專利名稱：在人類肝臟中表達(dá)的表達(dá)序列標(biāo)簽的制作方法
技術(shù)領(lǐng)域：
本發(fā)明涉及生物技術(shù)領(lǐng)域，尤其涉及一類在人類肝臟中表達(dá)的表達(dá)序列標(biāo)簽。
背景技術(shù)：
肝臟是人體內(nèi)最大的消化腺。也是體內(nèi)新陳代謝的中心站。據(jù)估計(jì)，在肝臟中發(fā)生的化學(xué)反應(yīng)有500種以上，實(shí)驗(yàn)證明，動(dòng)物在完全摘除肝臟后即使給予相應(yīng)的治療，最多也只能生存50多個(gè)小時(shí)。這說(shuō)明肝臟是維持生命活動(dòng)的一個(gè)必不可少的重要器官。肝臟的血流量極為豐富，約占心輸出量的1/4。每分鐘進(jìn)入肝臟的血流量為1000-1200ml。肝臟的主要功能是進(jìn)行糖的分解、貯存糖原；參與蛋白質(zhì)、脂肪、維生素、激素的代謝；解毒；分泌膽汁；吞噬、防御機(jī)能；制造凝血因子；調(diào)節(jié)血容量及水電解質(zhì)平衡；產(chǎn)生熱量等。在胚胎時(shí)期肝臟還有造血功能。
肝臟疫病分為肝炎、肝硬化、脂肪肝、肝癌等。現(xiàn)代醫(yī)學(xué)實(shí)驗(yàn)證明，肝病病毒侵入人體后，并不直接引起肝細(xì)胞的損害，只是在肝細(xì)胞內(nèi)吸收營(yíng)養(yǎng)賴以生存，并在肝細(xì)胞內(nèi)復(fù)制、繁殖。其復(fù)制病毒的“零部件”如表面抗原(HBsAg)、e抗原(HBeAg)釋放在肝細(xì)胞膜上，引起人體免疫系統(tǒng)對(duì)這些抗原物質(zhì)產(chǎn)生免疫反應(yīng)，這種反應(yīng)造成肝細(xì)胞的損傷、壞死。免疫反應(yīng)的強(qiáng)弱決定于肝臟受損程度及臨床癥狀輕重。這場(chǎng)由病毒引發(fā)的、免疫系統(tǒng)對(duì)肝細(xì)胞的戰(zhàn)爭(zhēng)，使大約25％的患者的肝臟成為戰(zhàn)火連綿的戰(zhàn)場(chǎng)，肝臟的損傷由此加重。肝病的危害絕不僅僅限于肝臟本身，它還可以引起其它多種疾病。常見(jiàn)的有(1)糖尿??；(2)胰腺炎；(3)膽道感染；(4)功能性腎衰竭；(5)膽汗性腎病；(6)腎小球腎炎；(7)腎小管酸中毒；(8)溶血性貧血；(9)再生障礙性貧血；(10)心肌炎和心包炎；(11)結(jié)節(jié)性動(dòng)脈炎；(12)消化性潰瘍；(13)自發(fā)性腹膜炎；(14)性激素代謝紊亂；(15)甲狀腺功能改變；(16)肝性骨病，等等。肝病不僅對(duì)患者的身體甚至生命造成危害，而且對(duì)患者心理上的打擊也是十分沉重的。無(wú)論是肝病患者還是病毒攜帶者，在生活、社交、求職、升學(xué)等方面都會(huì)受到嚴(yán)重影響。
生物基因組中可轉(zhuǎn)錄表達(dá)的序列(即基因)僅占總序列的3-5％，對(duì)這部分序列進(jìn)行測(cè)定，將直接導(dǎo)致新基因的發(fā)現(xiàn)，并獲取基因組中與產(chǎn)業(yè)化關(guān)系最為密切的信息。20世紀(jì)80年代，高通量的自動(dòng)測(cè)序的出現(xiàn)，使從質(zhì)粒互補(bǔ)脫氧核糖核酸(Complementary DNA，簡(jiǎn)稱cDNA)文庫(kù)隨機(jī)選取許多cDNA克隆和決定來(lái)自非載體兩端的幾百個(gè)堿基的DNA序列成為可能。這些短的DNA序列叫做“表達(dá)序列標(biāo)簽”(Expressed Sequence Tags，簡(jiǎn)稱ESTs)。表達(dá)序列標(biāo)簽的概念最早是由Adams等在1992年提出來(lái)的(Nature，355，642-644)。1992年Sikela和Matsubara(Sikela，et al.Nucleic AcidsRes.19，1837-1843；Matsubara，et al.Nature Genetics，2，173-179)針對(duì)獲得大量信使核糖核酸(mRNA)序列的迫切需要，提出大規(guī)?；パa(bǔ)脫氧核糖核酸(cDNA)測(cè)序的研究戰(zhàn)略。隨后Venter創(chuàng)立了大規(guī)模表達(dá)序列標(biāo)簽技術(shù)。其基本特征就是從以質(zhì)粒為載體，構(gòu)建完成的目的組織互補(bǔ)脫氧核糖核酸(Complementary DNA，簡(jiǎn)稱cDNA)文庫(kù)中，隨機(jī)選擇許多cDNA克隆，利用質(zhì)粒上攜帶的通用引物對(duì)cDNA兩端進(jìn)行一輪脫氧核糖核酸序列測(cè)定，所獲得的來(lái)自3’端或5’端的幾百個(gè)堿基的非載體短脫氧核糖核酸(DNA)序列。簡(jiǎn)而言之，表達(dá)序列標(biāo)簽是來(lái)自表達(dá)基因片段3’端或5’端的短脫氧核糖核酸序列，代表一個(gè)表達(dá)基因的部分轉(zhuǎn)錄片段。
表達(dá)序列標(biāo)簽可用于新基因克隆、人類基因組圖譜繪制、基因組序列編碼區(qū)的確定等。如果一個(gè)表達(dá)序列標(biāo)簽在基因組中只出現(xiàn)一次，那么它可以作為序列標(biāo)簽位點(diǎn)(STS)。由表達(dá)序列標(biāo)簽構(gòu)建的物理圖譜叫表達(dá)圖或轉(zhuǎn)錄圖(expression or transcript map)。利用表達(dá)序列標(biāo)簽進(jìn)行基因圖制作，可以加快序列標(biāo)簽位點(diǎn)的制作和新基因的染色體定位。表達(dá)序列標(biāo)簽可以作為基因特異性探針，對(duì)組織特異性基因表達(dá)的研究具有重要的作用。表達(dá)序列標(biāo)簽還可以進(jìn)行新基因的遺傳進(jìn)化關(guān)系分析。表達(dá)序列標(biāo)簽可以對(duì)所有動(dòng)植物的基因作為一種數(shù)據(jù)庫(kù)，通過(guò)不同的序列比較可以獲得保守序列片段，從而獲得基因的遺傳進(jìn)化圖譜。正因?yàn)楸磉_(dá)序列標(biāo)簽具有如此的優(yōu)越性，因此表達(dá)序列標(biāo)簽測(cè)序已經(jīng)成為許多基因組研究機(jī)構(gòu)的工作重點(diǎn)。
由于本發(fā)明人類肝臟特異表達(dá)基因與一些肝臟疾病相關(guān)，因此，研究人類肝臟中特異表達(dá)的表達(dá)序列標(biāo)簽對(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(wèn)題是提供一類在人類肝臟中表達(dá)的表達(dá)序列標(biāo)簽。
本發(fā)明要解決的技術(shù)問(wèn)題通過(guò)如下技術(shù)方案實(shí)現(xiàn)本發(fā)明提供了一類在人類肝臟中表達(dá)的表達(dá)序列標(biāo)簽的序列，其包括(a)SEQ ID No.1～SEQ ID No.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SEQID No.1～SEQID No.50所示的序列。
本發(fā)明還提供了一種探針?lè)肿?，所述的探針?lè)肿雍猩鲜鲂蛄兄屑s8-100個(gè)連續(xù)的核苷酸。
由本發(fā)明的在人類肝臟中表達(dá)的表達(dá)序列標(biāo)簽，可以方便的尋找出在人類肝臟中特異表達(dá)的表達(dá)序列標(biāo)簽，從而尋找出人類肝臟疾病相關(guān)基因，從而在研究肝臟疾病的致病機(jī)理以及開(kāi)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)合附圖
對(duì)本發(fā)明作進(jìn)一步詳細(xì)的說(shuō)明。應(yīng)理解，這些實(shí)施例僅用于說(shuō)明本發(fā)明而不是限制本發(fā)明的范圍。下列實(shí)施例中未注明具體條件的實(shí)驗(yàn)方法，通常按照常規(guī)條件如Sambrook等人，分子克隆實(shí)驗(yàn)室手冊(cè)(New YorkCold Spring Harbor Laboratory Press，1989)中所述的條件，或按照制造廠商所建議的條件。
實(shí)施例1人肝臟組織的mRNA的分離組織分離(Tissue isolation)肝臟來(lái)源于5個(gè)成年男性，在肝臟切除手術(shù)后，將肝臟組織立即置于液氮中冷凍保存。
mRNA的分離(mRNA isolation)取出肝臟組織，用研缽研碎，加入盛有裂解液的50ml管，充分振蕩后，再移入玻璃勻漿器內(nèi)，勻漿后移至50ml新管，抽提總RNA(TRIzol Reagents，Gibco，NY，USA)。用甲醛變性膠電泳鑒定總RNA質(zhì)量。用帶Oligo d(T)的纖維素柱分離總RNA中的mRNA，定量。
實(shí)施例2cDNA文庫(kù)的構(gòu)建(Constuction of cDNA library)以mRNA為模板，合成雙鏈cDNA。補(bǔ)平末端后，加含EcoRI切點(diǎn)的接頭。磷酸化EcoRI末端后，用XhoI限制性內(nèi)切酶消化1.5小時(shí)，再進(jìn)行片斷分離。過(guò)柱篩選長(zhǎng)度＞500bp的片段，用酚-氯仿抽提，乙醇沉淀，無(wú)菌水溶解，連接至Uni-ZAP XR載體(Strategene，CA9203，USA)，以ZAP-cDNA Gigapack III Gold Cloning Kit(Strategene，CA9203，USA)進(jìn)行包裝，宿主菌使用XL 1 Blue MRF’(Strategene，CA9203，USA)細(xì)菌。涂板并測(cè)定滴度。
實(shí)施例3測(cè)序及數(shù)據(jù)庫(kù)建立(Seqencing and Database Constructing)挑選文庫(kù)中有外源片段插入的克隆，擴(kuò)增后抽提質(zhì)粒(QiagenGermany)，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(Bi g-Dye，Perkin-Elmer，USA)的方法，在ABI 377測(cè)序儀(Perkin-Elmer，USA)上進(jìn)行EST大規(guī)模測(cè)序。測(cè)序結(jié)果用FACTURA軟件去除載體序列，傳輸?shù)絊UN Ultra 450 Server上進(jìn)行下一步的處理。所有的序列信息再用GCG軟件包(Wisconsin group，USA)中的BLAST和FASTA軟件搜索已有的數(shù)據(jù)庫(kù)(Genebank+EMBL)，將無(wú)同源性或同源性低于95％的序列視為新基因建立數(shù)據(jù)庫(kù)。
實(shí)施例4基因的全長(zhǎng)克隆(Cloning of FuIl-length cDNA)在得到的新基因片段序列信息基礎(chǔ)上，進(jìn)行cDNA全長(zhǎng)克隆，分兩階段進(jìn)行(1)“電子克隆”(Electronic Cloning)以新基因片段序列作為探針?biāo)褜bEST數(shù)據(jù)庫(kù)，將重疊序列＞50bp，同源性在98％以上的表達(dá)序列標(biāo)簽(Expressed Sequence Tag，簡(jiǎn)稱“EST”)序列認(rèn)為同一序列(Consensus Sequence)，取出并用AUTOASSEMBLER軟件進(jìn)行連接，部分EST可以延伸探針序列。再用STRIDER軟件分析被延伸的序列是否具有完整的開(kāi)放閱讀框架(Open ReadingFrame，ORF)，用BLAST搜尋Genbank或SwissProt以確定該序列的核苷酸和氨基酸水平上是否與其他物種有同源性，以幫助判別所得到的基因全長(zhǎng)完整性如何。通過(guò)電子克隆的方法，通?？色@取人肝臟相關(guān)基因的全長(zhǎng)序列。
(2)cDNA末端快速擴(kuò)增(Rapid Amplification of cDNAEnds，RACE)如果通過(guò)“電子克隆”方法仍未得到完整的cDNA全長(zhǎng)，則在已有序列5’或3’端設(shè)計(jì)引物，在人類肝臟Marathon-Ready cDNA文庫(kù)(Clontech Lab，Inc，USA)中進(jìn)行長(zhǎng)距離PCR反應(yīng)。然后對(duì)PCR產(chǎn)物克隆、測(cè)序。用AUTOASSEMBLER及STRIDER軟件分析被延長(zhǎng)的序列有無(wú)完整的ORF，如無(wú)，重復(fù)上述過(guò)程直至獲得全長(zhǎng)。
(3)RT-PCR對(duì)于5’和3’端的已知的序列，如果中間有一段間隙(gap)無(wú)法從已有的公共數(shù)據(jù)庫(kù)或自身數(shù)據(jù)庫(kù)獲得，可考慮采用RT-PCR的方法。在序列5’端設(shè)計(jì)引物，3’端引物采用Oligo-dT，在肝臟總RNA庫(kù)中進(jìn)行擴(kuò)增。然后對(duì)產(chǎn)物進(jìn)行克隆、測(cè)序。最后拼接便獲得全長(zhǎng)。
通過(guò)組合使用上述3種方法，可獲得人肝臟相關(guān)蛋白的全長(zhǎng)編碼序列。
序列表<110>上海人類基因組研究中心<120>在人類肝臟中表達(dá)的表達(dá)序列標(biāo)簽<130>NP-10156<160>50<210>1<211>449<212>DNA<213>Homo sapiens<400>11 ttttttttta ttgaaaaagg aaagaagaaa gaactataag agatctatta ctgtgcttgt61 tattgaaatt ctataaaagc tatagctatc taacttttcg tcataatctc taaagatgct121 tccacattct agaaatgcct tttttcagct tctcttatgg gtaattgctt ttaaaaaaac181 actgagaaaa atggnattat gggaaaatta tttgttagtt atatctttat caacctttta241 atactgtttt taaataaact tttactacca ggaagggcta taaactcaaa ttactggtac301 attatctata ttaaaccaaa gggtattaaa ataacaggga atggactgga tctaccctta361 atggtatggg aaaggggntg gaacttccct tctacccggt tccatcctac acttaatccg421 gtgggttnaa cccttgttcc ctgggccct<210>2<211>427<212>DNA<213>Homo sapiens<400>21 tttttttttt ggaagagata gtatattctt ttaatgtact acaaaacctc ccaaaaggcc61 ttgcttagca ttacactcct aaggaataga atttaacaat gtctgctaaa ttaaaatatt121 aattagacaa ttatagggga taatcaaagg aaacaacttt gtagtacttt tagtagcaga181 acttatcaaa ttgttaatac cagaaagaca atttgaattt tttatttttt caaactattt241 ctatttttca gtggaaaact ttgcatgtat gttgcctgtt ttcagtatgt atgtcagaaa301 tcaaaaaagt ctgataaatg ttgccacttg gaaaaaaata tcagaaagtc ttatttttac361 acaggantat actatacaan ttaatgatgt aggtacttta ggctactgta taggggnaaa421 cttnttg
<210>3<211>491<212>DNA<213>Homo sapiens<400>31 ttttttttgt aagtatttaa atacaattat ttttttctct caatggtata gcatattcct61 atgcttgaga agtatagggt ctactgaaaa accattgtaa atggacgtta caggtatgct121 gtatttttga aggtattttg ttgtattaag tttgatgaag ctaaaattag ggnactctga181 acagatttgc agggaaaaaa tgttttaaag gctttaaaac attaggggag gcagtctagg241 gtgataacga acaggggtta agtattaaat acacggaagt tacatttttg ttcatgtttc301 attgtccngg aaagcaggca gggaaactat ttcagttgtg atccaagccg ggaaaaaagg361 aaacacccac agttgcccgt gtttttgctt tttagcctaa agcntagtga ggtgcttgag421 gagtctttgc tacccggggg tttntagacc ggcngtctga ggggctttcc gccnttttng481 ggcccccgcc c<210>4<211>511<212>DNA<213>Homo sapiens<400>41 tttttttttt tgagtcaata taacatttat tctgtattaa taatcagtac ataaattaat61 tcaacttgaa accttttttc tacagagtac tatttaatat tatcatctga tccatagtaa121 tttagtacta attttaatga gaaaaaatga aacttttact ttcataatag ctcatccact181 taacattttt acaaagaact actataaata tgtaacacta tggcaggctt ttttctacac241 ctaggtcaca aatcaaaata aggcatactg tttatttaaa aacgggaaca ctttcaaact301 gactggctgg tattcggatc accaccttcc ccacaccaaa ttaattggct ctctctgtgg361 tactcccctc tgtggccact catggttggc gggcattatc ctggggttct ttggccttaa421 cccaaccggg gttccgttgg tcanggctcc nggggtnggg tttgggtggg ccgggggggc481 ccggttcccc ttttncatgg gggtaggggg n<210>5<211>454<212>DNA<213>Homo sapiens<400>51 tttttttttt aaaatcaaaa gcataaaagt gtttatttcc taagnaagca caaagggaaa61 caattatgtt attgatagca gatatattag tcgggagtgg tggtgcgtgc ctataacagc
121 tacttgggag gctgaggccg taggatcgcc tgagcccagg agttcgaggc tgcagtgagc181 caagattgcg ccactgtact ccagcctggg aaacagagac tatttcttaa aaacaaaaca241 aaaacaaaca aacaaaaagc cactagtata taacttttta ctaagtacta ttcaaaactc301 tgtcaagcat tttttctttt taaaaattat tttaggatta ttttagggtt gcttgtatgt361 cttcttttgg ggtaatgtct gttcatgtcc tttttccccc cttntggggg nttgggtttt421 atttcttgta tgaggttctt tgtaggattc cggg<210>6<211>519<212>DNA<213>Homo sapiens<400>61 ttttttttgg tgctactgta aacaatgcta tggtgatcat ctttgtaact gagtctttga61 ggtcagtaac aaactatcct ctggagtgat ttatgctgac taagcagtga ctgagcaaga121 atacaggttt ccccattttg gttggcatta cctttacccc tgttctaagc acattagaaa181 agccctgagg cctcagctgt gggttttggg ctcttccaag ggagacaaag ggaggctatc241 ataatgctgg ggaatgatgg gatccgggct gtgggggatg ctattgtggg acacaggggc301 aggcatcagg aggcttggga aaagcctgca tggctgggcc agggcttcag cgttttccaa361 ggaaagggat cttaaaggat gggatggaag gcatcttccn tattccttca acagggcagg421 ccttcagggg atggggctat ttttcagctt agggtngctt tttttaccnt cccaagttat481 tttaaggctt ccncgacttc aaccagcnta gggtnggcc<210>7<211>458<212>DNA<213>Homo sapiens<400>71 tttttttttc ctcttgaaaa gcatttttaa tataattttg cttttaatat cataattatc61 tatcaaagtt tctgatatat tttgttttga tttgttttgc attactaata attgcagttg121 taacagttca aaccaaaaat gttaatgcct agaagttaaa taaaagttaa gtttatgtac181 atatttttat atgctagggt gataaaagac ttgaaagcat aggaaatgca ttcagggtaa241 aattctggga gggtagtggg ggataggtat acaagctcac ggngggatat agggcacngc301 ttcatttttt gcaggttgac tttttttttg ctttttccaa attgaggggt tgtgggccca361 ccctgtatcc cagccaggnc tgttggggcn cccctttttc ccaccaggca tggttcctca421 ccttncatgg cctatggtcc gggggatttt gttagggc<210>8<211>503<212>DNA
<213>Homo sapiens<400>81 ttttttttta tgagaatttt gttggcttta tttttgttta cttgttgaga agatgaacat61 gaaattaata agaaaatata gttatagctt ctggcaagta tttagtaagg caaagattta121 acacatttca ggggatttct gccacttcct tttagatcag cagtaatttc ttatatttat181 caactctcaa tttttagttt tcatagatac ctggggtatt ataaggctga tttgtaatta241 ctgatttata cttggacttt tgaaatcatt atgtgtcctt aaaaataagg ttatacaagc301 taaccttctt aacagggatc acatgggcta attaggtgac ctaaactgat gtttggggac361 cnctcagccc caggtgttca tttcaggcac tgtcacttgg gnttcccctt atcttgccag421 ggngggcctg gaaaaaaacg gnatttttcc cnttttctac ccngactctc agggatttct481 gaggnctggt taccctgggg ggc<210>9<211>393<212>DNA<213>Homo sapiens<400>91 ttattaacag tcaaaaactt cacacaattg gaaaataaat gtttcttcaa tgaataatca61 aacaaaaatt atccaggacc ttatagggtt ttcagtatgt accaggcttg atgcacatct121 tagaagacag gacattatct tgctgggatc attagggtat gactgaaagt gaggaaacag181 taatttgtaa aacatttacc ctaataatag ctttccccaa acaggtactt cccctggggn241 atttaaaaca ggggaaatac caatttatgt ttatccgtng gggtttaggg atatggnctc301 caatatacca taggatttta cctttttggg gttgggggat tacctttttt taagggccgc361 ctcccatagg gnaattccaa atcctcccct ttt<210>10<211>458<212>DNA<213>Homo sapiens<400>101 ngnctaaaaa tttggnngta ttgtgactga agacattgcc aacttacata tatcattttt61 atttgggagt atttttttgc ccttgcagtg ctcctgagaa attcaaaaat gcattaactt121 tagctctata aataacacaa cctaatatta aggttgcgtt ggaaatttcc cacgtttaga181 tatttcccta aaaatcaaaa gacaatttaa attgttttac atagaggaaa ccttaataag241 gtatttaact ttttaataag gttaaaaagg taaagactgg gccaaataat caccaaatgt301 caggaaccat taaaggtggc cattttttcc ntagggggnt atataaaaat aaatatcctc361 ctatacctta ccttggatat ttaccaaacc tttaagggtt aatttttgtg gggtggggng421 ggtgtccttg gatacntccg gttgtggggg nacctncc
<210>11<211>388<212>DNA<213>Homo sapiens<400>111 ggcaagtgac ttatctgaac ttttttcttt tttataacac tggatgataa ttaaccctca61 ggattgtgag gatttaataa ctaagtcctg actcaaatta tgttaccaat aaatgctact121 taaatgtaaa gtccttgatt tattttttcc cctcagtcct gtttagtgtt gaaattcttc181 aaaggagggt gagtctggca tttacctgct attcaagagt tttcagaatt caaccccagc241 caaaattttt ggccacatct cttgtcactg ctttgctgtg tactaaagct cccaggacac301 acaaggaatc ttctaggtca tgggtcaaac tttttctggc aaggggcact tacagtctat361 tggcatattc tttgttttta gtgttcag<210>12<211>406<212>DNA<213>Homo sapiens<400>121 aggtctatct tgatttcata ggtccttctc aatccaaggt caaaaactga gaatcttatt61 ttctgcacca ggaactcagg gttatcccca acctatgccg ctggacatga tggtcatcca121 acctgtgttt ttgtgagtga gtgaatgtgt gactggttgg cctctgagtg gatgactgga181 tgcgtgaatg tgtgagtgaa tgggggagtt aatgaatccc tacctaactg tgaagagaag241 aaaaatgagg gagcccctct cccactgaaa cccataactg ccccatcaag gtcatctttc301 ttttgactca agatgacatc tcaattttga tgcttgtagg gnccccaagc tgnataaggg361 gccacagctt ttttaggagg ccacatttnc tggggggggc ccccca<210>13<211>451<212>DNA<213>Homo sapiens<400>131 ctttaaatca gtcgtaaccc tccctgataa gaaattaaat tagatttgag gattaatagt61 gggagaatta aaattttgac ctatctcacc aagcgagagg gaggcaagcg gagggatggt121 ttatcatagc ctcgccaccc aagagcagag aagccgcaga agctttacca gctcctgcct181 ggggccacac acaggccaaa atatgctcca atttttgaat caattttttg ttgtctctac241 ttttttaatg agtttttctc attattaaaa gtatttgtgt gtatatagga aaatctgggg301 aaaatatagg caggtaaagg accaggncca aaaatcactt attattcccc accttcccct361 accaccccac cttcnttgtc ttccccnggg ggggggcagg ctttttgtcc tggtggcaca
421 tggtaccccc cggtattttt tttcccngtg g<210>14<211>475<212>DNA<213>Homo sapiens<400>141 ttgttttaaa gacacatgca cacgtatgtt tattgtggca ccattcataa tagtaaaaca61 ttttcttttt ggtgtgagag accctcccat tccttagtaa aaacgtattt acttgcatgt121 tattattgtc cttacaaact tgtttttccc tagagcaatt gattttgctt taggtactag181 ctgaaggtct agaggcaata caatttagga tccttgtcta gaaatcaata tgattcaatt241 cttttcaagc caaatgatat ctgtaggact ccagttgtgt gcaagccctg tgtgggagcc301 tcaaggcatc tgcgttaggc cnagcttccc tattcttggg aaatcagctt tgcttgattg361 ggccctatat tggccatggt ttaatggttt ggatgggtgg ccggggcctt tataaaggca421 taccaatttt gcaggtggct ccctctcagg ggtaggggng tcctttgccc caagg<210>15<211>395<212>DNA<213>Homo sapiens<400>151 ngtgagaagc tctgttgtat tacttggcac caggaatgtt acaaaaatgt tgttgctagc61 atattgctaa cctagtcctt aagtttcagg gattcctgta atatgttgag tttggagtat121 taatagcagg ctaacagaat acagtaccaa tatgccaagt taaataattg agaatatata181 cagtatagtt tgctatgtat aatagacctc atttcattta cagtacacct cacacttggg241 gattaattca cctattaacc tctgtggaac tgcgagtgct cgggcggaag gcaggccctg301 tgtctttaca tgtcttacat ttatatttat atttatattt ntttttttga gacgggtctc361 actctgtcac ccggggntgg gtgcgtggcc tggtt<210>16<211>457<212>DNA<213>Homo sapiens<400>161 tcctaccagg cacttatttc ttcttctctt ctaaaatagc atcccaattt ccctttcagg61 gaacttgtcc ccctggctga ctatcagcca gggantcctt gcctcccctc actatggcgt121 atacatgtac cctgaggtta gccagcctct ctcctgtgtc ctgtattttc caaagccaca181 ttattctgct cttcctgtga ttctgaagct cttctgtgtc cttccaataa attccttttt
241 tattgcccat gaacaatggg cacgtgggag ggaaatacgg gaagggtaat ttaggcagga301 ttgttgggca agttaaggtt aggcaaggat aaggtggggt ttctat tggt tggcaactta361 aatatctttt aaaatatata tcattgggga aataggacat tggtaatgtt ctttttatgg421 gaataatgga aaccaggctt aaccatttac tggattt<210>17<211>536<212>DNA<213>Homo sapiens<400>171 ttttttnctg tttttcatca ttcagctaga aagtgagaag ttttatcntc catagtcctt61 ttaaatctta tgttagaact agcangacgt aggtggaaag atgaagaaat aancttgtcn121 agactaaaga aaggaaagca ggttataaaa gccatagtag ccagtccagt tcattctgca181 gatggcccca taccaatcgc tgttagagtt tgccacctcc actttcccac tgagaactgc241 agcaatttta aaggatatga gaaagccaag actcaagaga tgagaagacc cccttggcga301 aatatagtgt actcttcact gccactgcca ccaccaaatg ggtttttaga gctttgaaac361 acaatctttg taaattaatc aaaacctccc tgtgacccac ctgccttctc cccataccca421 aatttgacca tactggccta aaaggaagat ggggttcgat atagaggnct gctaagccag481 taggaagggc tncacgggag tgacagtagg tcttcctctc canatgggat ntacac<210>18<211>411<212>DNA<213>Homo sapiens<400>181 ttaaactctc aggactttta tttgcacctt ggatgacgaa acaaattctg cagttaacat61 taagaaaaac aagtcaatat gtaaacagta aaagtgaatt taccaatttt tccttttgcc121 ttcccagaaa ctcttttttt ctttcactcg tgacttgatt actaattcta atctagaaac181 gaactctaga ttagaatgct aggttagaat tagtaatcat cttgacaact aggtaatcac241 aagtgtttgc cattctcatt acccaggaag tatactcata ccacatagtg gataggccaa301 ctagaacaaa atccaatcag gtgtaaaaaa tgtactttgg ggcccggtgc agtggctcca361 cacctgcaat cccagcaccc cggggaggcc caggtgggga ggattgatga g<210>19<211>478<212>DNA<213>Homo sapiens<400>19
1 acttttttga tattttttat tataaaagaa aagagaacaa cataaaacta gtggggtact61 tgacattgtt tttgagaaac taatccatca gtatctggct tgatggaagt agttgcaatt121 ctcagtgagt tctcaaggtg ctcatcagat attttggntc taattttact cntcgngntc181 ctcnaccctg gaaaatngta gcccccaaat gtaagtgctg ccaaaaagca atgacatgaa241 caaggtgtga ttgtgaagca agggatattt gtcattgggg aagacaggtc cttacaaaaa301 gtccagtaaa gaggcaaaat caaatttttc tataagttga acatcagatt gcagctctag361 gcattccatt tcaaaattgg ccaggtaaca tatatatgtc gactgaaaat gggagttgca421 aatataccna aatattggat gattttttcc cgaaatcctg gnaatacccg gttttcca<210>20<211>406<212>DNA<213>Homo sapiens<400>201 taagacaagg tcttactctg ttgcccaggc gggacanctn ttgatttaag tgaaaaaact61 caatgcatcc tggaggatat cctagaacag aacatggaac tcttctgcat tccttttaat121 agttgcatag aattccattg tgtatatccg atcgtgattt cttccaccag attttgttga181 tgggtatttt tttgggttgt ttctggtctt ttgttctcat gactacatct taaccagtgg241 ttctaaagat gtggtaccca gaacaacatc attactacct aaaaatctat tagaaatgaa301 aattattggg tggaagccag atcttacctg aatccgatac tcnggagtga ggnccaggga361 atcttggcac catacgtccn ggtanaggga tcnggacgcn agcccg<210>21<211>440<212>DNA<213>Homo sapiens<400>211 aacctgtgga gcacgtgtat atctatacat atcgactgaa gaattcatct agtaattctg61 acaaaaatga tagacttaaa ttaagtcaga agaattgggt acaaaattgg gatgggtttg121 ggagaaattt aggtaatgtc agaagctggt taacgactga ctagttctga gggtcagcag181 ttgtaaangn ccngggaagn tgntgcttaa gatgaccctc caaggtttag gcttggatga241 cctgggtgga tgatgccatt agtcagcata ngtgaataag aggtgcaggg agggcaggcc301 cactagggta gttagacaga agttcagttt tggatgtgga caatgttttc tcatatgtct361 ttcatcacta tattgtcagc tacatgactt tagcnaatac taacttactt gacttttgag421 atttttagcc agcctataat<210>22<211>640<212>DNA
<213>Homo sapiens<400>221 tttggaacat tgaattttct ttattgcaaa ttcttagggt ttctgtcaaa agagatttga61 aatacaacat gaaatgatgt actcacatcc ctcaccacca tctccaaata actgaattac121 ataaataaaa cattatatga aaagtgcttt gctacaattt atgggaggta aatttaagaa181 gagctggctc attgtaggaa aattcaactt atcttttcct gatcctttta tttaatacag241 ggagagaaat ttatggcagt taaaaaaatc tattactgtt tctcataact gaatccatta301 tttttctcca tgatccatca gggtaaaaac aagaataata gattgctttg acagaacctt361 ggaacataaa tgtccccaag aatcaaacac agtaagttaa acngggtatc aggtgggatt421 aaaacaggaa aggataactt cttttcatat ttcaaaatca gatcttactt aaaaatttat481 naattattag ctacccaaaa ggaccaacta tataggggcn gaattggcaa ttggaatggg541 ggatattcca atccttccaa atgngcgcng gaaaatttaa cctggaaggg ttccaggaag601 ggaccatttc cttccntttt ggcaccgggt attaaaattc<210>23<211>454<212>DNA<213>Homo sapiens<400>231 tataaattca tgggatatga gtataattta actatattga tatattgcac tatggcgaat61 tcaaggcctt cagtgtatcc atcactggaa caacacatat tgtatccacc aagcaacctg121 aaagattttt taaaatcagc aaacattctt aattgtatta tatgtaatta actttttcca181 ttatggttag tactttatgt atgtagttta agaaatattg gtgtattcaa gatcataaat241 tcccctaggc attctctaga agctctattg ttttacctat cacatttaga tcaacaatcc301 atctacaatt tcgttatgaa tgatgtgaag tagagaatca acatnacatt ttttccataa361 acatatttat tgaaaagacc atcctttctc cactgctcta ccgtggtcat ctttggtggt421 tatagactga atgtttgtgt gtcccccaaa ttca<210>24<211>548<212>DNA<213>Homo sapiens<400>241 tgagatgggg ctctcactat gttgcccagg gtggtctcta tcttctggga tcaagtgatc61 cttctgcctc agtttcccat gtggctggta ctactggtgc atgccactgt gtctgtcaca121 ttttttaaaa tcataaactg attctaaatt ataaataaat caagaggaaa gacagaggac181 ttactatggt gctatcttga caacatcaaa gtaactaatc cccaaaangt ttattcaaaa241 atcacaagtt gtttcatctt aagacccaat ttctgtaccc aaataaagcc tattatactc301 cataatgaaa agtacagata attgaaaagt acagagccca gtgatgctta aatgatgcca
361 tgtaatctaa tagctttgat gagtcagttt ccaagatata taattatatt caaagagttc421 tgtctggttc ngttgatact acaatccaat tcctncctcg gctgcagaca acacctggta481 ccttaagcng aagctgaggc atggnccccc actatacgcc tctaacaacg gntatgtgga541 aggcctag<210>25<211>478<212>DNA<213>Homo sapiens<400>251 gaatttaaaa tcctgggagg cattgcactg taatagtaag tctgcccatc caggatcatg61 catgtctttt ctttcattca agtcttattt tatatctttc agtaaatttt catatagatc121 ttgtgaatcg aattattttt acatttcaaa ttcaactaac aattattaat agaaaatgaa181 aacattgatt tttttcaata tttattttgt gtccaagtat atattaaata ttttangtag241 actttcttgg atatttgaaa gtatattctg caaataatag catcctgtga tccagcaatc301 attttaggaa tctatcctat aganatagca atgtagtaag cctggtgcng tgggctcacg361 cctggtaatc ccagcacttt taggagggcc gngngtgggg tggatcacga ggatcaggag421 ttcnagacca gtctgggcca aganggtgga accccgtctc tactaaaaaa tacaaaaa<210>26<211>441<212>DNA<213>Homo sapiens<400>261 ttttcaagct ggggaaaaca cctgttaaat ataatgacag aatatgctct catcaaaacc61 caggaaactt taagaataca ctaaacctca caaaatgggg gcgaaataca atgatgacca121 cacgtatgag aaatggtcaa tggtagaatt gaaagaaatg caagggaaat aaaaggtaag181 gggtcctttc cgagcaaagt ggcaacgtca caacagctca cagtcaggct tggcgggaca241 agaatgctgg gcagtgctgg tttgcaggga ggggtcaact tttctggaag cagcccagca301 aagtgcccca gagccatcaa ttattcctgt gcttcgcagc cacagcccac cgaatgcagg361 tgcagccaca gaagcgctgg cagaggggag gctgagagtg gcgctggttg aagatttctc421 acaggaaaca aaanggcccc g<210>27<211>487<212>DNA<213>Homo sapiens<400>27
1 tttgagatgg agtctcactg tcacccaggc tggagtgtag tgctgcgatc ctgactcgct61 gcaacctcca cctctggagt tcaggtgatt ctcctgcctc agccttccga gtacctggga121 atacaggaat gcaccaccat gcccggcgaa tttttctatt ttcagtagag acggagtttt181 gccatgttgg ccaggctggt ctcgaactcc tgaactcagg tgatccaccc gcctcagtct241 cccaatagat tagatatatt attaatgaat tgcttccttt aacaccctat tcattgaatt301 ttccagtaaa ccacaattac taattactcc tgaaatcaga aaagaggtta aaaagatttt361 ataacagtat cctatgaaat ctactacttt caagtaatag tagttgaatt accaaaaccc421 gtcactcaag ccaatgacta caattaagat atgagtaaca tttcctaaga taataaagtc481 aattaat<210>28<211>551<212>DNA<213>Homo sapiens<400>281 gttcggaaac ttcttttatt aaaaaagatt ttaaatatta atgctatttt caatacaggt61 gtgataacac tcaataaagc atggtgtact tgatataaat ttcggaatgt aacagtccat121 ctagttcctg gtcccctcca gtctccacca catagcctag taagcaaaac gtacacaccc181 gtttaaaaat gaagaagctt ttgggcattg ggtgagcaca gtggggtggg gcaaggaaag241 tgctcgttcc tgaattattc atgcttttgg ctttgacttc agttaagtaa catcaattct301 aagagaactg agacaaactc ttctatgttc ccgcaaagga atgggagaaa aaagcctgcc361 attccgcnag cagctntggg cnaaaaccag cgccagagta cagggggtcc gggaaatgag421 gtattaaaaa aaaagtccgg ggtaaagtgc ncagttaccg tcaaaatata ttatttgatc481 cnaagaaatt taaagattta tccaatgggc tngattgcng acctttaaac attgggtttc541 atggacatca t<210>29<211>643<212>DNA<213>Homo sapiens<400>291 gtttaaagtt aaagtttatt tgtattcttt gtaggaatat caataaaaga cctcaaacgt61 atctatatct gtacatgtac aagaactgtc aaaaattatt cacagaacaa aaataaatct121 tctttagaac aaacccaggt aatgaaatgc tgatacggat ctcacatacg gaataatcta181 aatgctacta gcacaaaaat atggctttaa aaataaaata aaatcttggg ttttgttttt241 ctaaggtgta tttctctttc ttgaaataaa aaataaatta tttagagcta tcattgtaaa301 atagtcgtgt gttaacacac tctntattaa ggccctggag atgaaaaaca aaatcaaatt361 tagaaggtca tttcctcaca ggtggtaact ccaggttaat gtgctgctgt ctgccttaag421 gttaatataa ctaggaaatg tctaagcacc aggtccaaat ttaacccaat ttacnattta481 actttcccga ggtggtcatt gnggccatta ggaattaacc ntttggtgga cnggggaatt
541 gaaaggttcc ccccganaat tgggaatccc cctaaatggg atttcccnta aaatctgtnc601 cccccnaggt ggtggngggc ccnaaacaca nctcggggga aac<210>30<211>431<212>DNA<213>Homo sapiens<400>301 tatatttaaa taagtttaat gttacagtat tggtatttgg taggttttct tataaggttc61 ccttatccat tttgctgtaa ttaacaatcg gataatgtat tagccagcca aaaattatgt121 atgctgtcag gataaatcaa gtcaaaatgt ttttcaatgt cactacagaa attgtttttg181 gttcaactat atgactatca aaggttatgt acaacgcaca actctaccca gatactcatc241 cttgcactgt tctaaataaa ggaaacaaga ctcttcagta ctctgttttt caaactgtag301 gtcaagatct gttagtgagt tgtaaaatca atttagtcac cattgggcaa taaaatagaa361 tagagaggca agtatccacc atggcatcca aacccaaagg gattgnaccg gtggnaaccg421 ccctgccttc c<210>31<211>511<212>DNA<213>Homo sapiens<400>311 aaattcctat gttagttgtg aacatttaaa taccaagaca tttctagctt ctctcaaaat61 gcaggagacc caactacctg aagtctgagt tcccatatgg caatgtttct ggtgctgaac121 agtcactgcc acctctggac tctacaaagc atctcctcct gcccacagtt cccactccat181 ccctggctgg cccttgtggt cattcgagtt tgcaaccctt cccaaggaat tcataaatac241 atattctatc actaagagtt taaacgaaaa actgtattat gcttgtangg aattctggct301 tgtaagtgaa ttgtttgcat acaaattggn cttctgtaag aactgctgga gttggcaggg361 gatgaaaggt caggtggtng tcagcatttt tcntggagtt taatatggcc tttccccctg421 ggaatgggca ctgggctggt tcacaggatt ggagtgaacn tggctggata gggatagcng481 gttttagagc aggggnagtt taanaagcng g<210>32<211>607<212>DNA<213>Homo sapiens<400>321 gcatagccaa tcttttcatt tttattgctt taacacacat tttaattttc agttgaacaa
61 attcttaatg agctacagag tgacatgagt tgaaattaga ataaagtaaa ataatactat121 ataaccaaaa caaacccagt gttacatatc gtgaaataat gcaattaaga gcacaactaa181 aaaaaatcat tgattcagtt aaacacaaaa gacatgcagg gtctcaaaca aggagtattt241 gggcttctat gtcaatgtca taggaaagag ctttttctat ttctggataa atatttcatt301 tttattgatt tggcaaaaat actttaagga taaatatggg accagaaagg cctacagtat361 ttttgccaaa ttttatctat agccaaagca caaaactggc tttgaactgg gtcattaata421 taatggggca gttcattcca tcatattccg gtcnctgcag agccggggtg aaatggaacc481 agccaagatn ggtccggaac nccctcaacg gccnctaacc ntaagttccc caggatattg541 cnggccataa cntggccnat tatggatngg gacctttatt ccccccngaa gtcctaggtt601 aaccggc<210>33<211>454<212>DNA<213>Homo sapiens<400>331 ttgtgagcaa catcggctgt ttattcactt gtgtgtgagt gggctgagtc cgagaaaggg61 gtcagcaaaa ggtggtggga ttatcattgg ttcttatagg tttgggatag gcggtgtagt121 caggagcaat tttttacagg caggggatgg atattacaaa gtacattctc aagggtgggg181 aggatgttac aaagtacatt cacaagggca gggagggtgt atcgtcacaa gggcagggag241 gatgtattgt cacaagggtg gggaggaatg ttacaaagta cattcacaag gacaggagta301 tcacaaagta cattatcaca agggtggggg aatgtcaccg tggcttgacc attagtgcag361 ccagctccag aggaccttac caaaaagttt ccatacttgc acgtgttttc ctggtggcca421 aaaatataaa acntttaatt tctgggattc cttt<210>34<211>480<212>DNA<213>Homo sapiens<400>341 aaaagttctc tcccagacat gagtatattt taaagtacat attaaaagcc agcagttttt61 ttttaacagc aaaagccata aaacaagcag ttctcaattt acagttaaca tagcagccca121 tcaagtgctc ctctccctta gcatatatgg tactttgatg catattgttg atattgacag181 tcattttgca aataaatgtt ctgaaagctt tcatcttatt taaaggagta aacatggaaa241 taaaggcacc attttaatca ggttattgtg ataagaccaa aaacattcca caaagtgcat301 acctcatttt cgacttctct attaaattta aacttgagtt aaaatgttaa taatttggct361 ttaattgaag agagagttca ttcagagaat tacagagttc gaattgggat gaatccccag421 agtttattta atctggtacc cncattaatt ggnagaatgt gaggctcaaa atggaatgac
<210>35<211>574<212>DNA<213>Homo sapiens<400>351 tcatttccaa gttttaatta aatatctcta atggttagaa aatcaatgtc aaatacgaac61 attggtatac agcttaaaat acaaatgtca gcaattatta aagaacatga ttaatcattg121 ttccaagtaa atgctagatc attatttccc aggaggcaag ttaagcatca ggtgcctgag181 gggtaaggga cagggcttca gtcggctctg atagctgcat ggctgt ccca atgagctttc241 cactcagata gtgccagggg agctctcatc acaggctggc tcactggcct ttatccccag301 ctccaaggaa acaccagggc tttttctgcc atgagaatcg tgtttcagag tcaaatgatc361 cactttaaga tgnaatttgg acagctccag ttnccggaat attcnaggtt taacctgggn421 agttaagact tcccaanggc tgaagatang gctactaagg ggctgattgg acaagggttn481 agggccaggg tccctcttna aaanatcttt ggtttgggcc cgganaaatn aattnaccgg541 acctccttta gnaacccagt tcaagncccc aaat<210>36<211>500<212>DNA<213>Homo sapiens<400>361 cttagaacac ctaaatattt atttggataa aataaaataa caagaatctg gagaaaagaa61 actaagagcc ccaaagttaa agctggtaaa atagttcaag aacttgcagc aagtacctag121 aaaatattaa atggttagga caaaacattc acagttcaag gtcccaagaa aatgatctgg181 tgagcaaata catatacaca cttaaaacta atctggatga attagtgaag caatgaataa241 ataggtcaat tactaaaccc acataactta ttcaaataaa atctaataca aaaaataaac301 ttaaaaaaat aggttaaaac actaaatctt aactaaaata ttaggcaaac tagaacagga361 gggccgttat taaattggtt caccataact tactatttgg ggaccaaact ggaatnggaa421 aatctggaat tgtggagaat aaaccagttg gtttctcaac tacaatttat ttgacagcta481 ccccaaaaag nggcttatnc<210>37<211>580<212>DNA<213>Homo sapiens<400>371 ctgtaggcac cattctgcat cttgaaccca gactgaagtg tgcctctcac agatggaagg61 tgcacacgct cctgtctcct cctcactctg ccacgttcac ttggcttttt cattggtacc121 taggaattta agaatatcga agcgaganag taacaaacca tagatgagca gactcccaca
181 ccgggttttc ttgcccgtct ttaaggcact gtttctaaat tttgaactta gctctgaatc241 cccaagaact tgagcacagc aagggttgct gagctgctgt cgccgcagcc ctggcccctg301 gtgctggagc tgcagcacct ttngggagag gtcctgcgtc gtcctcagct gcgtcgctgt361 gaactcccgc tctccactgt gttcctcagt gtctgctttt caggaagtct gctgtgacct421 ttgcccaact tctgagctcc tcagggacta ggaacaattt cagtagcttt gccctgaacc481 aaacgagaaa acaaaaggga actcccgtat gacccacgtc acgtggtgca ctcagagtgt541 gtgcggcatg atcctcggtt gctcctcctc tcaatttaaa<210>38<211>434<212>DNA<213>Homo sapiens<400>381 ctttttaaat tatatagtcc catggatttt caaatatttt atactagtta tataataaca61 ctattttaaa aactatatag aataaacagc actgaggaga gatgaagcaa tagaaaggtc121 aaagttcaaa cttgttaaaa tatgtttggc tttgtttccc taaggttgga attattaaac181 tggtgtgact ttagaaggtt ttcgaggaat tggtgtgtgt tactgcagaa tcactagctc241 ttaatttgta atttgatggc taaaaacgga caagtcactt aaaggaatat atcgtattaa301 aaagttactt tccttgacat ttggccacca gtcagccctg tctcccctag cctctgtctg361 aagtatggga agacatttag cctgcaggtc catgcctatg cagtaccaga gggaatgtgg421 agggcgcttg ccat<210>39<211>494<212>DNA<213>Homo sapiens<400>391 tggacggant cgctctgtca cccaggcacg caccaccatg cccagctgat ctttgtattt61 ttagtagaga cgggttttca ccatgttggc caggatggtt ttgtactcct gacctcaagt121 gatctgccca cctcggcttc ccagagtgtt gggcttacag atgtgagcca ccacacctgg181 ccaaaagatt tccttttaag aaaaatgtgg gattttttct acgaaggctc tttaaccaca241 caagcacaga atactagttt atgcaactac attatacgac aactccctaa ttttaatgca301 gaaacatcca tcttattttt ctttttgagg cagggtttcc gctctttcac ccaagctggg361 agcccagtgg tgcagtcaca gttccctgca gcctgggacc ttctgggttt caattgatcc421 tcccacctca gtctcccaag tagctangac tacaggaagc acaccatgac gggctnggct481 aaganttcta attt<210>40<211>465
<212>DNA<213>Homo sapiens<400>401 aactttttaa aagtaagctg tctttaattt cagaaaatct gctattatac aacaaattat61 tttttcattc ataaaaaaca gtccacagca ttcataaaac agggtggcag aagaaataaa121 aagacacttt tcaggtggat tctttaagaa cagataagtt agcaatttaa tacagatgaa181 aacaaataca atccatataa aaacagaatc tgaatgggag tgggagcgaa gatgtatcaa241 ccaaagtaaa ttcagagttt tcacacatgc aactcaacac ctgcattctc ttcgcttaaa301 aagcaaacta agggccgggc gcggtggctc acgcctgtaa tcccaacact ttgggaggcc361 aaggcaggcg gatcacaagg tcaggcgatt gagaccatcc tgggctaaaa cggtgaaacc421 ccatctctac ttaaaataga aaacattagc cgggaatggt ggcac<210>41<211>435<212>DNA<213>Homo sapiens<400>411 ttattttatt tctaatttat taatttgtca ttacacaaac aatacataaa tgcatattca61 aaaacatcaa acattacagt taaagctaat gcacgctacc aaactactgt tgacagtttg121 gttagtatcc ttccagacct tctctctata taatacacaa atatgtactt gtagaagtac181 actatacagt atttgtgtgt gtgtgtgtgt gtgtgtgtgt gtgtgtgtga tgtgatttaa241 catcactagt atcatatgta ttacaggtat tgtctttcaa tttttccccc aaacttttaa301 cattgtcncc tgggagatcc ttccatgccg gacatgtagg actctctctt tttcattgat361 acttaatact tcatcatgng taccatagtc catcctcttg atgagtattt tggnttttcc421 aatttcatag tatta<210>42<211>467<212>DNA<213>Homo sapiens<400>421 tccaaacatt agttctgatt acgttattta acaaatacat ttttaaaatt ggacctgata61 tatcaagaca attataaatt atagaaatac cacactaact gataacagac taaactcatc121 tgttaagaat taaccagcag tcaaacaata atatagttta atcacttatt atttgccagg181 tcttagcttt catatattac taaatctttg attctcacaa caattctatc aggtaagtaa241 caatattatg cccattttga tgatgaggga atagatgcac agagtggtta aataacttgc301 ccaaggtcac ataactagga aatggcagag cttgggttcc acccttgcaa tctagttcca361 aaccccagag ctcataaaca tatttaaggc cttctggaaa tgggccaggc tagaggtatc421 actctcgcag anggcaacta tcatctctca gttaaaagct gcatcct
<210>43<211>531<212>DNA<213>Homo sapiens<400>431 acatttaact gatatatttt ttatttatta atgtaggcta aacaagcaga agccatcagt61 aagagacaag aggaaagaaa caaagcattt attccaccna aggaaaaacc aattgtgaaa121 ccnaaggaag gtaatgcttt ctatgatgta aaagtcttta ttaattagga aaagtaaacc181 cataataaat ttgtctgaat ctttttaaga aacagttgta tcttttcatc agttctctta241 gcatttcatt aattactaat ccnaaggaca agggatggct gagataattt ataatttaga301 ggcagcnaat gcctatttca gtgcaaactg gattgacagt cctctcctgg acctctggtc361 tggtgcttgg aaaagactcn ttgttgtgaa agataccaac ccagggcagc agtgcatcnt421 ctggtagnaa tggcagaaga ttccngagct ctggnggtca tggctcncca agaggaatta481 tcngaagttg gactttttcc tcnccttang gtgatcctgg cttagagttg g<210>44<211>624<212>DNA<213>Homo sapiens<400>441 tagacatatc cccaatttta ttccctttgt ccaacattcc gagagggaac ggggcaaatg61 agtcaatgtt gcccctcaaa accatcaagt aggggccttt gggggtcttc agttgatcaa121 ccagggtgat agacccctac cccttcctca tggtcctggc ttgtcacaat taatggggga181 aagttttcca gaaggggatt ccgggcttct caccgctcat cagggcacct tcccaaaacg241 ttctcagcaa aaagtctgca cttctcagag ttaaatacag gagacgggga gactccttga301 ggagccagaa gtgggtatgt tctcaggggt caagagaagg gcgtctcagg ctctccctgt361 ccaccggggg tcgtcctggc tccccgtacc ttcgggcaag taagctcttg gcttngacac421 tgtccagccc gccagcgtcc caggccgccc caagccctca tgggggagga agcaccgacc481 tgtctccaag catcggaaaa ggcgggctcc cttgccgtca tcacggggtt ctctagggcc541 ctgcgtcgcc aaggaggant ctctggaatc cccaattcgt caagctagtc tcttaagact601 tntaacttag gngggttcca nttc<210>45<211>557<212>DNA<213>Homo sapiens<400>45
1 aagtcttgtt ccccatttat ttttttgttg tgattcagaa atacaaggta tgaaaattag61 attacaattc tgccacaaaa gcttctaaag tagcaaacac aactttgtgt atcaaaatag121 ccatgtgcgc ttttatcagt taaaaagtct ttagagttat cacatcaagc aagtgtaaaa181 tataatagct actatctccc cttcaaaatt gcaaatccac agttactgca ctgaagtata241 atccgaagag caagatttag tccagaatat ggaaggttct ggttggcagg tactttttaa301 agctgactta ctaagaacta aaagaaatga gaaatataca aagcatctta tgtcaaagag361 tatgaatatt taaaagtggc ctcaagtgag taatacatgt ttaaattaga acctgatgta421 attaaatgtt tatgtaattt agcnaaaata tatatataat tgccttcttc tagaaagata481 aagacntaaa attccttgga ccaagcnata ttaccaaatg gttttcatca cctaaatact541 aggaaccatc tctcaaa<210>46<211>431<212>DNA<213>Homo sapiens<400>461 ttttaagaat atgaatgttt tattatgcaa atctaaaaat aaaacaaaca aaaacaaaat61 atttgttaca aagttaaatc ttaatgatgg tcccttatga acttcaactt tttatttaag121 ggcactatat tgccttaatc gtgcattaaa atgatttcat tttgtctcca ttcataccat181 gagctgaaat taaattatgt ctaattgtca gtgtacatag tgggcagtat tgaatcaaca241 aatgcttaga aaatgacctt tttttttttg agactggttc tcactctatc atcaaggcca301 gagtgcagtg gagcngacaa ttcatngact cactggcagc cttgacttcc taggctcaag361 cgatcctccc acatcagcct ccagagtagc tggggactac aggcatgaac catcacatct421 gggtcaattt t<210>47<211>589<212>DNA<213>Homo sapiens<400>471 agttgataaa aactttattt aaaacatgta aagaatcata tagttcaaaa ctgcaaaaat61 aaaagacaat ttcttgtaac ttaaaaataa agtatatatc tagaaaccac cacattaaca121 tctactattt atagtacaat ctccaattca aagctaatct ttgtatttct gtattttgca181 acttttgagc tagaatcttc ctccctatcc aactatactg ttatgtaacc ccattgtttt241 aacatttaac aatacaactt gggtattctc tgacaagcaa gaatatatac tattgatcac301 ttctatacac aaaataaaaa cagttcaaat gactagaaac taattttaca aaagaaaaaa361 aaacaggtta gtaaaacatt tcttttggaa aacaatgggt ggattagtat tctgaattga421 gctagagcac atttttgcct ggagactctc catattaggg cactatgcnt ttatatagta481 cnggacattg ccaaatgccn ttcaccattt attagggctc ccnacacctg gggcgcnggg541 ggaatagccg ggcctaccnc gggttacccg gggggaccca gggcncccg
<210>48<211>568<212>DNA<213>Homo sapiens<400>481 gatttaaaaa tagttactaa ctttatttgt attcgtttta aaaacagaac ttgttacagg61 taatcacgaa gcttccaaaa aaaaattaca ttctgctttt gtcatcttga taggacaagg121 aatgtttaga tgtccttaaa acacagggta aagttgacaa ataacaaact actacaaact181 atggattgtc acttcaagca cactaaaatg tggaatacat gtacataaat tactgaccag241 ttttttgcaa tacaaagagt atgcactaca gcttatatac cataaaggta acatgcccca301 aaatataaca gaagattcac aaacaccgtt ccggagaaaa taataacttt gactcttggg361 ttcaatttaa gatttgaagt gaaatggatt ggggaaagtt ttcnggaaac ctggaagggg421 cacgcacatt ataggcagaa ccgtcaatcc accatcacgt gggggttgga aaagcngcca481 ggangaatat gggcncggta acngggggta ccnccttctc tctcctcagt ccccatttgg541 ggttaggaag ntgggggcct aaccggaa<210>49<211>587<212>DNA<213>Homo sapiens<400>491 ctaatggtac aagaacaatt tagtaaataa catcttcaac ttaagataaa aagtaggata61 tatttataat gaaattttca agtattattt caaaattaac cctgtacaaa tgatatattt121 tggaaattcc aatatttgct agagaatatt ttttaaatac caaacatctt tgtggttaat181 gctaccttaa ccttaccaat taaccttcta aaagtatatt acaacagaac acaaatagct241 taaaacacac catactgttt tctccacaaa acagacacca gacaccgaca tgagcacatc301 tggcctggcc agtggactca gaacctcatt tcagaccagt acatctgcag aggaggccac361 gcgggaccca ttctctctct cctaactcct ataataaata ttattttaga ttttcttagc421 aaactagggg acaacttaca gaccccacct ctcccagtca gccagtggtc tgcaggggtt481 caggganttg ggggtaggga acnggagatc tcacacatgg cgtggctgga ttttaaataa541 ggcatctggc tctggagaca cctggggggg gcccagccac cnttcct<210>50<211>488<212>DNA<213>Homo sapiens<400>50
1 gcaagtaaag attactttta attataaact ggccataaac ccaaatgagg atatagtcat61 tgtagagcaa aatgatacaa tgcacccaac ccgatattta cattaaaata tttccagtca121 cattaacttt caaacaaaaa gacttaacga atttacaaat ttttccaaga cgtgagaagt181 gaaaaatgtt tttgaatgcc atctgagcag gatagtaaaa tcactagaat agtcttttta241 agttctcagt tactggactg aaaagataaa gctgatgaaa attggtgaac aatttgttcc301 tttccataac tactatcaga ttaatttaaa aaagattatt tttaaatcta tgccaactat361 ggggagtaga tcacaagaca gtcagttcca gtagcatgtg attaggtggg gggaggaaag421 gggggttata aaggaatatt tccttgtttg gggtgacnta aagatgaatg ggccattgtc481 ctacnggc
權(quán)利要求
1.一類分離出的在人類肝臟中表達(dá)的表達(dá)序列標(biāo)簽的序列，其特征在于，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所述的一類分離出的在人類肝臟中表達(dá)的表達(dá)序列標(biāo)簽的序列，其特征在于所述序列包括具有SEQ ID No.1～SEQ IDNo.50所示的序列。
3.一種探針?lè)肿樱涮卣髟谟谒龅奶结樂(lè)肿雍袡?quán)利要求1中所述的序列中約8-100個(gè)連續(xù)的核苷酸。
全文摘要
本發(fā)明公開(kāi)了一類在人類肝臟中表達(dá)的表達(dá)序列標(biāo)簽的序列。利用本發(fā)明的在人類肝臟中表達(dá)的表達(dá)序列標(biāo)簽，可以方便的尋找出在人類肝臟中特異表達(dá)的表達(dá)序列標(biāo)簽，從而尋找出人類肝臟疾病相關(guān)基因，從而在研究肝臟疾病的致病機(jī)理以及開(kāi)發(fā)治療肝臟疾病的藥物中發(fā)揮重要作用。
文檔編號(hào)C12Q1/68GK1970758SQ20051011059
公開(kāi)日2007年5月30日 申請(qǐng)日期2005年11月22日 優(yōu)先權(quán)日2005年11月22日
發(fā)明者韓澤廣, 黃健 申請(qǐng)人:上海人類基因組研究中心