常染色体STR突变率的研究

Mutation Rates of Autosomal Short Tandem Repeat

【目的】观察10 000例肯定亲子关系的三联体案例中STR基因座的突变事件,获取STR基因座的突变率资料。【方法】采用PowerPlexTM16系统进行15个STR基因座的检测,从10 000例肯定亲子关系的三联体案例中筛查出包含STR基因座突变的案例,确定突变等位基因的来源和步数,统计各STR基因座特异性、父源和母源特异性及等位基因特异性的突变率及其95%置信区间,分析突变的特点。【结果】10 000例三联体亲子鉴定中检出368例发生突变的案件,共计379个突变事件。突变案件的发生率为3.68%,15个STR基因座的突变率为0.10×10-3～2.30×10-3,平均突变率为1.26×10-3。各基因座的父源和母源突变率分别为0.05×10-3～1.35×10-3和0.05×10-3～0.70×10-3。统计FGA、vWA和D18S51等三个基因座一步突变的等位基因突变率分别为5.0×10-5～40.0×10-5、5.0×10-5～50.0×10-5和5.0×10-5～35.0×10-5。15个基因座的父源/母源突变比值为1.3∶1～17.0∶1,平均为3.57∶1。【结论】STR基因座突变现象普遍存在于亲子鉴定中,各基因座的突变率、父源和母源的突变率、各等位基因的突变率均存在差异,获取这些数据资料对于更准确地评判亲子鉴定结果非常必要。

[Objective] To observe the mutation events of short tandem repeat （STR） loci in 10 000 parentage confirmed triocases and obtain the mutation rates of STR loci.[Methods] 15 STR loci of 10 000 parentage confirmed trio-cases were genotyped with PowerPlexTM16 system and the cases containing mutant STR loci were screened.The sources and steps of mutant alleles were ascertained.The locus-specific,paternal or maternal specific and allele-specific mutation rates with the corresponding 95% CIs were calculated,respectively.The characteristics of the mutations were analyzed.[Results] 368 mutant cases,a total of 379 mutation events were observed in 10 000 trio-cases for these 15 STR loci.The incidence of mutant cases was 3.68%.The mutation rates of 15 STR loci were between 0.10 × 10^-3 ～ 2.30 × 10^-3,and the average mutation rate was 1.26 × 10^-3.The paternal and maternal mutation rates were 0.05 × 10^-3 ～ 1.35 × 10^-3 and 0.05 × 10^-3 ～ 0.70 × 10^-3,respectively.The allele-specific single-step mutation rates for FGA,vWA and D18S51 were between 5.0 × 10-5 ～ 40.0 × 10-5,5.0 × 10-5 ～ 50.0 × 10-5 and 5.0 × 10-5 ～ 35.0 × 10-5,respectively.The ratios of paternal to maternal mutant events for these 15 STR loci were between 1.3 ∶ 1 ～ 17.0 ∶ 1,and the average ratio was 3.57∶1.[Conclusion] STR mutation was commonly existed in paternity testing.The mutation rates of various loci,paternal and maternal sources,and various alleles showed significant differences.It was necessary to obtain these data to accurately interpret the genotyping results in paternity testing.