基因组AIM-InDel基因座的甄选、验证和法医学应用研究

Ancestry-informative markers (AIM) play an important role in anthropology, population genetics, association study, personalized medicine as well as forensic science. Insertion/ deletion (InDels) is a newly developed genetic marker that combined the desirable characteristics of the other genetic markers most commonly used. InDels are abundant in the genome with a low mutation rate, showing high polymorphism. With a small amplicon, InDels could be coamplified in a single tube PCR reaction and be very simply genotyped through a direct capillary electrophoresis (CE) of the amplified products. Recently, InDels has been the focus of both genetic and forensic scientists. In this study, we selected AIM-InDels with high ancestry-information and forensic application value in Chinese population through a systemic genome wide screening procedure. Depending on the PCR-CE approach, a fluorescence labeled multiplex amplification system was developed. Genetic polymorphism, mutation rate, recombination rate and linkage disequilibrium analysis was performed in several groups in China using this system and the specificity, sensitivity, stability and material suitability was detected to evaluating its value in forensic application. In this study, we developed an AIM-InDels panel for Chinese population for a better understanding on population structure at genomic level. By providing a new perspective and strategy on indicating the likely genetic ancestry of the donor, we hope the AIM-InDels would help direct the course of investigations.

始祖多态性位点对人类学、群体遗传学、疾病关联分析、个体化医疗和法医学研究有重要科学意义和实用价值。插入缺失位点是近年新发展的遗传标记，基因组含量丰富、突变率低，多态性较高、扩增子短、可复合扩增、分型简易，是目前遗传学和法医学研究新热点。本研究利用全基因组扫描策略，系统甄选中国族群始祖多态性高和法医学应用价值大始祖多态性插入缺失位点（AIM-InDel），建立基于毛细管电泳分型的荧光复合扩增体系，对甄选AIM-InDel位点进行中国多族群和家系样本遗传多态性、突变率、连锁不平衡等调查，评估该复合扩增体系特异性、稳定性、灵敏度、组织同一性及在法医学检案中应用价值。 本研究有机整合AIM和InDel遗传标记的优势，项目的实施和完成一方面有利于在基因组水平上进一步了解我国族群的始祖构成，另一方面也为法医学检案提供了新的策略和思路，有利于法医检材始祖信息推断，缩小侦查范围，为科技强警提供支持和保障。

本研究扩大了课题组原有群体的样本量，并采集了新的研究族群，利用全基因组扫描策略，系统甄选中国族群始祖多态性高和法医学应用价值大始祖多态性插入/缺失位点（AIM-InDel），建立基于毛细管电泳分型的39个AIM-InDel位点的荧光复合扩增检测体系，对甄选AIM-InDel位点进行中国多族群遗传多态性、连锁不平衡等调查，评估该复合扩增体系特异性、稳定性、灵敏度、组织同一性及在法医学检案中应用价值。 研究一方面在基因组水平上进一步了解我国族群的始祖构成，另一方面也为法医学检案提供了新的策略和思路，研究有利于法医检材始祖信息推断，缩小侦查范围，为科技强警提供支持和保障。本研究及相关研究目前共发表SCI 4篇；目前已申请发明专利一项，专利目前处于实质审查状态。前期研究参与获得陕西省以及西安市科学技术奖一等奖各一项。