本發(fā)明涉及致病基因，尤其是涉及一種mmaf新致病基因及其應(yīng)用。
背景技術(shù)：
精子尾部多種形態(tài)異常(mμltiplemorphologicalabnormalitiesofthespermflagella,mmaf)是一種隱性遺傳的導(dǎo)致男性不育的畸形精子癥，是一種很少見的遺傳疾病，其主要臨床特征是五種精子尾部異常的總和，包括短尾、無尾、卷尾、彎尾以及尾部寬度不規(guī)則。早期研究中也有文獻(xiàn)稱這個病為纖維鞘發(fā)育不良(dysplasiaofthefibroussheath，dfs)、短尾精子癥(shorttails，stumptails)。國外早期的分子方面發(fā)病機(jī)制研究發(fā)現(xiàn)dnah1基因發(fā)生了突變(1)，該基因編碼纖毛軸動力蛋白重鏈1(dyneinaxonemalheavychain1)蛋白。
目前mmaf的基因突變譜尚未完全發(fā)現(xiàn)，基因型和表現(xiàn)型的關(guān)系也不明確。目前單基因疾病的研究開始大量采用全外顯子組測序(whole-exomesequencing)及全基因組測序(whole-genomesequencing)的方法，這兩種方法被成功的應(yīng)用于發(fā)現(xiàn)稀有單基因疾病的致病基因。全外顯子組測序及全基因組測序技術(shù)已被證明為降低稀有單基因疾病候選基因甚至發(fā)現(xiàn)其致病基因的有力、有效手段。僅通過對幾個很少的個體(包括患者及正常對照)的全外顯子組或基因組進(jìn)行測序來篩選與疾病相關(guān)的變異，其成功率大為提升。
因此本領(lǐng)域?qū)maf的研究尚不清晰，對造成該疾病的原因更不明了，因此本領(lǐng)域迫切需要對mmaf的致病機(jī)理進(jìn)行研究，找到新致病基因及突變位點。
參考文獻(xiàn)：
1.benkhelifam,couttonc,zouarir,karaouzenet,renduj,bidartm,yassines,pierrev,delarochej,hennebicqs,grunwaldd,escalierd,pernet-gallayk,joukps,thierry-miegn,tourea,etal.mutationsindnah1,whichencodesaninnerarmheavychaindynein,leadtomaleinfertilityfrommμltiplemorphologicalabnormalitiesofthespermflagella.amjhumgenet.2014；94(1):95-104.
技術(shù)實現(xiàn)要素：
本發(fā)明的第一目的在于提供通過外顯子組測序的方法確定mmaf的新致病基因。
本發(fā)明的第二目的在于提供mmaf的生物標(biāo)記物。
本發(fā)明的第三目的在于提供突變的cfap44基因。
本發(fā)明的第四目的在于提供突變的cfap44蛋白。
本發(fā)明的第五目的在于提供一種檢測mmaf的方法。
本發(fā)明的第六目的在于提供通過pcr檢測cfap44基因或cfap44蛋白突變中使用的引物對。
本發(fā)明的第七目的在于提供突變cfap44基因互補(bǔ)的核酸探針。
本發(fā)明的第八目的在于提供檢測突變cfap44基因或cfap44蛋白的試劑盒。
本發(fā)明的第九目的在于提供檢測突變cfap44基因的試劑盒。
本發(fā)明的第十目的在于提供一種mmaf新致病基因的應(yīng)用。
所述通過外顯子組測序的方法確定mmaf的新致病基因。
所述mmaf的生物標(biāo)記物，即突變的cfap44基因或cfap44蛋白，所述生物標(biāo)記物是具有選自如下的突變的cfap44基因或cfap44蛋白：
在外顯子14中錯義突變(c.1769t>a；p.l590q)；
在外顯子22中無義突變(c.2935_2944del；p.d979*)；
在外顯子23中錯義突變(c.3262g>a；p.g1088s)；
在外顯子14中錯義突變(c.1718c>a；p.p573h)；
在外顯子16中移碼突變(c.2005_2006del；p.m669vfs*13)。
所述突變的cfap44基因為seqidno:1的序列中具有以下突變：
在外顯子14中錯義突變(c.1769t>a)；
在外顯子22中無義突變(c.2935_2944del)；
在外顯子23中錯義突變(c.3262g>a)；
在外顯子14中錯義突變(c.1718c>a)；
在外顯子16中移碼突變(c.2005_2006del)。
所述突變的cfap44蛋白為seqidno:2的序列中具有以下突變：
在外顯子14中錯義突變(p.l590q)；
在外顯子22中無義突變(p.d979*)；
在外顯子23中錯義突變(p.g1088s)；
在外顯子14中錯義突變(p.p573h)；
在外顯子16中移碼突變(p.m669vfs*13)。
所述突變的cfap44蛋白為seqidno:2的序列中具有外顯子22中無義突變(p.d979*)，所述突變的cfap44蛋白的序列是seqidno:11；
所述突變的cfap44蛋白為seqidno:2的序列中具有外顯子16中移碼突變(p.m669vfs*13)，所述突變的cfap44蛋白的序列是seqidno:12。
所述一種檢測mmaf的方法，所述方法包括檢測受試者的cfap44基因或cfap44蛋白中是否存在突變位點，若有突變位點，則所述受試者被鑒定為患有mmaf或易患mmaf，所述突變位點選自如下任一種或其組合：
在外顯子14中錯義突變(c.1769t>a；p.l590q)；
在外顯子22中無義突變(c.2935_2944del；p.d979*)；
在外顯子23中錯義突變(c.3262g>a；p.g1088s)；
在外顯子14中錯義突變(c.1718c>a；p.p573h)；
在外顯子16中移碼突變(c.2005_2006del；p.m669vfs*13)。
所述cfap44蛋白為seqidno:2的序列表示。
所述cfap44基因為seqidno:1的序列表示。
所述檢測mmaf的方法包括如下至少一組引物擴(kuò)增的步驟：
seqidno:3和seqidno:4；
seqidno:5和seqidno:6；
seqidno:7和seqidno:8；
seqidno:9和seqidno:10。
所述檢測mmaf的方法中檢測突變位點通過選自如下進(jìn)行：測序、電泳、核酸雜交、原位雜交、pcr、逆轉(zhuǎn)錄酶鏈反應(yīng)和變性高效液相色譜。
所述通過pcr檢測cfap44基因或cfap44蛋白突變中使用的引物對，所述突變是選自如下任一種或其組合：
在外顯子14中錯義突變(c.1769t>a；p.l590q)；
在外顯子22中無義突變(c.2935_2944del；p.d979*)；
在外顯子23中錯義突變(c.3262g>a；p.g1088s)；
在外顯子14中錯義突變(c.1718c>a；p.p573h)；
在外顯子16中移碼突變(c.2005_2006del；p.m669vfs*13)，
其中所述引物對分別基于選自如下的位置前后設(shè)計，使得擴(kuò)增該位置(編號基于cfap44的cdna序列)：1769、2935_2944、3262、1718和2005_2006。
所述與突變cfap44基因互補(bǔ)的核酸探針，所述突變是選自如下任一種或其組合：
在外顯子14中錯義突變(c.1769t>a；p.l590q)；
在外顯子22中無義突變(c.2935_2944del；p.d979*)；
在外顯子23中錯義突變(c.3262g>a；p.g1088s)；
在外顯子14中錯義突變(c.1718c>a；p.p573h)；
在外顯子16中移碼突變(c.2005_2006del；p.m669vfs*13)，
所述探針與突變cfap44基因的互補(bǔ)區(qū)包括選自如下的位置(編號基于cfap44的cdna序列)：1769、2935_2944、3262、1718和2005_2006。
所述檢測突變cfap44基因或cfap44蛋白的試劑盒，包含一組或多組引物對，其中所述突變是選自如下任一種或其組合：
在外顯子14中錯義突變(c.1769t>a；p.l590q)；
在外顯子22中無義突變(c.2935_2944del；p.d979*)；
在外顯子23中錯義突變(c.3262g>a；p.g1088s)；
在外顯子14中錯義突變(c.1718c>a；p.p573h)；
在外顯子16中移碼突變(c.2005_2006del；p.m669vfs*13)，
其中所述引物對分別基于選自如下的位置前后設(shè)計，使得其擴(kuò)增產(chǎn)物涵蓋該位置(編號基于cfap44的cdna序列)：1769、2935_2944、3262、1718和2005_2006。
所述檢測突變cfap44基因或cfap44蛋白的試劑盒，包含選自如下的至少一組引物：
seqidno:3和seqidno:4；
seqidno:5和seqidno:6；
seqidno:7和seqidno:8；
seqidno:9和seqidno:10。
所述檢測突變cfap44基因的試劑盒，包含一個或多個核酸探針，所述突變是選自如下任一種或其組合：
在外顯子14中錯義突變(c.1769t>a；p.l590q)；
在外顯子22中無義突變(c.2935_2944del；p.d979*)；
在外顯子23中錯義突變(c.3262g>a；p.g1088s)；
在外顯子14中錯義突變(c.1718c>a；p.p573h)；
在外顯子16中移碼突變(c.2005_2006del；p.m669vfs*13)，
所述探針與突變cfap44基因上包含選自如下的位置的區(qū)域互補(bǔ)(編號基于cfap44的cdna序列)：1769、2935_2944、3262、1718和2005_2006。
一種mmaf新致病基因的應(yīng)用。
本發(fā)明將為mmaf的發(fā)病機(jī)制研究奠定重要基礎(chǔ)，有可能為mmaf的患者治療提供全新的理論依據(jù)。
具體實施方式
在本發(fā)明中，采用本領(lǐng)域通用表示法表示突變。例如，突變(c.1769t>a；p.l590q)中，c表示cdna，p表示蛋白質(zhì)，dna水平的突變對應(yīng)蛋白質(zhì)水平的突變；移碼突變(c.2005_2006del；p.m669vfs*13)中，c.2005_2006del表示dna水平第2005～2006位缺失，p.m669vfs*13表示從第669位起算的13個氨基酸的移碼，形成的突變蛋白質(zhì)僅有681個氨基酸，如seqidno:12中所示；無義突變(c.2935_2944del；p.d979*)中，c.2935_2944del表示dna水平第2935～2944位缺失，p.d979*表示第979位的氨基酸d突變?yōu)榻K止密碼子，形成的突變蛋白質(zhì)僅有978個氨基酸，如seqidno:11中所示。
野生型cfap44基因的cdna序列如seqidno:1所示。
seqidno:2：野生型cfap44蛋白的氨基酸序列。
對于本發(fā)明說明書和權(quán)利要求書中，提及基因序列，本領(lǐng)域技術(shù)人員應(yīng)當(dāng)理解，實際包括互補(bǔ)雙鏈的任意一條，或者兩條。為了方便，在本說明書和權(quán)利要求書中，雖然多數(shù)情況下至給出了一條鏈，但實際上也公開了與之互補(bǔ)的另一條鏈。例如提及cfap44基因的cdna序列，實際上包括該序列以及其互補(bǔ)序列。例如，提及seqidno:1，實際包括其互補(bǔ)序列。本領(lǐng)域技術(shù)人員還可以理解，利用一條鏈可以檢測另一條鏈，反之亦然。
本申請中的基因序列包括dna形式或rna形式，公開其中一種，意味著另一種也被公開。例如提及cfap44基因的cdna序列，實際也包括相應(yīng)的rna序列。
實施例1確定mmaf的致病基因。
本發(fā)明收集到27例mmaf病例，所有患者均表現(xiàn)為不育，尾部畸形包括短尾、無尾、卷尾、彎尾以及尾部寬度不規(guī)則等典型的mmaf疾病特征。
本發(fā)明對所有患者進(jìn)行了全外顯子組測序，具體步驟如下：
樣品制備：采集所述患者及其父母家人外周血，利用試劑盒抽提外周血白細(xì)胞中的基因組dna(qiaampdnaminikit51304.qiagen,usa)，利用nanodrop2000測量dna的濃度及純度(thermoscientific,usa)，所得的每個標(biāo)本基因組dna的od260/od280均位于1.7～2.0之間，濃度不少于100ng/μl，總量不少于30μl。
然后，對上述四個樣本的外顯子組序列進(jìn)行了測序。測序平臺為illuminahiseq2000，依照illumina標(biāo)準(zhǔn)建庫說明書(參見http://www.illumina.com/)進(jìn)行測序，簡述如下：
1)使用illumina公司試劑盒truseqdnalibraryprepkit制作dna文庫。在外顯子捕獲過程中使用agilent公司試劑盒sureselecthumanallexonv5；
2)使用illumina公司hiseq2000測序平臺對捕獲的外顯子區(qū)域進(jìn)行平行測序讀取長度為90bp，每個樣本的平均測序深度最少為100；
3)使用burrows-wheeleraligner(http://bio-bwa.sourceforge.net/)將測序結(jié)果比對到人參考基因組中(hg19)。使用samtools將重復(fù)讀取結(jié)果去除，通過gatk(https://www.broadinstitute.org/gatk/)進(jìn)行調(diào)整和校準(zhǔn)。然后使用samtools(http://www.samtools.sourceforge.net/)挖掘出snvs及indels，并用annovar(http://www.openbioinformatics.org/annovar/)命名。
將等位基因頻率大于1％的突變位點剔除(參考數(shù)據(jù)庫包括dbsnp，1000genomes，exomeaggregationconsortium(exac))。
發(fā)現(xiàn)5個患者在基因cfap44上具有純合或復(fù)雜雜合突變：通過兩個家系中3名患者和5位正常人snp篩查共分離，這些位點可能是致病位點。
結(jié)果顯示于表3。
因此本發(fā)明認(rèn)為cfap44基因極有可能為mmaf的致病基因。
實施例2在其他病例中確認(rèn)上述mmaf的致病基因。
本發(fā)明納入所有mmaf患者，對cfap44基因為mmaf的致病基因進(jìn)行驗證。驗證中利用sanger法測序驗證cfap44基因的突變，其中考慮了家系內(nèi)、家系外、散發(fā)等樣本驗證情況。
分別對5名患者、5名家系內(nèi)正常人(即其中3名患者的父母，他們均為發(fā)病)基因進(jìn)行檢測。
具體方法步驟如下：
1.dna提?。?/p>
分別提取5名患者、5名家系內(nèi)正常人的外周靜脈血，按照實施例1的方法提取基因組dna和測定dna含量。
2.引物設(shè)計及pcr反應(yīng)
引物設(shè)計參考人類基因組序列數(shù)據(jù)庫hg19，引物序列參見表1。
表1
pcr擴(kuò)增體系參見表2。
表2
pcr反應(yīng)條件：
94℃變性5min，然后進(jìn)入每個循環(huán)，即94℃變性30s，退火(通常為55℃，根據(jù)不同引物的退火溫度設(shè)定)30s，72℃延伸1min，總共設(shè)定30個循環(huán)。所有循環(huán)結(jié)束，最終72℃延伸10min，并將pcr產(chǎn)物保存在4或-20℃。
3)將步驟2)中獲得的獲自5名mmaf患者、5名家系內(nèi)正常人(即該5例患者的父母，他們均未發(fā)病)的pcr擴(kuò)征產(chǎn)物直接進(jìn)行dna測序，方法同實施例1。
本發(fā)明收集到的27例mmaf病例中有5例在cfap44基因中檢測到有意義的突變位點。同時所發(fā)現(xiàn)的突變位點在家族正常人中均未能檢測到。這些突變位點在exac數(shù)據(jù)庫中的頻率極低或無頻率(見表3)，提示所檢測到的位點很可能并非snp。因此認(rèn)為cfap44基因為mmaf的致病基因。
表3
序列表說明
seqidno:1：野生型cfap44基因的cdna序列
atgaaggaaccagatgatcaggatactgatggggagaaatcagttacatcaaagagtgatgggaagaagtctctgaggtcttctaaatcagaatcaagatctcctgttcaagaagataacacatttttagaagatgacacagatgaaacatttaccaaaggggaaggatcatatttagaagaagactcagatgaggaacgtttggaaggaagtttgagttcatttcagtatggtgatttgcaaagcactacagtacctcagcaaacccctgctccagctgtggaagaagcagaggaggaagttaagaagaaaatatcagagagcttcttctatgattatatggagcttgcttcgatgccttttgtgactctggattcaaacataccactggatcttctcacacttgtacattcttttggttatgactgtagaaagcgagccaacctacaacttctggacgacagtatcgccatatacatagctgggaaccaactgatctttctgaatttgaaaaccaaggaacagatctacctgcgaagtagcagtggtgaaggaattggcgtcattggggttcatccacataaaacttatttcacagtagctgaaaaagggagttttccagatattatcatctatgaatatccttctctgagaccatacagagtccttcgagatgggactgagaagggatatgcttatgtggactttaactacagcggtaacttgctggcctctgttggtagtaaccctgactacacactgactatctggaactggaaagaagaacaacccatactaaggacaaaagctttttctcaggaagtttttaaggttactttcaatcctgataaggaagagcagcttactacatcgggatcaggccacatcaagttctgggaaatggcttttacgttcaccggtctcaagctgcagggatcactaggtcgatttggcaaaacaatcactactgatatagaaggctacatggagctcccagatgggaaggtgctctcagggtcagaatggggcaacatgctgctttgggaaggtggtctgatcaaagtggagctctgtcgagggacaagcaagtcatgtcacaatggtcccattaaccagataatgctgtatgagggtgaagttatcactgttgggtcagatggatatgttaggatatgggattttgagacaatagacactgctgatgtaatagatgagactggattgttggagattgagcctattaatgaacttcaagtagacaagaatgtgaatctcttctctatgataaaaatgaatgaaactggaaataacttttggttggctcaggatgccaatggagccatatggaagcttgaccttagtttttcaaatattacccaggacccagaatgcctcttctccttccattctggagctattgaagccgtggctgtttctcctctcacttatctcatggccacaactgccttggactgctctgttcgaatctatgattttgctagcaaaactcctttggcccagatgaaattcaaacaaggaggtactgcccttgtttgggtaccccgaatggtaaacttcactggagcacaaattattgtaggatttgaagatggagttgttcgaattcttgaactttatgatccaaaagggctcacgatttttgcgggacggaagaaaattttggatgctgatattcagttgaaacaggttttcaaaccccatactgcttgtgtcactgctttagcttatgaacgtgatggggaaattctagccacagggagtaaagatcaaactgttttcttctttgaagtggaaagggattataagccgattggttatattaatactcctggacctgtgtgtcagttaatgtggtctcccatgtctcatcctgaaagtactttactaattatctgtgaaaatggctatattcttgaagctccacttccaaccataaagcaagaagaggatgatcatgatgtagtctcctatgaaatcaaagacatgtgcataaaatgtttccatttttcaagtgtcaaatctaagattctgagattaatagaaattgaaaagagggagagacaaagggagttgaaggagaaaataagggaagaaaggaggaacaagctagcagcagagatgggagaagatggagaaaaagaatttcaggaggaggaagaggagaaagaggaggaggaggaggaagaagagccattacctgaaatatttattccgtcaaccccctctcccatcctctgtggattttactcagagccagggaagttctgggtttctttgggtggctatgattctggttttctatatcactgtgagttccccccttgtgatgaaagcagtgatttcaaagaacaaaaagatgaacctattgatgtccgttatcttgcggatacagaggacaatcccatccaaactatcactttcaacattaacaaagttatgatgttttgtggaatgaaaaatggagcaattcgagtctatgtcctaaatcaaaatgatccttcattgaccagtttggtggactactggcacttcaatatgcatgacaataattatggatgtattaaaagtattgctaatagctttgatgatcgtttcttggtgactgctggagcagatggcaatatctttgttttcaacattttttctgaatttatgctaaggaaagacatgaaggccaaagttccatctcccaggtttggaattgaaacagagccaattccagaagacattgaagatcccaaagcctacagtatcgagaatgctaggagaaaaagagaacatgacaagttaatgaaagaagtgggagaaataaaggcacggaagagagagcaaatcaaagctttgaggagtgaattttgtaatctattagaaatgaatgaaaaattaccaaagcatatgcagtttaaacgaacagattttgatgtagattcccaaatccgtgctgagatgcacagaaaaacagctttcaaaattcaacaagtggaaaaggaattagcttgggaaaaagagaaacatgaactcggcctaatgaagctaaagaatcgatttcgagatccactggaaagtgatactattgtggttcatgccatactgagtgaccacaagatatcctcttacaggctggtgcagccctctaagtactccaaattcaaacgagctagtcaatcagagagaaaaccaagcaaattggacaggtttgaaaaagagggacctggaagaaaggacagccagagagatgcaggtgggagtgttaccatacaagaagaatcaataatagaaaaagggaagaaatttcggcctaaaaccctaagtgaaatcatcgtggaaaatcaaattgagaaaacgagaaaacttatattaaaagctgaaagggcacaactaaagattcaacagcgaaaaaaagaatgggaggaactatacaagagtaaacctggtgatgactatgaagatcccaaagatcttcaagccatcaaagaagcccaggtgtatatgggagatttcaatctgaagacagccccagactacaagatacctgagcacatgagaataaatgctgccaagaaggaagaggaactaggacacctagattctttggtccatggaaataaaaggcacatgaacaagtgcattctctctcttagagaccttaaagtggctgttgttgaggaaatacagtgcctggtacaagaactgaagaacattcagtcgactcttcacatatccaagcacatacccattcccaaaattcctcagatacacccagaagaagttccagaaaagagatttcagtatgatgaagaaactctcctaaattttaagcaacagcaaatgaaaagtaaagatgaaaagtcccccggagtggaacagacagggtctggaggcccagttggaggattcctcaaactctcttctagaaaggatggggatttgacaacccgtgattcaatatctagatcatcaaaggcatcaacattcagcctagatataccaaagtgtttggaatttgaaaaagcagagccaacggatgtggagctggaaattatgaagagagacgagattaaacacgtgtacatgcaacagtatttggtcaacaggatcaaagaactggttgtcactttcgatgcagaactccgtctccttagacatcagaaactaaaactagatactcagatgaaattatctgacctgcaccatgtcaccttatttcaagaaatacttctcctgaagaattttgaaaaacaggagaacatacttcaagaacgtgttaattccttagacaaagaggaacagtacatgcaatggaaaataaatgaaactcttaaagagatggaagagaaaaagaatgaaatcaccaaactccaggagcaagaaaaggcactctatgctggttttcaagcagccattggagaaaacaataaatttgcaaacttcctcatgaaggtcctaaagaagaagattaaacgggtaaagaaaaaagaagttgaaggagatgctgatgaagatgaggagagtgaggaatcaagtgaagaagaatctagcttggagagtgatgaagatgagtctgaatcagaagatgaggtttttgatgattctatttgcccaacaaattgtgatgtggctctttttgagctggcccttcaccttcgagagaaaaggctggacattgaggaggctttagttgaagaaaagaaaattgttgataacctcaaaaaggaatatgatacattgtcaaaaaaagtgaaaattgtggcaactaatctgaatgcagcagaggaggccctggaggcttatcagcgagagaagcagcagcggctgaatgaactgctagttgtgattccgctcaagctccaccagatagagtatgtggtatttggagaaatacctagcgatctttctggtactttggtcttctctaaccatgccttgagacggctgcaagaacgaatccatgagctccaggaggaaaattccaagcagcaaaaacttaacaaagaatggagagagagacgtaaacagctcatccgagaaaagagagaaatgacaaaaaccatacacaaaatggaggaaacagtccggcagctcatgatcagcaagtttggccgtgtggtaaatctagaagcccttcaaacgctttctgttaatacaacacttgaagaactgaagatcagaaaacttcgaaaggagctagcaaatgcgaaagagatgaagatgtgggaggaaaagattgctcaaatgcgatgggaactgatgatgaagacaaaagaacacaccagaaagctttatcagatgaatgatttgtgtattgaaaagaagaaacttgattctcggttgaatacactacagaatcagcagggcaatgccttccagggccctcgggaagcagatgttgtggcaagagaggaggtcactgaattgatccaactccaggcggaaaggatttcggccttaaaggaggagattgctcttttgcgtaggaaaggcagtcttatcctcccacccattcagtctccacgagagaaagagatacagcccgcagacctttga
seqidno:2：野生型cfap44蛋白的氨基酸序列
mkepddqdtdgeksvtsksdgkkslrssksesrspvqedntfleddtdetftkgegsyleedsdeerlegslssfqygdlqsttvpqqtpapaveeaeeevkkkisesffydymelasmpfvtldsnipldlltlvhsfgydcrkranlqllddsiaiyiagnqliflnlktkeqiylrsssgegigvigvhphktyftvaekgsfpdiiiyeypslrpyrvlrdgtekgyayvdfnysgnllasvgsnpdytltiwnwkeeqpilrtkafsqevfkvtfnpdkeeqlttsgsghikfwemaftftglklqgslgrfgktittdiegymelpdgkvlsgsewgnmllwegglikvelcrgtskschngpinqimlyegevitvgsdgyvriwdfetidtadvidetglleiepinelqvdknvnlfsmikmnetgnnfwlaqdangaiwkldlsfsnitqdpeclfsfhsgaieavavspltylmattaldcsvriydfasktplaqmkfkqggtalvwvprmvnftgaqiivgfedgvvrilelydpkgltifagrkkildadiqlkqvfkphtacvtalayerdgeilatgskdqtvfffeverdykpigyintpgpvcqlmwspmshpestlliicengyileaplptikqeeddhdvvsyeikdmcikcfhfssvkskilrlieiekrerqrelkekireerrnklaaemgedgekefqeeeeekeeeeeeeeplpeifipstpspilcgfysepgkfwvslggydsgflyhcefppcdessdfkeqkdepidvryladtednpiqtitfninkvmmfcgmkngairvyvlnqndpsltslvdywhfnmhdnnygciksiansfddrflvtagadgnifvfnifsefmlrkdmkakvpsprfgietepipediedpkaysienarrkrehdklmkevgeikarkreqikalrsefcnllemneklpkhmqfkrtdfdvdsqiraemhrktafkiqqvekelawekekhelglmklknrfrdplesdtivvhailsdhkissyrlvqpskyskfkrasqserkpskldrfekegpgrkdsqrdaggsvtiqeesiiekgkkfrpktlseiivenqiektrklilkaeraqlkiqqrkkeweelykskpgddyedpkdlqaikeaqvymgdfnlktapdykipehmrinaakkeeelghldslvhgnkrhmnkcilslrdlkvavveeiqclvqelkniqstlhiskhipipkipqihpeevpekrfqydeetllnfkqqqmkskdekspgveqtgsggpvggflklssrkdgdlttrdsisrsskastfsldipkclefekaeptdveleimkrdeikhvymqqylvnrikelvvtfdaelrllrhqklkldtqmklsdlhhvtlfqeilllknfekqenilqervnsldkeeqymqwkinetlkemeekkneitklqeqekalyagfqaaigennkfanflmkvlkkkikrvkkkevegdadedeeseesseeesslesdedesesedevfddsicptncdvalfelalhlrekrldieealveekkivdnlkkeydtlskkvkivatnlnaaeealeayqrekqqrlnellvviplklhqieyvvfgeipsdlsgtlvfsnhalrrlqerihelqeenskqqklnkewrerrkqlirekremtktihkmeetvrqlmiskfgrvvnlealqtlsvnttleelkirklrkelanakemkmweekiaqmrwelmmktkehtrklyqmndlciekkkldsrlntlqnqqgnafqgpreadvvareevteliqlqaerisalkeeiallrrkgslilppiqsprekeiqpadl
seqidno:11：突變cfap44蛋白(p.d979*)的氨基酸序列
mkepddqdtdgeksvtsksdgkkslrssksesrspvqedntfleddtdetftkgegsyleedsdeerlegslssfqygdlqsttvpqqtpapaveeaeeevkkkisesffydymelasmpfvtldsnipldlltlvhsfgydcrkranlqllddsiaiyiagnqliflnlktkeqiylrsssgegigvigvhphktyftvaekgsfpdiiiyeypslrpyrvlrdgtekgyayvdfnysgnllasvgsnpdytltiwnwkeeqpilrtkafsqevfkvtfnpdkeeqlttsgsghikfwemaftftglklqgslgrfgktittdiegymelpdgkvlsgsewgnmllwegglikvelcrgtskschngpinqimlyegevitvgsdgyvriwdfetidtadvidetglleiepinelqvdknvnlfsmikmnetgnnfwlaqdangaiwkldlsfsnitqdpeclfsfhsgaieavavspltylmattaldcsvriydfasktplaqmkfkqggtalvwvprmvnftgaqiivgfedgvvrilelydpkgltifagrkkildadiqlkqvfkphtacvtalayerdgeilatgskdqtvfffeverdykpigyintpgpvcqlmwspmshpestlliicengyileaplptikqeeddhdvvsyeikdmcikcfhfssvkskilrlieiekrerqrelkekireerrnklaaemgedgekefqeeeeekeeeeeeeeplpeifipstpspilcgfysepgkfwvslggydsgflyhcefppcdessdfkeqkdepidvryladtednpiqtitfninkvmmfcgmkngairvyvlnqndpsltslvdywhfnmhdnnygciksiansfddrflvtagadgnifvfnifsefmlrkdmkakvpsprfgietepipediedpkaysienarrkrehdklmkevgeikarkreqikalrsefcnllemneklpkhmqfkrt
seqidno:12：突變cfap44蛋白(p.m669vfs*13)的氨基酸序列
mkepddqdtdgeksvtsksdgkkslrssksesrspvqedntfleddtdetftkgegsyleedsdeerlegslssfqygdlqsttvpqqtpapaveeaeeevkkkisesffydymelasmpfvtldsnipldlltlvhsfgydcrkranlqllddsiaiyiagnqliflnlktkeqiylrsssgegigvigvhphktyftvaekgsfpdiiiyeypslrpyrvlrdgtekgyayvdfnysgnllasvgsnpdytltiwnwkeeqpilrtkafsqevfkvtfnpdkeeqlttsgsghikfwemaftftglklqgslgrfgktittdiegymelpdgkvlsgsewgnmllwegglikvelcrgtskschngpinqimlyegevitvgsdgyvriwdfetidtadvidetglleiepinelqvdknvnlfsmikmnetgnnfwlaqdangaiwkldlsfsnitqdpeclfsfhsgaieavavspltylmattaldcsvriydfasktplaqmkfkqggtalvwvprmvnftgaqiivgfedgvvrilelydpkgltifagrkkildadiqlkqvfkphtacvtalayerdgeilatgskdqtvfffeverdykpigyintpgpvcqlmwspmshpestlliicengyileaplptikqeeddhdvvsyeikdvhkmfpffkcqi。
序列表
<110>廈門市婦幼保健院（廈門市計劃生育服務(wù)中心）；首都醫(yī)科大學(xué)附屬北京婦產(chǎn)醫(yī)院
<120>一種mmaf新致病基因及其應(yīng)用
<130>2017
<160>1
<170>patentinversion3.3
<210>1
<211>5565
<212>dna
<213>homosapiens
<400>1
atgaaggaaccagatgatcaggatactgatggggagaaatcagttacatcaaagagtgat60
gggaagaagtctctgaggtcttctaaatcagaatcaagatctcctgttcaagaagataac120
acatttttagaagatgacacagatgaaacatttaccaaaggggaaggatcatatttagaa180
gaagactcagatgaggaacgtttggaaggaagtttgagttcatttcagtatggtgatttg240
caaagcactacagtacctcagcaaacccctgctccagctgtggaagaagcagaggaggaa300
gttaagaagaaaatatcagagagcttcttctatgattatatggagcttgcttcgatgcct360
tttgtgactctggattcaaacataccactggatcttctcacacttgtacattcttttggt420
tatgactgtagaaagcgagccaacctacaacttctggacgacagtatcgccatatacata480
gctgggaaccaactgatctttctgaatttgaaaaccaaggaacagatctacctgcgaagt540
agcagtggtgaaggaattggcgtcattggggttcatccacataaaacttatttcacagta600
gctgaaaaagggagttttccagatattatcatctatgaatatccttctctgagaccatac660
agagtccttcgagatgggactgagaagggatatgcttatgtggactttaactacagcggt720
aacttgctggcctctgttggtagtaaccctgactacacactgactatctggaactggaaa780
gaagaacaacccatactaaggacaaaagctttttctcaggaagtttttaaggttactttc840
aatcctgataaggaagagcagcttactacatcgggatcaggccacatcaagttctgggaa900
atggcttttacgttcaccggtctcaagctgcagggatcactaggtcgatttggcaaaaca960
atcactactgatatagaaggctacatggagctcccagatgggaaggtgctctcagggtca1020
gaatggggcaacatgctgctttgggaaggtggtctgatcaaagtggagctctgtcgaggg1080
acaagcaagtcatgtcacaatggtcccattaaccagataatgctgtatgagggtgaagtt1140
atcactgttgggtcagatggatatgttaggatatgggattttgagacaatagacactgct1200
gatgtaatagatgagactggattgttggagattgagcctattaatgaacttcaagtagac1260
aagaatgtgaatctcttctctatgataaaaatgaatgaaactggaaataacttttggttg1320
gctcaggatgccaatggagccatatggaagcttgaccttagtttttcaaatattacccag1380
gacccagaatgcctcttctccttccattctggagctattgaagccgtggctgtttctcct1440
ctcacttatctcatggccacaactgccttggactgctctgttcgaatctatgattttgct1500
agcaaaactcctttggcccagatgaaattcaaacaaggaggtactgcccttgtttgggta1560
ccccgaatggtaaacttcactggagcacaaattattgtaggatttgaagatggagttgtt1620
cgaattcttgaactttatgatccaaaagggctcacgatttttgcgggacggaagaaaatt1680
ttggatgctgatattcagttgaaacaggttttcaaaccccatactgcttgtgtcactgct1740
ttagcttatgaacgtgatggggaaattctagccacagggagtaaagatcaaactgttttc1800
ttctttgaagtggaaagggattataagccgattggttatattaatactcctggacctgtg1860
tgtcagttaatgtggtctcccatgtctcatcctgaaagtactttactaattatctgtgaa1920
aatggctatattcttgaagctccacttccaaccataaagcaagaagaggatgatcatgat1980
gtagtctcctatgaaatcaaagacatgtgcataaaatgtttccatttttcaagtgtcaaa2040
tctaagattctgagattaatagaaattgaaaagagggagagacaaagggagttgaaggag2100
aaaataagggaagaaaggaggaacaagctagcagcagagatgggagaagatggagaaaaa2160
gaatttcaggaggaggaagaggagaaagaggaggaggaggaggaagaagagccattacct2220
gaaatatttattccgtcaaccccctctcccatcctctgtggattttactcagagccaggg2280
aagttctgggtttctttgggtggctatgattctggttttctatatcactgtgagttcccc2340
ccttgtgatgaaagcagtgatttcaaagaacaaaaagatgaacctattgatgtccgttat2400
cttgcggatacagaggacaatcccatccaaactatcactttcaacattaacaaagttatg2460
atgttttgtggaatgaaaaatggagcaattcgagtctatgtcctaaatcaaaatgatcct2520
tcattgaccagtttggtggactactggcacttcaatatgcatgacaataattatggatgt2580
attaaaagtattgctaatagctttgatgatcgtttcttggtgactgctggagcagatggc2640
aatatctttgttttcaacattttttctgaatttatgctaaggaaagacatgaaggccaaa2700
gttccatctcccaggtttggaattgaaacagagccaattccagaagacattgaagatccc2760
aaagcctacagtatcgagaatgctaggagaaaaagagaacatgacaagttaatgaaagaa2820
gtgggagaaataaaggcacggaagagagagcaaatcaaagctttgaggagtgaattttgt2880
aatctattagaaatgaatgaaaaattaccaaagcatatgcagtttaaacgaacagatttt2940
gatgtagattcccaaatccgtgctgagatgcacagaaaaacagctttcaaaattcaacaa3000
gtggaaaaggaattagcttgggaaaaagagaaacatgaactcggcctaatgaagctaaag3060
aatcgatttcgagatccactggaaagtgatactattgtggttcatgccatactgagtgac3120
cacaagatatcctcttacaggctggtgcagccctctaagtactccaaattcaaacgagct3180
agtcaatcagagagaaaaccaagcaaattggacaggtttgaaaaagagggacctggaaga3240
aaggacagccagagagatgcaggtgggagtgttaccatacaagaagaatcaataatagaa3300
aaagggaagaaatttcggcctaaaaccctaagtgaaatcatcgtggaaaatcaaattgag3360
aaaacgagaaaacttatattaaaagctgaaagggcacaactaaagattcaacagcgaaaa3420
aaagaatgggaggaactatacaagagtaaacctggtgatgactatgaagatcccaaagat3480
cttcaagccatcaaagaagcccaggtgtatatgggagatttcaatctgaagacagcccca3540
gactacaagatacctgagcacatgagaataaatgctgccaagaaggaagaggaactagga3600
cacctagattctttggtccatggaaataaaaggcacatgaacaagtgcattctctctctt3660
agagaccttaaagtggctgttgttgaggaaatacagtgcctggtacaagaactgaagaac3720
attcagtcgactcttcacatatccaagcacatacccattcccaaaattcctcagatacac3780
ccagaagaagttccagaaaagagatttcagtatgatgaagaaactctcctaaattttaag3840
caacagcaaatgaaaagtaaagatgaaaagtcccccggagtggaacagacagggtctgga3900
ggcccagttggaggattcctcaaactctcttctagaaaggatggggatttgacaacccgt3960
gattcaatatctagatcatcaaaggcatcaacattcagcctagatataccaaagtgtttg4020
gaatttgaaaaagcagagccaacggatgtggagctggaaattatgaagagagacgagatt4080
aaacacgtgtacatgcaacagtatttggtcaacaggatcaaagaactggttgtcactttc4140
gatgcagaactccgtctccttagacatcagaaactaaaactagatactcagatgaaatta4200
tctgacctgcaccatgtcaccttatttcaagaaatacttctcctgaagaattttgaaaaa4260
caggagaacatacttcaagaacgtgttaattccttagacaaagaggaacagtacatgcaa4320
tggaaaataaatgaaactcttaaagagatggaagagaaaaagaatgaaatcaccaaactc4380
caggagcaagaaaaggcactctatgctggttttcaagcagccattggagaaaacaataaa4440
tttgcaaacttcctcatgaaggtcctaaagaagaagattaaacgggtaaagaaaaaagaa4500
gttgaaggagatgctgatgaagatgaggagagtgaggaatcaagtgaagaagaatctagc4560
ttggagagtgatgaagatgagtctgaatcagaagatgaggtttttgatgattctatttgc4620
ccaacaaattgtgatgtggctctttttgagctggcccttcaccttcgagagaaaaggctg4680
gacattgaggaggctttagttgaagaaaagaaaattgttgataacctcaaaaaggaatat4740
gatacattgtcaaaaaaagtgaaaattgtggcaactaatctgaatgcagcagaggaggcc4800
ctggaggcttatcagcgagagaagcagcagcggctgaatgaactgctagttgtgattccg4860
ctcaagctccaccagatagagtatgtggtatttggagaaatacctagcgatctttctggt4920
actttggtcttctctaaccatgccttgagacggctgcaagaacgaatccatgagctccag4980
gaggaaaattccaagcagcaaaaacttaacaaagaatggagagagagacgtaaacagctc5040
atccgagaaaagagagaaatgacaaaaaccatacacaaaatggaggaaacagtccggcag5100
ctcatgatcagcaagtttggccgtgtggtaaatctagaagcccttcaaacgctttctgtt5160
aatacaacacttgaagaactgaagatcagaaaacttcgaaaggagctagcaaatgcgaaa5220
gagatgaagatgtgggaggaaaagattgctcaaatgcgatgggaactgatgatgaagaca5280
aaagaacacaccagaaagctttatcagatgaatgatttgtgtattgaaaagaagaaactt5340
gattctcggttgaatacactacagaatcagcagggcaatgccttccagggccctcgggaa5400
gcagatgttgtggcaagagaggaggtcactgaattgatccaactccaggcggaaaggatt5460
tcggccttaaaggaggagattgctcttttgcgtaggaaaggcagtcttatcctcccaccc5520
attcagtctccacgagagaaagagatacagcccgcagacctttga5565
<210>2
<211>1854
<212>prt
<213>homosapiens
<400>2
metlysgluproaspaspglnaspthraspglyglulysservalthr
151015
serlysseraspglylyslysserleuargserserlyssergluser
202530
argserprovalglngluaspasnthrpheleugluaspaspthrasp
354045
gluthrphethrlysglygluglysertyrleuglugluaspserasp
505560
glugluargleugluglyserleuserserpheglntyrglyaspleu
65707580
glnserthrthrvalproglnglnthrproalaproalavalgluglu
859095
alagluglugluvallyslyslysilesergluserphephetyrasp
100105110
tyrmetgluleualasermetprophevalthrleuaspserasnile
115120125
proleuaspleuleuthrleuvalhisserpheglytyraspcysarg
130135140
lysargalaasnleuglnleuleuaspaspserilealailetyrile
145150155160
alaglyasnglnleuilepheleuasnleulysthrlysgluglnile
165170175
tyrleuargserserserglygluglyileglyvalileglyvalhis
180185190
prohislysthrtyrphethrvalalaglulysglyserpheproasp
195200205
ileileiletyrglutyrproserleuargprotyrargvalleuarg
210215220
aspglythrglulysglytyralatyrvalasppheasntyrsergly
225230235240
asnleuleualaservalglyserasnproasptyrthrleuthrile
245250255
trpasntrplysglugluglnproileleuargthrlysalapheser
260265270
glngluvalphelysvalthrpheasnproasplysglugluglnleu
275280285
thrthrserglyserglyhisilelysphetrpglumetalaphethr
290295300
phethrglyleulysleuglnglyserleuglyargpheglylysthr
305310315320
ilethrthraspilegluglytyrmetgluleuproaspglylysval
325330335
leuserglyserglutrpglyasnmetleuleutrpgluglyglyleu
340345350
ilelysvalgluleucysargglythrserlyssercyshisasngly
355360365
proileasnglnilemetleutyrgluglygluvalilethrvalgly
370375380
seraspglytyrvalargiletrpaspphegluthrileaspthrala
385390395400
aspvalileaspgluthrglyleuleugluilegluproileasnglu
405410415
leuglnvalasplysasnvalasnleuphesermetilelysmetasn
420425430
gluthrglyasnasnphetrpleualaglnaspalaasnglyalaile
435440445
trplysleuaspleuserpheserasnilethrglnaspproglucys
450455460
leupheserphehisserglyalaileglualavalalavalserpro
465470475480
leuthrtyrleumetalathrthralaleuaspcysservalargile
485490495
tyraspphealaserlysthrproleualaglnmetlysphelysgln
500505510
glyglythralaleuvaltrpvalproargmetvalasnphethrgly
515520525
alaglnileilevalglyphegluaspglyvalvalargileleuglu
530535540
leutyraspprolysglyleuthrilephealaglyarglyslysile
545550555560
leuaspalaaspileglnleulysglnvalphelysprohisthrala
565570575
cysvalthralaleualatyrgluargaspglygluileleualathr
580585590
glyserlysaspglnthrvalphephephegluvalgluargasptyr
595600605
lysproileglytyrileasnthrproglyprovalcysglnleumet
610615620
trpserprometserhisprogluserthrleuleuileilecysglu
625630635640
asnglytyrileleuglualaproleuprothrilelysglngluglu
645650655
aspasphisaspvalvalsertyrgluilelysaspmetcysilelys
660665670
cysphehispheserservallysserlysileleuargleuileglu
675680685
ileglulysarggluargglnarggluleulysglulysileargglu
690695700
gluargargasnlysleualaalaglumetglygluaspglyglulys
705710715720
glupheglnglugluglugluglulysglugluglugluglugluglu
725730735
gluproleuprogluilepheileproserthrproserproileleu
740745750
cysglyphetyrsergluproglylysphetrpvalserleuglygly
755760765
tyraspserglypheleutyrhiscysglupheproprocysaspglu
770775780
serseraspphelysgluglnlysaspgluproileaspvalargtyr
785790795800
leualaaspthrgluaspasnproileglnthrilethrpheasnile
805810815
asnlysvalmetmetphecysglymetlysasnglyalaileargval
820825830
tyrvalleuasnglnasnaspproserleuthrserleuvalasptyr
835840845
trphispheasnmethisaspasnasntyrglycysilelysserile
850855860
alaasnserpheaspaspargpheleuvalthralaglyalaaspgly
865870875880
asnilephevalpheasnilephesergluphemetleuarglysasp
885890895
metlysalalysvalproserproargpheglyilegluthrglupro
900905910
ileprogluaspilegluaspprolysalatyrserilegluasnala
915920925
argarglysarggluhisasplysleumetlysgluvalglygluile
930935940
lysalaarglysarggluglnilelysalaleuargsergluphecys
945950955960
asnleuleuglumetasnglulysleuprolyshismetglnphelys
965970975
argthrasppheaspvalaspserglnileargalaglumethisarg
980985990
lysthralaphelysileglnglnvalglulysgluleualatrpglu
99510001005
lysglulyshisgluleuglyleumetlysleulysasnargphe
101010151020
argaspproleugluseraspthrilevalvalhisalaileleu
102510301035
serasphislysilesersertyrargleuvalglnproserlys
104010451050
tyrserlysphelysargalaserglnsergluarglysproser
105510601065
lysleuaspargpheglulysgluglyproglyarglysaspser
107010751080
glnargaspalaglyglyservalthrileglnglugluserile
108510901095
ileglulysglylyslyspheargprolysthrleusergluile
110011051110
ilevalgluasnglnileglulysthrarglysleuileleulys
111511201125
alagluargalaglnleulysileglnglnarglyslysglutrp
113011351140
glugluleutyrlysserlysproglyaspasptyrgluasppro
114511501155
lysaspleuglnalailelysglualaglnvaltyrmetglyasp
116011651170
pheasnleulysthralaproasptyrlysileprogluhismet
117511801185
argileasnalaalalyslysgluglugluleuglyhisleuasp
119011951200
serleuvalhisglyasnlysarghismetasnlyscysileleu
120512101215
serleuargaspleulysvalalavalvalglugluileglncys
122012251230
leuvalglngluleulysasnileglnserthrleuhisileser
123512401245
lyshisileproileprolysileproglnilehisprogluglu
125012551260
valproglulysargpheglntyraspglugluthrleuleuasn
126512701275
phelysglnglnglnmetlysserlysaspglulysserprogly
128012851290
valgluglnthrglyserglyglyprovalglyglypheleulys
129513001305
leuserserarglysaspglyaspleuthrthrargaspserile
131013151320
serargserserlysalaserthrpheserleuaspileprolys
132513301335
cysleuglupheglulysalagluprothraspvalgluleuglu
134013451350
ilemetlysargaspgluilelyshisvaltyrmetglnglntyr
135513601365
leuvalasnargilelysgluleuvalvalthrpheaspalaglu
137013751380
leuargleuleuarghisglnlysleulysleuaspthrglnmet
138513901395
lysleuseraspleuhishisvalthrleupheglngluileleu
140014051410
leuleulysasnpheglulysglngluasnileleuglngluarg
141514201425
valasnserleuasplysglugluglntyrmetglntrplysile
143014351440
asngluthrleulysglumetgluglulyslysasngluilethr
144514501455
lysleuglngluglnglulysalaleutyralaglypheglnala
146014651470
alaileglygluasnasnlysphealaasnpheleumetlysval
147514801485
leulyslyslysilelysargvallyslyslysgluvalglugly
149014951500
aspalaaspgluaspglugluserglugluserserglugluglu
150515101515
serserleugluseraspgluaspgluserglusergluaspglu
152015251530
valpheaspaspserilecysprothrasncysaspvalalaleu
153515401545
phegluleualaleuhisleuargglulysargleuaspileglu
155015551560
glualaleuvalgluglulyslysilevalaspasnleulyslys
156515701575
glutyraspthrleuserlyslysvallysilevalalathrasn
158015851590
leuasnalaalagluglualaleuglualatyrglnargglulys
159516001605
glnglnargleuasngluleuleuvalvalileproleulysleu
161016151620
hisglnileglutyrvalvalpheglygluileproseraspleu
162516301635
serglythrleuvalpheserasnhisalaleuargargleugln
164016451650
gluargilehisgluleuglnglugluasnserlysglnglnlys
165516601665
leuasnlysglutrparggluargarglysglnleuileargglu
167016751680
lysargglumetthrlysthrilehislysmetglugluthrval
168516901695
argglnleumetileserlyspheglyargvalvalasnleuglu
170017051710
alaleuglnthrleuservalasnthrthrleuglugluleulys
171517201725
ilearglysleuarglysgluleualaasnalalysglumetlys
173017351740
mettrpgluglulysilealaglnmetargtrpgluleumetmet
174517501755
lysthrlysgluhisthrarglysleutyrglnmetasnaspleu
176017651770
cysileglulyslyslysleuaspserargleuasnthrleugln
177517801785
asnglnglnglyasnalapheglnglyproargglualaaspval
179017951800
valalaargglugluvalthrgluleuileglnleuglnalaglu
180518101815
argileseralaleulysglugluilealaleuleuargarglys
182018251830
glyserleuileleuproproileglnserproargglulysglu
183518401845
ileglnproalaaspleu
1850
<210>3
<211>20
<212>dna
<213>人工序列
<400>3
tcgaggtcagccttctttgt20
<210>4
<211>20
<212>dna
<213>人工序列
<400>4
caactagcatggtccccagt20
<210>5
<211>20
<212>dna
<213>人工序列
<400>5
aactgaggcaagtgctgtga20
<210>6
<211>20
<212>dna
<213>人工序列
<400>6
tgcacagaaagctcaggaaa20
<210>7
<211>20
<212>dna
<213>人工序列
<400>7
tttcatgacatcctggttgg20
<210>8
<211>20
<212>dna
<213>人工序列
<400>8
acagcagcatccagtcctct20
<210>9
<211>20
<212>dna
<213>人工序列
<400>9
gcagagtttccttggcagtc20
<210>10
<211>20
<212>dna
<213>人工序列
<400>10
ttccagcctttattgccatc20
<210>11
<211>978
<212>prt
<213>homosapiens
<400>11
metlysgluproaspaspglnaspthraspglyglulysservalthr
151015
serlysseraspglylyslysserleuargserserlyssergluser
202530
argserprovalglngluaspasnthrpheleugluaspaspthrasp
354045
gluthrphethrlysglygluglysertyrleuglugluaspserasp
505560
glugluargleugluglyserleuserserpheglntyrglyaspleu
65707580
glnserthrthrvalproglnglnthrproalaproalavalgluglu
859095
alagluglugluvallyslyslysilesergluserphephetyrasp
100105110
tyrmetgluleualasermetprophevalthrleuaspserasnile
115120125
proleuaspleuleuthrleuvalhisserpheglytyraspcysarg
130135140
lysargalaasnleuglnleuleuaspaspserilealailetyrile
145150155160
alaglyasnglnleuilepheleuasnleulysthrlysgluglnile
165170175
tyrleuargserserserglygluglyileglyvalileglyvalhis
180185190
prohislysthrtyrphethrvalalaglulysglyserpheproasp
195200205
ileileiletyrglutyrproserleuargprotyrargvalleuarg
210215220
aspglythrglulysglytyralatyrvalasppheasntyrsergly
225230235240
asnleuleualaservalglyserasnproasptyrthrleuthrile
245250255
trpasntrplysglugluglnproileleuargthrlysalapheser
260265270
glngluvalphelysvalthrpheasnproasplysglugluglnleu
275280285
thrthrserglyserglyhisilelysphetrpglumetalaphethr
290295300
phethrglyleulysleuglnglyserleuglyargpheglylysthr
305310315320
ilethrthraspilegluglytyrmetgluleuproaspglylysval
325330335
leuserglyserglutrpglyasnmetleuleutrpgluglyglyleu
340345350
ilelysvalgluleucysargglythrserlyssercyshisasngly
355360365
proileasnglnilemetleutyrgluglygluvalilethrvalgly
370375380
seraspglytyrvalargiletrpaspphegluthrileaspthrala
385390395400
aspvalileaspgluthrglyleuleugluilegluproileasnglu
405410415
leuglnvalasplysasnvalasnleuphesermetilelysmetasn
420425430
gluthrglyasnasnphetrpleualaglnaspalaasnglyalaile
435440445
trplysleuaspleuserpheserasnilethrglnaspproglucys
450455460
leupheserphehisserglyalaileglualavalalavalserpro
465470475480
leuthrtyrleumetalathrthralaleuaspcysservalargile
485490495
tyraspphealaserlysthrproleualaglnmetlysphelysgln
500505510
glyglythralaleuvaltrpvalproargmetvalasnphethrgly
515520525
alaglnileilevalglyphegluaspglyvalvalargileleuglu
530535540
leutyraspprolysglyleuthrilephealaglyarglyslysile
545550555560
leuaspalaaspileglnleulysglnvalphelysprohisthrala
565570575
cysvalthralaleualatyrgluargaspglygluileleualathr
580585590
glyserlysaspglnthrvalphephephegluvalgluargasptyr
595600605
lysproileglytyrileasnthrproglyprovalcysglnleumet
610615620
trpserprometserhisprogluserthrleuleuileilecysglu
625630635640
asnglytyrileleuglualaproleuprothrilelysglngluglu
645650655
aspasphisaspvalvalsertyrgluilelysaspmetcysilelys
660665670
cysphehispheserservallysserlysileleuargleuileglu
675680685
ileglulysarggluargglnarggluleulysglulysileargglu
690695700
gluargargasnlysleualaalaglumetglygluaspglyglulys
705710715720
glupheglnglugluglugluglulysglugluglugluglugluglu
725730735
gluproleuprogluilepheileproserthrproserproileleu
740745750
cysglyphetyrsergluproglylysphetrpvalserleuglygly
755760765
tyraspserglypheleutyrhiscysglupheproprocysaspglu
770775780
serseraspphelysgluglnlysaspgluproileaspvalargtyr
785790795800
leualaaspthrgluaspasnproileglnthrilethrpheasnile
805810815
asnlysvalmetmetphecysglymetlysasnglyalaileargval
820825830
tyrvalleuasnglnasnaspproserleuthrserleuvalasptyr
835840845
trphispheasnmethisaspasnasntyrglycysilelysserile
850855860
alaasnserpheaspaspargpheleuvalthralaglyalaaspgly
865870875880
asnilephevalpheasnilephesergluphemetleuarglysasp
885890895
metlysalalysvalproserproargpheglyilegluthrglupro
900905910
ileprogluaspilegluaspprolysalatyrserilegluasnala
915920925
argarglysarggluhisasplysleumetlysgluvalglygluile
930935940
lysalaarglysarggluglnilelysalaleuargsergluphecys
945950955960
asnleuleuglumetasnglulysleuprolyshismetglnphelys
965970975
argthr
<210>12
<211>680
<212>prt
<213>homosapiens
<400>12
metlysgluproaspaspglnaspthraspglyglulysservalthr
151015
serlysseraspglylyslysserleuargserserlyssergluser
202530
argserprovalglngluaspasnthrpheleugluaspaspthrasp
354045
gluthrphethrlysglygluglysertyrleuglugluaspserasp
505560
glugluargleugluglyserleuserserpheglntyrglyaspleu
65707580
glnserthrthrvalproglnglnthrproalaproalavalgluglu
859095
alagluglugluvallyslyslysilesergluserphephetyrasp
100105110
tyrmetgluleualasermetprophevalthrleuaspserasnile
115120125
proleuaspleuleuthrleuvalhisserpheglytyraspcysarg
130135140
lysargalaasnleuglnleuleuaspaspserilealailetyrile
145150155160
alaglyasnglnleuilepheleuasnleulysthrlysgluglnile
165170175
tyrleuargserserserglygluglyileglyvalileglyvalhis
180185190
prohislysthrtyrphethrvalalaglulysglyserpheproasp
195200205
ileileiletyrglutyrproserleuargprotyrargvalleuarg
210215220
aspglythrglulysglytyralatyrvalasppheasntyrsergly
225230235240
asnleuleualaservalglyserasnproasptyrthrleuthrile
245250255
trpasntrplysglugluglnproileleuargthrlysalapheser
260265270
glngluvalphelysvalthrpheasnproasplysglugluglnleu
275280285
thrthrserglyserglyhisilelysphetrpglumetalaphethr
290295300
phethrglyleulysleuglnglyserleuglyargpheglylysthr
305310315320
ilethrthraspilegluglytyrmetgluleuproaspglylysval
325330335
leuserglyserglutrpglyasnmetleuleutrpgluglyglyleu
340345350
ilelysvalgluleucysargglythrserlyssercyshisasngly
355360365
proileasnglnilemetleutyrgluglygluvalilethrvalgly
370375380
seraspglytyrvalargiletrpaspphegluthrileaspthrala
385390395400
aspvalileaspgluthrglyleuleugluilegluproileasnglu
405410415
leuglnvalasplysasnvalasnleuphesermetilelysmetasn
420425430
gluthrglyasnasnphetrpleualaglnaspalaasnglyalaile
435440445
trplysleuaspleuserpheserasnilethrglnaspproglucys
450455460
leupheserphehisserglyalaileglualavalalavalserpro
465470475480
leuthrtyrleumetalathrthralaleuaspcysservalargile
485490495
tyraspphealaserlysthrproleualaglnmetlysphelysgln
500505510
glyglythralaleuvaltrpvalproargmetvalasnphethrgly
515520525
alaglnileilevalglyphegluaspglyvalvalargileleuglu
530535540
leutyraspprolysglyleuthrilephealaglyarglyslysile
545550555560
leuaspalaaspileglnleulysglnvalphelysprohisthrala
565570575
cysvalthralaleualatyrgluargaspglygluileleualathr
580585590
glyserlysaspglnthrvalphephephegluvalgluargasptyr
595600605
lysproileglytyrileasnthrproglyprovalcysglnleumet
610615620
trpserprometserhisprogluserthrleuleuileilecysglu
625630635640
asnglytyrileleuglualaproleuprothrilelysglngluglu
645650655
aspasphisaspvalvalsertyrgluilelysaspvalhislysmet
660665670
pheprophephelyscysglnile
675680