Department of Genetics, Yale University School of Medicine, New Haven, CT, 06520, USA.
Hum Genet. 2021 Dec;140(12):1753-1773. doi: 10.1007/s00439-021-02382-0. Epub 2021 Oct 13.
Single-nucleotide polymorphisms (SNPs) and small genomic regions with multiple SNPs (microhaplotypes, MHs) are rapidly emerging as novel forensic investigative tools to assist in individual identification, kinship analyses, ancestry inference, and deconvolution of DNA mixtures. Here, we analyzed information for 90 microhaplotype loci in 4009 individuals from 79 world populations in 6 major biogeographic regions. The study included multiplex microhaplotype sequencing (mMHseq) data analyzed for 524 individuals from 16 populations and genotype data for 3485 individuals from 63 populations curated from public repositories. Analyses of the 79 populations revealed excellent characteristics for this 90-plex MH panel for various forensic applications achieving an overall average effective number of allele values (A) of 4.55 (range 1.04-19.27) for individualization and mixture deconvolution. Population-specific random match probabilities ranged from a low of 10 to a maximum of 10. Mean informativeness (I) for ancestry inference was 0.355 (range 0.117-0.883). 65 novel SNPs were detected in 39 of the MHs using mMHseq. Of the 3018 different microhaplotype alleles identified, 1337 occurred at frequencies > 5% in at least one of the populations studied. The 90-plex MH panel enables effective differentiation of population groupings for major biogeographic regions as well as delineation of distinct subgroupings within regions. Open-source, web-based software is available to support validation of this technology for forensic case work analysis and to tailor MH analysis for specific geographical regions.
单核苷酸多态性 (SNP) 和包含多个 SNP 的小基因组区域 (微单倍型，MH) 迅速成为新的法医研究工具，可辅助个体识别、亲缘关系分析、祖先推断和 DNA 混合物的拆分。本研究分析了来自 6 个主要生物地理区域的 79 个人群中的 4009 个体的 90 个微单倍型位点信息。该研究包括对来自 16 个人群的 524 个人进行多重微单倍型测序 (mMHseq) 数据分析，以及对来自 63 个人群的 3485 个人的基因型数据进行分析，这些数据来自公共数据库。对 79 个人群的分析表明，该 90 plex MH 面板非常适合各种法医应用，在个体识别和混合物拆分方面的总体平均有效等位基因数 (A) 达到 4.55(范围 1.04-19.27)。人群特异性随机匹配概率从低至 10 到高至 10。用于祖先推断的平均信息量 (I) 为 0.355(范围 0.117-0.883)。使用 mMHseq 在 39 个 MH 中检测到 65 个新的 SNP。在鉴定的 3018 个不同微单倍型等位基因中，有 1337 个在至少一个研究人群中的频率超过 5%。90plex MH 面板能够有效地区分主要生物地理区域的人群分组，并描绘区域内的不同亚群。有开源的、基于网络的软件可用于支持该技术在法医案例分析中的验证，并针对特定地理区域调整 MH 分析。
