96个常染色体SNPs应用于亲权鉴定的研究

A study on paternity testing with 96 autosomal SNPs

目的探索用常染色体单核苷酸多态性（singlenucleotide polymorphisms，SNPs）进行亲权鉴定的可行性。方法下载HapMap（r27）的SNPs分型结果，用自行编写的计算机程序提取基因频率在世界11个人群中一致分布于0．30-0．70区间的SNPs，进而选取互不连锁的96个SNPs整合于IlluminaGoldengate微珠芯片中，对3个父-子-母三联体亲权鉴定案例（共9份样品）进行SNPs分型，依分型结果计算出累积亲权指数（cumulative paternity index，CPI）等参数，并与上述案例的短串联重复序列（short tandem repeats，STRs）分型结果进行对比。结果案例l的被控父有9个SNPs或7个STRs不符合孟德尔遗传规律；案例2的被控母有13个SNPs或7个STRs不符合孟德尔遗传规律；案例3有1个SNP或0个STR不符合孟德尔遗传规律。以96个SNPs对案例3进行亲权鉴定，其CPI=1207，而以15个STRs对案例3进行亲权鉴定时其CPI=355869。结论当应用于亲权鉴定时，单个SNP的亲权排除率值一般不及单个STR的1／3。在排除亲权关系的案例中，就不符合孟德尔遗传规律的遗传标记个数占检测标记总数的比例而言，SNPs系统可能不如STR系统明显。由于SNPs的突变率极低，即使1个SNP位点不符合孟德尔遗传规律也能极大地降低CPI值，故SNPs应用于亲权鉴定时对检测方法有更高的要求。

Objective To explore the feasibility of applying autosomal single nucleotide polymorphisms （SNPs）on parentage testing. Methods All SNP genotyping results of HapMap （r27） were downloaded from the website. With self-made computer programs, SNPs were extracted when their minor allele frequency （MAF） were ≥ 0. 30 among all of the 11 HapMap populations. Ninety-six SNPs were chosen and integrated into the Illumina Goldengate bead arrays on the condition that no linkage disequilibrium was found between them. Three father-child-mother trios （9 samples in total） were tested with the arrays. Cumulative paternity index （CPI） was then calculated and compared with genotyping results using 15 short tandem repeats （STRs）（IdentifilerTM）. Results Family 1 was found to have nine SNPs or seven STRs that did not conform to the Mendelian laws, Family 2 had 13 such SNPs or seven STRs, and Family 3 only had one such SNP but no STR. For Family 3, when all of the 96 SNPs were used in combine, the CPI was 1207, which had contrasted with the CPI by the 15 STRs, i. e. , 355 869. Conclusion When applied to paternity testing, the paternity exclusion （PE） value for a SNP is usually less than 1/3 of that of a STR. The proportion of SNPs not comforming to the Mendelian laws for the tested SNPs may not be as high as that of inconsistent STRs over all tested STRs. Because of the low mutation rate of a SNP, the CPI will be greatly reduced even if one SNP did not conform to the Mendelian laws. Therefore, highly accurate testing methods are required to reduce artificial errors when applying SNPs for paternity testing.