專利名稱:人類肝臟中表達的表達序列標簽g組的制作方法
技術領域:
本發(fā)明涉及生物技術領域,尤其涉及一類在人類肝臟中表達的表達序列標簽。
背景技術:
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,在肝臟中發(fā)生的化學反應有500種以上,實驗證明,動物在完全摘除肝臟后即使給予相應的治療,最多也只能生存50多個小時。這說明肝臟是維持生命活動的一個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。每分鐘進入肝臟的血流量為1000-1200ml。肝臟的主要功能是進行糖的分解、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)學實驗證明,肝病病毒侵入人體后,并不直接引起肝細胞的損害,只是在肝細胞內(nèi)吸收營養(yǎng)賴以生存,并在肝細胞內(nèi)復制、繁殖。其復制病毒的“零部件”如表面抗原(HBsAg)、e抗原(HBeAg)釋放在肝細胞膜上,引起人體免疫系統(tǒng)對這些抗原物質(zhì)產(chǎn)生免疫反應,這種反應造成肝細胞的損傷、壞死。免疫反應的強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、升學等方面都會受到嚴重影響。
生物基因組中可轉(zhuǎn)錄表達的序列(即基因)僅占總序列的3-5%,對這部分序列進行測定,將直接導致新基因的發(fā)現(xiàn),并獲取基因組中與產(chǎn)業(yè)化關系最為密切的信息。20世紀80年代,高通量的自動測序的出現(xiàn),使從質(zhì)粒互補脫氧核糖核酸(Complementary DNA,簡稱cDNA)文庫隨機選取許多cDNA克隆和決定來自非載體兩端的幾百個堿基的DNA序列成為可能。這些短的DNA序列叫做“表達序列標簽”(Expressed Sequence Tags,簡稱ESTs)。表達序列標簽的概念最早是由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)模互補脫氧核糖核酸(cDNA)測序的研究戰(zhàn)略。隨后Venter創(chuàng)立了大規(guī)模表達序列標簽技術。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脫氧核糖核酸(Complementary DNA,簡稱cDNA)文庫中,隨機選擇許多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’端的幾百個堿基的非載體短脫氧核糖核酸(DNA)序列。簡而言之,表達序列標簽是來自表達基因片段3’端或5’端的短脫氧核糖核酸序列,代表一個表達基因的部分轉(zhuǎn)錄片段。
表達序列標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。如果一個表達序列標簽在基因組中只出現(xiàn)一次,那么它可以作為序列標簽位點(STS)。由表達序列標簽構(gòu)建的物理圖譜叫表達圖或轉(zhuǎn)錄圖(expression ortranscript map)。利用表達序列標簽進行基因圖制作,可以加快序列標簽位點的制作和新基因的染色體定位。表達序列標簽可以作為基因特異性探針,對組織特異性基因表達的研究具有重要的作用。表達序列標簽還可以進行新基因的遺傳進化關系分析。表達序列標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化圖譜。正因為表達序列標簽具有如此的優(yōu)越性,因此表達序列標簽測序已經(jīng)成為許多基因組研究機構(gòu)的工作重點。
表達序列標簽(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記,而且來自不同組織和器官的EST也為基因的功能研究提供了有價值的信息。此外,EST計劃還為基因的鑒定提供了候選基因(candidantes)。
在本發(fā)明之前,還沒有出現(xiàn)涉及本發(fā)明的一類在人類肝臟中表達的表達序列標簽的公開報道。
發(fā)明內(nèi)容
本發(fā)明要解決的技術問題是提供一類在人類肝臟中表達的表達序列標簽。
為了解決上述技術問題,本發(fā)明通過如下技術方案實現(xiàn)在本發(fā)明的一個方面,提供了一類在人類肝臟中表達的表達序列標簽的序列,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分子,所述的探針分子含有上述序列中約8-100個連續(xù)的核苷酸。
由本發(fā)明的一類在人類肝臟中表達的表達序列標簽,可以方便的尋找出在人類肝臟中特異表達的相關基因,從而在研究肝臟疾病的致病機理以及開發(fā)治療肝臟疾病的藥物中發(fā)揮重要作用。
具體實施例方式
下面結(jié)合具體實施例,進一步闡述本發(fā)明。應理解,這些實施例僅用于說明本發(fā)明而不是限制本發(fā)明的范圍。下列實施例中未注明具體條件的實驗方法,通常按照常規(guī)條件如Sambrook等人,分子克隆實驗室手冊(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個成年男性,在肝臟切除手術后,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。
實施例2cDNA文庫的構(gòu)建(Constuction of cDNA library)以mRNA為模板,合成雙鏈cDNA。補平末端后,加含EcoRI切點的接頭。磷酸化EcoRI末端后,用XhoI限制性內(nèi)切酶消化1.5小時,再進行片斷分離。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)進行包裝,宿主菌使用XL 1 Blue MRF’(Strategene,CA9203,USA)細菌。涂板并測定滴度。
實施例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,采用終止物熒光標記(Big-Dye,Perkin-Elmer,USA)的方法,在ABI 377測序儀(Perkin-Elmer,USA)上進行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上,進行cDNA全長克隆,分兩階段進行(1)“電子克隆”(Electronic Cloning)以新基因片段序列作為探針搜尋dbEST數(shù)據(jù)庫,將重疊序列>50bp,同源性在98%以上的表達序列標簽(Expressed Sequence Tag,簡稱“EST”)序列認為同一序列(Consensus Sequence),取出并用AUTOASSEMBLER軟件進行連接,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@取人肝臟相關基因的全長序列。
(2)cDNA末端快速擴增(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’端設計引物,在人類肝臟Marathon-Ready cDNA文庫(Clontech Lab,Inc,USA)中進行長距離PCR反應。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’端設計引物,3’端引物采用Oligo-dT,在肝臟總RNA庫中進行擴增。然后對產(chǎn)物進行克隆、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>人類肝臟中表達的表達序列標簽G組<130>NP-10043<160>63<210>1<211>566<212>DNA<213>Homo sapiens<400>11 tgtcgtagag ctttttattt tgcatctgga gtgtatttgg acacgtgggc tgggtggggt61 aacaggataa tgagcagttt gggaaagagg caggctccaa gcaggctggt tcactcactt121 ggcagtcact gggcggctat tcttgtgcct ggatgtgtta caatgcaggg gacacagtgg181 tgagcaaggc tgctccaagc cctggctggg atgggggatg cacagacagg ctgatcaggg241 ctgggatggt ggacacgcat cctctttacc ctgatcactg gttagaaata ctgcactgtg301 gccgggctca gtcggctcac acctgtaatc ccagcacttt gggaggccga ggcgggttgg361 attactcaag gtcaggagtt cgagaccagc ctggccaaca tggcaaagcc ccgtctctac421 taaaaataca aaaaattagc caggcatggt ggtgcatgcc tgtaatccca gttacttggg481 ggggctgagg caggagaatc acttgaacct gggaagtgga ggctggagtg agctgagatc541 acgccaccgc actccagctt ggacga<210>2<211>492<212>DNA<213>Homo sapiens<400>21 gcatgtacaa agctattggt ttattcagct gccaantggt ggaaaggctt cctttcgaag61 tgaatagcaa aaatgcattc atgagcaagg cacttttata cacacacaga gagaaaaagg121 aacgtattat gaacacatga acataaacat attttaatat tcagacctct tccctacctc181 ctcccacctc cacttaaaca aacaaacana aaaaaaggaa acagtttcct gtaacatttt241 agaaaccagt ttcacagaat acctacatag gaacaatttc tgatacattc agttacacta301 acnntatgat atggtttcag gtcaataatt tccactaaca aatactttta ttctacaatt361 ccctctnttt ttccttttag acaagacaac ttnaggctca gcngaaatat ttcactaggt421 taataaggca ttcttctctc ttcttaaagt tgctatatat ttacncaatt ggtgnttcct481 aacctttttt tt
<210>3<211>683<212>DNA<213>Homo sapiens<400>31 gttgttgcca attgtttttg ttgtcttcca gaggtaatac aaggctttgc tcctttagca61 ggattcccag ttggaccctc tccagagagg attcatattt gaattcccat ctgaatacca121 acccaaatgt tgatacagaa cactcctgta ttaaaattaa tatccatccc agataaacct181 actctgtgac taagacaatt gagatcttct aggtgaagat gctataattc aaaatattac241 atggaaaacc atgtcttact taaaacgggt acttgttttc cggccataat tattccagtc301 tcttccacag aactgcttct gcaaacagtt tttttaatgt atcaaagaga gtctctcgcc361 aacatttaat acagtcaaat ctattccaac ttcagagttc ttatatgtct tatttagcag421 acactatgat tctatcttct tattctctgg aaatccatca gatgtgtgtt ccaacacaga481 agtgccttcc ttccttctca tggtggcaaa agcatatcca tcatccccaa ggttntaaca541 atcccttggt aatcaactct tttctacaag ccctgaagag taaacnttta tcactacagg601 gctgaccatt caggggaatt nccataattt tcagcgctga taacaggnaa ctgcggaaat661 ccccggcgat ttgccgggna atc<210>4<211>592<212>DNA<213>Homo sapiens<400>41 gcactaatgc tgcttttaat ggcggcgcaa tagagaagta caaggtttta ctagcttgag61 ctactagaag gtgtaaaaga tgcccgctga cactaccaag tagcctctta atagaaatgt121 agaaaatata caggacaggg tggagatgag ctcttgaatt tagtagggtg aaagagttaa181 ctgccaaccc ggcactatca ttgtacttgt ttggagaaaa tctgttttgt tctggtgatg241 atggttttat cttccctttt agttgggtgg gaagtaacag aaaatttgtt tccccaaaag301 tttgacattt tcttgttaat acacgtttca tttcagtacg atgccaactg ttaagcctgc361 aggaatcctc ctgggtattt ctgaattgtg ctgtgtgcat gtgtgtttga aagctcaaac421 agcttgtctt cttacagcat cgagttgttt gctttattgt tagacacaat attagcagtg481 tatcctttcc gtattcccta ccatcgaacc cattaagact aaaatccttg tcaagtactg541 gcttaaaagt tgggagatgg tggtttanaa aaaaaaagcc ttgcaaaacc at<210>5<211>664<212>DNA<213>Homo sapiens<400>51 aaatggtatt catttttatt tcaacatgtc aactgtgcat ttccaaaaca gcaggctttt61 caaaggaata aatcagaact gtaaacacaa gatacagtac aagtttttga cttcctacag
121 tcagtttcac aaatccacat actgtacatt cataggtgag gttaagcctg tcacccattt181 ctttatttct ataattacac aagcataata aatacatctg cttttaaagg tcacttaaaa241 tgagtcataa tttacagtac agtacgtttc agttcaagtg caaaaaataa ctatttgctg301 aattctattt ctttcagtta ttttattttt aagctgtgtt ttattgtgaa gcgagacatc361 caagtgtaga atttcttatc ccaaatgcag tattgggcag aactatggtg tctggagaag421 ccctcacttt acaattgatc cgtctaatcg ggtcagaggg taaggtgagt tgctcattcg481 actgttcttt cttcctctct ctccgtgctc atccacagct attataaatt atataattca541 ctttattcag ctaaaacagt ttccctttcc acactncccc caggtttccc gttaaccctg601 cttgatttta gtggcagctt acgtggatca nccaccatgt ctggngcatg gacggtgcgg661 tgca<210>6<211>449<212>DNA<213>Homo sapiens<400>61 tacatttggt tatgtgttta attacaagtg tttcaatagc tataaacatt gtaaaattca61 gtatcaagtg aaatatttgg agagccccta tggcaacttg gaaaaaccct gggattctga121 ggaacaggga gtagcgcacc agtcccagta aaatccagaa ctttctagaa ggagataaat181 gcaggatgac tgcctgcttg ccctgggcca gctcagccag aaaaccatgt ccctgaaaga241 tgggaaactg gttccttgat acagcagaaa aacactgatt ctaccccaaa tgtactcaca301 agacagaaga acgtgcatat gtcaaggagg aatgttcaat ggctgggcac caggcttaaa361 atatccgctt gacccagtgg cttaaaagca gttccttctg aattgaacag agaatccctg421 cggagatcaa aggagcctca gctcgtttn<210>7<211>428<212>DNA<213>Homo sapiens<400>71 gaggtggttt atgtgcccca tagccaagag aggtgngcac caaaggagga tatcatcaaa61 tctgacaatc tggaaagcct ttgaaactgt tcttttccta agcacagtat tcagctgtgt121 cctcttgaac ccatatctat caggtcaaca gctttagccc attccacatg atattggctg181 tgggtttgtc atatatagct cttattattt tgagaaacgt tcnatcaata cctagtttat241 tgagagtttt tagcatgaag ggcttttgaa ttttgtcgac ggccttttct gcatcnattg301 agataatcaa gcggtttttg tcattggttc tgtttctgtg atggattatg tttantgatt361 tgcatatgnt ggaaacagcc ttgcatccca gggatgaagc ccancctcgt gccgaattcc421 tgggcctc<210>8<211>332<212>DNA
<213>Homo sapiens<400>81 tttatcagtt gaaatacttt atttaactta ttttaaaaat tgattcaaaa ctttttatct61 tctttattag gtattctacc cttagattta acactcattt ttcccgagta tattttctct121 tcaatataca aaggaatata ttttcataga gtgtgttgaa tattaggaaa atcaagagtt181 ctggttctgt caggtgcagt atttagagtg ttattttgat aaaatccagt tgctctgata241 tggcttgaaa atacttgctc ctttggagta taattgcagg ggaaaaactg tggaataggt301 agaaattcac cataatgact tgaattggtt tt<210>9<211>428<212>DNA<213>Homo sapiens<400>91 tttcaggcaa ctgcttctct tttattatga atatgatttg aatctaccca ctgcacactg61 aggctactgc ctctctttat aaaaaggaag gaagaaattt ccgtttcccg cagatgtgat121 gtaggaagct acaactgcca actcctgagc atgagggagg ggacaggaga atcactgagg181 ccctgacccc aaggcaaccg agacttagct gtgtgcccac agctgccctc gccaggcttg241 ttttgtgagg gaataatcct tagtgcttaa tccattactg ggggagtttt gctattgtta301 agaaatgtca gcattaaaaa actaggagac ttcacataaa aatacaggga tgtggatccc361 ctgtactcta tctagggtaa gcctgcgcaa cagtggacta acaatgggga tcccagtgga421 gagagggc<210>10<211>304<212>DNA<213>Homo sapiens<400>101 gagagcttag atagagtgta tttttattct tttttttcca tttccttttc tcttttcatc61 ttttttcttt ctttctttct ttcctttttt tcctttgtat ttttatctta acatgcctag121 acagagaaga acactggatt gtacataatg ggctttcttt gactctcttt tccagagtgg181 aaataggatt ctgtgctcca tcattctgag ccatcaccag gggccgtcca taatcaacta241 tgatgatgag agtgggaaga catgtgtaca tatcgcagcg gcaggtgctt cagcgatatt301 attc<210>11<211>487<212>DNA<213>Homo sapiens<400>11
1 taaaacttcg aaatatttat tattaagata taaatacata ttttaaaaat gtacaagtta61 aaaatacctt caaagttaaa tgtcagttct ttcacaatca ttgtgccggg gtaatacgta121 caatatcttg gcttactagt aattttatac cagtcacttg aaacaacatc cttaaacttt181 aataatatgt tgtaataatt ccatttttca ctttttagag tttgatagaa gacagtcaat241 atcgtgaagg atttcagagg tttttttcaa tgctattgat actctatttt cattaacttc301 tcctagcaag gtttctgaag atcccgggtt tataatgatc aaaagactgt tgttcatttt361 tcttgttaga aatctggttt aggataccac tattttctag tagcaagtta aacttctgta421 tcttttcaag ttcagaagca acagaccaat tttcttggag aacagaagat gacgaatgag481 tgggcat<210>12<211>591<212>DNA<213>Homo sapiens<400>121 tttaggctga tcatactaga gtatatttat taaatttcac cattatgatc actttgttat61 aactaaatta accctgacat aaactttgac attttaaaaa cagagaacat actgattttt121 caactatttt acttacatgt gttttttaat tctcatgcag tgctcataat taggagatac181 tacatattca ccctcacatt atgcttatta agaaccaagc tcagagggta gaaaagtgcc241 aacttcattt tccataaact tcccatacat atattaagcc actgttcttc taattatata301 cttatggtac attcttctgt aaaatgtata actgtagtca cataaccatt gttatgacaa361 ggcggcaaca tcatttcaga ttacaacaaa tgagaccaaa agttgaagag accacagcat421 ataaaagtca tgagaacacc acacacattt caatattttc cactttccag tcaaaaaaac481 atgcacaaag ttttcttagc agatagttgt cagaagtgca taaaaaaact ggctttcagg541 tcatatatgt tgagtgagga tcaatgccat tgcgtgaaga gagctgtgtt c<210>13<211>755<212>DNA<213>Homo sapiens<400>131 gcaccaaagt gacttgctta ttttttttat taaatgatac attgaaagta taaaaagttg61 ccgcagtaca aacaaattac agaataatgc atataaaagc gctatggact acacgtgaca121 attctgctta acttccatct tgatgatttt atatcagtat ccaaaattat atactccagc181 attttttccg aatatagtct tacatgattg caattcctga ggtaaactaa gtgtccactg241 ccaacatcct tggacgaaaa ccaagtcccc cgggagaatt cagatattta tattcacaca301 tacaatacaa cggaattcat caatgtaatc agatattgca gatttaaaaa tggaaaatgg361 actcttgcaa tacttctgca tccatatata attttaccag cagggcctcc cagaatggtg421 tgttagttta aatggatttc agtaataggt ttctgcattt agatagacat tcttggctaa481 tctgnntaga gtgacactga ctagcattgc gaacagaaat caaagttttc acatttgcaa541 gcagcacaga ttgtccctta aagaggagca atttgctact acagtcctac catcttctca601 tgaaaacttt agcaaaggtg tcatgttagg ttgcggcaaa ttaattcgaa atccacgact
661 ttccatcagg gcgtcacaca agtcgtgttc cagaagagcg tgtcctcata aggctcttaa721 attcgagtgc gatggagcca tctattcgtc cagaa<210>14<211>555<212>DNA<213>Homo sapiens<400>141 tttaccataa ttgacttttt atttaaaaaa ttacacggag caatttccag cttatctttt61 tttataaaag tactgcctat atcaaacatt ttatatcacg ttaattccat tgaagagctg121 cctttttctg ttaaggtact gattccaatt gatgggatac atgcccttaa tacagaaagt181 ttccattatt tattcaaata tcaaaattaa gattattgag aagtttattg ctttatggct241 gggcaagatg ctactagcac attttaggta aataatattc tttattaaaa actatgaggt301 cattctgttt aaaactttca agataattca cggaaaacag atatatctat tcaaattaaa361 cattaaaggg ccaggctact agctatagac atttatatgt gaagcagctc tttttttttc421 ttttctgaga tcgagtctca ctctgtcgcc cagggtggag tgcagtgggc caatctcagc481 tcactgcaac ctccggctcc aggggttcag caattctcct gcctgggccc ccaagtagct541 cggaatacag gcgcg<210>15<211>476<212>DNA<213>Homo sapiens<400>151 tttttttttc acggacagac agggtcgttt gtcacagcag agaagcacct cacggctcct61 acccgcactc atcgcggaca gtgcctgcag cgggacgacg cagagcaccc tccccagatg121 aaaacaccag caccaggagg tgggccgtag ccagagctga gggaggaggc tgggggctgg181 ggctcagggc cccccccggc cacagcgcca ccctgagtgg ccctgaaaat agtgcacagt241 gctgggtact gccccggccg gacgacacta gttgttgagc attccggcca caggcacacc301 gctggccctt ccttggtgtg gcacgagacc acgggcactt gcaggagctc cctgcatgct361 gttttgtgct ttggtctcag ggagcaccct cctacctcgg ggtcccagag tgggcagccg421 ggcaggtgtg aacagtgtga caagggtacc gtggggcacc tggtagtgca cccaga<210>16<211>390<212>DNA<213>Homo sapiens<400>161 ttatattcgc ggccgggcgg cgtgtttttt tttttttgct gcatatatag ctgtggtaca61 ttttaatgtg aaatgatgac tgcatcagct tatatccatg gagcagattt tagcattcag121 cttgggtctc ccagtcaata tctacgagtc tcttcttaag gagatcgatg acacagatac
181 atacagacta acaaatgtga taccaataat caagaattca ctcagttaag attttgccca241 ctgatttcca cacaagaaac ctagaattta ctagattctt gtgcctgtga ggctccactc301 atttccctga atcacaaaag ctacagagta tttagataga aatataccta ctcttaacat361 gaaccatttt aaatatatgt attactgtgt<210>17<211>514<212>DNA<213>Homo sapiens<400>171 tttttttttt tcctttaata cagaaacttc attgaaaaaa cctagccctg tacagctgcc61 cttttaaaga ggtggccatt gcagggtctc tgcctcccca gcaggtggca gatgctcccg121 gccactcgtt taaataactg tcccctggag gggnccgggg tttgaaggca gggccctgcc181 accctcctgg gggacacccg tgcatgttta cgccttttct ggttgtgtca gtggccggag241 catggcagct gggcatcaat aaacacctcc gaggaagctg gactcgtgtg tgctggcacg301 gggagggcgc cgggcggggc cgtggtgggc atggcgtgat gtcacggtca ctccgggatg361 tcgatcacca ggtcatcgtc tccatccaag gcatcgtccc cgctacctgc atcgctgaac421 atctgccgag ggaccgtgct caggatcgtg ggggtctcac aaaccctcct agagagctct481 gtgggtctct ctgcagtccc gtgctttgtc tgtg<210>18<211>502<212>DNA<213>Homo sapiens<400>181 ttttttctcc ctcggcagga tatcccacag caagggcatc ttgaaaagca tgattttctc61 ggtaatgttt gccaacactg ttcactttcc acatggtcac gactgaaaac acatttacca121 atacctttca agcgatatga ctaccagaaa tagatcttct ttactaccct ctctgaaatg181 agtacacaag aaataaattc agaaggtagg cttttgaaag aaaaagaaaa aaaattgctt241 gcggcttcac agtgaaaaaa attggagtgt ttgtgccggt taagatttca atgttttctt301 aatcaaaatt ctctgaagtc attctcaatt tacaaggtta gaactccttc aaagacaaga361 catacaagac tctagcttta attatcattc taaatgtcca ctagccctgt atctttggtc421 atgaaagcag caaaacattc acattttcat catactacat tcaattgcct tccaagttta481 gaccattcta cattttaaaa aa<210>19<211>507<212>DNA<213>Homo sapiens<400>191 tttttttttc agggcaggcg acctaatgta ggaaacttaa taaacccttg cattgatata
61 atgatctgtc aggttttcat ttgaacagtt ctccaacatt ctctgaactg ccaaataaac121 tgaatctaag ccctattttt tcttatgcta aagtgtgaat gattctggac tatcttactg181 ggaaaacatt tcctaacaat gtttttaaaa gtcataaggt caaaactgca gttataagaa241 agaagggtga atgcagtggc tcatgcctgt agttccagtg ctttggaagg ctgaggcggg301 aggactactt gaggccagaa gttcaagacc atcctaggca acacagcaag acctgtctct361 acaaaaaaaa attttaaaat tagccaggtg tgacagtgca gaaaggtgag gtgagaggag421 cacttcagtt caggagtttc aaggctgcag tgagctatga ctgtgccact gcattcctgc481 ctgggtgaca aaatgagact ctatctc<210>20<211>557<212>DNA<213>Homo sapiens<400>201 tttttttttt ttagcagccc ccacataatg actttatttg cttaatcccc aaattaaacg61 ccgtttcaag cgagggtcct gtgttattac tctcatcatg tcgagaacat tttcctgccg121 agaccaattt gaataaaaca aggggccttc cttgaactca atcaaggagc cataatgtgg181 tgggtaatag aggttgctga tagatttgca ggcaaaagtg ttatacctaa tgatgggata241 tggataatag tcctcctgga ggtcctgatg cgattccagt tggctgccag atgcttggct301 cgaatgcgaa aattctccag gtgtctctga cgtgattcct ttagtatctt ctttagtcga361 gtcttatggc aatataacag ccaagcaatg gcaatcacac ctgatgccca cttctgctgg421 cgataaaaga ggaagaattt tcttgctttg tagcatttcc atgtggcttg gatcttcatg481 gcggcctccg aatttccatc ttggcccttg tacctttgcc ctggaagatt tatcagcatt541 tggacatgag ctgggtc<210>21<211>222<212>DNA<213>Homo sapiens<400>211 tttttttttt tttttttttt tttttttttt tttttttttc ctttgacagt gaccatttat61 tacacacatc agactggggg aagaccattg acatagctga gcaccaggta gggtgtcctg121 ggtattcggg catgagagca gcaggggcct cctgacgcgg gcaggagaaa catggcaccc181 accaggagga ggaagaggag gaagaggata aggaggaagg tc<210>22<211>534<212>DNA<213>Homo sapiens<400>221 aaaaggattt aaaagtcttt atttcctctg aaaacttact ggtaaagtat acaatttatg
61 aataatcata tattcatgct ttttgaaata tatctgaata aaagacaaat tattcaatat121 caatagcagt aaataactta tttgcaagaa aattattaca attcctactg taaagaatca181 ccaaccacta tttagcaatt aaatttcaac acattttttt tggaactctt taggacttta241 gacaaaggct accaaggctg acaatccagg taactatggc agtgacagaa gtcaatcatt301 aatactgcca ttattttaga caaagggctg acaatctcag aaactagttc tagaaattat361 catcaatgtg gccattttac tatggacaaa taaatatggg agatagggaa cttgttactc421 cattttccta tagaaaaata tataaattga ccttttatat atacacaggt atgtatacac481 atacagtata tgtttttctg agcaggcaca ccaactagga aaaaatacaa tagc<210>23<211>497<212>DNA<213>Homo sapiens<400>231 ttttcacttg tttaaaacat ataatgcgat ggttttggta tttacagagt tgtgcaatat61 cactacaatc taactttaga acattttcct taacccctaa ataaacctca tcctcatcag121 cagtcacttc ccatccatcc caccccaact ccaaggccca aggatccact ttctgtctct181 gtggatgtgc ctacggaatc tgtttctcaa cacacttctg ggtgattctg ctcctgcagg241 tccacggtcg agcattcagg aaccagtgga ccagactgtt ccaagatcct ttcctagtct301 aagctttcat agccggaaca atgaataccg acgaatangc aggtgctttg cttggtgctg361 gggttgtaaa agaaatatgg tacaccctac tcttgagaac ctacagtcag tgggaaaaat421 ggaatcataa atgactaact ttaatacaat gtgagaagcg ctctaacagc atgtgcattc481 aaaagaggcc caggatg<210>24<211>304<212>DNA<213>Homo sapiens<400>241 tttttgctat tcaaatgcac atttatttaa atgtttggaa ttaagagcaa cctagaaaca61 gaaaacgtgt tcaaatattt attttaacag catcttttgg aacatgttta tttcccttaa121 aaacgacaca gaggaaacat gtacactgta acaacacctt cccctctgtt tctccagaag181 aaaaatgttt ctgcatgcct gataacagat ggtgcaacca acagtaaacc tggctctcta241 caccagtgaa gaaccattct ccaaatgccc agtgtgcctc agaggaaata tacaatttaa301 aagt<210>25<211>459<212>DNA<213>Homo sapiens<400>25
1 tttggtttta taatgtatat attttaagta ggacaggttt tttttttttt aaacttttgg61 atgttttata aatttgtcca atttagtcat ccaactgaca aagcaaagca accccgcgct121 tgatccagtg ccgagtaggt tggtctgttt ttaacaacat tgcaatgaca aagttagtag181 aatgtcccgt agtggaaaga gttcctttac gttcacttgt cttgtagagg ggacagacat241 aggcatccga ctttataatc cgagattttt gagttggttt tatccatatg atgggcatca301 ggtcaaacag aagtttggga tattgtcagc aagcaatcca ctttctcggt cccagcgtgc361 gccatcgaga tacagtccgt ggatataaac accatcttct ggtgatgtgt cagatgtatc421 agatgggata acctcaaatt catatcctag caaatcaat<210>26<211>459<212>DNA<213>Homo sapiens<400>261 gcaggggatg gtgaggcact aacatcacag ggataattta tacaagatgg atgatattgt61 agattcattt gcattgaagc caaatcctca atctcttctt catacatatt gctgctaaat121 tgtattactc taattccaag ccagtactct tggctttttt gaaccataca ggaaggattt181 agatttattc ctattactta tcaccctgtt agattcatca accatttgcc cctggccaag241 gatgttttcc acttattgct gcagaatgct tctagtctct cccatgttta tgaaatccat301 gatttgctct ttaggtactc taaatgctca caaaccatct gaataatact ttgggactga361 taccaaactt tcagtctata atttacagca cacgtttccc tttaacttgc tcctgcttcc421 cagaattcca cactgatcat aatcagtgat tactgatat<210>27<211>549<212>DNA<213>Homo sapiens<400>271 tttatggcta atggtgacac actttgttaa tttaaaaaca cgcccttccc acatagtgcg61 tgaggcatgt gcacattttc ctagaaggac atgaatagtg atgtggaggt acggtggagg121 tcaggcatct acagggtcat tcgaggagga acagattcaa gctttcggac gatcagtgtt181 ttgtaaatag cagcatcatc agatctaaga caacattgga cctggcaggg ccttttcttt241 gggtggcatt aattactcca gattcagacc aggccatcct ctcccggccc aggatctgcc301 tctccctcct ctgtccccac acctagacat gaaagccata acccttgggc ccctcagagg361 gaaaacacaa ggggtgcgag gggtgggggg gcggcgatgg ggggcattgt tgagcagtcc421 tctcacggct gggagcctct gctgcttcca gttaactgcc tttctggaaa gcgattctat481 tacatgatgg aggcagcgga atgaaacatt gaattacacg gcacgagatc caagctagtt541 gttctcatc<210>28<211>742<212>DNA
<213>Homo sapiens<400>281 ttttttaaca tgattgcctt ttatttatta tgcaggttgt tgatttacat agggagttgg61 agatgctaac caagcatgga gttttcacat ggtctatttc tgctgagttc agggacttgg121 agacagcctt taacttctgg caaaaagaca atttcacaaa ggtgtttaaa accatccttt181 ggtttttgat cctgagtcag agacggacat gtgcttatga aagaaggtag agtttcaacc241 cttaggtaac cttaaaagag caggaactat gttgtgtgta agtcatgtgc agtatacaaa301 cttgatatta aatgacaaat tggaacaatc tttctctagg aatgcctctc tttcatagag361 gcatcacagt gagtctctta aagccttgat ctaggtgtgt tacagatggg cttacagagt421 atgaatgcac gataagaagg aaattggata gggagtgagg atatgaaatt taaaagaagg481 aagaactgga acaaggcata ggcctctttc aatttttcgt ggtgtgcagc tgccaattct541 tggacattca agaaacgctg gttgacatta tcttttttct tcacaatctg atcaacgttg601 aaagtcccgc tggagagcaa atcttcagcc aatgtattca ggtccttgag tgcatnctct661 cgagccaaca tctctctctt ncatagctga tgcttcttga gtaggtttct gctgaagcca721 agtcctgggc tgatctttat gg<210>29<211>458<212>DNA<213>Homo sapiens<400>291 ttttttttac catcactttt ttatttggca gtaatagtaa tacatccatg ttacagtgct61 tattttggct aaagagccag tgcaattttt tctgctactg tagtgtttta cttttacaca121 aattaatgag tacagtcctt acatttagga gacagaaaca tttactgaca tcagctaagt181 aaagctaata catggttgtt cacaaactaa acaaaacaat aacataatat actcattagg241 aacaaagtag ggatgttctt atttccacta atcacagatt atataaattc ttaaatttca301 cttacatatt tctaaatcta agcaaaaaaa ttagaattca gcttaattcc tataatcatt361 ttgaaattta catcaaataa tttctgaata tatattcaca ttaaaataaa agtaaatggg421 ttatataaac ataatttaaa atttctgatt atgaaaag<210>30<211>542<212>DNA<213>Homo sapiens<400>301 ttgagaaatt tttttattgt atttgttttc aagtgattct ggtaaccaaa gtattacagt61 tacagggcaa gcaaacattt aagccaaaaa acaatcatat ggcaaaggcc tctgctttaa121 tctactacat gagaggtcat tgttactcat ttccaaagct gttatagact tggaatgtgg181 aattggagag gcttttcgaa tgtagttagt ggtgttcaca aaagaaccac tgcctttcaa241 cttggaccct aagaatgaac ttatcacttc catttagaac ttatataagc aaaaatatct301 gaaggcaaat atcaagccat gtttccacac tcccaaagta tctcatttgt catgagccat
361 gagtgtcact ttttaaactc cttccctgaa tgcccaatca acaggaaaag agcttgagag421 caagggcaga agagtctaga ccaggtgttg ggaactatag ctcacagact ggccacttgt481 ttttgtttgt ttgtttgttt gtttgttttt gagacagtct tactctgtcg cccaggctgg541 ag<210>31<211>558<212>DNA<213>Homo sapiens<400>311 gctttttttt tttttttttt ttctttatat aatttaatat ataccctatt aacaccagtg61 tgcagatgta cagtactgac agtatactaa atagttagta ttaaaaatta ctttaaaaat121 gttttcaaca ttaggtactg gtggaaccag agctgttatt ttgtacatca tatcatttat181 gtgttgcaaa ggaaaagtaa aatttccagt agcattagaa aaaaatgtac tgatatttta241 tgtaaatata caaaatctca tgacatctat tgaaaacctc acaattctat tgtgcactaa301 taaaaacacc ttttcaaaca acttgcactt atactgagtt cataaaggct actataaaaa361 tattgcaaaa gcaataaaaa cacaatatcg tacaaagtct tttgtctttt aaaagtcaaa421 ttttaaaagg actgtattta tataaatgtg caanactttt tagtgaccct gactaacatt481 tttgtttagg attatctgat tttagaaaac taagttaaat gtttttcctt attttctgtt541 tcagaatgag aagaccta<210>32<211>528<212>DNA<213>Homo sapiens<400>321 ttttttttac tttgagaagc catttatttt gcagccttca gtccaaaaaa agtcaacatt61 ttcagaattt ttttatataa gttgtaggtc atttttataa caataaactt tctattatct121 atttatctct cacatacatt tcatgtatcc tgagtattat gttacaacaa tctgctcttg181 atagtaatgt tcctgataga ttaaaagatt gagaaatact tgaagaacga tcaaagatac241 aatgagcatg gtatactttt gggttaaaat gtattctttg ataactgatg tcatatagat301 ccctaagtaa atcaaatatt taatttccta catctgtcta ccttagttaa ctggcccatt361 cctataagct taacaaaaac tcactttaca attatttaaa aaaaacattt aagagatttt421 tagaagttaa atggaaagat acttttggac attacaatat ttttaatgag ttattatttt481 aaaattagag atttcacata aaaaccagga ttctttgttt tctcttta<210>33<211>449<212>DNA<213>Homo sapiens<400>33
1 aagatacagg gtctcaccct gtcgctcagt ctggaggtgt ggcatacagc cttgaactac61 tggcctcaag ctagtctcct gctgcagcct cccaaagcac tgagattaca ggtgtcagcc121 attgcacctg gcctttctct atccttcttt aagaatggta atttactgct ccagggaatt181 ttgggaaaaa caggtgattt ttggtgagtt acggatcact gggaagagac cctaaacaca241 tatacacgca tgcattcgag cacacacacg cacacatgtg catagacaaa taaaattagg301 caaggagaca aaatattatt gaaaacaaag tacccacaca gacaataaca gatgcagcac361 atctttgtgt ggctttccat gctaccaagt ccccaatggg gacttcacaa ctgctgatga421 cacaagccca aggaagtgac atgccagat<210>34<211>536<212>DNA<213>Homo sapiens<400>341 ttgcatgctg ctgcatggtt ttattcctca tgggtagatg aacacacact ggtatatggg61 gaaatcctca cccgccctcc gctgctcttc tggaggtctg tcctcttgct ttcctcctct121 gccccagcct ggtgctgccc caagccctgc cctggcaaag agagaactgt gcacagcggg181 gaggctctcc aagccagagg cctcgcacgc agctgaggaa tgacgcaggg gcctgcaggc241 agctcacgcg gagacaggtc tgtggggccc cgcgtcagaa cccacttcac atcccaaagc301 cccacctgct ttgatcttca atgctgggct caatgtcaga tctggctgac cagaggggct361 caatgaggct cactggctct tcatgcaccc tgctgtggcc tgagcacgtc cccccaaaac421 ccacctgctt aagtcctcac ctgcaagggg atggtattag gtggggcatt tgggaggtca481 tccggtcaca gggcaggggc acagcctcat catgggacca tcacccttac aaaaga<210>35<211>737<212>DNA<213>Homo sapiens<400>351 aagaatcatc tgcttattta ttttacagag taatgattta aattgagtac atttgggcac61 agtagatatt tgacacgaaa aatagttgta tcagaatgag catcagaaaa atagcaactc121 atcttacaca taataactag aaaatattat tctgtctgat catttaagtg ttacaaatcc181 tgagaatgtt atacattgaa caaattaggt actaccttat aattaaatct cgcttggaaa241 gaatccttta aaaaatgctc tgaggtacaa atcacctatg tattaaacat gagtctctga301 cattatacaa agagtttaaa caaatatatc aaacaattac aggccagtgg ctcttaaaac361 agctatcagt caggttcaag gacacactgt tccacaattt cccgtaagtt ggggttttcc421 attgcagctg ccactcgctc tttgtcattt atctgcttat tgatgtcttc ttctgttgag481 tgggttcctt cagaaatgta gatttccaac ttatgtttaa atggtaaaca tcgctgaagt541 tttactctta agcacagccc aataagagtc gccaaagagc aatgaggtac tggtggcgtg601 aacctgataa taaccagata ttcttcttca tttattctcc tgaacttcca cacacctttt661 ccgagaccac ttccagttct tcctaaagaa ttgggccttt ctggggcccg ggatagtcta721 atcaaatcat aaacctc
<210>36<211>582<212>DNA<213>Homo sapiens<400>361 gatcaatacc acagtttatt tgtaaacatg ttatatgtgt caataatcaa attgacaaca61 ctttatagat ttcattgtat aatattaaca tcctaacaga aaacgatcca ctgtactcag121 ttacagtttg gtattttaaa atccttaaat acaaattgta tttgaaacac tgaacacaaa181 aaagaaacat gaatggcaga gaaaactgaa aacaacaagt aaaagaaacc aatattccgc241 tccccttgaa aaaaaacata aaatcatctg attacataat ttaaaaaaga aaccaaggga301 attcagatga cattttttga tttaaagttg catttcttca aatccatttt tagaggtgaa361 attgtatcaa tattaaaatt ctaatgtctt tttgngatat ttgttcttct ttcccctctg421 gttcttaaaa gatggtgggc caggtttaaa ttactttaag ggaagggaaa aaagaaggga481 ggaacttgga aaaagcccag gaaattctat tttcgcaaaa attgttggcg gaattttcga541 gatctttgtg ggaaaaaaaa aggcgcttat taaaaacctt ct<210>37<211>451<212>DNA<213>Homo sapiens<400>371 tccaatgaaa gtctatttat ttgctcgtaa tgagacagaa cgctacaatc tgttcaacac61 tgggctggac actgcagtga ttaggggcag gtgtggggca gaaatagaaa tcacatgatc121 gccactgatt cgcagtggag agggcgctga gctgggcccg gcaggcaggc agcctcagca181 gagattcagg cagtcagcat ggtgcggccc tcccgccagc actgtcaggt cagcagaggt241 tcaagcagtc agcatggcgc ggccgctagg accctctgcc atggctttgt gacactgcag301 ctatgctggg cgggactccg ccccccaccc cacccctgca tcggagggca gggcaggcag361 caagcagcat ttggaatgca gggtggagag gatgctagaa gtatgtgatg cacctgcggc421 actgacagca tctctgccct cagaggctga g<210>38<211>532<212>DNA<213>Homo sapiens<400>381 gattgggtaa aatatataca agataatgct atacttttaa aagagaaaaa gcactttaca61 ttggttaggt ctttggatct gcatatgtcc ctgaggtaag tattccagcc atgggaaact121 gaagcacaga gaggtagtca cccaccaaag ctcagggctg gcctccagag cttgaaccct181 tgcctgagct ggggtcacca gcctgggtgg gccacggagc gatcatcatt tctccatctg241 atcggaaagt cacccaccac tctgttctgg ggcccagccc gcctggctcc aggcaggctc
301 ggaggccgtg ctctcctgga cctggtgcat ctggctgcag ccagcactgg gcaggaaaat361 accgctggag cagtgccagg tgcaggacgt ccccactacc tgcttcctcc tgggtctgga421 gggccaccat gagcccacaa tcccggccag gcccaagccg gtggctgaag tgggcagctg481 tgtctagaag taaggcaatg aggtaggcgg cttcctgggg ctctgggtct tc<210>39<211>334<212>DNA<213>Homo sapiens<400>391 tttggtatag aaatgtttaa tacattaaat cttatgaggt aaaatacaaa aggtagtatt61 cataaaagag ctattttgtt ttatttcact tgaagttctt aagagaaaaa cataagagga121 gatatagaca gacctcatct gtaaactcat gttgctcttt acaaaggaag agacccagca181 gcttttaagc cagttagtgg tagagacagg caagagtcac caaaaaaggt cattttagta241 ttctgtttaa tggaacttag aaagagacta catcgtgggg ttgggggagg aggggggagg301 gcantangga tntacctaat gtaaatgacg agtt<210>40<211>562<212>DNA<213>Homo sapiens<400>401 tgcttaacaa gcagttttat tcctaacaga caaaaataag aagcaataac atatccataa61 gcagatgaat tcgtatacag tgatttccat agcatgtcat attctaagat aaaaagaatg121 aactactcat atatcatgat tgatgaatgt caaaatatgc atccctgcta tgtgaaataa181 aaataataat aaagaaaaaa gaagaacatc taaataaata gggctcagga gagtactcag241 gtatgaaaag aggaaacatg ttatatcagt catataaaat tccagaaaat tgacattaat301 ctactgttaa gcaaatattg taattcagtg attgtctgga ggatggagag gccagagaga361 aagatagtat ttatttttta agagacaggg tcttactatg ggacccaggc tagtctcaaa421 cttcttacct caagcaatac tcccaccctg gactcccaaa gtgttgggat aacaggcatg481 agtcaccatg cccagtctta ttacagcttt aaaaatttaa tttgaaagaa ctatctggat541 ttaacattat ttttgacaaa ta<210>41<211>542<212>DNA<213>Homo sapiens<400>411 gcggccgcgg gacgcgctgg ggccgggcag ccgggaagcg gggcgctgac ggtgagtggg61 cctggccccg ggccggtggg tccccgcggg gcggccgggc gaggagagag gcagcttccc121 ttcccggagc ccgcctgggg cgtggaggct cagcgtccct atcctccatc ccgccccggg
181 acggcggaac cgggcctcag ctggggacct caccaggggg cggggcctcc cgcggtcccc241 ggcgctgctc ccaggactgg aggggcgtcc gcgcccggga gaggggttcc ccccgacagg301 gccccgggcc gccacgaagt tagggaagcg ctctctccag ggtggaacct gggcccgcgg361 ctcccgggag aggagctgcc cgcggaaggg gtcggngtgg gctccaggct gggagaagga421 tctgactntg ctgacctcgc aggctggtag gggaagctgc cccccagagc agcatggatg481 ccccgcgaag ggacantgga gttgctcagc aacagcctgg ctgcctacgc gcacatccgc541 gg<210>42<211>561<212>DNA<213>Homo sapiens<400>421 tttttgagcc aagaagtgca gtaggctgcg gggattttat ttctgccccc agaccaaggc61 aacggagccc tcacctgcct gccaccccca cactgggccc aagcaagctc aggtgagcgc121 acatacatcc accgtggcgg gctcctctcg ggtgaagcca tcaccgaagc cctcatcgtc181 caccaggtcg ggctcacggc agcacatggg acagaggctg ttgcgcacag cagaggctcg241 gagccagacg acaaggttcc aacgctcacc agtgcccaag ggccgggctc catgcagctg301 gccgccacgg tggaggacac cctggcccac cacgtgctcc acctccaggg gctccgtcag361 ggctgtgggt gcctggaaga ggcccccaaa atacagggcg ccccctgtga agaccttgcc421 caaggccaca ttgagggtga gctcggcatt atcatagtgg cagcccagct ccaggtcctg481 gcccggtgcg tatttgacca caaaggcccg gtggctgtcg agccggcccc cgccacagtc541 agggtacagc agggccatca g<210>43<211>484<212>DNA<213>Homo sapiens<400>431 tatgatccaa ttacaaaaaa gttatctgat tttatttctt atatatttgg cacaaacagc61 agagactgaa agctactaca catgttgaac tgctgacagg aaaagaaccc agtagataaa121 tctaggcttt ccactccata tattagctgg ggctgccata acaaaacatc atagactggg181 tggcttaaac aacaatttac ttctcacagt tctgaagtct ggaagtctga gaacaggtcg241 ccagcatggt taggttctcg tagggttctc ttcctgttct gtagacagct ggcttcttcc301 tgcatcctca catggtgcag agagcaagca ggctttctga tgtctttttg agacgagtct361 cgctctgtcg cccaggggtg agtacagntg gcggatcctg gctcactgca acctccgcct421 cctggttcaa gcgattcttc tccttcagcc ctccgagtag ctgggactac aggcacatgc481 cact<210>44<211>544<212>DNA
<213>Homo sapiens<400>441 tttaaaaaag attacaaaac tgaatttatt gagattcaca caagatgcac ttataaaatt61 agtactgaat gccattaaaa cagaagaaat gaacataatc ccgaactccc aacagcatct121 gcaaaggaat ggaaatcttc tgaaaatgac agcgcagtaa cagaataatt caagcggaac181 tgaagatcta tccaaaccat gttcctgctc tgaaatcagg gttgtgtttg gcaaagcttt241 ccccaaacta ttccattcac ggtggcattg ttccttttgt tggtaaaggg agacggaaaa301 aataactcta aaatggggct ccattaaaac acacacaaag caattaaaag ctttttcatt361 tttaacttaa aatacttcct ggtttcacaa aggcatgtcc atacaatttc ctcaacatta421 atcttcagat ttctttagtt aatgcaaaac attaaaattc acttactttt ttgtatttca481 aatgaacaag tcagaacatt aaagcttgct ttatatttca tccaagagac agacaaatca541 ccta<210>45<211>587<212>DNA<213>Homo sapiens<400>451 tttttttcac aggtttgtct tttaatcagc atttttgaaa attcattaaa aggtctgata61 cgaaaagcac caggctaaca aatcagtcct gaattcaatt ttacaaaaac accctctcct121 cttccatctc atccctaata ttcctacgtt atctcgaggt gcagagaaat ataaaaggga181 tccttgacat aaaaacgtat taaaaagcca ccatgagtag aatgtacggt aacagcgtct241 gactcggccg gcaggacagg aaacctacag aaccaccatg ccagggcttt gtgtgagcag301 gcgggcactc cacatgggca cgtgtgtgag caggcaggca ctccacatgg gcacgtgtga361 gcaggcgggc actccacatg ggcacgtgtg tgagcaggcg ggcactccac atgggcacgt421 gtgagcaagc gggcactcca cattggcacg tgggagcagg cgggcactcc acatcggcat481 gtgtgtgagc aggcgggcac tccacaatgg cacgtgtgag caggcgggca ctccatatgg541 gcacgtgagc aggcgggcac tccacgtcgg cacgtgtgag caggcgg<210>46<211>535<212>DNA<213>Homo sapiens<400>461 tgtagtggca agtgatgtat ttggcttaaa gaagcttgtg ttactgaagt taacgcagaa61 gtctggcctc cgtttgtggg attattaaat atatatccta cgggatcaga gtcatctatt121 agaaacagtg atagccctgg gtataaataa acatttcttt agagtttggc gtcagttttt181 caatgtccat cctcaaatca gacagtctgt ttgaggggtc agttttcagg gtgcatctgc241 accgagaggc ttgaggcagc aatgacccct gggctgcagt tcggttgcag gcgctggtgg301 cgggcagtcc aggttggagg gtggagatgg gccaaggtca cagatgctgc agggcttcct361 gtccttgctc tgtgtaaccg tcatcgcggg ggggggttgg gcacttgtcc aaagggaccc
421 ggggatgcgc acgttccttc tgtgtgtggg ccaggcgctt cttatctcgc aggctgccca481 tctcctgctc cttggtctgc aggtctgcct ccagctccac cttctgttcg atcag<210>47<211>469<212>DNA<213>Homo sapiens<400>471 ggcatgtcat cattttaatg atgtgatctt tggtgtttcc ctcattagct gtagactatc61 ccctctcctc ccaccacaat gtttctatga tgagttacaa acagaaagga aatcacattt121 tcatactaaa aacaaaatga tcagagcctt gatttctcca ctagaaacta cacgtacagt181 taagagtcca catgcaacac cttaaatcac agactgagac ctcacattct gacctggagt241 ctcctcccct tccccagcct tgggctagct ttggcctagg ctcaggtaat actgacaccc301 acaggcgctg ctctgagggc cttgcgggga gaagactggt ggacaagccc tgggggctgg361 ccagcctaca ccccccactc ctgagtgagg acctgcccac tgtcccttga ccccatcctg421 tatcaggcaa gcaggcgccc ccttacccca cagtantccc ccattagta<210>48<211>427<212>DNA<213>Homo sapiens<400>481 tttttttttt tttttttttt tttttttttt aaacagggtt tttaattgaa aataaagcta61 aagcatgctt ttcaacaggg caaatttcca taattttgat ttactggttc catcatcaca121 acacagtaca ccagcatggc ccttacccag ggctagaccc tagcatttgc atgttgaact181 actttgattt taagggcaaa tataaatagt cacctctgat tgtcacttgc agtaaaaact241 ctcctgcttt atacacagga tggtctgaaa acacaagttt tagagagatg caaaaaaagt301 ttaaggtcat aaaatccaag ggcctgagtt ctggtcccaa aaagccctga aaaaactggt361 atttttcatt tggggtattg caactctgac ccctcatttt ctttttcttg gggggattta421 ctgattt<210>49<211>508<212>DNA<213>Homo sapiens<400>491 tttttaatag tgtcttgctg ttactcagac tgaagtttcg ccatcatagc tcactatagc61 ctcaaactcc tgggctcaag ctatcctcct tcttcaccct cccccaccat gctcggctaa121 tttttaaaat ttttagtaga aatgaggtct tgctgttttc caggctcgtc tcaaactccc181 aatctcatgc aatcctcctg cctcagcctc ccaaagtgct gggattacag gtgtgagcca241 ctgtacccag ctgagagctt aagtttcttg cataaaactc agctgtatgc tgaagtgttt
301 agaagtgaaa tgtaatgatg tctgcaactt actttgaaat acattaataa aatggataaa361 tgaatggata gagggatgga taggcagatt gacatgtgta aaacaaatag agaaaaatgt421 tatttgtaga atctaggtga tgctaaaggc cacacagcca gtggggactg agccaagcta481 ggaatccagg tccaccaatt caggagag<210>50<211>507<212>DNA<213>Homo sapiens<400>501 ttttttagaa aagtcctttt tatttcttta aatcagaggc cccctctagc gtttgaaagc61 agtcacaggc aacacacaat gcaattgaaa gtaaacagtc acagcatttt accgcagacc121 ttccaaaaca taaggcttgc ttctgttcca ttcaagtggc acaaaaatca atgagagaaa181 aatagctaac cataattaat attgcaaatt cctgctatga ttcagattca ttatcctctc241 attcagtaat ttctttatta tttactgctg ggttattttt tactagatta atactctgtt301 aataaggaaa aaatatataa taaatatagg gactttaatt tccctaataa gaaatatacc361 tcatttgaaa tgaccgaaaa ttaatgttac catatatcct actctgcttt gatggaagtt421 attggtaact tcctaaagta tatacttaat tttaacttta ttatatttgg aaatcagaac481 tttttaaagt acatatattt tgaaatt<210>51<211>541<212>DNA<213>Homo sapiens<400>511 tttttttttt taaaagaaat ggatgctttt attcaacctg agttaaaacc acaatgaatc61 atatcagagt tcatgggaat cataataaat gactagtaaa ccactcacaa aatcaaagct121 atcaacatac taggatcaca cacattaatt agtgctatag ttcaaaacat accctttaac181 ttatttagca cgcaaaataa tcataaaagt aatgtctata agctctaacc aaaaatttta241 aaaattaaaa atagcacaat tctacaattc tgattttacc aagaaaataa accttttttg301 gcacatatta tcctatgaaa atggaaagct gagtcaggct gctctgcttt tcacagcaca361 aataagcatt catgctatca gacttgggaa attaactcgg tgacaaaaat tcactggaaa421 atagaatcct tggaaaaatg gggtcaggtg ccatccactg agaggcaatg ataatgtgtg481 tccttcgtta ttagcacaaa gttaggcagc acactataat tntagctaca tgcaactcta541 t<210>52<211>369<212>DNA<213>Homo sapiens<400>52
1 tttttttttt tttttttttt tttttttttt tttttggcta aaatttacca catttattcc61 aaattgggat tttataacaa ggagaagtct ttaaaatact aagggggcaa aaaaatacat121 aatgggagac tgacatattt tcaaacttaa gtcacattgg catgaatcaa aacaaagtta181 ccccaactaa aatacatata agaaagagcc actgaaggaa aagcatcaca agacacagca241 acacacttca gttcatttgg aaaatctaaa attaagggtc aaagcagctc acttaattga301 atctgatttt caaaatacac atttcaggga caagcatttc cacttacctg cttcattatg361 ctcttaaaa<210>53<211>298<212>DNA<213>Homo sapiens<400>531 tttttttttt tttttttttt gggtttgacc catttttata gaaagccagc taccaaaagt61 aatgagtccc cagggccaac cacattggag gcctgggtga gggaccaccc agcagggagc121 aagggaggga tgcagacaaa ggtagcagag accctggcaa cctccttcca gtactcagca181 gtcacaggtt aactgtggga gaacccagca acacactggg tccccagcac agtcttgggt241 gggcccttca tggaaggggc agggaggctc tggatgcttc tgcagtcatg ctgaccca<210>54<211>520<212>DNA<213>Homo sapiens<400>541 ttgtttttta gtataaagag tagtatttta ttgaataaga tttgctcaca gaaaaataag61 cttacatcta caatgaatgc cagaccctac agcagaaagc cattttctca cttttccaca121 cacaatggtt cctactaagt gaaaaaaaaa gccataaaat ttcattcaca aatgtactac181 tctgtctcaa aacatcgcac ataatcatgc actgtactaa agccattaga tcagttcttc241 agtcaggtta aagaagtatc cctctaataa ctgactttta taatgctatc aatatccact301 cccaatcagt ctgccattgt taatggtgta cagcattact gaatacaatg gaattgatga361 cgcccatatc cacggacaaa ccgtgactta tgatggtttg atttacgatt tttcaacgtt421 atgatgggtt tactggaata ttagatgcgt ttctgagtta cactgggttt atgagtatgc481 gaccctatac tccaganaca gctgtagaag gaaaaacagg<210>55<211>166<212>DNA<213>Homo sapiens<400>551 tttttttttt ttttttcagc agcacaaatc ccttttatta accatcttcc ctttctcgag61 tatacacaag tagaaaagaa acagggaagt accccgatag ggagggtggg gagaggatgg
121 gagggggctc ctgaggttag gacaagaggc cagattccag ctcctt<210>56<211>462<212>DNA<213>Homo sapiens<400>561 tttggttttt gtgatgctgg aagaatgacc agaatgagtc ataggaagag tatacattcc61 tgtagtattt tccaggacag aggtgtgacc tcctagagta ctgggaccaa aattcccaag121 tgtctgcaac cttgctttaa cagtatggga gatcacctct atcacctgga attcccctgg181 aactctggaa tatacaagag aagtatgaga cttgggtctt cccttggctg tgtttaattc241 actcttctat ggaataccaa tgattctcac taagactggc cttttcataa gcacaatgtg301 cattttatgg agaagatttt acactttgct ctatttagaa agaataaata tgagcagtgg361 tttaggtttt atgccctgga cttaatatgt ttctgattcc tgttttgaga ttaaattctc421 atgtaaatag aaaaatactt attatttctc ataaggccaa gt<210>57<211>424<212>DNA<213>Homo sapiens<400>571 tatgaacaga gtggtttaat gaaactactt tttttttgtt tttgtttttg ctttcctttt61 cccataaatg ccatcgtttt ggtaaatgtt attactacag cctttttttt tttagttctt121 tttttgagaa ctaccattta ttgagaatgt cttattccag gttcctacat gggttttcat181 aactactgtt ttcaacaact ttgagacaga cataataaat aatgtagtaa acagcatgga241 tataccctca gatctctaaa acccatggtt ttggcacaat gccattccaa cctctgccat301 cttcatcctc ctgctttaac caggaaaaca tatttactgg gcagtagaca tgtcaaaggt361 gaaggtattc atatccaaat aatactgtgc tgttgttttc aaagcaatcc atgtttcacg421 agcc<210>58<211>515<212>DNA<213>Homo sapiens<400>581 tttttttttt tttttagaag ttatgattaa attttattgg ggcataaaac ttgtgataca61 ttgtaaataa aacagtagca aaacataatg ccagttgtga aacgtctgtg tatacgtgca121 catgctattc tggttctttg gtttggtttg gttttttttt tgaggcagag tctcaaaaaa181 aaaaaaaaaa cgaaacaaaa ctccagtgtc ttaatgtcct ggcgtgccat ctcctggtca241 actggtaaag cagcaatcct ttcctataag ccagtggccc tttggagaag ggcacactga301 acacaataag catgactttt agttttgtat ttttctccac ctctccctga tgctaattca
361 tacaatatta aatttcaaaa ttcagcattc ttgttcttcc agggagcatg aataggaatg421 aaccacacct aatgaagtag gccctatcat tttattgatt ccttcccaaa gatcataatg481 aaaggcctgt aagaaaagca taaaatcaac agatc<210>59<211>604<212>DNA<213>Homo sapiens<400>591 tcagataatc aaaataattt ttatttggtt gtagaatgtt gtagtacata aagcaaaatg61 tgtctgcagg atactccaaa tttaccaact tcaaacaaaa taatgcacag tgaagaatta121 gaaaattatc aaccttactc aatacatgga agtattcctt aatcttcatc attttcatta181 aacaaaataa tattttggat gagttcaaca tttctatcct atgctttatg tttagtgcct241 tccctgaatt ggaaaaaatg aggtgtttta tttaaattta acactggtct aagggagata301 tagaattaaa ctaaacaaga atcggttatc acaacctcac aacatatatc aaagtattga361 gattgttggt ttactgactg tcacttttca ctggatatta aatatcctga gggctacaac421 tgtatttttt aacctgtccc agtacctcaa caaaattttc actgaatgta tgaataaatt481 atgttaacaa aaagttaaca ataaaagtat aatgaagatc cctttaatta attntaaaat541 ctgaaaggaa aactggagtc acaaaacata tgttcaaatc ttaattcatc acaaattttg601 tgat<210>60<211>792<212>DNA<213>Homo sapiens<400>601 tttttttttt tgtttgtaaa aatcggcatg ctcctttatt tgttcagaag agcagccagc61 atcaccctcg ccactcaaac ctggcacata cgcttcggag acaatggcct cgggaccctc121 atgctgctgg gcccaggaga gacagttctg aggcagaaac tcggcgtcca aggggggccg181 cgggtcaggc actgtggtga agggaacgcc ggggagtccg gccccacctt gcagctgggg241 acacgggggc gcaaacagag ggggcaggct agtgtcccgc tgccccagga acagacctca301 gggccccagg agggtctgca ggcagctagg agcctgccaa gtgctggtgg aagtagaggc361 cgaaaaggct ggcgagcagc tggcaggcag ccgtccacca gatgaggtag gccaggacgc421 cacggaggaa gaggggagta agcaggccac ccagggcccc ggcaatccgc gctgcagtct481 gctggacttc gtcctcccca gagccgatgg gggcagcgct ggctgaggat gggtcggggg541 atagtagagg agtgggccca ggccccagga atagcctccc agcgtcttga gagagtgtgc601 gtttgaggtg agatgagcgc gtcagtactg cagctcacca ggtcacatag agagactcga661 ccacctctgc tgattcacgg gctcatgcgc cagcctctcg tccgaatctt gcctgaggca721 aatcccctat gaagcgataa atcgaatcag ncaagtggnt ccgtggaatg tatcgtacat781 tccccacata ca<210>61
<211>558<212>DNA<213>Homo sapiens<400>611 tttttttttg gttacaggtt ttactgtctt acagtgtgaa taccccatga aatcgtagaa61 ctctttgcaa cttatgtcac acctgtatct tcaagggcaa ggattatttg ttgctatagt121 ttttatgtca ctaaagtacc ttttagtgtc atatacatag tagataacac tggataataa181 taataaaaaa gactaagaat gctaaagtag tctaggaatt cctaaatctt aataaaaact241 gagaaataaa gttgtgatac tatataacac ttaaggcacg agtaattttt ttttcaccgt301 ttcccctcca tggctatgaa ggaactggga gaaggatgct cctttcatta attaaaattc361 ttcactttga aaatttaagt ttattaggga aggaaggaag aaaaatatga agatgtaagt421 atacatacct tggagtaagt atttccttat attggagttt ctctaattta gctggggcta481 ctaatgacat gggaatcaca atgttatcta tgtcataaga gctctcactt ctcaatctcc541 gtcgtgcagt attctgca<210>62<211>478<212>DNA<213>Homo sapiens<400>621 ttatgcaatg ccttgcgttt atttcggaga cgtgattggt gcctagactt ctaaagtaac61 agaatttgat atggagtgtt gaaagctgaa ctttatcaat tatcacagca aaaatctaag121 taagcgcccc gtgagaaccc taaaattaat aaaagctatc ttgtatgggg cacttacagt181 tccacaggca cttgtaggcg ctttattcac aataatcgca gaagagcagt ataaagagca241 tgcactctgt taccaaacca catccctgct ctacaggtgc tcccttagcc catctgtgcc301 tcaattccct aagccgtaaa acggaggcct tgttctgacg ctgtgataat ttagtgcggt361 aataggaatg atgcactgaa cacaaccctg gagcatagta actgattaat attagttaga421 atattcatta tgatgataat gattggcaga gccctcgctc ttcacatgta ttcccaaa<210>63<211>211<212>DNA<213>Homo sapiens<400>631 tttttttttt tttttttttt tttagatagg aattgggttg caaaaagccc cttttgttta61 ttttattttg gaaaaaaatt ttattgggaa aattcacata tatatataaa aaattcaatc121 aatacaaaag gatagacaat gaacaaatga attccccttc cactccagat ccccacccca181 gatccagacc tcctgagccc actttcccca t
權利要求
1.一類在人類肝臟中表達的表達序列標簽的序列,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.如權利要求1所述的表達序列標簽的序列,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。
3.一種探針分子,其特征在于,所述的探針分子含有權利要求1中所述的序列中約8-100個連續(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的表達序列標簽的序列。利用本發(fā)明的在人類肝臟中表達的表達序列標簽,可以方便的尋找出在人類肝臟中表達的相關基因,從而在研究肝臟疾病的致病機理以及開發(fā)治療肝臟疾病的藥物中發(fā)揮重要作用。
文檔編號C07H21/00GK1955297SQ200510030829
公開日2007年5月2日 申請日期2005年10月28日 優(yōu)先權日2005年10月28日
發(fā)明者黃健, 韓澤廣 申請人:上海人類基因組研究中心