连锁遗传标记在区分同级亲缘关系中的应用研究

The successful use of genealogy search based on DNA databases in a series of case detection shows us the development prospects of the latest biotechnology in forensic science. As a representative, kinship testing has more and more widely used scenarios in the present. However, the existing technical methods based on unlinked genetic markers still have some deficiencies. Namely, the support conclusion for a certain relationship could not exclude other relationships belonging to the same kinship class, which will bring great difficulties and hidden dangers to the practical work. To resolve the problem of distinguishing pedigrees belonging to the same kinship class better, the project will explore further on the basis of previous work. Taking grandparents, uncles and half-sibs as a representative, the project will select and construct a complex system of actual linked markers, collect DNA samples from unrelated subjects and real relationships in the northern Chinese Han population, and perform accurately genotyping using Massively Parallel Sequencing and High-density SNP array. On this basis, the project will use the pedigree likelihood ratio model and perform analyses from both simulation calculation and real samples respectively. Furthermore, the project will systematically evaluate the testing efficacy of linked markers in distinguishing pedigrees belonging to the same kinship class, to provide a quantitative and accurate technical solution for the problem of complex kinship testing.

基于DNA数据库的家族谱系搜索在一系列案件侦破中的成功应用，为我们展现了最新生物技术在法医学中的发展前景。以之为代表，家系亲缘鉴定在当下得到了越来越广泛的应用。然而，现有基于非连锁遗传标记的技术手段仍有其不完善之处，即对某一亲缘关系做出支持结论的同时尚无法排除其他与之同级的亲缘关系，而这将为实际工作带来极大的困难和隐患。为了更好的解决同级亲缘关系的鉴定难题，本项目将在前期工作的基础上作进一步探索。以祖孙、叔侄、半同胞三种常见的同级亲缘关系为代表，本项目将通过筛选和构建真实连锁遗传标记的复合系统，并在北方汉族群体中收集无关个体及真实家系的DNA样本，利用高通量测序及高密度SNP芯片技术对其进行准确的分型。在此基础上，本项目将应用家系似然率模型分别从模拟计算与真实样本两方面进行分析，系统评估连锁遗传标记在区分同级亲缘关系中的鉴定效力，为解决这一复杂亲缘关系鉴定难题提供定量的准确的技术方案。

随着法医系谱学的快速发展，通过嫌疑人样本与亲属个体之间的亲缘关系鉴定从而间接确定嫌疑人身份的技术帮助越来越多的案件得到侦破。然而，利用非连锁遗传标记对某一具体亲缘关系做出结论的同时，并不能排除其他与之同级的亲缘关系可能。为解决这一问题，本项目以祖孙、叔侄、半同胞三类亲缘关系为代表，对同级亲缘关系的鉴定展开了研究。本项目从连锁STR和SNP两方面，分别构建了包含173个连锁STR基因座的分型体系和不同规模的连锁SNP复合系统组合Ⅰ-Ⅹ。在同级亲缘关系中的分析中，连锁遗传标记对祖孙、叔侄、半同胞等亲缘关系的区分能力有所提高，可初步为同级亲缘关系的鉴定提供新的方向和思路。同时，本项目对增加额外亲属、检测分型错误、参考人群选取等若干问题进行了探讨，为同级亲缘关系鉴定效力的提升优化提供了经验借鉴，进一步探索并完善了连锁遗传标记在法医学领域中的应用，为法医系谱学技术的规范和成熟做出了有益贡献。