基于毛干蛋白质组nsSNP进行人群来源推断的方法技术

本发明专利技术公开了基于毛干蛋白质组nsSNP进行人群来源推断的方法。本发明专利技术选取104个中国汉族样本和105个中国维吾尔族样本的毛干样本进行了毛干蛋白质组的提取，通过质谱检测毛干蛋白质组，筛选得到772个包含SAP的特异性多肽序列，对应703个SAP位点，并将所述SAP位点与千人基因组数据库中的SNP位点关联进而反推得到527个nsSNP位点组合。通过实验证明，本发明专利技术提供的nsSNP位点组合可用于非洲、东亚和欧洲三大人群推断。

The method of population source inference based on nsSNP

The invention discloses a method for crowd source inference based on nsSNP. In the invention, 104 samples of Han nationality and 105 samples of Uygur nationality are selected to extract the hair stem proteome, and the hair stem proteome is detected by mass spectrometry, 772 specific peptide sequences containing SAP are screened, corresponding to 703 SAP sites, and 527 nsSNP sites are obtained by associating the sap sites with SNP sites in the database of thousand human genome Combination. It is proved by experiments that the nsSNP site combination provided by the invention can be used for inference of three populations in Africa, East Asia and Europe.

【技术实现步骤摘要】
基于毛干蛋白质组nsSNP进行人群来源推断的方法
本专利技术涉及生物
，具体基于毛干蛋白质组nsSNP进行人群来源推断的方法。
技术介绍
随着法医DNA检验技术的发展和进步，常见血液/斑、唾液/斑、精液/斑、脱落细胞、带毛囊的毛发、甚至骨骼都能获得STR分型。然而，毛干由角质化细胞组成，细胞核DNA含量非常低而且降解严重，虽然也有报道采用低扩增体系、增加循环次数和多次平行扩增的方法可以获得部分STR分型，但是由于其准确性和稳定性差而未在案件检验中应用。目前对于毛干的检验方法是通过测序的方法检测线粒体DNA的高变区的碱基差异，存在识别率不高(数值)、具有异质性、只能排除不能认定等缺点，限制了其在法医检验鉴定中的应用。与毛干中的核DNA相比，蛋白质要更加稳定，可以长期保持稳定。与基因组DNA类似，在不同的个体中，蛋白质序列存在一定的差异，是由于编码基因上的非同义单核苷酸多态性(non-synonymoussinglenucleotidepolymorphism，nsSNP)通过转录翻译后形成的，称作单氨基酸多态性(singleaminoacidpolymorphisms，SAP)。液质联用的串联质谱法鉴定蛋白质是目前蛋白质组学研究的首选平台。蛋白质经胰酶消化形成的肽段先进入液相色谱进行分离，再进行质谱检测，从而鉴定出特异性多肽序列。研究显示可以通过质谱方法检测获得SAP的特异性多肽，这种特异性多肽被称为遗传多样性多肽(geneticallyvariantpeptides，GVP)。基因组中SNP作为法医遗传学的新的遗传标记，目前已经用于法医人群推断，研究报道了大量人群推断体系，在洲际范围内，不仅可以实现非洲、东亚和欧洲三大人群推断，而且Kidd等的55个SNP组合可以实现七个洲际人群的区分(非洲、欧洲、西南亚、南亚、东亚、大洋洲、美洲)。目前，利用外显子中的nsSNP开展人群推断研究非常少。一项美国的外显子测序计划(ExomeSequencingProiect，ESP)包含约2203非裔美国人和4300欧裔美国人，分析显示nsSNP在欧美人群频率具有较好的杂合度，其中35000个nsSNPs位点最小等位基因频率大于0.8％。
技术实现思路
本专利技术的第一个目的是提供用于区分非洲、东亚和欧洲三大人群的nsSNP位点组合。本专利技术提供的用于区分非洲、东亚和欧洲三大人群的nsSNP位点组合由如下527个nsSNP位点组成：rs111433922、rs35340855、rs74058627、rs16829071、rs77912442、rs75073861、rs33931638、rs2274540、rs181507001、rs1340472、rs10776792、rs138286826、rs3790549、rs6587649、rs142660239、rs141677205、rs150525217、rs78489268、rs35492900、rs73004856、rs9793541、rs11205064、rs143680696、rs111350576、rs4329520、rs75424193、rs150172690、rs7527180、rs137886860、rs116208483、rs11544443、rs35358752、rs140222211、rs146608925、rs79957178、rs61743921、rs76446715、rs291102、rs3738046、rs2234697、rs35273824、rs55873785、rs61739198、rs147571909、rs61741026、rs3127679、rs61850830、rs61737718、rs41277978、rs11200927、rs144135625、rs2281878、rs150218827、rs149172507、rs3781409、rs142332607、rs146366062、rs77752215、rs114405390、rs117868609、rs78838117、rs73428416、rs147366020、rs61744476、rs115660558、rs112245148、rs74706151、rs1695、rs188029416、rs199773487、rs1945783、rs78786722、rs11604169、rs75068802、rs141425229、rs111738856、rs61750769、rs34495134、rs13312793、rs112319661、rs25680、rs35819349、rs1063193、rs114865992、rs76226247、rs74095220、rs4761786、rs2071588、rs202205489、rs79897879、rs183358379、rs140635030、rs2852464、rs61740813、rs112554450、rs61630004、rs1732301、rs36004911、rs61730587、rs2658658、rs1732263、rs61730589、rs1791634、rs61730590、rs148287450、rs2232387、rs142860834、rs138021918、rs11540301、rs17845411、rs201201647、rs148276250、rs11170177、rs35043606、rs76412202、rs74660757、rs2634041、rs636127、rs200729891、rs78374723、rs36143766、rs139252457、rs2638497、rs116117459、rs143673140、rs61743822、rs138008625、rs201904127、rs35645287、rs114939776、rs145486599、rs4964460、rs2723880、rs117037408、rs113902407、rs139495129、rs35201084、rs78872760、rs143710874、rs139160172、rs17111188、rs35926651、rs2229462、rs141486741、rs762063、rs10148371、rs11125、rs45560241、rs941920、rs61745465、rs45542736、rs59773088、rs116761065、rs7149578、rs151256890、rs55863440、rs77734634、rs11549015、rs142368943、rs76831919、rs149516006、rs147209733、rs6083、rs141566933、rs182752537、rs143921047、rs8040674、rs114486517、rs138510119、rs13226、rs61733465、rs2745101、rs7202502、rs26856、rs149302444、rs8063727、rs61734749、rs74444511、rs4850、rs14359919本文档来自技高网...

【技术保护点】
1.用于区分非洲、东亚和欧洲三大人群的nsSNP位点组合；所述nsSNP位点组合由如下527个nsSNP位点组成：rs111433922、rs35340855、rs74058627、rs16829071、rs77912442、rs75073861、rs33931638、rs2274540、rs181507001、rs1340472、rs10776792、rs138286826、rs3790549、rs6587649、rs142660239、rs141677205、rs150525217、rs78489268、rs35492900、rs73004856、rs9793541、rs11205064、rs143680696、rs111350576、rs4329520、rs75424193、rs150172690、rs7527180、rs137886860、rs116208483、rs11544443、rs35358752、rs140222211、rs146608925、rs79957178、rs61743921、rs76446715、rs291102、rs3738046、rs2234697、rs35273824、rs55873785、rs61739198、rs147571909、rs61741026、rs3127679、rs61850830、rs61737718、rs41277978、rs11200927、rs144135625、rs2281878、rs150218827、rs149172507、rs3781409、rs142332607、rs146366062、rs77752215、rs114405390、rs117868609、rs78838117、rs73428416、rs147366020、rs61744476、rs115660558、rs112245148、rs74706151、rs1695、rs188029416、rs199773487、rs1945783、rs78786722、rs11604169、rs75068802、rs141425229、rs111738856、rs61750769、rs34495134、rs13312793、rs112319661、rs25680、rs35819349、rs1063193、rs114865992、rs76226247、rs74095220、rs4761786、rs2071588、rs202205489、rs79897879、rs183358379、rs140635030、rs2852464、rs61740813、rs112554450、rs61630004、rs1732301、rs36004911、rs61730587、rs2658658、rs1732263、rs61730589、rs1791634、rs61730590、rs148287450、rs2232387、rs142860834、rs138021918、rs11540301、rs17845411、rs201201647、rs148276250、rs11170177、rs35043606、rs76412202、rs74660757、rs2634041、rs636127、rs200729891、rs78374723、rs36143766、rs139252457、rs2638497、rs116117459、rs143673140、rs61743822、rs138008625、rs201904127、rs35645287、rs114939776、rs145486599、rs4964460、rs2723880、rs117037408、rs113902407、rs139495129、rs35201084、rs78872760、rs143710874、rs139160172、rs17111188、rs35926651、rs2229462、rs141486741、rs762063、rs10148371、rs11125、rs45560241、rs941920、rs61745465、rs45542736、rs59773088、rs116761065、rs7149578、rs151256890、rs55863440、rs77734634、rs11549015、rs142368943、rs76831919、rs149516006、rs147209733、rs6083、rs141566933、rs182752537、rs143921047、rs8040674、rs114486517、rs138510119、rs13226、rs61733465、rs2745101、rs7202502、rs26856、rs149302444、rs8063727、rs6...

【技术特征摘要】
1.用于区分非洲、东亚和欧洲三大人群的nsSNP位点组合；所述nsSNP位点组合由如下527个nsSNP位点组成：rs111433922、rs35340855、rs74058627、rs16829071、rs77912442、rs75073861、rs33931638、rs2274540、rs181507001、rs1340472、rs10776792、rs138286826、rs3790549、rs6587649、rs142660239、rs141677205、rs150525217、rs78489268、rs35492900、rs73004856、rs9793541、rs11205064、rs143680696、rs111350576、rs4329520、rs75424193、rs150172690、rs7527180、rs137886860、rs116208483、rs11544443、rs35358752、rs140222211、rs146608925、rs79957178、rs61743921、rs76446715、rs291102、rs3738046、rs2234697、rs35273824、rs55873785、rs61739198、rs147571909、rs61741026、rs3127679、rs61850830、rs61737718、rs41277978、rs11200927、rs144135625、rs2281878、rs150218827、rs149172507、rs3781409、rs142332607、rs146366062、rs77752215、rs114405390、rs117868609、rs78838117、rs73428416、rs147366020、rs61744476、rs115660558、rs112245148、rs74706151、rs1695、rs188029416、rs199773487、rs1945783、rs78786722、rs11604169、rs75068802、rs141425229、rs111738856、rs61750769、rs34495134、rs13312793、rs112319661、rs25680、rs35819349、rs1063193、rs114865992、rs76226247、rs74095220、rs4761786、rs2071588、rs202205489、rs79897879、rs183358379、rs140635030、rs2852464、rs61740813、rs112554450、rs61630004、rs1732301、rs36004911、rs61730587、rs2658658、rs1732263、rs61730589、rs1791634、rs61730590、rs148287450、rs2232387、rs142860834、rs138021918、rs11540301、rs17845411、rs201201647、rs148276250、rs11170177、rs35043606、rs76412202、rs74660757、rs2634041、rs636127、rs200729891、rs78374723、rs36143766、rs139252457、rs2638497、rs116117459、rs143673140、rs61743822、rs138008625、rs201904127、rs35645287、rs114939776、rs145486599、rs4964460、rs2723880、rs117037408、rs113902407、rs139495129、rs35201084、rs78872760、rs143710874、rs139160172、rs17111188、rs35926651、rs2229462、rs141486741、rs762063、rs10148371、rs11125、rs45560241、rs941920、rs61745465、rs45542736、rs59773088、rs116761065、rs7149578、rs151256890、rs55863440、rs77734634、rs11549015、rs142368943、rs76831919、rs149516006、rs147209733、rs6083、rs141566933、rs182752537、rs143921047、rs8040674、rs114486517、rs138510119、rs13226、rs61733465、rs2745101、rs7202502、rs26856、rs149302444、rs8063727、rs61734749、rs74444511、rs4850、rs143599196、rs61764619、rs149180816、rs139027672、rs115575792、rs35959859、rs11646443、rs115334480、rs142294143、rs111653425、rs8068049、rs140044904、rs33923045、rs139361222、rs2269859、rs7213256、rs112557906、rs112120285、rs17843023、rs17843021、rs142154718、rs721957、rs2010027、rs151267951、rs140634473、rs3829598、rs138200823、rs150218495、rs9635728、rs6503578、rs36006291、rs113142104、rs201968324、rs139615301、rs1497383、rs366700、rs34361798、rs61746658、rs444509、rs385055、rs111435962、rs428371、rs149778906、rs62067292、rs144662088、rs144085234、rs35424651、rs9894258、rs140430944、rs150620728、rs71373411、rs114488848、rs61741663、rs143499346、rs12450621、rs77779192、rs112544857、rs187425812、rs17737019、rs35371972、rs16966811、rs9916475、rs9916484、rs9916724、rs139509509、rs9893787、rs117083040、rs116901031、rs2604955、rs2071563、rs16966929、rs57682233、rs73983451、rs146792525、rs2071560、rs2071601、rs139209783、rs189378138、rs138303882、rs139838007、rs200825300、rs2301354、rs9675246、rs8082683、rs73294423、rs11551760、rs117484558、rs148173278、rs111383277、rs2229512、rs143043662、rs41283425、rs34891485、rs143967758、rs62636624、rs59657238、rs112984118、rs116700192、rs116640209、rs35074489、rs75138404、rs62621822、rs142608913、rs11871357、rs2228306、rs140743740、rs2853533、rs3737374、rs78014467、rs1455555、rs151208927、rs3746173、rs7250822、rs55862054、rs890850、rs10410943、rs80251258、rs2287813、rs62638750、rs117612375、rs150023166、rs10846、rs7249305、rs8111625、rs116923487、rs75291244、rs61731193、rs114254919、rs146740964、rs773902、rs12983721、rs61995739、rs61742630、rs151268424、rs112433506、rs2229259、rs148300955、rs185356090、rs116440799、rs143467587、rs191886465、rs189187210、rs114308190、rs4802741、rs144495841、rs73938668、rs116363585、rs115704323、rs57920974、rs533617、rs62130126、rs143205707、rs192390933、rs1109758、rs13413205、rs72937663、rs142729495、rs75630766、rs202041757、rs6761276、rs6743376、rs77686710、rs34355135、rs112797950、rs35852101、rs35830636、rs76148000、rs113701414、rs3815849、rs181520135、rs73996408、rs2233384、rs2233390、rs2233393、rs6431437、rs73102303、rs61732303、rs214814、rs114998364、rs34205880、rs111730906、rs145658539、rs6061066、rs3746609、rs17301126、rs41293138、rs200948404、rs17856024、rs2231619、rs61750835、rs36068952、rs78386672、rs45486695、rs61750208、rs2830585、rs141102396、rs113360916、rs3804010、rs61748317、rs16986753、rs73901140、rs113504861、rs151147550、rs117415039、rs115002444、rs74429119、rs79258920、rs16987932、rs78121368、rs61753641、rs76994627、rs181516402、rs233252、rs465279、rs111668637、rs411254、rs140821764、rs73909208、rs79740360、rs462007、rs78191358、rs78821735、rs73909210、rs34302939、rs61745911、rs7277175、rs201439546、rs115031369、rs61742280、rs112405400、rs133072、rs147348682、rs191014345、rs61730105、rs76321736、rs3796375、rs2228561、rs17080284、rs138055453、rs57006145、rs140995238、rs116174869、rs77141175、rs77299600、rs5955、rs144811342、rs61995956、rs186892593、rs115253144、rs17029215、rs3811813、rs10513155、rs76155491、rs73757391、rs147178651、rs148509798、rs77499935、rs181914313、rs149861653、rs35610885、rs150956127、rs146522449、rs2278371、rs61743236、rs6872614、rs145827614、rs77767937、rs112465391、rs77758574、rs2076299、rs28763966、rs28763967、rs6929069、rs1225746、rs34286843、rs138815183、rs73736234、rs9261293、rs199834022、rs41293883、rs45624537、rs145921744、rs61746206、rs2621330、rs2070121、rs60336135、rs115292676、rs11969595、rs111265263、rs138694074、rs1676015、rs2227885、rs2295005、rs9478144、rs141119961、rs4716346、rs16901311、rs185762794、rs11548791、rs5743342、rs150151168、rs73692834、rs145942606、rs10256、rs114926839、rs2437100、rs10953934、rs1062154、rs114560708、rs73463436、rs61745481、rs149880251、rs72475803、rs35781576、rs114896954、rs148249848、rs145786248、rs76489557、rs150147780、rs116816681、rs7013127、rs117589117、rs11539895、rs540473、rs34250374、rs35791393、rs16929374、rs146467307、rs3750501、rs7025814、rs114612810、rs144749820、rs76003300、rs145771944、rs1538660、rs142111180、rs76057724、rs144181457、rs3812561、rs7850438、rs139415880、rs16997659、rs17147624、rs17847095、rs41306133、rs144825978、rs138895359和rs142447204。2.用于区分非洲、东亚和欧洲三大人群的产品，其包括检测权利要求1中所述的527个nsSNP位点基因型的物质。3.根据权利要求2所述的产品，其特征在于：所述检测权利要求1中所述的527个nsSNP位点基因型的物质为检测权利要求1中所述的527个nsSNP位点基因型的试剂和/或仪器。4.权利要求1所述的nsSNP位点组合或权利要求2或3所述的产品在区分非洲、东亚和欧洲三大人群中的应用。5.权利要求1所述的nsSNP位点组合或权利要求2或3所述的产品在构建非洲、东亚和欧洲三大人群基因分型数据库中的应用。6.一种构建非洲、东亚和欧洲三大人群基因分型数据库的方法，包括如下步骤：(a1)从千人基因组数据库中选取非洲、东亚和欧洲三大人群基于权利要求1中所述的527个nsSNP位点基因型形成原始分型库；(a2)将所述原始分型库里所有样本进行structure聚类分析，从中选取祖先主成分大于90％的部分即构成非洲、东亚和欧洲三大人群基因分型数据库。7.一种区分非洲、东亚和欧洲三大洲际人群的方法，包括如下步骤：(b1)按照权利要求6所述的方法构建非洲、东亚和欧洲三大人群基因分型数据库；(b2)提取待测者的基因组DNA，并进行527个nsSNP位点的基因型检测，获得待测者在527个...

【专利技术属性】
技术研发人员：李彩霞，丰蕾，江丽，季安全，王桂强，
申请(专利权)人：公安部物证鉴定中心，
类型：发明
国别省市：北京,11