采用Identifiler系统进行全同胞关系判定的准则探讨

A Primary Study for Criteria of Full Sibling Determination with Identifiler System

目的探讨采用Identifiler系统进行全同胞关系判定时共有等位基因数(IAn)和全相同基因座数(A2)的标准。方法依据IAn和A2的有限分布,将IAn的31种取值代入已建立的判别函数,获得判定全同胞时IAn和A2的阈值,据此确定4种标准,对经Identifiler系统分型的280对全同胞和2003对无关个体对进行全同胞判定。采用ITO法计算累积全同胞指数(CFSI),并采用CFSI>1、CFSI≥5、CFSI≥20、CFSI≥100 4种标准同样进行全同胞判定。计算上述8个标准判定全同胞的敏感度、特异性、准确度、阳性预测值和阴性预测值,通过Kappa检验比较基于IAn和A2的判定标准与CFSI标准判定结果的一致性。结果满足(Ⅰ)IAn≥15且A2≥4、或(Ⅱ)IAn≥16且A2≥3、或(Ⅲ)IAn≥17且A2≥3、或(Ⅳ)IAn≥18且A2≥3者均可认定为全同胞。上述4项标准与CFSI的4项标准进行全同胞判定的准确度、特异性和阴性预测值均大于0.9500。标准Ⅱ与CFSI≥5、标准Ⅲ与CFSI≥20、标准Ⅳ与CFSI≥100 3组判定标准的各项指标均接近,Kappa值分别为0.904 9、0.9204和0.9083,其中,标准Ⅲ与CFSI≥20对全同胞的阳性预测值和阴性预测值均大于0.950 0。结论 IAn≥17且A2≥3是采用Identifiler系统进行全同胞判定的简便易行且有效的标准,这一标准与CFSI≥20相当。

Objective To investigate the criteria of the number of identical allele（IAn） and the number of matched STR locus with 2 identical alleles（A2） for full sibling（FS） determination with Identifiler system.Methods According to the limited distribution of IAn and A2,all of the 31 potential values of IAn were substituted into the published discriminant functions to obtain the cut-off values of IAn and A2 for FS determination,and then 4 different criteria were determined to distinguish 280 FS pairs from 2 283 individual pairs,respectively,which had been genotyped with Identifiler system.Cumulative full sibling index（CFSI） of the samples were calculated with ITO method,and 4 different criteria of CFSI（1,≥5,≥20 and ≥100） were also utilized to determinate FS,respectively.Indices including sensitivity（SEN）,specificity（SPE）,accuracy（AC）,positive predictive value（PPV） and negative predictive value（NPV） of the 8 different criteria for FS determination were calculated,respectively.Concordance of FS determination between the criteria based on IAn and A2 and that of CFSI were statistically tested with Kappa index.Results All the individual pairs,which meet the requirement of（Ⅰ） IAn≥15 and A2≥4,or（Ⅱ） IAn≥16 and A2≥3,or（Ⅲ） IAn≥17 and A2≥3,or（Ⅳ） IAn≥18 and A2≥3,could been concluded as FS.AC,SPE and NPV of the 4 criteria mentioned above and the 4 criteria of CFSI were all over 0.950 0 in FS determination.Indices between criterion Ⅱ and CFSI≥5,criterion Ⅲ and CFSI≥20,criterion Ⅳ and CFSI≥100 were similar with each other and the Kappa indexes of the 3 groups were 0.904 9,0.920 4 and 0.908 3,respectively.PPV and NPV of criterion Ⅲ and CFSI≥20 were all over 0.950 0.Conclusion The criterion of IAn≥17 and A2≥3 was feasible and efficient for FS determination with Identifiler system,power of which was similar with the criterion of CFSI≥20.