目的 Y染色体为男性所特有,其遗传标记蕴含着丰富的生物地理信息,故可溯源家系,在嫌疑人排查和追踪中发挥作用。Y-STR突变率较高,而Y-SNP突变率极低,几乎不会发生回复突变,所以后代男性群体携带祖先特有的Y-SNP。本研究期望通过现在我国Y库建设中通用的17个Y-STR的单倍型数据预测Y-SNP单倍群细支。方法 基于前期观察,选取千人基因组计划III期中的513例东亚人群（中国及周边区域）作为基础数据集,在Java平台和Microsoft Excel软件框架下,以遗传距离计算和Y染色体进化树构建手段相联合研发Y-STR数据的家系特异性单倍群归属判别分析软件：EA-YPredictor。结果 本研究揭示了15个单倍群大支下的核心单倍型。通过随机选取70个公开数据库样本,EA-YPredictor软件预测准确性达到92.8%（95%置信区间：[84.1%, 97.6%]）。结论 在Y-SNP复合扩增检测尚无定论的情况下,本软件可基于二代测序样本对Y-STR数据库样本进行单倍群细支的准确预测,能适用于辅助家系单倍群判断。随着测序技术的不断换代和优化,更多高通量的Y-STR和Y-SNP数据补充将会使本软件进一步优化。此外,本软件对于Y数据库中Y-SNP遗传标记的筛查建库有一定指向作用。
Abstract
Y chromosome, male specific, carres the genetic markers that could indicate the bio-geographic information of unknown male individuals, therefore playing vital and unique roles in pedigree searching and individuals tracking. Y-SNPs, the genetic markers hardly occurring of reverse mutation, harbor extreme low mutation rate compared to Y-STRs. Thus, male individuals of the same lineages always carry the specific Y-SNPs of their identical ancestors. However, Y-SNP typing is time- and cost- consuming, making it not an ideal tool for investigation. To target suspects’ pedigree for investigation purpose, Y-SNP haplogroups were here tentatively predicted from the current 17 Y-STR haplotypes that are commonly used for Y-database construction. With re-evaluation of previous research results and analysis of the open East-Asian datasets from 1000-Genome Project (Phase III), one new Y-STR-based pedigree-specific haplogroup prediction software, EA-YPredictor, was developed through calculation of genetic distance and Y chromosomal phylogenetic tree reconstruction, hence successfully having screened the 15 Y-SNP major haplogroups out from the core 17 Y-STR haplotypes on the adaptable Java platform or Microsoft Excel formulation. Randomly selected of 70 new samples, EA-YPredictor was tested of its prediction accuracy (92.8%, 95% CI: [84.1%, 97.6%]), revealing the exact Y haplogroup affiliation to the males of East Asian ancestry, thereby demonstrating its validity to predict the Y-SNP haplogroup of samples in existing Y chromosome database. Following the next-generation sequencing technology to confirm the location and annotation of more Y-STRs and Y-SNPs, EA-YPredictor will be definitely optimized further so that more indications would be provided on screening which set of Y-SNP markers from Y chromosome databases.
关键词
法医遗传学 /
Y染色体单倍群预测 /
Y-STR /
Y-SNP /
东亚男性人群
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Key words
forensic genetics /
Y chromosomal haplogroup prediction /
Y-STR (short tandem repeat) /
Y-SNP (single nucleotide polymorphism) /
East Asian male populations
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脚注
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基金
“十三五”国家重点研发计划课题（2016YFC1201700）; 上海市市级科技重大专项（2017SHZDZX01）; 中央级公益性科研院所基本科研业务费专项资金项目（2017JB004）; 公安部物证鉴定中心开放课题（2015FGKFKT01）; 上海市刑事科学技术研究院现场物证重点实验室开放课题（KEH1322878）
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