Standage Daniel S, Mitchell Rebecca N
National Bioforensic Analysis Center, National Biodefense Analysis and Countermeasures Center (NBACC), Frederick, MD, United States.
Front Genet. 2020 Aug 7;11:781. doi: 10.3389/fgene.2020.00781. eCollection 2020.
Microhaplotypes are the subject of significant interest in the forensics community as a promising multi-purpose forensic DNA marker for human identification. Microhaplotype markers are composed of multiple SNPs in close proximity, such that a single NGS read can simultaneously genotype the individual SNPs and phase them in aggregate to determine the associated donor haplotype. Abundant throughout the human genome, numerous recent studies have sought to discover and rank microhaplotype markers according to allelic diversity within and among populations. Microhaplotypes provide an appealing alternative to STR markers for human identification and mixture deconvolution, but can also be optimized for ancestry inference or combined with phenotype SNPs for prediction of externally visible characteristics in a multiplex NGS assay. Designing and evaluating panels of microhaplotypes is complicated by the lack of a convenient database of all published data, as well as the lack of population allele frequency data spanning disparate marker collections. We present MicroHapDB, a comprehensive database of published microhaplotype marker and frequency data, as a tool to advance the development of microhaplotype-based human forensics capabilities. We also present population allele frequencies derived from 26 global population samples for all microhaplotype markers published to date, facilitating the design and interpretation of custom multi-source panels. We submit MicroHapDB as a resource for community members engaged in marker discovery, population studies, assay development, and panel and kit design.
微单倍型作为一种有前景的用于人类识别的多用途法医DNA标记，在法医界备受关注。微单倍型标记由紧密相邻的多个单核苷酸多态性（SNP）组成，这样一次二代测序（NGS）读取就能同时对各个SNP进行基因分型，并对它们进行整体定相，以确定相关的供体单倍型。微单倍型在人类基因组中广泛存在，最近有许多研究试图根据群体内部和群体之间的等位基因多样性来发现微单倍型标记并对其进行排序。微单倍型为人类识别和混合样本解卷积提供了一种有吸引力的替代短串联重复序列（STR）标记的方法，但也可以针对祖先推断进行优化，或者在多重NGS检测中与表型SNP结合用于预测外部可见特征。由于缺乏一个方便的所有已发表数据的数据库，以及缺乏涵盖不同标记集合的群体等位基因频率数据，微单倍型面板的设计和评估变得复杂。我们展示了MicroHapDB，这是一个已发表的微单倍型标记和频率数据的综合数据库，作为推动基于微单倍型的人类法医鉴定能力发展的工具。我们还展示了从26个全球群体样本中得出的所有迄今已发表的微单倍型标记的群体等位基因频率，这有助于定制多源面板的设计和解读。我们将MicroHapDB作为一种资源提交给从事标记发现、群体研究、检测开发以及面板和试剂盒设计的社区成员。
