專利名稱:人類肝臟中表達的表達序列標簽e組的制作方法
技術領域:
本發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:
肝臟是人體內最大的消化腺。也是體內新陳代謝的中心站。據估計,在肝臟中發生的化學反應有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、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;調節血容量及水電解質平衡;產生熱量等。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。現代醫學實驗證明,肝病病毒侵入人體后,并不直接引起肝細胞的損害,只是在肝細胞內吸收營養賴以生存,并在肝細胞內復制、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,引起人體免疫系統對這些抗原物質產生免疫反應,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。這場由病毒引發的、免疫系統對肝細胞的戰爭,使大約25%的患者的肝臟成為戰火連綿的戰場,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)結節性動脈炎;(12)消化性潰瘍;(13)自發性腹膜炎;(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現,并獲取基因組中與產業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,使從質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,提出大規模互補脫氧核糖核酸(cDNA)測序的研究戰略。隨后Venter創立了大規模表達序列標簽技術。其基本特征就是從以質粒為載體,構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、基因組序列編碼區的確定等。如果一個表達序列標簽在基因組中只出現一次,那么它可以作為序列標簽位點(STS)。由表達序列標簽構建的物理圖譜叫表達圖或轉錄圖(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據庫,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越性,因此表達序列標簽測序已經成為許多基因組研究機構的工作重點。
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在新基因的發現、基因作圖和基因組序列編碼區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)。
在本發明之前,還沒有出現涉及本發明的一類在人類肝臟中表達的表達序列標簽的公開報道。
發明內容
本發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,本發明通過如下技術方案實現在本發明的一個方面,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.60所示的序列;(b)SEQ ID No.1~SEQ ID No.60所示的序列中每條序列的互補序列;(c)與SEQ ID No.1~SEQ ID No.60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)中一條或數條的組合。
較佳地,所述序列包括具有SEQ ID No.1~SEQ ID No.60所示的序列。
本發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個連續的核苷酸。
由本發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治療肝臟疾病的藥物中發揮重要作用。
具體實施例方式
下面結合具體實施例,進一步闡述本發明。應理解,這些實施例僅用于說明本發明而不是限制本發明的范圍。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,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測序及數據庫建立(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大規模測序。測序結果用FACTURA軟件去除載體序列,傳輸到SUN 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軟件搜索已有的數據庫(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據庫。
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數據庫,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,通常可獲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據庫或自身數據庫獲得,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E組<130>NP-10045<160>60<210>1<211>688<212>DNA<213>Homo sapiens<400>11 acagccacaa tagtttattt acaattgaac tctttataag atatttacaa gacaaccaat61 tttacacatc agaaatggta tcaaaagtta tgaattacaa cacagacaac aatatgaaat121 gggcataaaa caaagctgaa gtagacagac aagcaatttt ttttaattta ttaacactag181 cttaaacttt gttaaagaaa aacaaacaac tatgttttag gagaactgca gggccttcag241 ttgaacgatt gaattcacag tgttgtatcc catgtaggga aaaataagac taattttccc301 cccacactct aacacactgt aattttgcac ttggaacttt gctaatctac tgtccaacct361 ccttctcaac aaagtcaaat caaaggagaa ttaacctaga agaggggaca ataaaataag421 aggtcctcag ggagagggag aaccaaggaa atagaatcta cctaaatctg gccagataag481 cacctcgtgg nttcttctca gtcgnttcaa gtcagaaact ggggagtccc tgggtagggc541 acaaacacaa tggntaaatt ggctactcat ncccanattg ggaaccgnca catgctgnat601 ccngaagaac ngaggganca aggaccaagt cagagccctg gttgggnctt ttnccttttg661 gaccgtacga gaatntccat nggaagan<210>2<211>464<212>DNA<213>Homo sapiens<400>21 ttttaacaat ccatgaactt agattttatt ggtttcactc aaaatgctgc agtcatttga61 cctgaacttg tggcaagaga cttgtgcttt ctaaattcaa agactagaag gaaaatggat121 aaaaatcaca agtgccgttt ctcttgcaat ngtagcgcta ttctactgaa atttctttct181 tctcttttct ttacaaaatc ataaagaaaa aattaattca ttacttatat agtaggtaca241 actcagccta caaactctaa tctgcaagaa gcataacttt atttttctaa cacagaatgt301 aatttctatt aggaaccccg tttcagcagg tggtagaaat taatctcagt caattcaaag361 tctccccctg gaccttttcc tggggttaag ctcggtcggg tgggggtgtg gcttttaagg421 catggtaaga cttctggttc ctcggctatc atcatccgtc catg
<210>3<211>690<212>DNA<213>Homo sapiens<400>31 catacaactc atttataatt tattttcaca caactcacta tgttacaaaa ctgtacacct61 gcccccaaag ttggataacc caaagtcaca ttccttggaa agagaagaat caacactggg121 ccgctttttc aagagcagtc tcttctggat tgggcccaac aaggctagac cagaatgtgg181 agtacaggaa tggccattct tcaagtccga ggggtcaggt tcttagcctg gtgcttccag241 tcgttacagg aggggtgtct ctgtttggaa agccagcacc agcacccaga acacaggagt301 ccagagagac aggcaggcac tnttggccac catctggctg tggtgggaat gcccacggcg361 aagggagccg cagttcagtg gagatgtgcc tgtccaggac agggacctgg agttgcggga421 ctatgtcact ctcctccagg cggacccaca gatcgctgaa ttgccggagt cgcagcctnc481 gctgtgaccg cctccgcttc ttccggaanc tctgttcggc ctcactgggc gtgtcggcac541 ttccaggccg ggacacaagg ggaagcagct tgantgcctg aggatacggc ttctggtgcc601 ggncttccan ggtaaggact tttgangcaa natggtggac anattgggcc ntttggaggt661 ttttaccctn cctttgtgga tgggtcgnaa<210>4<211>574<212>DNA<213>Homo sapiens<400>41 nttttttttt tttaggataa cattatttat ttatttcctt ttatcaaaga aggtaattga61 tacacaacag gtgacttggt tttaggccca aaggtagcag cagcaacatt aataatggaa121 ataattgaat agttagttat gtatgttaat gccagtcacc agcaggctat ttcaaggtca181 gaagtaatga ctccatacat attatttatt tctataacta catttaaatc attaccagga241 actgtttgtt ttgtagtgaa ccttgagtat gtgctgttaa tataccaaat tgggtgaaaa301 aataagggat tcctttcaaa agttaagaga agtaagtgtg taagaaatta ttttgcttat361 naaatgttcg gtaaatggca ttctcttgtc agtaaaatgg agaaataagc taaaaataan421 tggctaagtc ctattaagtt agaggattaa gtgtattata tttgccatca aattgggtgc481 tcattaattt atgatcggta gtatagcnaa attgctatgt ttgtatcana tggagcanaa541 agttgctgaa ctgtctccgt tgaaccgaag tgga<210>5<211>627<212>DNA<213>Homo sapiens<400>51 tccagaataa gaacatgttt attcagatgt gccagaagtc cagggtcacg cggcttcgca
61 tttaggagat gctttacaag ctctcccatt ttcttttcag aacatacact gggggaattc121 acaaactaaa acaatttctg gtgacttcca atctatatat tatactttac agcttcaatt181 gaattttttt aaaagttaac ttccaagctg gcttgcctaa cactgtgagt caaaagtaac241 cctaaaaagg aaaaacacac agcactgaag ggtctctggg tggtaatgcc agcgtgggct301 ggggaggtga gactaagcac atggctagca gacctcagga tgggccctgg ggctcatcat361 acagaaatat tgacaagatg atgaagtcac aacttcagat gtcattggag ctatctgtat421 atgacacaca cattatnaac aaataacctg gaacattttc acagtgtacg acanctgttc481 tacctgggaa tgcnaaccct gagctgcaat taagacncag acgttggaga caccacggnc541 tgaagctgct ctcctcttcc cggtctcctc tcctccggtc cngtgatggg tacgctgagc601 cagcaatgtg cncgccttaa ctcccng<210>6<211>551<212>DNA<213>Homo sapiens<400>61 ntacattatg gaaatttatn cctcctgaat gtataaggca ggagactaat tcaatataca61 ttcactatgc agaattctac aagttctggg ctatgtgtaa atgtgccccc cttccctcca121 ttatcaggat gtttaaatgt gtttcctttt tttcatttaa aactttgctt agatgtttta181 cattgccatc acctcttcct gagaaaaagg tgtgtccccc accccaaccc ctaggagcca241 ngcagactat cttnctgagg ggccacaagc acactcccac ngtggagaac aagggcagtg301 gatgaaggga acggggattt ttcaaactaa tgttttccct caaacaggcc tcccggcgcc361 ngttagactt gaagcaatga catctattaa aatggggacc ccagctgggg gttaagaatg421 ttngtttaag aatgatgacg atatcttgaa aagaaattct tggctgggga tggngtaggg481 ggaaagggaa aaaaattaat tattttgact ttcccattgg caatgcttgc tacgtttaat541 ctgattgcat t<210>7<211>486<212>DNA<213>Homo sapiens<400>71 tagtggcaat caaatttatt aactgtaaag gacatcaata agaacagaca ggaccagaaa61 ttgtatcttg gtgatccaca tgccaggagt agcgcggcag aggatggaga gtggaactta121 gcgattgagg cgcactgnca gaaagctgca cttctgcact agagattaaa taagagggtc181 aaaatcaaca taaactaaac cctttttcaa agtcatgtaa acacaaatga ttgctgcaac241 tggaaaacaa cattgaaaat aaatgattcg tgtgatgcat atcgatttca acaaaccttt301 ccttaaacct ttaacgttac tcttacaagc aaataccgtt aatagcttac ttctgtctta361 atttttctaa ccacaggaaa attgaaacat aagtaatctg ataaacatca agttttacgt421 tgatgcnttt gaccacaggg tatatacagt gttaagaatt taaattctat ccatcagata481 tntttg
<210>8<211>579<212>DNA<213>Homo sapiens<400>81 tttttttttt tttcacactt tggaaaattt caactttatt gttccaaaca tgagaaaatc61 caacagttgc aaattatgcc agcagttaaa tgtgaatcct actcaagaac atgttccact121 ggtagttttg attaaactct ctactctgat ttaactgttc tctcttccat ttgaaaaatc181 agagtacttt ttaatcagtc tttgctaaac agcagctatt gctattcaat ggagacggtg241 gccaccattt cccctgcatc gtctctccta cgtaatcagt ccctgatgaa ctctcttccc301 ataaaaatcc ctgtgtccta aagtcatggc gtgctctatt tcatggtcat ttgtagagca361 cagcagcact gtgcctgtca ggaaaagtgt gtgctaactg gcaataagca tggatgactg421 ccatcacggt tttggtaatc tctgtccacc tccatggtct ctaaaatcag acaatcttta481 atctgaaaag gcagtgtcct aantcctcca ggaaactgga tagaaacgct cctcatctaa541 tgaagtcagc cnggtcatct acngatcctt ccagacaaa<210>9<211>312<212>DNA<213>Homo sapiens<400>91 gggaattgct tagtgaaact gtcacacagg cacaaacaca tgtcagcttt ccttctagtt61 tgtaaataat atttgtaatt tacaggccac tgtattccca actttgcacc atgtgattta121 gagaaagcaa agctccctct ttaaaaataa tatgttactt ctgacatacc gggatattcc181 acggcaagta agccatattg tcgccagagc aaataaaccg cagccccata tcataattca241 ctgggtgcta tagatgtaac ttggctttgc tttgaatgga agatcctgac gtctgtgatg301 tgatgagttt gg<210>10<211>774<212>DNA<213>Homo sapiens<400>101 accaaaccaa atcattttat tgtgcaattt ccttctacca gaaaattact aaaaatataa61 atattaactc tctaaaaaat actcagaata gatctgtaat cttcctcctc ctcctccgaa121 ctggagccaa tcttcttctt taaacgctga tggattgcat acatgtatgt cttccatatc181 agccacatac acaacattca gatacacttc cctctgtgca gggggataca ccagcctcct241 gccaggttct ggaagctcac cttataatct accaggataa agctgtgtgc tgagtaggag301 gttatggtgg ggttggggag taacaaggag ataaaagacc ttgtggtccc aacttcctta361 tgtggacaga gaagataggt cctttactcc tcctcattac cctgccctct catggactgg421 gctaactgaa ggccaagctc ccagagaagc tggactcact gtgtnggatt actgagggtg
481 tggctgccag gctacagtca caggaaggnc agactgttga gatggacatg gaaaccaggt541 gaggcttgga tggaaagctg gtctgggcca agggctctgg caggatgagt agtaagctgt601 ttcctggctg ggctttnggc agcccctaga ccctangcac caggtactat gtgcagcatc661 ttaagancca gacaccagtc ttcagagagc ctnccgaggt agccgcaaca ttcctgcagc721 aggggacggg caggttgtan gcagttagat tggagccagg tnccatggca ctgt<210>11<211>631<212>DNA<213>Homo sapiens<400>111 tttcctgtga aaccaccata gagaatttat ttttttctca ggtgaagtca gtaactaatt61 cttcctattc ccgttggaca caaggagtct gtgagggggt gtgaaggaag gaggctgcgg121 ctgcgtcctg gactccgtcc tgcggtaggg agtccagcag ggatggctca gcctccgcac181 ctggtgtgca gccggatctc catcctgagg aaggccttga ggttctcatc agccacgtgc241 tcctccaggg cagccagggc ccgctcccca ccgtcctgga agtgctgcag cagcctgtcc301 gcgtactcca cccacacgca gttggggcag ccactcatgc agcagtttgt gggcggctgg361 agctcaggtg gcagcgatgc ctttgggcgg cctggtgcgt ccgcacctgc ttgggagccc421 acctctacgt ggtctgtccc gaattttctg cgcccatcag gggcttgcgc tccgggatgg481 tgcctttgaa gaagctgcna cctccaggaa gcctctggag cagtccgggc tgganaaccg541 gcgagcccca atttcantaa ttaactagtc ctgcgaaggg catcatccgg ttcatgtcaa601 aggcaagtcc canagcccag gaggttgnaa a<210>12<211>542<212>DNA<213>Homo sapiens<400>121 ctctgctgtc ctgccctgtg tcgttggggg atggcgagtc tgccaggcgg catcactttt61 tcttgggttc cttacaagcc accacgtatc tctgagccac attgagggga ggggaatagc121 catctgcata ggaggtgtct tcaaacagga ccgagtagtc atccttgggc cgctgtgggg181 gcgcatggat cagggcgcgg tagaagcagg tagtctgggg atacagggcc agcacgagct241 gctccttctg gaacaaggcc tcagggtccg tctccgggtt ggccttccac tggggcagcg301 ggatgacacg gcgccggtca gggtgtgtct ctcttgcctt ctcatcgatg tcatctaact361 catacttgtt ggtnggatgg ctgtaactga ccactgggcc agattcactg ctcgttcccc421 attcaagggc ttcaaccggg caagcaacct gtctccagtt ttggcaagta ntctcctgaa481 ggcaggatgg ncccacaaag ggttgggggc ttgtnaacaa ggctttccga ttcanaaggg541 ca<210>13<211>649<212>DNA
<213>Homo sapiens<400>131 aaaattcaaa aaattagttt attagcttaa tataattagg tcaatggaat cctgttttga61 tctcaatact tcccatattg caatatataa atgtgacaaa ttcagctgtt ttgtggcata121 gataagtgtc taagctgggc agttagtcta cccgtttata gttcatgttc ttcatggctt181 tgcagcattt gtcactttct atgatgtgtt caaagaccag aaaaggccac acttgacctg241 tcagctggtc cttgaacagc tgtaggtttt tttttttttg agacagagtc tccctctgtt301 gtccaggctg gagtgcagta gcgcaacctc gactcactgg caacctctgg cctccaggtt361 caagtgattc tcctcctcag actcctgagt agctgggatt acaggcacat ggccaccatg421 gcccggctga tttttatatt tttagtagag atggggttcc accatgttgg ccaggctggt481 cttgaacttc ctgacctcaa gtgattccac ccanctcggc cttcccaaag tggctgggat541 tacagggcgt gaaacccaac acccgggccg taggttttaa anaataaatt aggggtatta601 acccctaatc attccctcca atcattcaaa tttctcccag ggtaactgg<210>14<211>549<212>DNA<213>Homo sapiens<400>141 ttgtacatca aaatgagtta ttttaatgaa tgaaaaacat taaatctacc agtctacaga61 aaaagaaaat gtgtatttga catcgtttaa ggtggctctt acatcaactc cttacttgga121 aaactggtat ttaaatgtca agaattaagc ttttctcctg tcttcccagc attgacgatt181 tcgaaaaatt tttgatacta ttctacgtaa cactgcttta nctaagtaag tatatcttct241 tagttccaag tgtcctatcc agcctgctct ccagtcattc ctgcttagga ctccctgtgg301 ctgggtgaaa caggactctt tcccttgctc cagatgagag accaaagctg gtttggaagt361 gggtggcact acaaaggcca cagcctcata gttctccagc atcacatccc tgtacaaggc421 cctctcggca ggcaccatga tggcccattc cttcgtagtg aagtacacag ccacgtcctc481 aaagccactg attcctgggg cctggttgtt aaggacacag ctgtcatcat ctgacctctt541 taatccttt<210>15<211>478<212>DNA<213>Homo sapiens<400>151 tgaagtgttg ggattacagg cgtgcagctg cgcccggcca attttaactt ttcataatag61 atttgtatat atttatggta gtaaatgata aaatagacta gtgtctacat atattatatg121 aattcatgac acaccttttt cttagttttt cagtatttct aagctacatg gtgcatctgc181 aagtttttta aattgttgca aatttccaaa aaaattttca atatatttat caaaatatgc241 atataagcgg tcctatgcag ttcaacccgt gtttgagaat caactttatg acttccagtg301 tcattctcca ccatttctgc agtttatcac attttgcttc aggcagattt ggtaaatctt
361 caatgatagt tctctaggcc attgttttgt aacatgatca aatgcttaat gggaaataga421 atatgtatat gtattctttg tctaccaact accagagaaa caaatactcc tcagtttg<210>16<211>510<212>DNA<213>Homo sapiens<400>161 aaggatggag acggtttatt gttataccaa aaatatatgt atatatctat atatatatgc61 agaaataaag gatcagaagg ctataaaccc aagtatcatt agcatttata tctaggtgca121 gcattaagcc tgaattcccc tttacacttt attttacact gaacgtgtat cctatgtaca181 atagagttaa gcaataaagc tgtcttcatt tggaaatcaa ggcaccatta tcatccacat241 cttcaccagg actgtggttg gggaccaagg ggagtaggga tgaagatgtc cctctcagaa301 accaggaaga gccaagccgc gactccccgc tccccaaccc atcctcattc ctcctctact361 gcctgtggca tcaccgtggg gcctgtgtta gagacaggtg gggaaaagag cccaagagcc421 gtctgcctgc acagagggca tcataaatga gaggggaggc gggcgcagtg gctcaccctg481 taatcccgca ctttgggagg cgaggcgggt<210>17<211>481<212>DNA<213>Homo sapiens<400>171 tttttttttt ttttttattt ttatattatt tatttatnct ncgttagttt cttcagatta61 tcatccactg agggtggaag gggagtgagc agacacactt gggaggtgtc ttgagattat121 catccgctga gggtggagct gagggtggaa ggggagtgag cagacactcg gaggtgtctt181 gagattatca tccgctgagg gtggaagggg atagagcaga cactccgcag tgtncttgag241 gctcagggag ttatcagtta tagaatgttg ttgagttgga ggaggtggct ggtggcccat301 cctgtttttt aaagtttcag ctgtnaggta gggccagcag ggcaatcctg aagaatgacg361 atgctctgct gccgccattc tgacctgtag ggccaaagga gggaatgttt tcacacatat421 tcatttgatg gacaaaatta ccgccaccaa cacagtctgc accttctgtt gctggtgata481 g<210>18<211>512<212>DNA<213>Homo sapiens<400>181 tttctggctg acaaagatat ttattgaggg tttactgggt acagcgagaa gggctgaatg61 gcttgggatg cagagagaga cccctcccct gggatcctgc agctccaggc ccctgtgggt121 ggggtggggg ctggaaccta tgaacattct gcaggggcca ctgacttctc cacggtgctc
181 ccttcttgca taacctggca gctgtagctt ctgcgggacc tccactgctc gggcgtcagg241 ctcaggtagc tgctggccac gtacttgttg ttgctctgtt tggagggcgt ggtcttctcc301 acgctctggg tgatgagggt accatctgcc ttccaggtca ccatcaagat tcccggataa361 agttattcat gagacacacc agtgtggcct tgttggcttg gggctcctca caggacggca421 ggaacagaat gaccgacggg gtagtcttgg gctgacctaa aacagtgagc tgggtcccac481 tgccaaacac atgcttcact gaattatgct tg<210>19<211>456<212>DNA<213>Homo sapiens<400>191 tttttctaat aaaagtgttc ctctgcttga cctggaggag ccagaagctt gtttatacct61 tcagtattca agggacagtc acaggcctgt tttgaccttt tcctgagaat tagctgaaac121 ttccctctga agtcaagtag tgaatctgtt ataggtctaa ggaaggtcct cttcatctgg181 gagttcttgg cattactttg gtccttcttt cagaaacttg gcaagttgga aagtgcaaag241 acaatataag ggcccatttt caggccaggt ccagcatgaa acagagtgaa caaaattagt301 tccacacatt agggaagagc caagtcagac gaatatccaa tcatttgcag tagtagaggc361 aggtgaaggg tccccagatc tgggaagcag ggctcaaaac ctggccagga ggtcttgttg421 ggccaggaat gtccgtggtt ggtgaggagg ctggga<210>20<211>449<212>DNA<213>Homo sapiens<400>201 gtatcaacaa ggaggaaggt agacaaaaaa atccagaaat ctatgtagag accccattgt61 gtacattgcg gaacactaag cctaacaatt ctcaaaatta gcgtgagatt gggaaatatc121 taatttccat ccagccacag tggagagtcc tgactgaaaa ccaggcattc gctaaagatc181 ccagaaaggt tgtgtgttac atacgtaggg ctaaactatc ctgactaaaa actacactac241 acttgctcct cacccccaca aaaagcttaa aaacaagcct caatagtata aagctgatct301 gtaagtaact aaactacctg cagaacaaag tccaaattta ttagttccag tactccaaaa361 aaaacacatg taaaaaaaaa atagatttac aagacattta tttggggaaa aaaagaatgc421 ctgagggttg aaatggagag gaagccaga<210>21<211>412<212>DNA<213>Homo sapiens<400>211 gtatttgcaa aagttttatt ttaaaggatc aaaaataaat actgcacata tacacagaga
61 aaatccactg atatttatgt tctttgacgc acactttcaa tacatggcac cttcatcttc121 tttattgaga aaataaactg ttatgggtcc ataactggta tgcacagtct ctgtgactct181 ggcaaataac caggagccaa gtccatataa taaagttgga ataccgaggt tgacgacctt241 gagcgccgtg aagaagcggt tctgccgggc caggtcctgc cagggagcct tggagcagtg301 gtacttgatg aaggggaagc agccggtgcg caggacgtgg tagttggcgc cctgcaccgg361 ccagttgaag tgcgagaggc cgaactggtc gttgcggacg gcgctgtagg gc<210>22<211>572<212>DNA<213>Homo sapiens<400>221 tttcaattac atgtaattgt ttatttaaaa taattttcca agtcttccaa tgatttaaca61 ggctttgctt cacttttatc atctcaaaca gctataaatc aacacacttt ttgtatttta121 ttttactact atgtatgcta ttttaataac atttttcttt attaatacta gaaccaaata181 tattgaccaa taagcagtat agatttaaat tatcttcttg ggttggtctg aggttgctga241 tggattcttg ggattgatct gatgctagaa gctatcttag gccctgtctc taactcactg301 tatgtttcag gcaaaacatg ccacggttct aggtctgttt tctcatctgc aaaattaaac361 acccaattta gatggaactt attgttttaa ctagctataa aattccaata ctatattccc421 catcattttc acttactttt acttaatctt tatttgctac ttttccacct ataaagcgta481 attttccata tcaagtaaac ataaattcat taaaaaataa acacaaaccc aaaatattct541 tattctaata tatctgcatt aatagataaa aa<210>23<211>468<212>DNA<213>Homo sapiens<400>231 ttgggatttt caaaagaact ttttactaaa acatcatcag aaaacaaaca acaaatgaac61 aaagaaaaga ctaaaagcac gaaagccatc ttcaaagcac ggatacggag tcctgcggaa121 tctccctgcc tcaccatggt tgtgggctgg ctcagcagtg caccctggaa cctggctgtc181 agacccccac ctttgcaccc cctgcccatc tttgccacct cctttctggg gagaaattct241 tgctacatga gagagaaatg atatgagaca catgggctgg tgtcacagct ggaaaagtgc301 aggccttgcc ctccagaggt tgccaggtgc agagaaagaa accagcagat ctgtgattgc361 tctccacttc cagggagtat ggtgggtaga gaccgggatg tgggagggag acagagacac421 ccacgacagc accccagatc tgccataatt cagcagcacg actctggc<210>24<211>655<212>DNA<213>Homo sapiens
<400>241 ttttttttaa taacgaaaaa gctttactag tgttttaacc gtgtacaaaa cactgtagca61 ataagagaaa ggcccgtgct atctgtgttt aaacaaaatg cagtggctgc ggggcttcca121 ggcagggctg gggaacaggc cgggcgcccg ccttgggant gctccgcctc ttaggggtaa181 gaggctcaga gcctacccct taggcctagt tggatgcggg tcggtcctgc ccaaggcccc241 agtgagggga gccgaggcta cgaaggggca agttttatgt gtttgggagg gggtgtctct301 tcccggcctc tgcgtcttcc ccctggagcg tcagtatggt caggctctgg tgacccagcc361 gctttgcctc ccgactttgg gaagagtagc aaggagaggt cctggcaagt acaccctggg421 tgacaaacgg ctatgagagt tccaggtgat ttctcgagca gcttcagttt atcggaggcc481 agccatgaga gagattttag cacaggaacg caatccgtgg tccagctctt agatacccgg541 actgggacaa agcacagact ttcccaggag gcaatgctcc aactcttctt aacctcactt601 ggagtcacag aattgtgtga gaagatacag gggattcttg actaaagctc agcct<210>25<211>600<212>DNA<213>Homo sapiens<400>251 tcattggcat ctgtttgttt atttatttgt ttttaataaa tgaaaggtca ctaaacacac61 tttgaaattt ttgtcacctc ccttgagatg ttgcttaatt gacttaagtc aaactgaaac121 tctggctgaa actcattttg tagatgcact ggcagggact tgttagggca gcagcatccc181 acagacccta gggaatggga gggaccacac ttctggaaag actggatggg aaggagggtg241 tagggatgta ggaggggagc tagggagccc tggagaggag taagtaggcc ccagaacgat301 ggggcctcga atcaggccac aagcttggcc taggcgtgag tggaccaggg accacatgat361 ttctcagagg ggcctgctca gaaaataaag tcacagagct cctggaaccc actgcacttt421 tcaacaaggg gaaagaaatt ttacgcctgg accaagtggc catgcctctg ccctgccttt481 gggtttttca acaccttcct ccgcactagg ctggctctga aatgcagtgc actttacttt541 ggactgctcc actgagggtc acagtacagc ctggcttggt ggcttttgca agtatgcgga<210>26<211>506<212>DNA<213>Homo sapiens<400>261 gaatctttta aaatatgctt tattaatgtc aattttaaaa aatatttgac cattacaagg61 aatttttata tacccccact aattaagaca agaattttgt acttgttgat gctctattta121 cacagttttc attggaaaac tgctcttcat tgctttactg tgatgctgac attgcttttg181 tgatgctgaa tgctgagtac aagttcctct cccatttcaa cctggatggg attatctaaa241 acaactgcag cttgtttcca gtgggaggct tcacttgaag tatccaacct aatctcttca301 tcaaggtaca tatgatacca aaatggaata gcagtcagtc ttccagattt acaaacgtat361 acctttactt ctctgttaga ggtgttcaaa tacggagtca ttaaatctag tcttaagagt421 tccactggct tgcttaaagg tatacagggc aatgaggata ggtccaaaat acacgtatag
481 gtactgaaac tggttaataa aaggtg<210>27<211>465<212>DNA<213>Homo sapiens<400>271 ttttcacagc agtagcattt ataatatcag agagttggaa acaaccccaa tgtctatgaa61 ctaatgagta aacaaactgt ggtatatcca tacaatgcag tattattcag ccataaagag121 gaatgaaaaa ctgatacatg ctacaacatg gatgaactct gaaaacgttc agtggtaaaa181 agccagacac aagaaaccac atattgtatg actccattta tatgaagtgt ccagaagagg241 caaatctaga catataacgt ggattagtgg ttgccagagc gtggaggaag agcgaatagg301 cagtgatgat aaggggtatg agggatactc acacacctga ggtcacacct gcacatacag361 gtggcatcaa cacatgcagg actgtcgcgg ttgcttctgg accgaacgaa ggacgacgaa421 tgcagaaatg agacagacaa aaggatctgt ttgacagaag gggtc<210>28<211>286<212>DNA<213>Homo sapiens<400>281 tttttttttt tttttttttt tttttttttt ttgagctcta gaatcatatt tatttgattt61 gcattaccat tattgatgac attttcacat ttaaaaacta cataagattt tataataaat121 gcaaccactc ttacctgctt aagcaaatat aaacaaacac tcccaggcct attgttttta181 aggctgtata tttcacttga tggaaaaagt gatgaacagc aatgacttcc caagaaaaaa241 gaaagaaaag tgggtgttac atattcctga aagccagact ctaatc<210>29<211>417<212>DNA<213>Homo sapiens<400>291 aagcattcag aaatgtattt attgacatca aactattgta tatatatgtg tgtgtgtgtg61 tatatatata tatatatata tatatatata tatatatact tttaactcaa agtaatatct121 tttcatgatc attcttttta atgtgcacca aattagcagt aaaaatagca gcagatggat181 cagagtggtt gtcaataaac cttttctccc caggttacta atatacaatt gccatgaaaa241 ataaaaaaat atatatatat atttacactt gactcatcac ctctgcttag gaccctgtaa301 gcacaagata ttgctgaact gctgtatttg ctacatatgg aacaattaga ctagcaataa361 gaagtagttt atgcatgtat gctggcctac atgtatatac cctttcgcat tactgag<210>30
<211>526<212>DNA<213>Homo sapiens<400>301 tttgcagcag ggaaatacat gactatgtta ttggtgaagg tgtcacaaca cgcatggtgg61 gggagttgag aagggtcaca gaagaaatta ggaatttcca catccttgaa gcaggtaatt121 tgcaaggcaa tcaaattgtg cagctgggag tctaaaagac tgagacaaca agacaacaga181 actagaaagc cacagaaaca tgggttcatg atggctgaat aatatagagg gtgacagatg241 gctacaaacc ggtcataggg ccatcacact caggagcatg tctttcttcc atgcctccaa301 aaatggcaaa aagagacatc tgagtcaggc agcccgcata ggagatgact gctgtgagat361 tggatgtcca caatcatctt ggggaccatg gtggaggtga aaacatgtcc ggcaaggaca421 ggttggagag gaagaagtac atgggggtgt ggaggtggga gtccgggctg acggccagga481 tgatgagcag gttcccagca cctgaccagg aacatggaca ggaaca<210>31<211>621<212>DNA<213>Homo sapiens<400>311 tggggggagg cagcggtgat ctttactgag tcagaaggga gaccctgggg aagtggggca61 gggcaggggt gggatggtgg tggtgagagg ccaggcagat gatcttgtct cgggagggag121 gaggcttctc agcagagatg gatccccggc ctggagggga gctggcagca ggccaggagg181 ctccgcagaa ggccgtgacg gtggcggacg gtgaccgcgc ctggctcggc agggttctct241 ctgcgggtgt gcacagcaaa gcttcggccc gtgggcaccg gggtccgctc agctctacat301 ccaccacgtg catgtccgtg aggctggtat cagccacgag caccccaatc accccatcga361 agcccaggct gggggcagcc agggcagccg ccgccatggt gttggaattt cgcggggcaa421 aggggcagag ccacggacag ggccttcgta gagcacagtg caaagcccag ggctgtgggc481 tgcagcangg ggtccctcaa gccggaagcc atcggggtgt gtggccatgg tgacacaaag541 gctcaggaga ttggcatggc gcaggatttg tgccccagat tcatggatta ttttgggatg601 ggccacttcc acaaccagat c<210>32<211>410<212>DNA<213>Homo sapiens<400>321 agagtatatt atactttcaa actggataca ctagaaattg gcaatgcaac ataagatgca61 aaggaatata ccagttactg tcaaaatgac cctgtacagc ctcgtaatgc aaaaagcttt121 atacaataca aattttcagt aatgtacaca aaccttgaca gtatgatcat ctgaacataa181 tatgaagagt tagaaaaagg atagaagaaa gaaagtgctg agaaccctaa ctgcattact241 atatggaaaa ataagctagt tttcattgaa gaatgcatag tgacaacaat tgaagttagt
301 tggtaggtga atttctcaaa gatgttagtg ttttatacgg aaaggatatc tatggaatac361 atccttccct gagtatcaaa ctgcaaacca aattcagggg tacatatttt<210>33<211>501<212>DNA<213>Homo sapiens<400>331 tttttttttt ttttttttca attcaagatg taacaaagat ttaatataaa gcataaaagt61 tttaagcaaa atcatggagg tatttttatt accttgtggg gaaggtcatt ctacgcacgt121 cgggaaaacc aggaattata aaatcaaaga gattaagttt acatcataaa acttaacttt181 tataacaaaa aaactataaa taaggttaaa agactaataa taacatggta aaaaatttgc241 aacacaagac aaagaaataa tgtcctcaat atacatagct cttaaacatc aagattcagt301 ataatgcaaa actatacagc cattaaaaac aatacaaatc tatatctatg gtcatgtaca361 aatgttctca ggattaagtg aaagaagcaa gttacaaagc agtacataga gtgtgatctc421 atctatgcaa aggtgtacat agttgtatat aagcatatgt aaatatgcac agagttgtct481 gaaagtaaat cttaactggt c<210>34<211>483<212>DNA<213>Homo sapiens<400>341 tttttttttt tcagaaagct aacgcactgt ttatttgggg gattgggggg aagcaccgtg61 ccgctgctca ctggtagcca gccagctgca gaatggtggg gtagcaagta cgatgggcca121 tgcacttctg gcggtcgatg aagacactgt tggtcatggc ggtgacgtcc ttctccaggc181 tcatgtggat gtccttgagg ttgcgcaggg actgctccgc ttgtagaagc ttctcccgca241 gcgctgtgat ggacttgtac agctcctcca cctcactcac cagcttgggg gtgttggggg301 gtgtgagctg gggctgaact gggctgcatc gcggcacagc tgcatgttgg gccggtgtga361 gagcagctac agccgggtct gggctatgtg cagaggttcc tccttgtcct tgatgggctc421 cttcagtgcc accacgttgt gttcccgatc tgtgatttcc ccgcagatct tgttcaagtg481 ggt<210>35<211>712<212>DNA<213>Homo sapiens<400>351 ttttttttta atatagagaa ctgattatgt tcacttgtaa cctgtcattc caaaattctt61 caggatgttt aatgttcaag tgtccatatt cccagtccca ctggatgcct ggcaggatgc121 aaccatctga atgagtggaa gtataatgtt tgcaccaggt attatattag gagccttgaa
181 cccagaatat gtctgattaa gtcttttagc ccaataattt gccactgctg ccaagtctgg241 taattttgaa ggagaaagtt caaccataac ggggtgatac agggcacccc cgtactcaaa301 aaactttcaa agtgctttct aaacaagttt ctctttctcc ttgaatacaa cgtcagtcac361 aactgatggc agtacaatcg atccatccat acactgctct aagaacatct tgatggtata421 atatgctgtc attcatgctc tacctgctac tagtttaatt tggtcaagta gctctttccc481 tggagactca aattctacta gactcaaatt ctattagacc aaagacaaat gatctcagcc541 atggtcttca cttaaaccaa tcactgggcc tgcattataa ctgagcaaca agtggcacaa601 taccatgtgt tggttgctgg agagctatca tcagggtgct gaattgcttc tgaacctgga661 gactgctggc acgattctgt cacgtgaccc ctactactat gcccaatgcc aa<210>36<211>584<212>DNA<213>Homo sapiens<400>361 acttgtaata cgtattttaa tttttgtttc atatgagttt aagtgttgtc taggtgacat61 caaaatctaa ggcaaacaga cttgaccatc ttcagaccca ctgcattctc aagctgaagt121 ggtctgctca tagtttgtgt gccaggttgc tcatcagtat tgatactgtc ccagaacagg181 ttgtaggtat aattcagaga ctgtcctttg caaaggaaat gaccagcatt tcaactgtat241 gtcttcctgg aagggtagat tctgctatat cttctttgtc tgcatcaaaa gactcaagag301 gaatgtggac acatttcata tcccatttgt agagtaaagc ttcaagtgac cagtcagcac361 tcctaacttg ataagtagac cacaattgga ccttgggatt cttgtgcatc aaaaaatata421 ttgtagccaa aatgtcttca aaatcttctg gttcaaagaa cacatcagat gcaaggataa481 tatcttgtgg tggtagagcc agaagatccc aagatatgac cccatgttag tcctaccacc541 tgcagatgtg gcaggttatt catttggcag ctttgcgaca gact<210>37<211>857<212>DNA<213>Homo sapiens<400>371 tttttttaca atgtaggaaa atttaataca tactatataa acaacattat ttacatcaga61 aatcactagg acagtggcat ttttcacaaa tataaattaa ttactgttta gtcaacaggt121 tttaaaagtc cacaatttta caataaagaa aaaccatctg tccccagatg agtggggcac181 agatggccta aagcagcctg gacccttggc atggctcccc tcgcccaacg tggcagccct241 cagaggagcc ggaagaccgc tggtgctggg cctgggctgc tgctcctgct gacaagtgga301 ttttggtctg taggatttca gtgtcattgt gtgacttcct aaatcaactg tgtttgcacc361 gtgaggactg atgcaacttt cagacacacg aggccagaat gtctgcagca cagcgtgcaa421 agtgtttggg cttccttcga agggctgagg aatgactgaa aggagagtga gccccgggct481 ctgctggcac ctgtctgtcc ggctctgaaa gaccgcagtg attagcttgg ggtttcacct541 ggcccttttc taaggccata gtgtatcatg tcaacccttg ttcacgtgca ggttttaggt601 gatgctaact ccctctttct caacctgtta tttctagcaa caaatgaaat cttccaaagc
661 cagactccag ggaataccat cctcacagaa ttcctggggc agcttcttcc cattcacagt721 tgagagaatt aactgtggca aatttttatt tagggcaatt atattcaaac tgattaaaat781 cattgaagaa atggctcctt tttcccagca cacttctcaa acatactcag caccctaaat841 atgtggttcc ttcgtgc<210>38<211>785<212>DNA<213>Homo sapiens<400>381 tatttcgaca ttttattgaa cttttcatat tacacaattt acccaaaaca tttaaagtaa61 cagtaagaca aacttaaaaa aaaaaagtca tacagacaaa acatctctag gtgaggcaat121 atgtaaattt cattgtcaaa tcatgatttt gttactctgc tatacaactt ggtaccatat181 caatgctact aaatgactca agagtaagac attatgcatt ccgtttatat gagaaaaaga241 gattatttac aactacttga aagagaaaca gaaatgccaa caacagtatc attcaaattc301 tagtgcaatg tcaattgtta ccaagagatc ttatttgctt atataaattt tgcaaataat361 tcaaacctgg ctatcttatt agaagccgac aaagtatngc ttttctgttg caaagatcag421 tggacaaaaa tcctccacaa cctcagctga taaaacaaat ttatagcagc tttttttttt481 cacatttcct gaacgatgta ctaatnacta ggtagaaaca ctaaaggctt tgtaacacat541 acataaagtg aaatgcttgt gacagtttaa caaagtcgtc tgcaaaaaga acgtttgtga601 gtggttcggt aaaatcggca tagtaagaca ggttctaacc ttacagtttc ggaaggctac661 tgaaaacacc cgcaagggta ttaaatatcc atttttaagt ggccctgttt ttacaatttc721 aaattatgac atccagtggc gagaatctcg gggcttaaaa agaaacccta taaaccccgt781 aattt<210>39<211>601<212>DNA<213>Homo sapiens<400>391 ccgagggctg tgtcagaagg ctgggcagcc atggcgtcct atttcgatga acacgactgc61 gagccgtcgg accctgagca ggagacgcga accaacatgc tgctggagct cgcaaggtca121 cttttcaata ggatggactt tgaagacttg gggttggtag tagattggga ccaccacctg181 cctccaccag ctgccaagac tgtggttgag aacctcccca ggacagtcat cagaggctct241 caggctgagc tcaagtgccc cgtgtgtctt ttggaatttg aggaggagga gactgccatt301 gagatgcctt gccatcacct tttccattcc agctgcattc tgccctggct aagcaagaca361 aattcctgtc ccttgtgccg ctatgagctg cccactgatg acgacactta tgaggagcac421 agacgagata aggctcgaaa acagcagcag caacaccgac tggagaacct ccatggagcc481 atgtacacgt gaggaggttg gggctgagtg ctggccctct gcgtcttcct tattaacctt541 gaatcctcat taaaggtttc tttaccctaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa601 a
<210>40<211>734<212>DNA<213>Homo sapiens<400>401 agaacgaacg gcttgggcgc gggtaatcag ctccctttcc cccactttct cacttattct61 aggtacttgg gactgtcgta gagtttccag accccatgta ggcgcccagt cgtggactgt121 cccactctgc tgctctactg ctcgtggtgc tcccgcgccc agactggtat ccggggactg181 tgacttgcag ggtccgccat ggagccagag cagatgctgg agggacaaac gcaggttgca241 gaaaatcctc actctgagta cggtctcaca gacaacgttg agagaatagt agaaaatgag301 aagattaatg cagaaaagtc atcaaagcag aaggtagatc tccagtcttt gccaactcgt361 gcctacctgg atcagacagt tgtgcctatc ttattacagg gacttgctgt gcttgcaaag421 gaaagaccac caaatcccat tgaatttcta gcatcttatc ttttaaaaaa caaggcacag481 tttgaagatc gaaactgact taatgggaag aacagaaaaa tttagttgct actgtagatt541 tacatgatta agaggcagct ttaattgcca tgatcattcc ctctttttgg atgtatcaag601 aaccttccgg acaacagaac ctatttctgg gattgcagaa ggttaacata tttcccttat661 ttttgattta atcaccctta aaccatacct attttaatga gtgtattctg tggcattttt721 ttctccggnt gtct<210>41<211>496<212>DNA<213>Homo sapiens<400>411 ggtcagaatg gcggcagtgg agcatcgtca ttcttcagga ttgccctact ggccctacct61 cacagctgaa actttaaaaa acaggatggg ccaccagcca cctcctccaa ctcaacaaca121 ttctataatt gataactccc tgagcctcaa gacaccttcc gagtgtgtgc tctatcccct181 tccaccctca gcggatgata atctcaagac acctcccgag tgtctgctca ctccccttcc241 accctcagct ctaccctcag cggatgataa tctcaagaca cctgccgagt gcctgctcta301 tccccttcca ccctcagcgg atgataatct caagacacct cccgagtgtc tgctcactcc361 ccttccaccc tcagctccac cctcagcgga tgataatctc aagacacctc ctgagtgtgt421 ctgctcactc cccttccacc ctcagcggat gataatctca agaaactaag gaagaataaa481 taaataatat aaaaat<210>42<211>318<212>DNA<213>Homo sapiens<400>421 atgtcagacg cagccgtaga caccagctcc gaaatcacca ccgaggactt aaaggagaag61 aaggaagttg tggaagaggc ggaaaatgga agagacgccc ctgctcacgg gaatgctaat
121 gaggaaaatg gggagccgga ggctgacaac gaggtagatg aagaagagga agaaggtggg181 gaggaagaag gtgatggtga ggaagaggat ggagatgaag atgagggagc tgagtcagct241 acgggcaagc gggcagctga agatgatgag gatgacgatg tcgataccca gaagcagaag301 accgacgagg atgactag<210>43<211>864<212>DNA<213>Homo sapiens<400>431 ataaacaagt gaacaaaggt ctctggtttt cctaggcaga ggaccctgcg gccttccgca61 gcgtttgtgt ccctgggtac ttgagattag ggagtggtga tgactcttaa ggagcatgct121 gccttcaagc atctgtttaa caaagcacat cttgcaccgc ccttaatcca tttaactctg181 agtggacaca gcacatgttt cagagagcac agggttgggg gtaaggtcac agatcaacag241 gatcccaagg cagaagaatt tttcttagta cagaacaaaa tgaaaagtct cccatgtcta301 cttctttcta cacagacgcg gcaaccatcc gatttctcaa tcttttcccc acctttcccc361 cctttctatt ccacaaagcc gccattgtca tcctggcccg ttctcaatga gctgatgggc421 acacccccca gacggggtgg tggccgggca gaggggctcc tcacttccca gtaggggcgg481 ccgggcagag gcacccctca cctcccggat gaggcggctg gccaggcggg gggctgaccc541 ccccacctcc ctcccagacg gggcggctgg ccgggcagag gggctcctca cctcccagta601 ggggcggctg gacagaggcg cccctcacct cctggatggg gcagctggcc gggtgggtgg661 ctgacccccc cacctccctc ccggacgggg cggctggctg ggtggggggc tgaccccccc721 acctccctcc aggacggggt ggctggccgg gggggggact gaccccccaa cctccctccc781 ggacggggcg actggccggg cagaggggct cctcacttcc cagtaggggc ggccgggcag841 aggcgcccct cacctcctgg acgg<210>44<211>470<212>DNA<213>Homo sapiens<400>441 caccagccac ttcatgacca tgtccacgca gctcttgcgg taggagctcc agacactgcc61 gctgcggggc cagggggtga gtggctctcg tcgccttggc cgcgccctga ccctgccccc121 cagccctgcc tcacctggtc tgccctttga cctcagtcag gtcgcctaca ctgactgtct181 cgaagatccc tgtgttgagg tcccatgcca ccttgaggct ggtgtgatag gtctttggtc241 tacagtggag agggacatag gacaaacgct gggacagccg ggctcctgaa ccaggcccca301 ggctaccctg agggcctttt gtctttggaa cagctatgga ggggcccagc caggttgtgg361 cacagggaga gccttctcac gtccccacac ccccaccgtg aagtgtctgc cagtggcccc421 cctagtggac agagagggca ggatccccgc gctcaccgga gctggccctc<210>45<211>527
<212>DNA<213>Homo sapiens<400>451 tttttttcat ctttatcatt attttatttt agtaataaga aactggggct cagaaagttt61 aggtaacaca gtaggaaatg atgaaactga aacaagaaat catgtctatt tgattgcttt121 tttcctgtaa agacagtcat taatgctctt caccaaatgt tttcatttct tctgacacat181 gccaagatcg cacttcccca tccttttgaa gttacttgca gccatgataa ttgccctggc241 ccaatgcaat gtgaacaggt aaaagacata ttttacttct gggccaaagc ttcaagaacc301 agtgcatatt ttgttgtctt ctctctctct aatgcagata acagaagtcc catgagcctg361 ggtcccacaa agagacatgg agtgtagcat ccagcaatgt cgttataaac ttgtagtggg421 aattaacaat acacatttgt tgttataaac taagatttgg ttataaacca ctaagcataa481 cctagccact gctgactgat taattcacaa agtggctata tcacttt<210>46<211>371<212>DNA<213>Homo sapiens<400>461 tttcagagaa agaagagaaa gtttatttag agacactggc gtggagagga ataatcaatg61 atgattatgg tggtcttggg cctgcaccaa aagcccttct ttgtgctggc cctgggagaa121 cacatggcac agaaaagccc agattcaagc agcttcttca accaaaacat tgacatattc181 tgctgacttg tcctcccatt ccttttcaga gataatttcc tttctttttg cctctgtggg241 gaatatttca gatgacatgc tgaacaccta tacctgcagg ccttcaccat cttcttctgt301 tcctcaactc tggtcagcat gaggttttgg ttgaaacagc aagatctgcc tgctcctact361 gttgtcccct c<210>47<211>489<212>DNA<213>Homo sapiens<400>471 tttcctttat aaattgcata tatttttaag atatattaac actttaaaac cgtggggtgg61 aaagtttaaa atgccataaa ataagaatca tatatgcatt ctttacactg taaagcattt121 taccagacat tagaatctgc attcagaatt ctttctcaga acgtaagtgt tcttgaagac181 atatattttg tcttactaat ctgtttcttc caagcactac tgtactaggc atacggtaaa241 gatatacatt caagttttaa aagtaaatac tttttcctgg tagtggccag ggcctgcgtt301 cctcagacca aaaggcgcaa actggcattg ctgtgatttc agaagagaag tgaaatgtat361 aaaacgaagt aattctgggg aaggaaaatg tcacaatttt tcttcagtgt tgtcaggcac421 actaacccgg gaagccgtct ctgggcctga actatccaaa ttagtgtccg aggaagtgtg481 acaaatgca
<210>48<211>585<212>DNA<213>Homo sapiens<400>481 tttttttgag tgttttacca ttaacattta ttgatgggat ggataaatac agattgagaa61 acatacttga cagcaagata tcaaactgat agccagacta taaaatgtat acatcctttt121 taaatttttt gaattttttt acaaagagcc cttactataa tggtcactta cctcctatca181 ttcatataac agcagtagat atcccagggg tagcatccag agctgaggtg ccccaaggaa241 gacagaggca atggcagaat aatatgctga gaaaggactc ttaagagcaa tacaaagaga301 acagacaaaa atctcaccac aaaattgtac ctgagtgaca gattggtaaa gnggtttact361 tttttttttt cttttcgctc tttggtctga caagaaaaga gttttaggtg tgtgaagtag421 ggtgggaaaa aaggtcagtt tcaaattcag taacatatgg taacactaag ttaggctgct481 gcattctttt ctttgggtac ttaagccagc tggcacttcc actttgtaac caattatatt541 atgatcaaca actaatcagt tagttcctca gcttcaactg aagag<210>49<211>560<212>DNA<213>Homo sapiens<400>491 tttttttttt tttgggtaaa aagtgaaaca ccaatagttt aattgaaatt tcagaaaatt61 gaacatatga acaaggcaaa taaatactaa gtaagttaaa aacacaaaat atgtccagga121 agtatcgatg agaatgttca agttaaagtt ctccaatgcc attgctacag caacctcaaa181 ccctaggttc tctctgcact attaacacag acatctcagg acatggtttg ctttttttta241 agacttaaat aggaaactaa tttttctttc tttaaagcaa ttgcgttctt cagtgaactc301 tttctttagg ccagttgatg gcttcttagc agtttattga cgagatccta gggtagcttc361 cgaagctggg ttgattgcat ttgggtgcgg atggccaaag tgagtggccc tactgcctgt421 gctgctcagg gctcctgggc tgatgtggtg gcttcttccc tttgtgctgc tgaacatagg481 gaaagtgagg ttcacagtcc accatccacc agccgccgtc tgtgagctcc accagcactc541 gcagcaagtc agtcgggctg<210>50<211>534<212>DNA<213>Homo sapiens<400>501 ttttttttat gttgaaacgg ctttattttt taatccataa atatctgtta ctgacaaaag61 tggaaaaatc cttaagacta aatcttacta aagtgtatct gtttacagta catgtagaat121 gtgctttgac aggtaagtag aacgatgaga tttgtacaga gaagcagtta ctagagcact181 gcttaccatg aagcttacat atgagtaacg aagaaactgc aaagatacag atagaaaggt
241 acttttcatc agtactacca tataataaac atggaattca taaattgggc taatgcataa301 aaatgttcat taatcccccc ttaggaaatt gtgtccccaa actaaaaata ttacagtaag361 aattgctttt tattagagaa tttcaagaat tctttactac aaaatgtcta gttgagttat421 agaactagag gaatatttgc cactacaaag ccaatgaatg agtcctccca tggtgtggca481 ttcaggggtc actgcagggt gggcagcaaa gttgagcagg gtcttctcct ccct<210>51<211>457<212>DNA<213>Homo sapiens<400>511 tttttttttt tttttttttt gcaagataca agactatttt taatgggaaa tccaagaaaa61 aaaacctgaa atgccatatt tatcacaacc ttagatagtc actgtaagtc aaggttcctc121 gccctctcca ttcaaagcaa agcatcactg tccatgaaag gcacccctca gtgacaggag181 gtgcacctcc ccacgtccgt ttagttacaa acaggagccc acattttctt aatttctata241 attagtgtta gcattgccta catttgagaa tgtttgatga tgatcaaaga gagtatggaa301 acagatttgg caacacttct acggttacga ccgtgaacag ttttcactga agcttactta361 gtgtcacagg tcccgccatg ttcctgtgaa ggtcactagg ttttcaggaa taattgtcct421 gtttagtgca tttcccaaga aaatccaagt taggaga<210>52<211>435<212>DNA<213>Homo sapiens<400>521 ttcatgattt gtataatgta atttatgctt tagtgagtta ttttccatat agtaaaatgc61 ctttatttaa aaaagaagag gtacagtaca ttataattcc aaggaaattt tcgtatttta121 aaaatgccaa tttttggcta aaaactcaaa agatttcatt taatacttga ataacaagga181 aattcacaat taaggctgaa atactgttca tattattgtg tatttctaag catgttattt241 taagcttgtg tattttaaac catggttaca gaattgtata ggaatatatt gaaggcataa301 ccttatattt attggaattt tggtttaatt gtttagaatt tcaaaatagt attgggatgt361 gaaacaggat gattatcact ctgataaaaa caagactgaa ctgagtcctt cactgtattt421 ttctaaagaa ctcac<210>53<211>386<212>DNA<213>Homo sapiens<400>531 tttttttttt tttttttttt tttttttgcc ttaaatacat aaaactttta tttgccaatt61 atactccaat aatgcaggac aaagtataca ggtctgacat ccagagaaaa atatcagcag
121 acttaaaata tctgatcatt ttcccccgga ggaggattgg acagtttttt taattgatga181 gtaacaattt tatgtagtaa gcctattcac tctctgttaa ccacatttat tgcaaacaag241 tttttcccaa atgtttagac atttattcct acttattctc acacttccct gataattcac301 tgaaattgcg atcaaggctt tattctcagc aggaagtact tgtacttctc taagtgacag361 acaggcttaa agagtgggct caaggg<210>54<211>717<212>DNA<213>Homo sapiens<400>541 tcaagagtca taccaatgac ttttatttaa gatgatttat gagttgatgt gtgagaaggg61 ttggtgaagc tatgtgggtg gctctttaaa taccttccat tatattttca aatttttctt121 tattctatta aaataccttt tattctcttt attcccataa aaaggcaacc aagcagatta181 tactctcaac taagatgcca gcagtaattg gggtatgatg caagtcatct tggagcagct241 acataccctg cccactgcag tcagtcagca tctgcagttg cttttataag ctgtttttac301 ccccaacccc gcccccatcc acatctgana tggtgaattg gggctcaaag aaaaaacaaa361 acagtagctc ttgatgtcat gaggcagagc cagagtataa ttcaggccct ttttcaacag421 ggagccccct gggtgcttct catgctcttc cctcctaaac tcccttcttt cttaccttct481 ttgggggaaa ttaactccat ctaagcattt cttttcattt cttccctttt ggttttcagg541 ggccaagaag agacgccttg gggtttaacc aaanngcccg tcaaaggctc ttgaaaattt601 taatatggag aggggaatct cctcttgaaa tcccgggggt cctttgatgg acctctctgg661 gtaatttttt gagaccccga cccgggggtc cggagttcaa ttttttgggc ctcttgg<210>55<211>435<212>DNA<213>Homo sapiens<400>551 ctaggcaagt ggagaaatat aatatttatt catggcttta tggacttgat cgatctttga61 gaacctacta ggtgtcagtc tctgtggttg gtactggtgt tcagaacagt cttctctcac121 ttgagggcac agtgagcgcc gtgaccatat catttgtggt aaattacacg ggaagttagc181 ttacccttgc agaggacggg agacagttgt tgctagcatt tgtacattca ttagcctccc241 ccttctccct gttggaaatg taactgtccc agctacacag caaatgtgta ttctagtaac301 ctgtgatgcc tgaactgttc aagatgatca agttaaaata tgaatgtgct gaattaaatg361 ctttattcag cttatctgca tctaggctct ctgaattacg cacccactta aaacattctg421 tcaccttttc tcttg<210>56<211>690<212>DNA<213>Homo sapiens
<400>561 tttgatttca agtcaagatt tattgcttta caaacaaaca ttatacttgg tcttaataga61 aaaatgacac cagatacatc caaaatacat ttcacattgg gatagctgcc agttcagcac121 aaaacataca ttactaggag cagggaggca tgaaaataaa ctatatctta ctttttggta181 cgtcaggaac acttttgcct gaagtaagcc ctttagtact attttttatt ttatttattt241 ttttaatcca cccatctgca cactggccct ttagtactct ntaagtataa aactnntact301 tgtcctgggc tttgaccttt ggnntttgat ctaaatgaca tttcaacata aatgtctntg361 aactagtggc ttctgngtat gacagattan anngggaacc gtttgatata atnctggcct421 gatcatggtt aaaaggtgat atttaaatag aaacgctttt tggggctatt ttactaagat481 attaattaaa tacttaaaac tatagccagg ggctggactg acacggcata ttgggacggg541 aatcatttgc tgacttcagt tgatacctgg actgactagg cagcatttag agatctttga601 taccaatgac tttagttaca gtgccgttgc agcatacaga aactgaggtt ctttgaagag661 acattcatga gggacttctg tgtggcaccc<210>57<211>550<212>DNA<213>Homo sapiens<400>571 aagtttcagt gaaaacattc tttattagta agcagacatt tcaaactttt tgattacata61 catcatgcaa aatgactgac ctcacagatg gttgtctgtt cattgtgaca tcttttttga121 gatgattata aatttaagat gactgcagta gtaaaaataa ttcatgaaaa tgactctcaa181 tgaagcaaaa cactacatag cacacatgaa atactgttca tccctccctg atgtttaatt241 ctctcctaat gtaaatctct atcttggaag actattatat acaaaaaatg gcagttggtt301 tttgatgtgc atctataggc actcaactga taaaaacaag aaaatttcaa ataattttac361 aaggattggg atttttcctg tttgtaatcc aaacagacaa tgccctttga ttacatgtta421 attcttttaa aaatatttct tcgaagatat ttgaccatga aaatgtttac cctgtaactt481 ttgaatgggg ctctgtacac atacccaggt tncagaagtg aaagagaggc tattcgaaat541 cttatatacg<210>58<211>434<212>DNA<213>Homo sapiens<400>581 tttctccagc ttactttatt gtaaaactac agcatagaat acatataaca tacgtaatat61 gtttaattga ctgttgatgt tattggtaag acttcaggtt ggcagcaggc tattgtagtg121 aagtttttgg cgagtcaaag ttatatgtcg attttcaact gcacaggggg ttggtgcccc181 aagcccccac attgttcaag agtcaactat ttttccacgt tcagcatccc ggcttaagga241 ggttccttag taatatgtcg ttgaataaat gaatacatga gtgaatgaag agaggactga301 agaagccaca catgagcctg tgaaaccctc catatctggg gcgctctgtg ccacgggtgt
361 cagacttttg caaaagccct gtcattctaa cgggacgccc tcctggagga agttgccccc421 tggcgcccgt cctc<210>59<211>554<212>DNA<213>Homo sapiens<400>591 tatgcatgta tacacacttt attaaatttg cattctaaga tatacacaag gccagcattt61 cacaaaactt cctattattc caaaagcagt aatcatgaaa cagtgattat ataagtcaat121 caagcaaaaa acattatcta tagggttgta tcatatcatc tcttatacct gttttcaaat181 agaagcctga aatatatgat atatattaga ataggaagag agaattttac tttataacaa241 tcgcttttca aatattagac tttatataaa aataaagggg tcttaacaaa gttcatctgt301 gagttagcat atctctttat ttcaaaacaa tccctgcaaa aacttaactt tccagtccat361 ttaaacaaca aaaactaaaa atgaagctgg gttaaataat aagggaatca tcttgctcct421 agttctcaca ccattggaac aacttccatt tcctgaccta attctatccc accattgaat481 ttcaaaaatt aatgtaaata ccatcatatt tcagttattt cttaacagtg ttaagttcga541 gcctaaaaat gatg<210>60<211>445<212>DNA<213>Homo sapiens<400>601 tttaggtaag atacacatct ttactgtgta tatgcgtgta caagaaggaa aacttgcttt61 ttttttttta agtagatgtt acgaaggatg gttttttttt tttttcaact tgcaaaatct121 cttgaaggtt ggagcagagc cgccggttac ctttgagcat cgaaataccg caagttatcc181 cgtttccttt tcccctcagg aaagatgggt gcagggttga gatgttacaa gagaattaaa241 agagagccac cagcttggca tagtagaaga aacaaaccca aaatgaaaac acccggattt301 taagcgcgga tcctgcgagg ccggtttgca ctggccgaac gcctgcgtta accctttggg361 cgccgcagct gggatccccg gtgtttgcgg acccgaccgg caggaacaga gatggagtgt421 cccgcgcccg catggggagt gagct
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.60所示的序列;(b)SEQ ID No.1~SEQ ID No.60所示的序列中每條序列的互補序列;(c)與SEQ ID No.1~SEQ ID No.60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.60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個連續的核苷酸。
全文摘要
本發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治療肝臟疾病的藥物中發揮重要作用。
文檔編號C12Q1/68GK1955295SQ20051003082
公開日2007年5月2日 申請日期2005年10月28日 優先權日2005年10月28日
發明者黃健, 韓澤廣 申請人:上海人類基因組研究中心