微单倍型遗传标记的法医基因组学研究

doi:10.16288/j.yczz.21-186

遗传 ›› 2021, Vol. 43 ›› Issue (10): 962-971.doi: 10.16288/j.yczz.21-186

微单倍型遗传标记的法医基因组学研究

李茜(), 王浩宇(), 曹悦岩, 朱强, 舒潘寅, 侯婷芸, 王雨婷, 张霁()

四川大学华西基础医学与法医学院,成都 610041

收稿日期:2021-05-26 修回日期:2021-07-29 出版日期:2021-10-20 发布日期:2021-08-10
通讯作者: 张霁 E-mail:lixi1105@foxmail.com;wanghy0707@gmail.com;zhangj@scu.edu.cn
作者简介:李茜,在读硕士研究生,专业方向：法医遗传学。E-mail: lixi1105@foxmail.com;|王浩宇,在读硕士研究生,专业方向：法医遗传学。E-mail: wanghy0707@gmail.com; 李茜和王浩宇并列第一作者。
基金资助:
国家自然科学基金项目资助编号(81571861);国家自然科学基金项目资助编号(81630054)

Forensic genomics research on microhaplotypes

Xi Li(), Haoyu Wang(), Yueyan Cao, Qiang Zhu, Panyin Shu, Tingyun Hou, Yuting Wang, Ji Zhang()

West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China

Received:2021-05-26 Revised:2021-07-29 Online:2021-10-20 Published:2021-08-10
Contact: Zhang Ji E-mail:lixi1105@foxmail.com;wanghy0707@gmail.com;zhangj@scu.edu.cn
Supported by:
Supported by the National Natural Science Foundation of China Nos(81571861);Supported by the National Natural Science Foundation of China Nos(81630054)

摘要/Abstract

摘要：

微单倍型(microhaplotype, MH)是在一定DNA片段范围之内,由至少两个单核苷酸多态性位点组成的遗传标记。MH兼具无stutter伪峰、多态性丰富以及扩增子较小等特点,有望成为法医学上的一种新型遗传标记。为了从全基因组维度上分析MH的特征,进一步发掘其应用潜能,本研究基于千人基因组计划中105个中国南方汉族个体的全基因组测序数据,构建了迄今为止最全面的MH数据集。结果表明,人类基因组中350 bp范围之内的MH位点数量共计9,490,075个,且微单倍型分布密度对染色体变异水平具有提示作用。从多种碱基跨度范围对MH的多态性分析表明,其多态性潜能可达到或者超过常用短串联重复序列位点的水平。此外,本文归纳总结了MH组装灵活等特点,并提出了构建微单倍型数据库的方案。

关键词: 法医遗传学, 微单倍型, 千人基因组计划, 中国南方汉族群体

Abstract:

Microhaplotype loci (microhaplotype, MHs), defined by two or more closely linked single nucleotide polymorphisms, are a type of molecular marker within a short segment of DNA. As emerging forensic genetic markers, MHs have no stutter artefacts and higher polymorphism, and permit the design of smaller amplicons. In order to identify the markers from a genome wide perspective and explore their potential application further, we constructed the most comprehensive MH dataset to date, based on the whole genome sequencing data of 105 Han individuals in Southern China from 1000 Genomes Project. The results showed that there were 9,490,075 MH loci in the range of 350 bp in the human genome, and the distribution density of microhaplotypes suggests gene variation. Polymorphism analysis of MHs from various base spans showed that the polymorphism of MHs could reach or exceed common short tandem repeat sites. In addition, based on their flexible assembly, a scheme to build the public database of microhaplotypes was proposed.

Key words: forensic genetics, microhaplotypes, 1000 Genomes, Southern Han Chinese

李茜, 王浩宇, 曹悦岩, 朱强, 舒潘寅, 侯婷芸, 王雨婷, 张霁. 微单倍型遗传标记的法医基因组学研究[J]. 遗传, 2021, 43(10): 962-971.

Xi Li, Haoyu Wang, Yueyan Cao, Qiang Zhu, Panyin Shu, Tingyun Hou, Yuting Wang, Ji Zhang. Forensic genomics research on microhaplotypes[J]. Hereditas(Beijing), 2021, 43(10): 962-971.

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染色体	#SNPs ^a	#MHs≤350 bp		#MHs≤150 bp		#MHs≤100 bp		#MHs≤50 bp
染色体	#SNPs ^a	A	B	A	B	A	B	A	B
1	463,261	684,624	224,137	307,923	160,070	211,609	127,357	112,562	80,220
2	485,172	697,551	235,330	312,548	167,213	213,273	132,583	113,234	82,973
3	429,260	648,976	208,260	289,892	149,992	197,993	119,687	104,404	75,230
4	444,134	719,321	214,966	322,127	158,179	220,652	127,643	116,157	81,220
5	369,559	536,677	179,135	240,372	127,576	164,475	101,232	87,636	63,535
6	406,810	855,491	197,195	380,915	145,792	258,670	118,720	134,514	77,942
7	357,021	560,129	172,793	252,329	125,618	172,901	100,917	91,761	64,047
8	323,908	538,902	157,309	239,578	116,180	163,404	93,911	85,902	60,124
9	264,750	408,354	128,051	183,076	94,273	125,067	75,556	65,695	47,502
10	310,578	493,463	150,444	221,083	109,703	151,560	88,309	80,883	56,820
11	290,938	445,661	140,840	199,579	102,589	136,071	81,970	71,787	52,025
12	287,513	430,602	139,153	194,229	100,173	133,241	79,814	70,791	50,312
13	217,352	335,132	105,264	150,042	76,429	102,775	61,026	54,319	38,801
14	194,482	293,076	94,194	131,568	67,706	90,024	53,957	47,739	34,160
15	176,222	274,166	84,933	123,892	61,570	85,058	49,433	45,461	31,845
16	187,593	331,113	90,597	148,132	68,613	101,035	56,023	53,349	36,743
17	155,592	237,431	74,611	108,076	54,056	74,898	43,371	40,510	27,684
18	172,512	267,593	83,271	121,279	60,482	83,014	48,506	43,974	30,786
19	142,771	254,075	67,813	117,069	51,542	81,348	42,076	44,002	27,689
20	127,126	186,986	61,427	84,197	44,252	57,717	35,181	30,649	22,301
21	86,049	140,790	41,396	63,550	31,033	43,662	25,070	22,955	16,084
22	85,052	149,962	40,808	68,111	30,586	47,028	24,982	25,065	16,427
总计	5,977,655	9,490,075	2,891,927	4,259,567	2,103,627	2,915,475	1,687,324	1,543,349	1,074,470

MH_ID	bp	Ae	Ho	DP	#SNPs	#Alleles	Position (GRCh37)
mh04zj0146583	346	66.6163	0.9905	0.9899	41	134	Chr4:30279658~30280003
mh01zj0675568	248	43.2353	0.9714	0.9905	15	88	Chr1:247032193~247032440
mh20zj0185187	347	32.6183	0.9999	0.9892	9	68	Chr20:62308266~62308612
mh09zj0366544	239	28.5622	0.9524	0.9883	12	60	Chr9:129479455~129479693
mh07zj0103025	323	28.3055	0.9714	0.9892	26	77	Chr7:18772264~18772586
mh04zj0352614	346	27.1218	0.9810	0.9859	22	105	Chr4:88537078~88537423
mh03zj0068937	350	24.2308	0.8762	0.9858	20	75	Chr3:11955851~11956200
mh02zj0082461	320	23.7864	0.9810	0.9874	12	56	Chr2:20701112~20701431
mh01zj0508420	337	21.7028	0.9619	0.9872	37	63	Chr1:200785797~200786133
mh04zj0474307	348	20.5307	0.9714	0.9870	11	51	Chr4:129682428~129682775

Ae	#MHs≤350 bp	#MHs≤150 bp	#MHs≤100 bp	#MHs≤50 bp
1~	1,634,742	1,345,361	1,116,786	741,819
2~	1,057,851	694,670	534,462	319,289
3~	171,637	56,715	32,419	12,211
4~	20,759	4941	2683	937
5~	6510	1875	957	213
10~	307	52	11	0
15~	80	8	5	1
20~	26	0	1	0
25~	15	5	0	0

微单倍型遗传标记的法医基因组学研究

Forensic genomics research on microhaplotypes

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