgggtc agtgacactg acancatcaa ggagtaacat ctagagccca601 ntg<210>26<211>560<212>DNA<213>Homo sapiens<400>261 gctgatgtcc aagttattta ttaacagagg ggtcatcaca gttgttggtt atattcacag61 actcagctgt gactataaat gctctccaac ctgctcaggg tctttaatga atggaagtgg121 gctttgtgag actaaaaaca atttggaaag ttcatgaaga ttacactgag gccctattga181 gaagctggaa gtgggagcaa taagatggcc ctctgagagc aaaaacatag gagcaatacc241 aggtatagat gggcagacca gcagagatgc ctcatgggac cacaaagcag caaggccatc301 agggttctca gaagaaagag agctggcctg atgtggggga acagggcaag gagagtccct361 gggggatacc attggcagaa cccacacaag cccccggcag ctgggttgca ctcatgggag421 ctggggagaa agagtgttaa anccaaacca ggtcctggcc ctcacaaggn ttggaacagt481 cttagtggga aggtnaccga aaaaccaacc aatccctaga accacttttn catttttcag541 gtggacattc agaccgattc<210>27<211>646<212>DNA<213>Homo sapiens
<400>271 gtatttaaat acttttattt tcatttcaca aaaaaagcaa cagtgtttgc agctacacat61 gcctttcagt cagtgctggt catatgcaaa acaagttatc agaaatataa agaaaaataa121 gccttttccc tttacaagtg aaacaacaca atttgcatat acaatattat atatacatat181 tttcaaaatg tttcacaaaa gacagattat gatacaaatt tataattcca cccacaagct241 cagactcaag gaattgaaga tctctatagg tgtttaaata taaaaatgta atacctttac301 aagtttccaa gtaactactt tccaaagtat ttgaaagagg ctattcttca cagcaacatg361 gaacacttgg ctttaatcaa gacagctgta aaactaagtt ttgtctcaat gtgagtttgt421 tgattaatgc aaatgctcca attatggcct aattctcttt tatatacaca tacatacaca481 gcgtattatt gtactgatgg tttacaagtc caatttctgg agctttcctt cagctaagcc541 agacctttac ttccttgagt attttaaatt aagaacgttc agaaatatcn ctaatgncta601 cnggtgttta cntccaaaaa gggncccttt tcttgatttt tggcaa<210>28<211>616<212>DNA<213>Homo sapiens<400>281 cacgccttca tatttacact ttgcctttac tttacagttc agtgccagaa atatttacag61 aaaatacaat aagaaaaaat catgtcttgg caacatactg aaattcatac aaactgtata121 tatgatttca agcaaataat gatactgctt attttttagc cacaactgcc aagcccttca181 gaggagaaag atgtcttggt cactataaga gatgaggact tgggaaactt ggtttgcttc241 aacaagtatt tactgggcgc ctactatatg caaggcactg tggaatccca aattatacct301 tttccctcac cattaaaaaa agaaaagcat ctgaagaaca tgagttgata ttctgagaaa361 cacactagaa gtacatggct tctttagcta ctaagaaacc caccgtttga ttccacatcg421 tacggataga ccacctccaa tctctccaac tcaggaaaag aggctgtctg gaaatcttaa481 aacagaccat ctgactccaa tgtctttctg taaacacggc atcagttctt tcggnagaga541 gaaccgaatg ggcttaaatg tgatagagac tactgccgca gcntgtcatt anctccatac601 aggttctntt tatgtt<210>29<211>583<212>DNA<213>Homo sapiens<400>291 acatatttac ttttatttac attagtaagg ctgtaaatta tgaatgtaaa tgtgcttagc61 tagaacaaat attgctcaga ataaaaaaga tatacaaata taatgctaat atacaatata121 ggctatcata aaaatttgta tttgtgtaca cacatacata attggctaca ttcgacaatg181 gggttcattt gattcctccg tagtaattag aacaggagac ttaactgatt acagccatga241 tgcggttact taaaaacaca cacacacaca cgcacacagg cacaggcaca cacnngcaca301 ccccacataa ataagtttgg gaaaatttta aattttctca cttaggactt ttcaaagcca361 tctcaaagga gcttcctcaa aacatttaat gttggcatca ccccacaagt actcagaaat
421 aagtgttaaa atagaaatcc aatccagtaa tgggaaactg acttagatta tctatttgtt481 tgtatattta tttgtcatct atctctctta ttcactggct ctattttcaa catctacaat541 agtgctagta atgaatacac agcgtacaca atgtgctaca cat<210>30<211>562<212>DNA<213>Homo sapiens<400>301 tcttaatcca aaatacttta ttatgggtaa tactcattta atatttattg gtaatcactg61 agagccaagg taaagtgatg atccaaatga attgaatgtc atgatttaaa taggcaattc121 tcaaattagg gggtttgggt agaaaaataa tatcaaaaag ttcttgtagt taaaaaaaat181 caatatgctt aacatgccta tttattttct taaactacag aaagcaaatc tcacatgctt241 tgcttgtaag aatatgcaaa aaaagtaaat gctgtattaa ctgaaaaact ctaagtacta301 tattttaatt tcgtgaatga tatgggtgat gtcatataga ctgctatttt cagtacatta361 taaaattacc aaaatgttca attttctacc tttaaaaagt aggaaaatat ccacttggca421 accaaccatc aaattaataa ctgattcnag taaganttat caccatacta aaagtagccg481 atgcnagttg gaagagaaac agcctatatg cagtatctgc ccccaattac ttattatttc541 ccaaagggaa aacnggggtg gt<210>31<211>404<212>DNA<213>Homo sapiens<400>311 tttttttttt tttttttttt tttttttttt tgttccaaaa cgttttaatt atcangaata61 tcataagtca tacaaaaaaa taaagaataa tacaaccaac actcatgcac ctgccatcct121 atagcttaaa catactatat cacatctgac tattacctag tctgtctttc cccaattagt181 gatgcctcta tagtgagatc tataaatgtt ggttctgttt cttttgtttc tgaaactcta241 gaacctgttc agtacatatn gaataaaaaa gcaacttttc actgaaagag aaggataagc301 ggacatcttt caacagcaga aaatgtatat cactgcctgt tccttctcca nccacaaggg361 ctgaggaggg gatgaaggct ggactctcaa tgggggagaa gtca<210>32<211>319<212>DNA<213>Homo sapiens<400>321 tttttttttt tttttttttt tttttttttt ttttttttga cttcctaaat tttttatttt61 aaaaatgccc agtttattta tttgctttgc ctaagatagc tgcattcatt attacagggt121 caggggactt gtaaaaacaa atatcaatta ttataaataa tcncagaaaa caaataaact
181 ggaaaataaa cagcggttac taatttaagg ttttaaccct taccccaacc acccaaaaaa241 agtagccatt tttaaaataa ngattaagag ttggnggaat ttaagggaaa tgccatccng301 gtaatgttac cnaaatact<210>33<211>541<212>DNA<213>Homo sapiens<400>331 gcctgcactt tacctgagag ttaccagaac tgccttgaac atatggatga attaaactac61 ataacacatc acccatcttg attcttacaa gttatagacc tcacagtagg cacttctaca121 gtgccaatag cattagcttt ttgtggggta taactgtgtg ggcttcttta atgaagaatt181 tctcttatac cattaagcag gaatctctca aagttccata acaaagacaa attgagtttt241 gatgtgaatt aagtccatgt gctgaattat caattttaaa gttttcctaa ggtattttga301 atgagcaatt cttataccaa agtgaaataa taaactcaac aaaaagaaat ggtataatac361 ttttcctgag gctcatttta ctgattatgc tgagtccaaa tccatgctca tcaagataac421 attactgtat ttttctggaa aaagcatcta ataagtttta aattattgat aatactggnc481 atacatctct accacactgc tgagcatttc taaagcattt ttaaaaattt ggagataggt541 a<210>34<211>527<212>DNA<213>Homo sapiens<400>341 tgagctttca aattatttat tttaggtttt attgaaactg aacaaacaaa atattattca61 taaatctatt ataagacaga gaaaaactgc tcaattctgg gnggggtgga agtaggaata121 ggggtacagc tctgtccttc gtcattctac ttatgcataa agcatgttct attgaattcc181 ttagagtctg gacagcacag tttgaaaaac cttcagtgaa atacaaagat cactagatta241 gaaatcgaag gatttagaat cccagttctg ctatcagcca gctgtgttac tgaacctcta301 tggtacagat ttcctcacct gttaaataag gagaatgaac taggtctctt tcaggtcaaa361 tatttgagga aaccattagc aactacatgt aaatcnccaa actcctatac tttatttggt421 tcctactgcc aaataagatg tttccngggg taaatccaca tgcccacctc aaagttctaa481 gtgtcnggag atttttcctt taaccctaag aattttaagg nggtcng<210>35<211>848<212>DNA<213>Homo sapiens<400>351 actaattgtg attcccagtt ctgggtgaat aaaaagtttt tgttttaatg taattgtgat
61 caacactatg cttgaagaca tagacaaagc tatttctacc accatgatgt ttacaaaata121 tctggtattt acgcctatat ggccattaaa aaaactagat ttgtggataa caaaccacca181 agttttaatt gtttttattt aataagggag aaataagaca gaaaaagaga attaatactc241 tttttcccag actgagaggc gggcttctaa gtaaaggtat gtgaaaaact gagtagaggc301 ttgtagtact aaaatgaacc tccaaaattt attcttttct ctgaggattt atctcagctt361 ctctgtgtaa ttggatatta acacatctta aattttttaa agagatgggg tctcgctgtg421 ttgctcaggc tggagtgcag tggttactca caggtgcagt catggcacac tgtaacctca481 aactactagg ctcaagcaat cctcttgcct cagcccactg agtagctggg gctatatgca541 tgtacgacca ctggcatgct taaatcttct aaggagcaac acatgtctct actcatttac601 taccattaga tattagatga gtcatttact aatgactgct catggtgtct ctttattctg661 gatatcagat ccattacagc acgccacact aggatttctg cgccacacta cgggggggtg721 gtcgttgttg gtaggtgtgt tcaccacgca ggcccatctt tggaaaaccg cattaagtgt781 ggggacgtct gggtttctcc gtggtcctgg cgtggccttc gttggttaat ccgttcgggc841 cctcgacg<210>36<211>354<212>DNA<213>Homo sapiens<400>361 aaaatgaatg tgaagatact gtttacagct tttgttaatt gcacttttca tcactctgat61 caatttcttg taaagtgcta tgggaattat ttttcctgtg aatattaatg attttactac121 tgcctccgaa gttttaaaaa aggttctgta gacagaaaac agttgttgca accanaaaca181 accaaaaana gaaaaaaagg gaaaactggc ttacctttct cagatgaatt aaatgatttt241 aataacttcc caattaccag ggttataaca ttgctttctt cagttattaa tacagtcaaa301 ttaattttaa caatataggc acaattcatt tacaanttca gtacagtagt ccag<210>37<211>586<212>DNA<213>Homo sapiens<400>371 tttaacataa aaaaataaat ttattttgag tctgaaatac tgaagaacaa gcatacagat61 aaatagtaca aagaacaaaa attagaacat gagtaatgac ttaagacaca ggcatttttc121 tagctattgc ntacagacac atttttacac acaaacatat tttttaaaga catctctcca181 acattctcaa aaggcaagag ctgtatttgt gacatttgta ataaatgcaa cagcttttga241 aacatccagt ttctttccta agtcatttga ttaaaattca cacaagtgat gattacctat301 tccattntct ganngntacg acatacagtc atgtttcgat caacaattga ccacatatga361 cagagatcct ataagattat aatggaactg aaaaattcct atcacctagt gatgccacag421 ccattgttac attggtagca caatgtatta tctgttcnat gtttagatta cacagatacc481 attgtggtta cagttggcct acagtattcn atacngtacc atggcggtac aggtctgtag541 cccngaagcg acggactttg gccatntgcc ccnggtgtgc ngtggg
<210>38<211>498<212>DNA<213>Homo sapiens<400>381 accaaactgt tacatgtggn tggccccagt aagctgacct ggttgccatc ttgagaccag61 acttaaatcc ccaaaaccaa atccacattt caagtatcag tgaacaggta atttttctga121 gaattttgaa aggagttaga agagagcttt tccttggagt cacacaaaat tacttaataa181 aacatcctaa ttagangttt ctgtcctgcc ccctagttcc taaagtcccc tacagaatcc241 agaagccccc tcccacatct ctagggtcct gcctctctcc ttcccttatg ctgagcaaat301 caacttctgg caggcagaga acaaggttga cagatggtac ttgctggata aatacttttc361 tcctgtcaca gtattagggc tcagaaaatg ataccccaaa atatggtgnc ctggcatcct421 gagncacttt gnaccaagga cantggaagg nctcgaagtc aagtctgtct ngatcttctc481 ctgancttct ttctcntg<210>39<211>507<212>DNA<213>Homo sapiens<400>391 attaaatggt gtttggagga aggtcatttc agaaggccca gggcangagn tgagtgtcta61 aaacttctaa tctggacttc tattgaagtt tggcagtaag ttaaacagga agttgaaggc121 taccatatgt aaatccagtt gttgcctgaa atcagtcatt tcaagggagt atcttgaaag181 gacacagact gggaaacagg catgagaaaa aaaaaaggaa gtagacagac atttggctag241 tatgtgcctg gaccacttta acactaaaga ttagaaacct agggctctga gtaagaatca301 tttgaccagt agctaaagtg agtcatggcc tgcacagaac ctagggcaca catgttgaag361 tcaggatgtt gagaacatcc aggcttacct aattttgcca aggccaggga gttgctgctt421 ccagtaaggg aattgtgatc cnggaatttc ncgggctcat tttcccagcc ttttcccaac481 cnggtgcaat caaggtcatc ccgtgta<210>40<211>427<212>DNA<213>Homo sapiens<400>401 cactactgta gttggaagtt aacaaaaaag tctacctcca aggaactggc agagtgtgag61 aactgtttat aaaaacttga gaattttctc aatcttgctt cgtttgcact ttcccctgga121 ttcccacatc tgattttata ttcttccttc cttgtgctgt ttcttctctt ccttctccac181 agctcttcac ccatcattcc tttttttcac tgatccttct ttagcaaatt ctttcactcc241 caaaggtcct gaacacttca taattttaga aatgactgta ttttagaata accaattatc
301 ctgaatgagt tttggttctt ttgcttcatt tataaatcag ctgggtttaa tgttatggtc361 tgccatttaa actttctact aaattaagta cttcttactt taccacaatc agccagcaag421 ccagttc<210>41<211>547<212>DNA<213>Homo sapiens<400>411 tttttttttt tttttttttt tcaggtagta aattttacac atttttattt ttaataatag61 gngtaaatac cttcccacaa caatataatg aacattacag gaaaattaag gcaacttatt121 atttacagaa tgcctttctg ngcaaaacag gacactatac tcttcctaca cattaaagca181 ttaaagatta aaataacnct aaaaggtact tattatcagn gtctttacng aggcaattac241 cagtgttcag ataaataaat gtcagagcta atccaaatat gaaacttgaa attttcccac301 cattctatac aaattcccac agcaaacaga ggaggttatt attttngata ngtcagggaa361 agactttgca gaggaagtaa catttctgag atggagaaaa ctaggagagg aacaggttgg421 agaacaggaa tccaaaagct gtttttgggt caagagatgc ctactagaca ttccaagtgg481 aaatggtaaa gccggtaaag ggttagagct tacngaagng gtccagtcag tgagagcngg541 tttttga<210>42<211>481<212>DNA<213>Homo sapiens<400>421 gatgcaattt tccattaatt atacgtgcac acaaggaagg tggggccagg actactactt61 ttaactttgc agaaagcttc atttttactg tgggttgtgg ttaagttaaa aacatttgac121 tatgccatgt aggcgactcc aacacttcag gaatacaaag ctctgaaaag aggttatgta181 gcaaagctca ttttcattca cattgataat aggtcagaca catttttgaa gaaaaaaatg241 gacagagcgt aaaggataac agagtacaca ttttcatttt ctatgatgaa aaggaatttt301 aaaaattgtc tgttgtacat aaaaactttt tttttaaacc aaacaaccta gaattaaatg361 gagtaaaatg tgagaagccc cccttttttc ctccttcagc agacaaaacc gctgtcaata421 gcttgatatg tgttatcaca gactcttttc tagggtgcac cacgcatata tgctacgtat481 a<210>43<211>472<212>DNA<213>Homo sapiens<400>431 ctactactac taaattcgcg gccctcgact tttttttttt tagaaaaact ataggtggtt
61 ttgacccact acactgattt cataaaacac taacaagttg tgatctgcaa gttaaaaatt121 ccaatatgaa attcctctgt cttcctatta ccctaagatt gctaggtctt cgctaagacc181 tttgttatta tgaatagcag caaacagata catacattat agagccaaca acagagatga241 ataacatagc tcagaatttc aggaaatgga cagaccagaa cttaatgctc ttcaaaaagt301 aaaatataaa gctatcctcc cacgtttagt acggagatct aattaaagta accatcttta361 aatgatactt tcaagtattt tccaaccata gtaggctcaa tagttgtact cttttgtagt421 tgttcccttt ttagttgttc tcatagaaag ggattaattc tgaacaatta gc<210>44<211>340<212>DNA<213>Homo sapiens<400>441 tcgacctcaa tcaagatacg gctcattcca cccttgggca ggagggcaat gctgatgagg61 ctgtttatag cttcggtgcc tgcgcctcca tgttatttag ttgttgttcc tccgctgttt121 ccaaacaagc agtctgtcca aaaaaaaaaa aaggatcaaa tggaaaactt tataaatact181 ccaaatggcg gaaacaggaa gtggaataaa aatgatgtgg ctcttcacag aaaacatgct241 gtcatttttt tttttctctg taaatataca ccattcattt tcagaaagag gctgtgctaa301 cagaagaatt aaaaaaaaaa aaaaaagtcg acgcggccgg<210>45<211>428<212>DNA<213>Homo sapiens<400>451 cgacgccttt tccccttaat tcgcaaaccc ttctttcttt tctttttagc gggctgtttt61 gcctctttat tcactccttc tgctaccatc ttttcctcta ccacatcttc ttcatctgta121 ttagaattaa taggaacaca tcccagaatc ccagaatcac taaaagtgtt gcatcttctg181 ccaggagaga gtgaagaaac tggtacactt agagtacata cactcattct ctttatgtct241 ccacaattcg taccagaatc tgttagtggg tttattactc aagcagaaat acagctgttc301 ctctctactt gcattacctt ttctccagtt tctatgggga atcaaattcc cactggacca361 ataacttcca agccaggtta tttttggagg aaaactgaca gcaatggaga acattcccga421 actctttc<210>46<211>543<212>DNA<213>Homo sapiens<400>461 atatttcaga tataagattt cagttctcag tgagtctaag tgacagaagg aatggagacc61 ctcttgggcc tgcttatcct ttggctgcag ctgcaatggg tgagcagcaa acaggaggtg
121 acgcagattc ctgcagctct gagtgtccca gaaggagaaa acttggttct caactgcagt181 ttcactgata gcgctattta caacctccag tggtttaggc aggaccctgg gaaaggtctc241 acatctctgt tgcttattca gtcaagtcag agagagcaaa caagtggaag acttaatgcc301 tcgctggata aatcatcagg acgtagtact ttatacattg cagcttctca gcctggtgac361 tcagccacct acctctgtgc tgtgagggac aatgacatgc gctttggagc agggaccaga421 ctgacagtaa aaccaaatat ccagaaccct gaccctgccg tgtaccagct gagagactct481 aaatccagtg acaagtctgt ctgcctattc accgattttg attctcaaca aatgtgtcac541 aag<210>47<211>398<212>DNA<213>Homo sapiens<400>471 agtagactta caaatattct atttcgcatt atattcaaga ctaaacatct tccaaaccat61 attcatgaaa tggtttgatg atatgtgctt tggcggtttt caagaaatat caatcaaacc121 gtaattaaat ttcaacgtat cggctaaaca tccactgagc acctcctctt gcagttagca181 ttagactaag tgcttaagga caagtagttt gatgcaataa attaagaaat acatatttaa241 gacttatatt attcacagaa ttcttggcat agttatttaa gttcctcctg ttgagaaact301 tgaggtttgt gttttctttc tttcagtccc aaaagctccg ttttgagttc tccacgcttt361 ggtggaattt caggtattgt ctgtagcagt tctcccca<210>48<211>344<212>DNA<213>Homo sapiens<400>481 aaaaaacatc ataggatact cgacctcact tatactcaag aaatacaaat tgaaatgaat61 actgtttccc acatactgga ttggcaaaga ttataaagat gtgtaaaacc tggtatggac121 attggaaaat caggcattct tgttctgagt tcatttatgc atgcaacaga tagcaactcc181 tgtgttcagg catgtnctaa gcactgggga tacagcactg aacaagaccc ccacctttaa241 agatcatagg ttccaactag gtgaaagctg atagtaaaaa tatatattat ttttgaggga301 ttaagtacat tgaggaaaag caagaaaggt aatggttagg tagg<210>49<211>294<212>DNA<213>Homo sapiens<400>491 gagattttca aaataagtca cttattcctg ttaacatcgc cctttttgtc aataatcaaa61 tcaagcaggt tgtgtttttt tatgtaagan ttccaacaag aagatgtaaa ccaccaattc
121 aggattgttt tcactttctt tttttgagat ggggcctcac tctgtcaccc aggctggagc181 tagagtacag tggtgtgatc tcagcttact gcaaccacct cctgggctca agcaatcctc241 ccacctcagc ctccccagta gctgggacta caggcatgca ccaccattcc cagc<210>50<211>372<212>DNA<213>Homo sapiens<400>501 gaataagata caagtttatt tatctttcat gtaacagtcc agggctaata gagcagttct61 gccatcctca tcacagggct tctgcctctg ggtccaaagt agttgcccca attcctgcca121 tcacatctgc accccagcca gtggagaggg taagagggca agggtaacac atacatattc181 ttttttaggg cacaaactag aaataataca tgcaacttcc gttcacatct cattggcccc241 aaactttgga caaacccaga tgcaagagaa gctggtaaat tagcctttaa ttgagaagcc301 aagcgcccag aaagcaggga gttagagtat acaaggaaag atcattttta tggntatcag361 tctcattcag aa<210>51<211>409<212>DNA<213>Homo sapiens<400>511 aacagtgtta tacaaatgtt aattttttaa ttttaaaagt accatggtta tgangatgtt61 aacattaggg gaagccgggt taagggtata tgggaactct ctgtactaac tttgcaatgc121 ctctgtaaat ctaaaattct tcaaaataaa actaccaaag aaacacaaag aaataaggtt181 ggggctactg tcaacaggat ttgctgatct caccatgtgt ctgttatcta gaagcaagtg241 gctgagtgat aggctgtcct agtaaagacc cagggtggtg ccaggtaggt ggacaccact301 ttgcaaagac taagtgatgt caggnaggtt gctggctgtg ctatgaatgg gacccagaaa361 caacttacag tggttttncc cttcatggct aaaaaacctc aaggttcct<210>52<211>533<212>DNA<213>Homo sapiens<400>521 tttttttttt taggcaaagt gttctttatt atcaataaac acaaaccatt aaagaaaaca61 ttgataaatt cgactttata aaaattaaaa gtttttgctc aacagtatta agagaacaaa121 tataagctgc agtttgggag aaaaacagtg gaaatcacca atatgacaaa gggcatgtgt181 gatagttact tgtacttgtc actgtgaccg agcaccaggg tccacggaca tttggccaaa241 catgattctg gttgtgttcc agagagtctt tcagatacga ttaacattgg gatgggcaga301 ctaagtgaag cagattgccc tccttaatag gggtgggcct catgcaatca atcaagggcc
361 aggagagaat taagaggcct aatgggaaac aaatgctttc ctgggtatcc agctttcctt421 ccatcttggg aatttcagcc tccataatct cagaagcaaa ttcatgtata tatatataca481 cacatataca tttcataggt atgtggctaa gattgtattt ttacaagttc agc<210>53<211>276<212>DNA<213>Homo sapiens<400>531 tttttaaaca aggataggtt ggggaggtgg gaaaagagtg tcaacaggag aaagggggct61 gggaattctg attctctaaa agagatgagt agtcctagaa agagaacagg ggcacgattt121 gcaggcaata aaatgttagt ctgggctcag gagagctgca gttacacagc cccctccatc181 caggaccgtg atgagtagtt cctcgcaggg ctccctggaa acgtgggtag tagatgaaca241 ggcctccaag cagctgctga cataatcatt gtggcg<210>54<211>437<212>DNA<213>Homo sapiens<400>541 ttctattttg cagactttct tttttaaaag caaaataaat tgacatgact tgttcagggt61 taactgtttg gcaggtggat gatctgtggc catccatgat gagatcacct ccctgccccg121 ctggccccca gcctctagaa gtcagggctt ctgaggccca gaagctcagc gccacacctg181 ttgaaggcca gtgatgtcag agttactctt ccttcctcca gcagcactga cagcagttta241 ttgtacgcaa tttctagaac tcagatgttc tagaaggaag caaacatatt ctgagatcac301 agactatgac tatgctctca gaatatgttc tagaacacct aagttgcaat tcttaaaatc361 aacacagcgt aagactgctt taggaggaag tgatcaagct caaagcaacc taggcatgat421 gtgccttgtt tgtttat<210>55<211>432<212>DNA<213>Homo sapiens<400>551 gtttaagagt tttgtattat gtcatacaaa ctgtcttcac atacaagtgc attaaaaaaa61 ttatcccccc ctcctcctcc ccaaacatca cagtagacca attcttgcta atatatgaca121 aagttaaaac atatgtcccc tctgaattct aaacagctaa ttctagacac taacatctgg181 atcttataat ttaccggtct ggtatggaca tgaacagttc cagtgccttt caacttatcc241 ctgaattttt ctcttctcaa agttctaggc agtaatttta atgccctcaa attagataaa301 gctgattact tagagcttat aaattagcta cactttatga cactaagaat agagctatga
361 cttatgcata tcatacctgt caagctacct agcaccacga ataggactaa tattaatgga421 tggactaata ca<210>56<211>529<212>DNA<213>Homo sapiens<400>561 tttttttttt tggccacatg tttattttta taaaatatct agaacaggca aatcatagag61 acagaaaatg gattattgtt tctagaggct gggggaagag gaggattaga gtggcagctc121 actggtatgg agtttctagg tagatggaaa tgttctggaa ttagatagtg gtgatgattg181 cacaactctg taaatatact aaaatccact gcatcattta ctttaaaggg gcaaatttta241 tggcttgtga attacatttc aataaaaaga agatgaggaa acctaggata tgtcacaatc301 ccatgccaca aactacttac acttccaata taaaaactat atcaacaata gtttacatca361 cgttcattgc ttgctaaagt aaggtcatga atgtatcaaa atattttata aaagttaaaa421 tttaggagat ccatcatttc tcttttcaat ccatcactga ttcattcaat atatatttat481 gtgtatgcca ggctcttcat caggtaaagt gtttaggaga gatataaag<210>57<211>399<212>DNA<213>Homo sapiens<400>571 tcgacttttt tttttttttt tttttttttt ttacatcatt tgcctttttt attttgaaat61 gaaaagtctc acatatttat tactgaaccc acccaactga cgtgttcata gcagattcag121 agaaaaaaca tattcccaat aaaacatttc caacactcca gatagtggtg acattttcag181 cttgatatgg taacgcgatt gtaatgctca cacagcataa atatgtgtgc catctcacgt241 gcaattcctt atagaccccg cttcgttctt ctccaatgtc tccttttgga gtcgtacctg301 attttattac cagttttgat ctgaatccac tgggggaatg gaatgatttt gcctttgttt361 cttggccagg tattgcttaa atctgaaagt cccgtgaga<210>58<211>451<212>DNA<213>Homo sapiens<400>581 ttttgtattt tggattattt gcattatata cttactggtt gagcattcca aatctgaaaa61 tctgaaatct tccagtggcc atttcctttg agcatcagtc atgttggtgg gtcagaaagt121 tttggacttt ggagcatttg aatttctgga ttagggatac ccaaactgtg tgtgtgtgtg181 tgtgtgtgtg tgtatcctca tccttttcaa ctcttggaaa atattccaga gtataaataa241 gccacctttt ctttcattgt accctaactt tggaaactca gtctgtttta aattgtttaa
301 aattataatg ttacagcaat ttctgtacat atacctgagt acacatttat tagtattctt361 tgagtttttg agaaatagac tgaatatatt taaaattttg atgatgtcaa ttttcctttc421 aaaaaggccc tatagtcagg tgtggtggct c<210>59<211>493<212>DNA<213>Homo sapiens<400>591 ttggggaaca ggttaaagct tttattttca ggttacagtt tttgatgccc ctttctgcta61 ctccacgggg tacttcaatc atccgcttcc gcacatctct tgactcattt ggcagaagag121 cccccacggg aacccttcgg cttcttttct gacacctcac gtacttgcag cctgaaggcc181 ccgcaggcga cacggttaag tggatgtttg gtggaaccct ccctgggccc acactccgcc241 cctccccagc aggccgcgca acaattccca gggcccaccg aggggtgctt agctcggagg301 agggggagtg acgtcacagc gatgttcaaa acaaggcctc ccctggcccc accatagaaa361 agcaccagga aggggaatgt ggcgagcact ccaggaaatg ctcggattgg ggaccaggtg421 acactgtagg aatgtgtgtg ctgggggatg ggatggtgtc ctaaatatgg gtcaccagga481 gcagaaggag ctc<210>60<211>447<212>DNA<213>Homo sapiens<400>601 ttttttttaa gaaagtattt tatttttgtg tctcaacaga tgaaattcat aaccttgttt61 tctgataaga caattcaaac atacaaatca attacaacaa tgtgcttatc agctcccctc121 ccacccctat attttaatgc aactgacagt tttgaaggac accaagacaa tagggcttag181 ctaaacaata cggcaattaa aaatggccct ctaagaaaat aattacaata gttgttgaaa241 agaatttgtc ctttgagcaa aacagactga aaaggattat catgaaatga ggagaattat301 agcttctctt ccaataaagg agaaaagggg atgtatgtta aaacaatgat acagaaagct361 ggggagtcag actgaaaaca gaaagcccca ggcaataaat gtctccaata aaatgcatcc421 ccttgaagat atccattcaa actcttg<210>61<211>463<212>DNA<213>Homo sapiens<400>611 gctattgtaa atggggtttt ctcttcgatt atatctcttt ttttttaaga ctagtcaagc61 gcagtagtaa caagtggaga aagactagaa caaggagttt aatctataac tgactgaaaa121 gtcaattgag ataactcagt tggacctttg gaccagcctt ccttatacct tctaactcat
181 tattgtttac atttatgaag gcttttgatt tttccatgtt aattttatca tacctattac241 cctattgagt tattttactg agttgggatt ttttaacgac tttattgaga aatcatttac301 atgccataaa attcactgat tttaaatgta ctattcaatg ggttgaagta tatttagaga361 gctgtacagc catcaccaca atgtaatttt agaacagttt catcacccca aaaagaaacc421 tttaggccca ttaggagtta ctccctatcc ctaccccatc tcg<210>62<211>441<212>DNA<213>Homo sapiens<400>621 tcatgatcac acagaacttt tgtatctcct aaagcaaggt taaaaatcct tggattttgc61 ttgcctttta tacatcaata ataatttttt agaaaaactg tatttttaat tatgtcacaa121 aatataaaag tcttcctttg ttgatctcaa aacaaatcct tctaattttt agtttattgt181 tttctttttt tttttttttg agacagggtc tcattctgtc accaaggccg gagcttaata241 gtgtgatctc agtgatcttc ctgtctcatc ctcccaagta gctgggacta caggagcatg301 ccagtttttt ttttcttttc tttttttgta aagacagggt atcaccattg ttacccaggc361 tggtcttaaa ctccaaactc ctgggctcaa gctatccgcc catttctgtc tctcaaaatg421 ctgagattac aggtgcaagc c<210>63<211>481<212>DNA<213>Homo sapiens<400>631 tttttttgag acaaagtctc agcttgtcac ccaggctgga gggcaatggc atgatcttgg61 ctcactaaaa cctccacctc ccaggttcaa gtgatcctct tgcctcagcc tcccgagtag121 ttgggattac aggggcctgc caccatgccc ggctaatgtt tgtgttttta ctagagatgg181 ggtttcatca tgttggccag gcttgtctcg aactcctgac ctcaggtgat ccactcacct241 tggtctccca aagtactggg attacaggca tgagccacca tacccagcct ttttttcttc301 taggtaccag cttttattta tcagattggt ataaatgtta gaaagcgtgc aatgaaatgg361 gcattttcac agtcgtggca gaaagtataa ttatctttga ctttctagaa agcagtctgg421 cattctagaa acttgcctaa cctcttccca tttagacaag atgaattctg acagggccag481 c
權(quán)利要求
1.一類在人類肝臟中表達(dá)的表達(dá)序列標(biāo)簽的序列，其特征在于，它包括(a)SEQ ID No.1～SEQ ID No.63所示的序列；(b)SEQ ID No.1～SEQ ID No.63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.63所示的序列中每條序列有至少70％同源性的序列；(d)上述(a)～(c)中一條或數(shù)條的組合。
2.如權(quán)利要求1所述的表達(dá)序列標(biāo)簽的序列，其特征在于，所述序列包括具有SEQID No.1～SEQ ID No.63所示的序列。
3.一種探針?lè)肿?，其特征在于，所述的探針?lè)肿雍袡?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)明公開了一類在人類肝臟中表達(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(hào)C12Q1/68GK1955293SQ20051003082
公開日2007年5月2日 申請(qǐng)日期2005年10月28日 優(yōu)先權(quán)日2005年10月28日
發(fā)明者黃健, 韓澤廣 申請(qǐng)人:上海人類基因組研究中心