Nonbinary SNP 遗传标记在法医亲子鉴定中的应用研究

短串联重复序列在遗传过程中具有较高的突变率，在用于法医亲子鉴定时经常出现不符合遗传学规律的现象，导致无法判断亲子关系甚至错误判断亲子关系。非二等位基因单核苷酸多态性（Nonbinary SNP）在以往的研究以及本课题前期工作中提示是一种具有低突变率的潜在法医学遗传标记。本研究将利用生物信息学方法从数据库中选择SNP，利用混池样本Haloplex靶向基因捕获芯片技术，寻找全基因组中的Nonbinary SNP；通过焦磷酸测序技术，验证芯片结果、筛选可用于法医亲子鉴定的Nonbinary SNP并建立数据库；基于筛选结果，利用SNaPshot法建立荧光复合体系，并检测家系样本，研究Nonbinary SNP在法医亲子鉴定中的应用价值和突变率。本研究将为法医亲子关系鉴定提供一种新的技术手段，同时可以建立Nonbinary SNP基因频率数据库，为其在法医及其它学科中的应用提供数据支持。

STR (short tandem repeats) mutations frequently occur in forensic paternity testing, because STR has relatively high mutation rate. The high mutation rate leads to the failure even the inaccuracy to identify parent-child relationship. Previous studies and our researches have shown that Nonbinary single nucleotide polymorphisms (SNPs) possesses quality of low mutation rates and have been regarded as potentially effective markers in forensic utility. In this study, we aim to develop an effective method to choose SNP from database and analyze them by Haloplex Target Enrichment System pooling method to obtain allele types and the allele frequency. Thereafter, we verify the Haloplex results by pyrosequncing method and select forensically applicable Nonbinary SNPs. All selected SNP loci are combined in one multiplex PCR reaction to develop a SNaPshot-based SNP-typing assay for forensic paternity testing. Then based on family samples, the mutation rate of Nonbinary SNP is examined by this assay. Through this research, we will provide a new effective assay in forensic paternity testing and meanwhile , establish data support for Nonbinary SNP's application of forensic science and other related subjects.