Department of Environmental Toxicology, University of California, Davis, USA.
Department of Environmental Toxicology, University of California, Davis, USA; Forensic Science Program, University of California, Davis, USA.
Forensic Sci Int Genet. 2021 Sep;54:102564. doi: 10.1016/j.fsigen.2021.102564. Epub 2021 Jul 17.
This study examines the potential of hair shaft proteomic analysis to delineate genetic relatedness. Proteomic profiling and amino acid sequence analysis provide information for quantitative and statistically-based analysis of individualization and sample similarity. Protein expression levels are a function of cell-specific transcriptional and translational programs. These programs are greatly influenced by an individual's genetic background, and are therefore influenced by familial relatedness as well as ancestry and genetic disease. Proteomic profiles should therefore be more similar among related individuals than unrelated individuals. Likewise, profiles of genetically variant peptides that contain single amino acid polymorphisms, the result of non-synonymous SNP alleles, should behave similarly. The proteomically-inferred SNP alleles should also provide a basis for calculation of combined paternity and sibship indices. We test these hypotheses using matching proteomic and genetic datasets from a family of two adults and four siblings, one of which has a genetic condition that perturbs hair structure and properties. We demonstrate that related individuals, compared to those who are unrelated, have more similar proteomic profiles, profiles of genetically variant peptides and higher combined paternity indices and combined sibship indices. This study builds on previous analyses of hair shaft protein profiling and genetically variant peptide profiles in different real-world scenarios including different human hair shaft body locations and pigmentation status. It also validates the inclusion of proteomic information with other biomolecular substrates in forensic hair shaft analysis, including mitochondrial and nuclear DNA.
本研究探讨了毛发蛋白质组分析在描绘遗传相关性方面的潜力。蛋白质组分析和氨基酸序列分析为个体和样本相似性的定量和基于统计的分析提供了信息。蛋白质表达水平是细胞特异性转录和翻译程序的函数。这些程序受个体遗传背景的影响很大，因此受家族关系以及祖籍和遗传疾病的影响。因此，相关个体之间的蛋白质组谱应该比不相关个体更相似。同样，包含单个氨基酸多态性的遗传变异肽的谱，即非同义 SNP 等位基因的结果，应该表现相似。蛋白质组推断的 SNP 等位基因也应该为计算联合父系和同胞指数提供基础。我们使用来自一个由两个成年人和四个兄弟姐妹组成的家庭的匹配蛋白质组学和遗传数据集来测试这些假设，其中一个人患有影响头发结构和特性的遗传疾病。我们证明，与不相关的个体相比，相关个体的蛋白质组谱、遗传变异肽谱更相似，以及更高的联合父系指数和联合同胞指数。本研究建立在前一篇关于毛发蛋白质组分析和不同现实场景中遗传变异肽谱的分析之上，包括不同的人发轴身体部位和色素沉着状态。它还验证了在法医毛发轴分析中包括蛋白质组信息与其他生物分子底物，包括线粒体和核 DNA。
