微单倍型遗传标记及其法医遗传学应用

Microhaplotypic Genetic Markers and Their Applications in Forensic Genetics

微单倍型是一种国际广泛关注的新型法医遗传学分子标记。它兼具STR和SNP遗传标记的优势,在法医混合DNA检验、种族地域推断、复杂亲缘关系分析等领域均具有重要应用前景。本文综述了微单倍型遗传标记的基本概念、命名规则,回顾了二代测序、高分辨熔解曲线、单链构象多态性分析等微单倍型检测手段,介绍了微单倍型法医遗传学应用的相关研究进展,并对微单倍型遗传标记未来发展做了展望,提出了其可能面临的挑战。

Although short tandem repeats(STR)and single nucleotide polymorphism(SNP)genetic markers have been being widely used in forensic individual identification,microhaplotype,defined as the combination of2-5SNPs within a segment of DNA up to200base pairs,is emerging its potential as a new type of molecular markers in forensic genetics.The microhaplotype genotyping includes single strand conformational polymorphism(SSCP),high resolution melting(HRM)analysis and next generation sequencing(NGS).SSCP is a traditional gene analysis method that can be conveniently performed at low costs.HRM has been applied to genotype SNP and DNA methylation as an alternative.However,DNA sequence information cannot be obtained directly from these two approaches.By contrast,the genotypes of microhaplotypes can be reported from NGS by direct DNA sequencing.NGS is expected to become a major method for microhaplotype detection.In addition,microhaplotype,possessing both STR and SNP markers,has important application prospects in forensic genetics,e.g.,the mixed DNA genotyping,ancestry inference and complicated kinship analysis.Since microhaplotype is a multiallelic marker without stutter peaks,it has great value for mixed DNA genotyping.The distinct pattern of microhaplotype has already been used to assist the ancestry inference from populations in Africa,Southwest Asian,East Asian,the Pacific islands and the Americans.Because of its high heterozygosity and low mutation,microhaplotype can also be applied to individual identification and lineage inference.In this paper,the basic concepts and nomenclature of microhaplotypes are introduced.Microhaplotype detection methods are presented,mainly targeting at NGS,HRM and SSCP together with the summary of their research progresses in forensic applications.Also,forensic perspectives of microhaplotypes are presented and the possible challenges discussed.