基于NGS-STR分型和IBS策略进行远亲缘关系鉴定的研究

The demand for kinship testing is growing in forensic practice. Due to the limitations of the power of current available genotyping systems, it remains a challenge to identify 2nd degree or more distant relationships. Ambiguous identification results cannot be used as valuable source of evidence. This study aims to establish a highly powerful typing system for distant relationships testing. Two hundred autosomal STR, 20 X-STR and 30 Y-STR loci will be detected simultaneously based on next generation sequencing (NGS) platform. Meanwhile, utilizing IBS strategy, the results from real pairwise relatives and simulated samples will be analyzed and an evaluation model will be established. And allele dropout, rare allele, mutation, recombination, linkage and linkage disequilibrium will be taken into consideration. Also the thresholds will be set and served as a standard for judging different degree relationships and software will be designed. It is expected that reliable conclusions can be made for 2nd and 3rd degree relationship testing with the methods established in this study, and the power for 4th and 5th are going to be improved, which will expand traditional paternity testing to more distant relationship testing and provide new approaches for family searching in forensic DNA database.

亲缘关系鉴定在法医实践中的需求日益增多，但囿于目前可获得的检测体系的效能限制，对二级及二级以上远亲缘关系的鉴定依然是个难题，经常不能获得明确的鉴定结果，不能充分发挥其证据价值。本项目拟基于下一代测序技术的最新进展，同步检测200个常染色体STR、20个X-STR和30个Y-STR遗传标记，为二级及二级以上远亲缘关系鉴定提供高效能的检测手段。同时，采用IBS评分法对远亲缘关系鉴定获得的大信息量检测数据进行评估。根据实际检测数据和计算机模拟数据，结合STR等位基因丢失、稀有等位基因、突变、连锁、连锁不平衡、重组等因素建立评估模型，进行各级亲缘关系的临界值设定，制定各级亲缘关系评判策略，研制亲缘关系鉴定分析软件。本研究预期能使二级和三级亲缘关系鉴定获得明确的鉴定意见，提高四级和五级亲缘关系的鉴定效能，推动远亲缘关系的鉴定实践，为法庭科学DNA数据库家系搜寻提供新的有价值的解决途径。

亲缘关系鉴定在法医实践中的需求日益增多，但囿于目前可获得的检测体系的效能限制，对二级及二级以上远亲缘关系的鉴定依然是个难题，经常不能获得明确的鉴定结果，不能充分发挥其证据价值。本项目基于下一代测序技术平台，同步检测265个STR遗传标记（包括206个常染色体STR基因座、41个X染色体STR基因座和18个Y染色体STR基因座），基于模拟家系和实际家系的配对亲缘关系样本IBS评分值的分布特点成功制定了针对生物学全同胞关系和二级亲缘关系的鉴定策略，对于亲子关系和全同胞关系，系统效能达到了100%（错误率小于0.01%）；对于二级亲缘关系，系统效能超过了99.9%（错误率小于0.05%）；对于三级亲缘关系的第一代的堂表亲关系，系统效能接近70%（错误率约1%），与预期的研究结果一致，实现了对其精准鉴定。尤其地，这些STR不仅可以实现不同级别亲缘关系个体对与无关个体对的区分，还能实现不同类型亲缘关系之间的精准区分。其中，全同胞关系和半同胞关系的甄别是法医实践中常见的受近亲干扰的亲缘鉴定，本研究方案可对该类案件进行鉴别且效能超过0.9999。此外，基于机器学习新方法，我们实现了高分辨率配对亲缘关系分析，通过代码编程实现了亲缘关系鉴定相关参数的自动分析。本研究成果使二级和三级亲缘关系鉴定获得了明确的鉴定意见，提高了四级和五级亲缘关系的鉴定效能，推动了远亲缘关系的鉴定实践，为法庭科学DNA数据库家系搜寻提供了新的有价值的解决途径。