Are microhaplotypes derived from the 1000 Genomes Project reliable for forensic purposes?

IF 3.2 2区医学 Q2 GENETICS & HEREDITY

Forensic Science International-Genetics Pub Date : 2025-03-15 DOI:10.1016/j.fsigen.2025.103273

Yifan Wei , Xi Li , Qiang Zhu , Tiantian Shan , Haoyu Wang , Xuan Dai , Yufang Wang , Ji Zhang

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引用次数: 0

Abstract

Microhaplotypes (MHs) have emerged as an important genetic marker in forensic genetics. However, most studies have overlooked the potential for phasing errors within microhaplotypes based on the 1000 Genome Project (1kGP), which may impact the evaluation of various forensic parameters and lead to misleading results. In this study, we constructed a dense and extensive set of MHs across the human genome, using the expanded 1000 Genomes Project data aligned to GRCh38 reference genome. We applied three different SNP minor allele frequency (MAF) thresholds (0, 0.01, and 0.05) to evaluate the reliability of these markers. Utilizing pedigree data from 18 populations, which included a total of 602 trios, we scanned for and confirmed suspected phasing error events at these MH loci. We also sequenced 50 MHs for one trio of the Southern Han Chinese (CHS) population to further investigate these discrepancies. The results revealed the presence of phasing errors in MHs from 1kGP when analyzed using targeted enrichment and next-generation sequencing. The probability of suspected phasing error events was strongly and positively correlated with the effective number of alleles (Ae) and informativeness (In) of the markers. Additionally, these mismatch probabilities varied significantly across different continental populations. Additionally, when selecting loci, applying MAF filtering and avoiding regions such as the MHC can reduce the occurrence of such events to some extent. Based on these findings, we suggest that relying solely on sequencing data of the 1kGP for forensic purpose may be risky. A thorough investigation of the true forensic parameters of MHs is essential to ensure their reliability in forensic applications.

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微单倍型（MH）已成为法医遗传学中的重要遗传标记。然而，大多数研究都忽略了基于 1000 基因组计划（1kGP）的微单倍型中可能存在的分期误差，这可能会影响各种法医参数的评估并导致误导性结果。在本研究中，我们利用与 GRCh38 参考基因组对齐的扩展的 1000 基因组计划数据，构建了一套密集而广泛的人类基因组微等位基因。我们采用了三种不同的 SNP 小等位基因频率（MAF）阈值（0、0.01 和 0.05）来评估这些标记的可靠性。利用来自 18 个种群的血统数据（共包括 602 个三倍体），我们扫描并确认了这些 MH 位点上的疑似相位错误事件。为了进一步研究这些差异，我们还对中国南方汉族（CHS）一个三人群体的 50 个 MH 进行了测序。结果显示，在使用靶向富集和下一代测序分析时，来自 1kGP 的 MHs 中存在相位错误。疑似相位错误事件的发生概率与标记的有效等位基因数（Ae）和信息量（In）密切正相关。此外，这些错配概率在不同大陆种群之间存在显著差异。此外，在选择位点时，应用 MAF 过滤和避开 MHC 等区域可在一定程度上减少此类事件的发生。基于这些发现，我们认为仅依靠 1kGP 的测序数据来进行法医鉴定可能存在风险。要确保 MHs 在法医应用中的可靠性，必须对其真正的法医参数进行彻底调查。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Forensic Science International-Genetics 生物-医学：法

CiteScore

7.50

自引率

32.30%

发文量

132

审稿时长

11.3 weeks

期刊介绍： Forensic Science International: Genetics is the premier journal in the field of Forensic Genetics. This branch of Forensic Science can be defined as the application of genetics to human and non-human material (in the sense of a science with the purpose of studying inherited characteristics for the analysis of inter- and intra-specific variations in populations) for the resolution of legal conflicts. The scope of the journal includes: Forensic applications of human polymorphism. Testing of paternity and other family relationships, immigration cases, typing of biological stains and tissues from criminal casework, identification of human remains by DNA testing methodologies. Description of human polymorphisms of forensic interest, with special interest in DNA polymorphisms. Autosomal DNA polymorphisms, mini- and microsatellites (or short tandem repeats, STRs), single nucleotide polymorphisms (SNPs), X and Y chromosome polymorphisms, mtDNA polymorphisms, and any other type of DNA variation with potential forensic applications. Non-human DNA polymorphisms for crime scene investigation. Population genetics of human polymorphisms of forensic interest. Population data, especially from DNA polymorphisms of interest for the solution of forensic problems. DNA typing methodologies and strategies. Biostatistical methods in forensic genetics. Evaluation of DNA evidence in forensic problems (such as paternity or immigration cases, criminal casework, identification), classical and new statistical approaches. Standards in forensic genetics. Recommendations of regulatory bodies concerning methods, markers, interpretation or strategies or proposals for procedural or technical standards. Quality control. Quality control and quality assurance strategies, proficiency testing for DNA typing methodologies. Criminal DNA databases. Technical, legal and statistical issues. General ethical and legal issues related to forensic genetics.