專利名稱:人類肝臟表達(dá)序列標(biāo)簽h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,具體地,涉及一類表達(dá)序列標(biāo)簽,尤其涉及一類人類肝臟表達(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?,F(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(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。這場由病毒引發(fā)的、免疫系統(tǒng)對(duì)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)糖尿病;(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)測序的出現(xiàn),使從質(zhì)?;パa(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(duì)獲得大量信使核糖核酸(mRNA)序列的迫切需要,提出大規(guī)模互補(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(duì)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(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,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)明人類肝臟表達(dá)基因與一些肝臟疾病相關(guān),因此,研究人類肝臟中表達(dá)的表達(dá)序列標(biāo)簽對(duì)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)問題是提供一類人類肝臟表達(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)明提供一類人類肝臟表達(dá)序列標(biāo)簽的序列,其包括(a)SEQ ID No.1~SEQ ID No.50所示的序列;(b)SEQ ID No.1~SEQ ID No.50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.50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.50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。
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??色@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(duì)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(duì)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(duì)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>人類肝臟表達(dá)序列標(biāo)簽H組<130>NP-10042<160>50<210>1<211>544<212>DNA<213>Homo sapiens<400>11 cccctaaaga ggagccagat atctgaattt taaagtaaaa tcccccccta ttttcaaatg61 tgggaaacga atcacattga aacaatagtg aacaactaca cagaagaaga catacctgtg121 gtccttggaa cagaagagca caaactagaa aaagaccaga agtctgctaa ctatccctcc181 cttgggcctc tctggtttat accttcaagc caccccactg ctcagggaac atgactggtg241 gagaagatct agtgatggag gatgattctg acagtcttca gtaaatactg gaggctttag301 tgaaacagtt acttttaaga tttcactgtt aaaaaaaaat catccctgaa ggtagggttc361 ctatgtcttc tggatgagag aaggatgctt tgtgttcggt ctagatgtta actggagagg421 actggatggc cctcttccat taaagggcca gacggccctg ctactttcta tcccatgtgc481 ttggctgaag tgaccagang gagactgggt gaagcactca ctgtggcana ctactganca541 ttcc<210>2<211>491<212>DNA<213>Homo sapiens<400>21 ttcaaatagt agccatccta atatttgtga agtgggaaaa tgaagtttca gccattaaac61 ttatttattt attgtttcct agtggactct attaggaagg cttattatgg aactatctaa121 gggatcctta catagttcca aggaaggggc tgtcacatca aaaagcccaa acatgtgatt181 agagattgga aatttcaaac ccaccccatt cccctaactt cctaggagga gagaagaact241 ggagattaag ttcagtcata tggccantta tttaatcant catgcctaca tantgaaacc301 tcattaaaaa cccggggaca ccatgctcag ggggagcttc ctgatactag gaggggcggg361 cacaccctga ctctgtgggg aggcagaggg ctcctgtgct catggaccct tccagtcctc421 ctcccatggt acctctttca tctgggcntg accatttgta taccntatta atggaatggg
481 gaattgaaat t<210>3<211>348<212>DNA<213>Homo sapiens<400>31 tcgccgtctg cctcccaaag tgctgggatt acaggcgtan nccnacaccc agcccaaaaa61 atgtttgtgc acagaactgt ggatgtttgt cacagaactt tccaaataaa gaagttctga121 taaaagagaa gatatttctc atttccataa tctttaaggt gtgggggata cgtaatctgg181 acttctcaaa tggatgattt ctaaatacgc gtcagatgaa gtgattctaa ctttctctgt241 agtaatatct tattttgttt tattcaaaaa caataaacca tgttggattt atttaggcaa301 aaaaaaaagg ggggggcccg gttaccccat ttcgcccttt agttgagt<210>4<211>431<212>DNA<213>Homo sapiens<400>41 tttttttttg tgagtaaata catttaatat aacaatagta ttataataac agtaattaca61 tatataaagt ctacggttcc cctgtcacac cctcctattg tttgcatagc ttcattgctt121 gtgacacctc agaatggagt caccagggac tccagttgac ctgggcagag atgattcttc181 tcagggaaag tcagggggtg agaaaagagg agaacatggg ctgccaggga gggctggcat241 gggagtgatg tcctgggata cagtgggccc agggatgggg aaagcaccgg aaggagggat301 aacttcccca cctccagggg tatgaaggca agcaatgtgg gctgctctga ctcctgncag361 gagnaaggca ccaagctagg ggagacttag gagattagtg ggttggcagg ggcaatactt421 ntggtncttt a<210>5<211>490<212>DNA<213>Homo sapiens<400>51 tttttcagga gttcattcca gttattttaa tgttatttac tagcagtgtg ccctcgtgca61 cattatcaaa ctcctctgac tcttggaatc ctcatttttc aataataact cacaaagctg121 tcaagcctaa gggttctaac agctcgaaca gcacctggna cagaagcaat agccgccact181 cagaggttac ttcttccttc tccgccttct ctggatcacc tccctacctc atcctcaatc241 taacgntgga aatattggat atgggggtag ggtcaccaaa tgttgccaga agactcaaat
301 tatgccaccc atatctcagc tggggaaggg gcttaccgtg ggcctgactc tcctcagggg361 tccaaggtcc ccatttatgg atgtcccggg gaaggaacac tttgttttct tgacacatag421 taggggccct gggaaaatnt taggtcaaat gaacgagggn ttgggtttgg ggnaagaagg481 ggnaattttg<210>6<211>961<212>DNA<213>Homo sapiens<400>61 aaaaaaaaaa aaaaaaaaac aatgcggggg cggggcagcg gcgacgctgg gtgtgtgggc61 gcaaatggcg gcggcgcacg gcgcctgagc gggccggggc catgagcgcc gcccggcccc121 agttcagcat tgatgatgcc ttcgagctgt ccctggagga cgggggccct gggcccgagt181 ccagcggggt cgcgcgcttt gggccgctgc acttcgagcg tcgggcccgg ttcgaggtgg241 ctgacgagga caagcagtcc cggctgcgct accagaacct ggagaacgat gaggatggag301 cccaggcctc tccggagccg gatgggggag tcggcaccag ggattccagc cgaacttcca361 tccgcagctc ccagtggtcc ttcagcacca tcagcagcag cacccagcgc tcctacaaca421 cctgctgcag ctggacccaa caccctttga tccagaagaa ccgccgagtg gtgctggcct481 ccttcctgct cctgctgctg gggctggtgc tgatcctggt cggcgtggga ctggaggcga541 ccccctctcc aggtgtctcc agcgccatct tcttcgtgcc gggcttcctg ttgttggtgc601 ctggagtcta tcacgtgatc ttcatctact gcgcggtcaa gggccaccgg ggcttccagt661 tcttctacct gccctacttc gagaagtgat cgcggcgcag cgtggacccc ttgcgcccat721 gggggcgccc ctcttgccct gttccgttcc cctcatctca agggaagagg ccctccagga781 ccctcgaaac cccagcccct agggagtttg ctcaggaagt tcggggcatg caggcctggc841 cctgggaaag ccgcccgtcg cctgctctgt gccttaactt attctcgggc cgtgcggctg901 ctaggttgct gttattttgt gctaataaaa gagtaattaa ttccaaaaaa aaaaaaaaaa961 a<210>7<211>1124<212>DNA<213>Homo sapiens<400>71 aaatgcacaa cccggacgga agtgcctctc cgacagcaga tccaggctcg gagctccaga61 cgctgggaca ggccgcccgc agaccacccc cgccgcgcgc gggacacgac gccccccgca121 ggacacgccc atcagcccgg aaacccctga gctgcttctc ccggaggccg atgcccaccc181 gggagccccc aaagactcgc ggctcccggg ggcacctgca tactcacccg cctgggcctg241 ggcccccgct gcagggactg gcgccccgag gcctcaaaac cagcgccccc cgccctccgt301 gccagcccca gccgggaccc cacaaggcaa agaccaagaa gattgtgttt gaggatgagt361 tgctctccca ggccctcctg ggcgccaaga agcctattgg agccatccct aaggggcata
421 agcctaggcc ccacccagtg cccgactatg agcttaagta cccgccagtg agcagtgaga481 gggaacggag ccgctatgtc gcagtgttcc aggaccagta cggagagttc ttggagctcc541 agcacgaggt ggggtgtgca caggcaaagc tcaggcagct ggaggccctg ctgagctccc601 tgcccccacc ccaaagccag aaggaggccc aagttgcagc ccgggtttgg agggagtttg661 agatgaagcg aatggatcct ggcttcctgg acaagcaggc tcgctgccac tacctgaagg721 gtaaactgag gcatctcaag actcagatcc agaaattcga tgaccaagga gacagcgagg781 gctccgtgta cttctaagtg cccctgcaga tgggcagagg gatgcatggg gatgcaggtc841 ccttgcattt cttggtatct ctcagctttt cctcttgcag ctccccctac caggggtcgc901 tttctcctgg attgcaaatg cctcttcagt ttggactcag ctctgacagc ccctcctcca961 ggaaggcctt ccaggacttc ctcctctggg tcctctagct ctgaccctac agggactcca1021 gatctcaacc tgttccctgg aagtagggcc tgctctccat cccagtgaaa taaacatgta1081 ttagacacct aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaa<210>8<211>904<212>DNA<213>Homo sapiens<400>81 gcgaccctct tcttggcgta gagttttcag attgctcttg ggaaccatgc cgaaagtagt61 gtctcggtca gtagtctgct ctgacactcg ggaccgggag gaatatgacg acggcgagaa121 gcccctccat gtttactact gtttgtgcgg ccagatggtc ctagtgctgg actgccagtt181 agagaaattg cccatgaggc cccgggaccg gtcccgtgtg attgatgctg ccaaacatgc241 ccataagttt tgtaacacag aagatgagga gactatgtat ctgcggagac ctgaaggcat301 tgaacgacag tacaggaaga aatgtgcaaa gtgtggactg ccgctcttct accaatccca361 gccaaagaat gctcctgtta ccttcattgt ggatggagca gtagtcaagt ttggccaggg421 ttttgggaaa acgaacatat atactcagaa acaagagcct cctaagaagg tgatgatgac481 caaacggacc aaagacatgg gcaagttcag ttctgtcacc gtgtctacca ttgatgaaga541 ggaagaggag attgaggcta gggaagttgc tgactcatat gcacagaatg ccaaagtgat601 tgaaaaacag ctggagcgca aaggcatgag caagaggcga ctgcaagagc tggctgaatt661 ggaagccaag aaagcgaaaa tgaaggggac cttgattgac aaccagttca aataaccagg721 cctttttcta agccctagac tagaggcaag catttagatc aggaggcaaa gtaatttctt781 gattacatag acggattcct atttatgccc tagcagaagg ctttacgttg tttcccattg841 attctcctac attcagtgag gtctttaact gagtccattt aacttgcttt cttttttttt901 tttt<210>9<211>1188<212>DNA<213>Homo sapiens<400>9
1 gctggcgctg cagctgcaga atggtcggcg gtggcgggaa gcgcaggccc ggcggggagg61 ggccgcagtg tgaaaaaaca actgatgtga agaaaagtaa attctgtgaa gctgatgtct121 ccagtgacct tcgaaaagaa gtagaaaatc attataagct ttctttacct gaagatttct181 atcacttctg gaagttctgt gaagaacttg atcctgaaaa gccatctgat tcactttctg241 caagccttgg acttcaatta gttggtcctt atgatatcct tgctggaaaa cataaaacga301 agaaaaaatc aacaggcctg aattttaacc ttcactggag gttttactat gatcctcctg361 agttccagac cattattatc ggagataata aaactcagta ccacatgggg tatttcaggg421 attctcctga tgaatttcct gtatatgttg gtataaatga agcaaagaaa aattgtataa481 ttgttccaaa tggagataat gtatttgctg cagtcaaatt atttttgacg aaaaaactta541 aagaaataac ggataaaaag aaaatcaatc tcttgaaaaa catagatgaa aaactcacag601 aagcagccag agaattgggg tactcgcttg aacagagaac cgtgaagatg aaacagagag661 ataagaaagt tgtgacaaag acctttcatg gtgcaggctt ggttgttcca gtagataaaa721 atgatgttgg gtaccgagag ctccctgaaa cagatgctga cctcaagaga atttgcaaga781 caatagttga ggctgcaagt gatgaggaga gactaaaagc ttttgctccc attcaggaaa841 tgatgacttt tgtgcagttt gctaatgatg aatgtgatta tggcatgggg cttgaattgg901 gaatggatct cttttgctat ggctcacatt attttcataa agttgctggc cagcttttac961 ctcttgcata taatctgttg aagaggaatc tgtttgcaga aattattgag gagcatctgg1021 caaacagaag tcaagagaac atagaccaac ttgctgcatg agtaaggtgg ctttgattgg1081 tgtacagtat ttcaaaggac tagtattaaa cttgtgattt ttgttttgtt tttaaggaat1141 acaaaaaata aacatttact aaaaacgttt aaaaaaaaaa aaaaaaaa<210>10<211>509<212>DNA<213>Homo sapiens<400>101 tattaattaa cttgacttta ttgatagtta cagcacaatt tattaattaa cttgacttta61 ttgatagtta cagcacaatc tgtccaaaac caccagaata tacattcttt tcaagagctc121 aaatggaaca tttaccacaa aagaccatat tctgggcttc aaaataagcc taaataaata181 caaaagcatt taggacctat gaatcagaag actgaatatg cacatataca aaatgagaat241 cattctctca catacaaaac ttatataggt agtaaagata cagttgatta ggtagatttg301 aatgttgaat cactgacatt tcctgaaggt agagctacaa attacttttt taaatccact361 aacccacccc acttacctca cttactcttt tggcttacac tactttgtca tacctatcag421 tactcagcca aaggcctcat aacaactcgt ataggggtaa tagctatgcc atcctcacat481 tanatcctgg gctgcagttt gcactactg<210>11<211>620<212>DNA<213>Homo sapiens
<400>111 gaaattgtaa gtaaaattac ttttattttc ataaataaaa agacaaccca ttatacactt61 ttagttgaag taacatgtta gttgtcactg cctagtatga aatccatgta atagttaaca121 aacagttaca cctctctata accttcatgc aacttctata catttgataa ttnccccaaa181 aatttcccaa catttccaaa aaaccattat atataatggg gataccttag gtccacaaag241 tggtcaacct ttggctgnag tcaacaaaaa ttatttaata tggctcatgg tcaaagatgc301 ctacctgatg taaaggtaat accaggtatt gctgcatttt acagaagcac tgngcatatt361 acattttcca tttcgtatat ggtagtatca tccccaaaaa tngtcaatgn tgaaaattta421 gtaagtagat taataagcnc aagtacctaa aagaaacagg tcccacagcc acgagtagag481 agctggcatc cagtaccgtt taaagttttg tcngtaagtg gccccnacaa acggaccagt541 gattcggtaa taaggccacc taaatacngg gggtttaaaa gnggttttcc ccggatatgg601 gaataaatta atgnccggng<210>12<211>530<212>DNA<213>Homo sapiens<400>121 agcagtttaa tttggtcctg agaatgttgc agtctttatt accccttttg cattaatcca61 cttttctaac caccttttaa gctttaattt ttaacactat acaccaagtc tttgaaatca121 gtgatctgtt atttaactct aaagcatttg acacttcttg ccttaacagt tttaaaaacc181 acacacaaaa aaactctgta agtaatacag taggccaaaa gtttcatcct atctatcttg241 cagtttacct atctgatctg atctctgtaa ttatagttct gtcatttaaa atatactatt301 taaatctaat ttttacattt caaaaattat cttcagtagt aactaagtat attttctgtg361 gattctgaga atgttatttt tcagaatgng gagaatacat atgnacattt ataatcctgn421 gaccttaaag tcnggtttca gatacagnat ggaaatacct gnaaaaaaat ttggaaaatt481 tggngataat ggagtttccc aaaaaantat tagangcata ggtatagnaa<210>13<211>599<212>DNA<213>Homo sapiens<400>131 taaatatcag tttaccacac aaaaacaaac aaaacaaaaa aacccataca aatcaaaaac61 agcagcagca gcaatgggtt atttgggaat tctcttcaaa taccaatggc atacgattgc121 tgggagaggg tgctttttac tcatgtaaga atatatatat atatatattt ttttaactgt181 acacaattta tagtacatga gggtttccaa aagaacagat tgataagaga tattggccat241 ttctgcataa tttcattctt tttacaatta tctcaaaatg tgaaagctgg atctaattga301 aatgctacat ttagtaggaa aatcagcaaa taacaaagga agcataacct caacataaca361 ttatttgtca ttaaagccag tagaggtccc agatatcttt aggcaagaga ctgggttagg
421 aagaccacta gagtcacaca ctgtccctga ggaccaaggc tagccccctg gaacatacat481 atggctagat tgatcatggg cagtcgatag ccttttttcc aagagcattt ctacagtaca541 gtactttttt gggatattcn gagagacatc atttccagac nccgccatac actgtaccc<210>14<211>437<212>DNA<213>Homo sapiens<400>141 tttctgtgga tgatcaattt taatacaatt atacattcat gctgtggtgg taacaacttt61 cacattattt gtaggactac ttttctcaac tcatgacaaa ggcacaatcc aaaagtataa121 attaacatta caataagttt taaacaaatg tggacaangg accaatctga agtattaaac181 agaaaacatc tgaatatgga tcaacttgaa tatatttnca ttccagaaaa tatttngtct241 tttcaacact gtcncatttn gctatgatgg cagttttgtg tacctggnga cttacnctta301 atacccattc aacatggtaa caattataat tangcattca catactggat agacaaccta361 gatttttaaa tatgtctgat tttttaaaat tatttttaaa tgaattattc tgctaaatgt421 cttacttttc catttcn<210>15<211>496<212>DNA<213>Homo sapiens<400>151 actttctacc atttttattc tgttgtgttg aggccagcat tgcaataaac aagctaaact61 acttacattg gactcatttt cagtaactga catttacagg aatatactag aaacggcact121 aaaaagttta agaaaagtta cggtaaactt gcatgcacat catacagaaa agtaacattt181 taaatataaa aaagaaaaac ttcctggaag cattatgcca gtattaagga acagtgctac241 tctggatgtg acaaattctg tatgtgggtg ttactctttc ccaaaagact gtcagaggcg301 tgagtgctgc aaaagaacaa caacaaaaac aaacacacaa aaaaatgtgt cttacagttt361 gtaagcaaga tgacactgcc caacacaaag aggggtctgg agttcagttc acgcccgaag421 cctggccccc tcgggcctcc aggggtcatt cagagtgttc tcaaatccaa ttccgacaca481 cgacttgtca ctactc<210>16<211>610<212>DNA<213>Homo sapiens<400>16
1 taggtgtgca tgtaataaca aaacacaata gatttccatt agaaccatcc tttaattcaa61 taaattcttt ggatgaactc tgtaaataga ctactgacac atagcactca aaaagtctta121 tgaaccttaa aacacaaagt agtagactgg gtagacatag ggacaataca gctcatcatt181 tcatttttga catgttggac ttcaccatgc aagtaaatta atgcatatat gatattttgt241 tttgttttga gaaagggtct tactgtgtta cccaggctgg aatgcagtgg caatgatctt301 ggctcacagc aaattctgtc tcctgggctc aagtgatcct cccaccccag cctcccaagt361 aggtgggact aagatgcata cctctatgct cagctaattt ttaaactttt ttttggtaga421 gatgaggtct cactatantg ctcaggctgg tcctgaactc tcgaagtggt ggggattaca481 atgtgagccc ccgtgccgaa ttcctnggcc tccgaggggc aaaattcccn atagtgagtc541 gaaggncttt ccggaatcca ggccaagctg gttcccgggg ngaaatggtt atccgntccc601 nattccncac<210>17<211>572<212>DNA<213>Homo sapiens<400>171 agggaagaaa actgagacct agaaaggtga agcggttgtc ccaaaggctt ccagctgctc61 ccagtactca agaacttgga gcacacttgg ggaaatgctc actgttgtat tcccgttcct121 cactatccag gaggcctgaa ctctcaaact ccgaatctga tttccactct cccaggaagg181 cttcggaaat cactgtggat tgtcaataca ggagtccata ctgactgaat ccctaatttt241 ggcctgtatt cttctccctc tgtgaaccat cttcttagaa gtcactgaac caagagtgcc301 agaaaaccat cccaagactc acacagagtt gttcttccat agtggatgtt ttggccactg361 gacatcagaa ccacattttg ggtttgaaga atcttctaca tgtgatgatc cagtaaatga421 tttcatagtc caccaaacgg tcacggttca cacttggaga cacccaatgc aggtctctgc481 tggctgagtg cactggcttg tggctggagg tgagtgctca ggaccacaga gggataaaga541 acctctataa ctcaacaaca acaaaaaaaa aa<210>18<211>583<212>DNA<213>Homo sapiens<400>181 gaaagatttg cctaaagtgt tgatattgaa ctacgcctgt ttacctttaa tcttcttttc61 ttcccttgca gtatctcatc agggttgccc ccagatggga actaagaatg aattttggta121 acttcctagg gatggttgca tgaccttgtt tttttctatg tgttctttaa gcagtgagtt181 ctaggatgta tattcagggg tatcatagta tgtttcccct tttgtggaaa aagtaaaccc241 cttctaggca tagactcaga cacaagaaaa cagctagtac gactgtttac atgatgtctg301 ccttctactg agcagttgtc acctttccca ttgcagtgtt gccttaaccc atctggtgag361 tgccattggt gttaccaaat tcttaaagac cttgtttgga ctttggcctt taaaagtggc
421 cagttctact cttcttagac tgattatgca atttttaaaa ttgcttttca ctctgtactt481 tttccctgtc tctaacttga tgcttactct tggcttttta acaattaggg gaactttcgc541 taaatgacaa tgaagataca cacacccaca cacaaaaaaa aaa<210>19<211>522<212>DNA<213>Homo sapiens<400>191 taacagtgga gtaattttat tcacataggg ttgcgattaa aaggttaact cattcaaaca61 catttttgct atgctaacat tcctttgcct cttattctta caaataaacc cccatcacag121 agcagaaatg ttagaaatta tatcacaaat ggagcacaat aagtattttt aaaacctttt181 aaaatatggc ttataatttt acacagcaag ttacctatta atatgttaca tattaacaga241 tctatttgga caatcagatt tccttgagat taaggatgga gttggcattt ttcctttaag301 aaggcatttt aaggccgggc atggtggctc atgcctgtaa tcccaatact gggaggtccg361 aggcaggcag attcacaagg ttcaggnagt ttcgagacca gccggaccaa cnggtggaat421 tccccatatc tactaaaaat acnaaaantt aggccagggc atagtggtgc nggccgtatn481 ccgctactgg ggggctgagg cnggagatcg ntgaacnggg ag<210>20<211>451<212>DNA<213>Homo sapiens<400>201 tnnttanaga caaggtctca ctgtattgac caggctagtc tcgagctcct ggcctcaagc61 catcctcctg tcttagcctc ccaaagtgct gagattacag gcatgaccca ccatgcctgg121 ccaaagacga tatattgtaa gacctctatc caattttaga aatgctaaaa tattaaaact181 gtgaaactta ggattcagtg aggtcatagt gtacctttat attttatatt tccatcagtc241 atattaaata atgacattat atagaggcat gacattgtca attaagggaa aaggcattat301 ccctaacctc aaataggtta ataacctaat ggggacaaac aggcatatac tggcactgcc361 tccaacttcc ntttcccnat ctttggaaca cccncaaaac cttaacaccc tggnaaaacc421 catcttgtaa nagggtcccc gttgnccccg t<210>21<211>525<212>DNA<213>Homo sapiens<400>21
1 tttttttttt ttttttttca ggtatgcatg attttattta aaatgtgtcc aataagactt61 gccacttgga atgaacattt ttacttcttt cctcatatta ttagaaacag tatttcctca121 tttcatggag tttcttagaa agttctaagt attaacagaa gagaaaaatg aaaccgtggg181 ggagattaaa taacaggaag tttacaccac agcaagggtg ctcacccatc ccantttcgg241 gggacacaca agtgactatt gggtgaaata gacccgatca tgcaaatcat cgtatgatca301 cttgggtatc ctttgggcag ttctgacatt cattgtcact aggcacagat attaaaatga361 ggtcaggatg actgcagtga ntgggggaaa tccatctttt gcttttgggt gggtgggaga421 ggaaggacag gggacacaaa gggcgcggcc taggggccct ttttccccaa catccggacg481 aganttttcg cagcttgacc cttcctttgn tttgaggccc ngagg<210>22<211>459<212>DNA<213>Homo sapiens<400>221 ctagtttgtg tagtaatttt actgcataag aaattacaga gattgcataa atcattaggt61 caacagcata cagagaagaa caaaacaaaa cattgtttgg atcaaataaa aaacagcagg121 aacaactcaa ttcttaaaaa taccacgaat tccccgaatg tggctccatt tgatagaaaa181 ttttgcattt tctggataat gtctgtagtt acattaagca aaatggaaaa cggcttcaga241 taaacacact aaaaagcagc ttacacagat gtgttgccct cttcaccttg gatgtaacaa301 aaataaagat gtgaggctgc ctgctcttgc ctaaagcatg gcttgaactt tcaattgata361 gtaaccgctt atgaaaatat tacattacat aatctcctgt gtattgaatt gcacaagtca421 gggcatccaa aacctcgtgc cgaattcctg cagccgggg<210>23<211>714<212>DNA<213>Homo sapiens<400>231 tttttttttt tttttaaaaa ggaaatgtta atggaatttg gatacatttc cacttatttg61 gtatatggct ttattttcag ttttatttta caaacactta catggtctta ctatgtgcca121 agtactgggt tccaaacgtt ttataaatat gaatgtattt catcctcata actctgtgaa181 gtggatacta ctgttatctc cattttacac aggtacagag aggttaggta acttacctaa241 ggtctttcag ttaaaaatgg cagtcgggat ttgaatcttg ccagtctggc ttcagagtct301 gtgatcttta tttatttttc aagagatagg gtcttgctgt gttgcccaag ctggagtaca361 gtgttagtca caggcatgat cccattactg gtgagcatgg gagttttgac ttgctccatt421 tctgacctga gccgcttcac acctccttag gtaacatggt ggtccctggc tcttgtgggg481 tcaccatatt gatgccaaac tgaggacacc caacgctcgt tgcgtgctac agccaagaac
541 tcctgggctc aagtgattct cctgcttcgg cttcactagt agctaggaca ataggcctgc601 accaccaagc caagccagag tctgtgatct aaccattcta ttatgccacc tttcccanag661 atgtttacag tttttcttaa actgtaccag tgtagaaaat aaaaatttgt ggag<210>24<211>871<212>DNA<213>Homo sapiens<400>241 ggaggaaaag agggattttt ctccctttta tcagaacaaa gagccctcgg tggtcttggc61 aggagacgct tgggaaaaat gggtacaatc tccagggatt gaaagtgtat ggacctgtag121 gatgggccac aggttctcag gaaccaccac ggctgctgag gtctgagtca tacaggcttc181 cccgggaagg actggcagag ccccacacag ggtggttctg tctgtggatc aatggtaaag241 caggatggct ctgccctgct gttcttactg gtccacaccc tgttctccac accagctccc301 agaaaagtag ctgtcctccc tgctgaagtg acagtgcttg gtgcctttct ccgagaagag361 gcagatctga ggaccgaact ggcaggagga tgcccatggc tcttcccaaa ggtctgagga421 tagaaaatct gtttcttcct ctttcctcct ccttgcaacg agtatggctc agggaactga481 gcctcaaccc attgaatact gcactgatta tccggaagca gaacagagag ggttggggtg541 tgactgcact catgaagagg caggaggaag ccagggacac tggcatcctc tgctgcctga601 ctcttgtcct gcgtgtaaca gttttctaca atcagctctg gcctgtggcc tgtgctcaca661 cactcttgct cacaacaacc tcaatgactt ggatgctatt attattattc ccattttgga721 gatgcagaaa caggcacaga gcggttctca tgtctcacat ggggtgaccc cttggggtgt781 gagaagtgcc naaaccaagg aaaagggagc ccaagcggtc agctccagaa ccctgtgcct841 cttacccacc actaccannn ncaaccctgg g<210>25<211>694<212>DNA<213>Homo sapiens<400>251 tttttttttt ttttttttgc agcttccact ctttatttcc aaagaatcag tgtcacacat61 gcagatcaca aagcgggtct ccctgtgctg cttccttctg tgttttctag tctctccccc121 aggggctgcc cagggccctc aggaactgag tgtgggcaag acactgctgg gccagagggc181 acgacgccca cgtgggcccg tattgcccag gccatttggc agtgcagagc ccccccagcc241 tccagcagga gccccctggc atgagctctc ccctcagggg tcctgagcaa cgtccctgcc301 agggctggtg ggtggcagcg ggggggcaga cacctcgctg aggtcctgca gcagagcttg361 cagccgctgc aggctggggt gcacgttttc ctccagccac tcctccacgg catccgggta421 gaaagccagc tgcagggcag cctccagctc ctgcacgagg gtgctccact gtgccaggag
481 gctgagcgct gcgggctgga tgtgctgaac catgaccggg tggatgagct tccgctggcg541 gtggtagggg ctgaaccagc cagtgacata cctgttgccc tccagcagcg catccacaga601 gctgcgcaga tggaggctga cttgtgtgac aagggcaagg atgttgctgc cagggaagga661 gccggccccc tccctaacag ggtccgtttt ttcc<210>26<211>594<212>DNA<213>Homo sapiens<400>261 cggcggacta ctggccatgg agccgcgcac aggggacgcc gcggacccta gggggagcag61 aggaggccgc ggccctcccc gctcgcgggc cctagcgccc ggcagctcct ggcgcggttg121 gacgcgcgcc ccctggcggc gcgagctgcg gtcgacgtgg cagcgctggt acgcagggcg181 ggcgccacat tgcgcctgcg ccggaaggag gctgttagcg tgctggactc tgcggacata241 gaggtcacag acagtcgcct gcctcatgcc actattgtgg atcaccggcc ccaggtcggg301 gacctcgtgc tccacatcaa cggagagtca acgcagggcc tcacccatgc ccaggccgtg361 gagcggatcc gagctggagg cccccagctc cacctggtta ttcgtcggcc tctggagacc421 caccctggca agcctcgagg ggtgggagag ccccgaaaag gagttgatcg cagcccagat481 cctggagggc cggaggtaac ggggtctcgc agcagcagca cttccctagt tcagcaccct541 ccatcccgga cgacgctcaa gaagacccgt ggcagcccgg agcctagtcc agag<210>27<211>628<212>DNA<213>Homo sapiens<400>271 gtaaagacag cagttctgcc catgtcccgt tcccaggcag ccagggcctg ggtttgaata61 attgcagggc cagcctgcca tgatctttct cacttactcc tctcccattc agcaatcaac121 cagactaagg agttttgatc cctagtgatt acagccctga agaaaattaa atctgaatta181 attttacatg gccttcgtga tctttctgct gttcttactt tttcgaatgt agttgggggg241 tgggagggac aggttatggt atttaaagag aataaacatt tgcacataca tgtattgtac301 aacagtaaga tcctctgtta aaaccagctg tcctgttctc catctccatt tcttcccatg361 ctgtaacccc aggctccacc agctgttccc cagtgatgtt acctagcttc cctctaccgt421 tgtctactga ccatttccac tacatgcctt tcctaccttc ccttcacaac caatcaagtg481 aatacttgat tattatctct tccttactgt gctttatctt tttgtttgga ttggttctaa541 ttaatgaaaa taaaagtttc taaatttaca tttttatagg gtattgtaaa taaaaacaaa601 tgtatacttt acaaaacaaa aaaaaaaa
<210>28<211>728<212>DNA<213>Homo sapiens<400>281 ggtggagagg attttagacc tctttgagca tctgaaaaaa ggctatatat gtatggtttt61 ctcttcagaa aaatcttaag actcacaata cggggacttc cttgttacca ggaagatttt121 ctggcaattc ctagttaata aatcttattc taatggaaca tacattgatc ttgagttaat181 gcgtggttga aaaaaaaagc gggggcaact tgaaatatat gcagtaaagt agtccatgca241 tacaagtccc taacatggta gatgatgttg cctcccggcc ctgctcagaa agaatacaaa301 aagtgtacat tcctttttct ataatttaag aagtctggaa tacagagtgt aacactgtgt361 actgctagca cccaaagtgg aaaatcttaa gcattcagat tgtttagtca aagaagaaaa421 ccagaagggc agttgcctat tgaggtgatt ttaaacctgt ttatttgtaa ggattaagta481 ccctaatagg cttaaactat gatagaggtt taatacagaa aaaattgaca ggtattataa541 attgtggatc cagttacttg cttatttaat ttgtaaagag gtaaaattag ctctggttga601 gatatcaagt atggcaggta tttgagaagg ctataaatca taattttcat ttagttaaaa661 tatggacctg attctgggaa nacctatcat tccatctcaa tgtttacaat aaaataaaac721 taagtgaa<210>29<211>857<212>DNA<213>Homo sapiens<400>291 agcgcacctt tccgcgggcc gcggggatgg cggcgcaggc ggtagggcct gggccggggt61 cggcggcgcc cccggggctg gaggcggccc ggcagaagct ggcgctgcgg cggaagaagg121 tgctgagcac cgaggagatg gagctgtacg agctggcgca ggcggcgggc ggcgctatcg181 accccgacgt gttcaagatc ctggtggacc tgctgaagct gaacgtggcc cccctcgccg241 tcttccagat gctcaagtcc atgtgtgccg ggcagaggct agcgagcgag ccccaggacc301 ctgcggccgt gtctctgccc acgtcgagcg tgcccgagac ccgagggaga aacaaaggca361 gcgctgcctc gggggagcat tggccctggc ggaacgcagc agccgcgaag gatccagcca421 gaggatgcca cgccagccca gcgctaccag gctgcccaag gggggcgggc ctgggaagag481 ccctacacgg ggcagcacct aggatggggc agagacttgt tgcatctttg tccccagcaa541 aggctacatg ttacctcctt caattgataa taaacctttc tgagatgcag agggtccagg601 gtcaaacaag acacaagaca cacaaaccag caccaacaca gcgagcaacc aacaacgaca661 cagacacaca gcacaacaca cgacgagggt gacaacacag aacagccgag cacagcagga721 cgagacaaaa caaaaagggg gcgaccaaaa ataaccacgg ggagagcgaa aagacacgac781 ccagtgtgaa agaggcccac agaaacggga caagacagag cggggcaaac aggggcggaa841 aagcgggggt gagaaac
<210>30<211>546<212>DNA<213>Homo sapiens<400>301 gactgacagg acaaggttta ttgggggtcc tggaaacact ggggagaggg acgagggggc61 aaggtcgagg ctcacagggg caccccctag ccaaatgccc ccttccccta gggattggga121 ggaagacaga gacagacaaa ccaacagaga tggagagaaa gaccaacgga tgctacggag181 agagggaagg aaaccccagt gtccaccacc tcccactcag atgagttcac aggataaaga241 attgcgtgga ccggtccaca cgctacagga aaagagagga gtgtccgccc tattcactct301 aaggaaggtg gcaggccaca gcctagacca gcccattcca tgtgatgggn ggtgtgtgca361 catagatcag tccattctac tgggcaaggg gatttcaggc cagtctattc tagtgtttgg421 ggcggggaag atcgttaggg tcgatccatt ccacagtcgg ggagggggga ttcgagggca481 gggggcatct accctggtcc ctctttcagc acagggaatg aaaaagggga aaggcagatt541 tcggct<210>31<211>721<212>DNA<213>Homo sapiens<400>311 caatctgtat caaaggttta tttggaagct tctgagtatg agggttcttg cattaaatga61 ggattcaagg ggggaggaaa aaagtgtgct tgtcagtttg gaaagtcaca gggagtttac121 cattctataa ttagattagg aggaaaatga gaacccactg gtagaagaag aagcaacagt181 cttctagggt ctggcatttg atgagatagg tattcagtta ctgtgcattt ccattgtttt241 tccatggcag aacatacggc agagatttgg gaactcgcat gcctgaagcc aggttattct301 tatgttctgt aactatgttg ctcgcagggc tgttgttgtc agagtagtga gttgtgcccc361 agacaaatgg ggtgctggtc tgctcccaca aatctttatc ccagtcttca tcgcaaggag421 ggcactgcca agtgctctca gccagagtct cttgtctaag gctcctggtt tggttgacaa481 catcttgctc aatacaactt ctgtcatcac agcttgagat atgatgacta atttcagctc541 gaggaacctg gtggcgagca ttgaagggac aagtagccaa ttttctttga acatcagggt601 gattctttct gcacttgatt agatgattaa ggaaccttgc agccctgatt tgatggtttt661 tgtcttgggg gcatttccat gctttctcag ggtccaggga gtcggtggta ttttcttcca721 t<210>32<211>640<212>DNA
<213>Homo sapiens<400>321 gatcgtttga aaattgaagc aaaaaatggg acattgagtg tatccgacac caccgttggc61 agcaaacaat tgacattcac gttaaagagg tctgaacagc agaagaagca acaggaggct121 gagaaactgc atcgacaaga aaggaaaaga ctccgtcgtt cggccggaca cctgaagtca181 agacacaaaa gaggacggtc gtttcattga tttgggaagt ggtcctacct gtgattaggg241 aggggtacgt ctcccccaaa ctgatcatcg ttagggtgtt aaacacagac gaggaaacac301 acgtttttaa agttcatgta cgttcttgta cacagaggta aagatttgaa aacctgtgcc361 ttgtgggttg gactttgaag ctggccccgc cgacggccac cgcacagccc caggggtgtg421 cttgcgagtc gttgctccct ggaaacattg tcctttcccc acggctttaa tcatgaaaac481 caggctgggg tttttttaat attgtgaaat gtacaccatg aaatgaaagg tttatcctgt541 gccagaaacc aaggtttatc atgctctagg aacttttttc ttacactgcc taccgncatt601 catgattaaa ccatccagaa ataccaaaaa aaaaacaaaa<210>33<211>942<212>DNA<213>Homo sapiens<400>331 ggaggttgca gtgagccgag atcacgccac tgcactccag cctgggcaac aagagtgaaa61 ctccgtctca aaaaaaaaaa aaagaaagaa aaacggcttg caggggactt gagaaaacaa121 tggggtgaga aaaggttgtg gtaaaaggat gtgtttatat tctgaatttc tgaattctgg181 gctatggcat tcttgacaat ttttcttaaa accagagagt gaaaggcata ttataaaaca241 atcaaatatc ttttagagta tggacaacta ttatatatca ataaaaaatt aattagaaaa301 aatatatctt ttagagaaca caccacctta tcccacccat gatatatgga tgtgtgatgg361 agaaagatta tttaactatt tttttaaatg tgtaaagcag cagggcatag ggggcttacg421 cctgtaatcc caacacttgg ggaagctgag gtggggagga tcaccttagg tcaggagttc481 aagaccagcc tgccaaccaa catggtgaaa ccccatctct actaaaaata caaaatttag541 ccagccatgg gggcacatgc ctgtagcccc cagctagtcg ggaggctgag gcggaaaatc601 acttgagcct gggagggtga ggttgcagtc aatgagattg agcatgatgg tattcagccg661 gggggaagct aattctgttc aaaatttaat aataatagtt agttactaat aattactaag721 gtttagacct ggttgggaat gagggaattg cggtttgttt acagggcggt aagaaaattg781 gcttggaagg gggaaaggat attcaattgg aaatatttct tggggaattt agaccattca841 agacaaatgg gggggatccc gaagaaatga gcgcaaaaga agagggaaac aatggtggac901 ccaaaaggaa agacacgcaa aaaagggaaa ctatgcggac tc<210>34<211>583
<212>DNA<213>Homo sapiens<400>341 ttttacattc tggaatcatt tattaatcca actggttact tttgaagagt tttatggtta61 gactaatata taacaaattg ccaatcgtta caggtattac agagaaccca gcaggcccct121 acgggcagag aacagataaa gagcttatag actggttgcg gctgcaagga gctgatgcaa181 agacaattga aaaggtaaat ttacaacaaa gaaattctta tgctgttgtt acacagctgc241 tcagctctta aggatctgat ctttgtttca gattgttgaa gagggttata cactttcgga301 tattcttaat gagatcacta aggaagatct aagatacctt cgactacggt aagagcctca361 aaacagtttg tataagagaa tacaactttt tatgtgtgaa tatgcttcaa gagcagaaaa421 caaagggctg ggcctccccc caaactctgg agttctatta ggttcaagct gggaaaaagc481 caaggtgggg cagaaactga aagccaggca gaagtcagaa ataggaatgt gacagagaag541 agctggccaa tctcctgcca ttaatgcctg gctgggagtg ggt<210>35<211>604<212>DNA<213>Homo sapiens<400>351 cttttttttt ttttttacta gtaagacatt tattaatgat attattacaa ttgtttctaa61 aatccattat tatttcagca gcgaagagat aaataccaga gtaacctcag tcagatggta121 acagttaggt ctaaagaaaa ttatatgaaa tactgactgt aatactgcta tagagtatac181 agtatgttaa aacatgatgg agaggctgca cacattggta acgttttatg tcattaaaaa241 aatcactgaa aatttaaaaa tgatgtttgc atttaagtgt atattagaaa agttttattt301 ttaaagttaa ttctgtatca ttcttctaaa aaaattatca tctgtaagat gcagatttgt361 attgtttata tcaagtgata tttgcattta tgtaaatata atttaagaca gttaaatata421 aattcatgtt tatcttcata taaaaatata tataaaaata gagtatttaa aggaggtgga481 tattcataca aaagaactga tcaatcaaaa taggtgtttt tttcttgtat ggtagtgaaa541 atgaggtatt tatacatttg gtaatttcag ccatgtattg aattaaccct ttcagcttcc601 cacc<210>36<211>761<212>DNA<213>Homo sapiens<400>361 aactgttttt ttcaagagct ctcatgatat ttgagccttg acaacagttc tatataaatt
61 cacttgtaaa tgctgctgtg tgtaattcta aatattttct aagataattt gaaagcaagg121 gaaatagtgg ccccttaatg agtatttttt tatcggggtg gggaaagggg caaaaagaat181 gatcttagtg tctttacctt tctcatatta actcacctct ttattcttgt ggtcttttct241 gaatagaaat gtatgcccta ggaagaaatc atgctgggtt tgcttttaga gataaaaggt301 ggtggattta tttgcctgca gtaaagattc tcagggtgtc agagcagcat atgtcaaatc361 ctgcttctgt tttatgtttc agtgtattca ctttcatttt cttacttact agaccatttc421 tgcagttggc ccaaacctct actgttggga cagtaagcca aatacctcat ttttaaaaag481 aagtcttcat ggcatcagtg ttaataaagt acatttttaa ctgagtctta atctctattt541 gaagaaaaag tagagaccaa aagttatgtc aatgtaatnc ccaggatcat gaaatgttta601 caaataaata agtaggagag tcgtgctgtc tagaaaaaaa aaataacaaa aaaacaaatt661 ttggggggcg tcgtggctga aagtttttaa caatctgtgg ggggggccaa ggttatggaa721 cggcaaggtc caaactggaa aagggggggt ttccaaaaag g<210>37<211>750<212>DNA<213>Homo sapiens<400>371 ctgcccattg tgtaatttat agttgacatg atgtgttgtt ttaaaaaaaa atgcatagta61 taaacccatt aaggatctgg gaaaagagaa gaagtttaat atagaactaa gcttttaaag121 ttgttttgtt tttaattctg gtctcggtgc aaatgttagt tatgccttat tcatatcaca181 gttagatcac catgctgcaa catggtttat attcatgctg ccctagaaac tttgtaatta241 tttgttgcaa atttgtgact gtccttatta actttctttt atgtaagtaa ttggtaaaag301 tttcttaaaa ttttgggctt tggcttattt aattttggaa taaacaggct aaaattccta361 ataaaaaaca ataaaaaaca aaaaataaaa aaaaacaaga aacacaaaac aacaaaaaaa421 aaaaacaaaa aacaaaaaca caaaaacaga acaaacaaaa aaaaaagagt cggggaggcc481 gacgaccccc acccacaaga agtaattgac caaacaacca acaacgataa aaaaacgaga541 ggcccgacgt actgatatgg tactagaaga agtatatata gcatcacacc tgggaggggg601 cggtcgcacc aaataaggag tagacccccc aaacaaaaaa atcgcgcgga gccagcgtat661 gtgaaggagc actcagcaaa aatacgcaac ggggacaatg atatccacga cgattatatc721 acgcgtgtaa ataaagacgg cgattatcgg<210>38<211>676<212>DNA<213>Homo sapiens<400>381 ggagcagtca aagtcttagc tatcaagagt gtgaatttga atcatggcac taggtcaggg
61 gtgctatgga ttgaaatgac cttagttctc aaggagtgat ttgtcctcat ttgtcaaatg121 aggaatgaga cacttaccat catctcaggt tgtttcttaa agacctaaat acaaatacaa181 ttgttaaaaa cttacagagg gcctatttga atgctttaag atgtaggcca agtaatgtat241 ttttctctta gtgtagaaag ttaagagaaa aagagctggt accataaatt ttttcaatct301 tagtgtaaaa tctgtatctc attgtaggct tctggtcaat acctatacat aacaacttaa361 tgtgatctaa ccaactcaac tgatagaaag ctgaattgtt cccagtggac aagtggtatt421 tgatgtttag caggtttttt tgtgttattt tttggtaaac tctgtggtaa aatctaaaat481 aatgttaaaa ccctaaaagt aactattgaa tattctgtaa tcttagacat gtatttttca541 agctaaccct ttgaagaaat gtgttcaagg taggaaaata taaaattttg gttatttgta601 aatccaaaaa aaaaaaaaaa aatttttggg ggcctgggcc tgaaagtttc taaccattgg661 tggggggggg cccagg<210>39<211>763<212>DNA<213>Homo sapiens<400>391 agcaagagaa acaaaatttg ttttcaagac atttccactg cagtttcaag ctgtagtggg61 catatgcttc atttacttcc aaagaggcaa aagcagctgg aatggcttac agcacatgct121 tgtttcatgt tatgggtgag gacctacata cactcttact ttagcagtca cttaaccttc181 tccagcaagg cagttgtggg gttcactagg atttagtgcc tgatcttttt ttgggaaggg241 gcgggaatga atgtgtgggg ctgggaggga agcagaagaa aatgggagtg tgagtgagtg301 tgcatgtgtc tgaagttcac cattgccccc acctgcacct agcaaggaac aggtgtttga361 tgtatttgct catgactgca gtatgcatgt atttttttcc ttctctgtgt tttctaaact421 tacactaaag gattcatcaa atcatcttgt tcagatggct caggatgtat ttatttgctt481 accccgtgct ctttgggttc tatagtattt ctataattat gtaacgagaa taggtgttgc541 actgtaatct atcatataga gctatatgta tggaaaattt ggatcaaatt ttttaagaaa601 tgtatcctgt ttgaaaggca cagtaaagtg gcatcttata gactataggc aataaaggta661 caataaactt tattaacaaa caatcatatc tctggtcttg gttggaaaag tagctattca721 gagttcggga atcttactta agatttgtta ttatttaatt ggg<210>40<211>526<212>DNA<213>Homo sapiens<400>401 ccgggcacca agggttttat tcgagtccaa tttttatccg cactgcggag aaagagggag61 gggggacata gagaaagcgg ggaacccgga ccagacccca gacccctccc cccactggag
121 cccggggcat ctgcctggtt gggccaagga agacttcatg agatccctga gggccccagg181 aggagggggc tgggagcagc agaagaggac tgggggccac cgcttcccca tcgacgcccc241 aggccagggc cctcagtctc tttcctcccc tcccttctga gggctgtagc ctccatctct301 acagaggctc ggctggccat gaccccatca gacccccaag gtactccctt gtcaggtcca361 aagcacatgt tatcctatgc ctgtgaccct gggctgccat ccagcccacg tcccagacca421 caggcacacg ctgccctcct cttgggtggg gctgggggca ctgctgacct gtcagctgct481 ccctccccag ggacccgtct ccactccctg ggggctactc agtcag<210>41<211>545<212>DNA<213>Homo sapiens<400>411 tttaaattta aaaagatgtc ctcactgcac aagtgactac gggctacagg caaggatggg61 agacggaggc ttcaacacaa ctcattgcac ttagaaccgt tactaaccga aacaccattt121 gcttgtcaac aatgtaccct tgacagcagg gagaaacttc tttatagtct ctgcttcaga181 caagatttac agctttctcc aaggccagag gccaattgtg accacaagtc ttgtttcttg241 tccaccagac ccaatcctct ggcaccttgt accccccgtt cctcagcaat atgctcggcc301 taggttccag aggcagctgg aaggaagcag ctatgggctc attcagttct gtttgcccaa361 atccagaagc cctaggaaag tcccgtctga gtcttgactc ctgacccttg cagtggctgg421 agtcggtact ggtgcacacc cccactccca cggtgtgggt agtgctgtga attggaaacc481 gcagataccc tggaggcctg gtagacagct gactgcccag cactgggcag actgatagtc541 cgtaa<210>42<211>489<212>DNA<213>Homo sapiens<400>421 tttttttttt tttttctcaa tattcaatat atattgaagt ggaaattttt aaacctagtg61 tttcctgaag catttaacat accaatttca ttattcccct cacgaatcta gtccatttaa121 atgtcgatgt tcaagggtag ggggtttata acttaagtaa ttaaatttct ttaaatatct181 tgatgtaact ttataaattt aacataacca gtgttcttaa gtttataaat actcatccta241 aaaagcagga ctttcctggg ttcctaaata gttcttgaaa tttaataagc tgataaatat301 gatgactatt agttctctga aacatttcaa aacttacaaa cttggctgaa tccacttccg361 gtgttctgct taaaatcata agcttaaaat cagctactca attacccgtt ttaaatgggg421 attggaaggc caatctgtta gatactctga tacgcctaat tctccttaac atgacaaatg481 tgtgaaatt
<210>43<211>524<212>DNA<213>Homo sapiens<400>431 cggccgccat gtttcctgaa cacaaaatgg cgacacgtgg ttagcattcg tcgccaacga61 gaaattgggg tcggcccgaa agctctagaa tgcacccctc ttcctccccg gggccttcca121 cctccgcgag ttttatgact taaaaaagcc cacaggctgg tctgaaggtc ggaggcctaa181 ttttaacgcg ttttcctccc tttaatttga aacgggaacg cgaatgactg taaaatgtgg241 gcacaatatt taatctctcg cctttttaaa gcttaatagt ggataatagg ggggcagtat301 caagggataa tttgggtccc cacagtacca aagcatttag aaacctctgt ttaatttaag361 gaatgagata agttactgct tttctagact tcctagcatg ggctgttgtg ctggagagaa421 cgagagctac gaagagacta cagtgcctct gactttttca taggacagtt ggncggtgaa481 tcttattaat agtttaccac aattaagtgt tcatttttag tcta<210>44<211>649<212>DNA<213>Homo sapiens<400>441 tttttttttt tttttttcat gctgaaattt ttttacaaat tttattgcgt catacacaac61 tacaagagta acagttataa ctgaattaaa aaaatagcat tttgggggca tttctatttg121 tttgctatta tcataagcat gttttgttac atgaacagca ataataatta caattacaga181 actgctcaat tcataaatgt agtaagtgtg tcatgatgga ggctactaca taatataaac241 agtaaatgcc caaacatatt ttcatattct atattattta ttatataact agaatcaagg301 attagaatct aggtaatacc atcattcaaa tatctgacca agtcaatcaa gtgagcaagc361 acgtcaaatc attttccaaa atctgttata gtttagttct aaagaaaaat ataagatgaa421 acacataagg catggcttgt taataattta tgcctaaaac cattatataa taaaaatctg481 catattttgc aacttggcat ttgtttcatc tgacacaata ataaaaaaga tgaatagtac541 tatcagcact tggaattacc caactacagc tgatatagta cctcccagac ttctagtttc601 taaaattctg ggtgaagtgg gacaatttga actataacag tctacatgg<210>45<211>479<212>DNA<213>Homo sapiens<400>451 tttttttttt tttgtttcat ttcctgagca tcgactctct gccaagcacg atcttaggca
61 tgaaaagatt tgagatgaga gttcagggac aaagagaaca aagctgaaga gatgagcaag121 gagagctagc ggaggatggg gagcatgaga caggacacgc ctgcaaaaaa ctcccaatgt181 ggagaagaac gtggaagaac agcagagctg ggcagatgtg agtgggcggc gtggggctgg241 gagagccaag accagagagc ctggtatgcg caggagtcct gggctgcctg caggctcgcg301 ggagctctgt gctcgggcgg agagcaatga tttgaaggtg ggaatgcaag catacactca361 agtaagaaaa aaaaaagaga gagacgtgat tataaataaa agacatttgg cgtcaatgaa421 ggaactactt aagagacaag caacatcttt tggagccgaa taagctttac ctccctttg<210>46<211>501<212>DNA<213>Homo sapiens<400>461 cggccgctgt tgcctttggt gtccttgttt tgaaggatgg ccacgatttg gccccgaggc61 agagtcaggt ccagagtccc agtcccactg atgttgcttg tcacctggta cagcttccca121 gggccatacc tgctcaggag agcctgcacc tggcgttcag accctggaag gagcggttgt181 gtggtgggag gtggctgcac tttctcaaag gtctcttgaa aggagcgaag ctggttactc241 gtccggccca gtgcgtcctc caccagcttc ctgaaggcag gctctgggac gtggtggtgg301 ggcagctggg ccatgcttcc ctctgccctc tgcagcactt gctttgcaag gtccctctgg361 agggtcacga atgtgcacag gatctggccc agccactgca tgaccagctg gttaaactgt421 gggagctcag ccactagcag cgagttgagt gcctggtatg tgtgccgggc ggcctcctcc481 tggtangtca ccctcgtgcc g<210>47<211>545<212>DNA<213>Homo sapiens<400>471 ttttaaaatc caaggccttt aatttagttt ttggtaatga ccataaatgc cttcacaaaa61 cctctttttc actgtaaata gaaggcacta ggcattacat aataccctta aagcagtgat121 tcctcctgat gctggtagag ataaaacatt taatgtcagg gtttacatag taacaaattc181 ttcttaaaaa aaaaaagaca aatctaaaaa aaacgcacca aaaattatca gtcactcttt241 cccaggttcc cagtgcaaat ttacatcatt tttacaagta catagtttga aattaagaga301 taaactaggt atgatatggt tttcaacatg tgttaggttt cagttaaata cagtaaaaat361 gaagacacca ttatcatgct aattggcatc ttttgctact gtttagctgt gcaaaataga421 cttgaaatga tacatcctgt agtggcataa tttaaaagat ccttgatatg actccaacaa481 cttacaaatt ctggtcacaa actgtatata aattgtacaa ttattaaaat ataccttttt541 gaaaa
<210>48<211>941<212>DNA<213>Homo sapiens<400>481 gggggttcac ctgtgccagt gcccaaccct ctgccctgat tatgcacgtc tgctcctgag61 tggagcttgt gttccaggat gagacatctg gaggtgagcg tgtgcgtccg gctcgtgtgt121 aggaggctgt gtgtgtgccc atgtgaaacc gtgtacttga gtgtgtgtct gtgtgcagcc181 tatgcctgct gctcagagca cggtggccac cccctgagcc tctgctggtg ctgtgctgcg241 tggtccccac ccagagggtc ctggggggcg gggaggagcc accgttggga ggcccctgta301 cggggtgtct gccctgcgtg agggcataga atgtcaaatt attttaactg gtgaaactgg361 agagtttcat gtcattttca atacatagca gtatctaaag acgtaggcga tgagactaga421 ccacattaaa tgcatttgat ctctcttgaa gaaacacacg caaacaacac tccgaggcac481 ccctcgaacc ggcggcgcaa aaggggtaac ggagggcgcc cagcgcccta cccgtccccg541 gaacacagct ccccggcacc aagcggagac ccgggcggct ccccaaacgg gggccgcacc601 aaccgagaga gccaggcaac cgggctcaca ggagccggga ccgggccaca gcatgcgccg661 cgcgcgcccg acggtggcgc ccatgcggca ccggtgacac gcgagcgggc agcccagggc721 cgcccgaggc ccgtgcggag caggcgcggc gccaggcggc tgcgggccgg ctcgcgagac781 ctgtgcgggc gcacgcgaca ccgaccagcc cgcgcggagc cacacgcggg acacgacggg841 acaccgtcag tcgtgacacc tcgcgcggcg gcaccggacc ccgggagacc ccggcggccg901 cgcgcccggg gcccgcgagc ctgcgacacc gggaacggaa c<210>49<211>536<212>DNA<213>Homo sapiens<400>491 tttttgaaaa accattgcct ttttattgtc tccttttaac atcaaatgtt ttataacaca61 cttgatcctt ttgtttctac cccctattca ttacagtcaa attaacaggc aatataatag121 gtctaacaga atgcttgcat ttcattaggg aaaaatgaac gtctctctcc tgaaacaggt181 tgtcggtacc ttgaatgaca taatattggt gtatagacta ggttcagcag agggattttt241 tccacatctt gaatgaaaat gttaaacatg tgatgcacag agtattaacc tgtttcaaaa301 aagtatagat aaataattta ttaaaaaata tatatacctt gtatatttaa gccatatttg361 agaacaggct aggataggat tatttaaaaa aagatattta ctagagttag aaattacaac421 ctactgatta aataatgcag gtttggtcct gtaagatttt aaccactttt catgctttta481 gagcttctga gcagttggag agagagttca ngaggtattc ttggcattca gtgctt<210>50
<211>522<212>DNA<213>Homo sapiens<400>501 ttttttgagg gagctgtaat tatttttatt ggttcgttca gcaatatttc ttaacttctg61 gggaaaatac atggtattgc catttcttaa ttatcacaga cactgaactc aaaaattaaa121 ggaagttcgt tgcagatgct ttttttttag agacaggaca attcttgagt gccgtccttg181 gccttcaccc tgattcctgt gagcagatga cttcctctga agcagcctga ttttgtgtat241 cctttcacca atcaaggatc agggtgtgtg ctccttggtt cctgaaacct ccctcttctt301 tcttatagct ccagcttcag cagccccaaa cgcggggagg gagacccatc ctggtcttcc361 tcccgttcct ggctgaggct caaggaagaa aaataccctt cagagatggc ctctttggca421 cttggattat ttccctcctg atagcacagc ggttctcttt ctagaaagga tgaccctttg481 tttcttctcc ttctacaaaa ttcactttct atgtatcttg ta
權(quán)利要求
1.一類人類肝臟表達(dá)序列標(biāo)簽的序列,其包括(a)SEQ ID No.1~SEQ ID No.50所示的序列;(b)SEQ ID No.1~SEQ ID No.50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.50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所述的一類人類肝臟表達(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.50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)明公開了一類人類肝臟表達(dá)序列標(biāo)簽。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)C07H21/00GK1955291SQ20051003082
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