Evaluation of a Custom SNP Panel for Identifying and Rectifying of Misjudged Paternity in Deficiency Cases

Abstract

Parentage testing is routinely performed by genotyping short tandem repeat (STR) through capillary electrophoresis in the present. However, ambiguous or even misjudged paternity based on STRs happens from time to time in cases where only one putative parent is available. We analyzed STR data of 7,818,969 unrelated pairs and 75 close-relative pairs and found that although the probability of a random false match between non-relatives was 4.22 × 10^-6, the incidence of false or ambiguous paternity results between children and first-degree relatives of their true parent was as high as 18.67%. These results highlight the risk of false inclusion of a relative or even non-relatives in parentage testing with STRs. We then validated all ambiguous STR results by targeted sequencing with a custom panel containing 4,830 individual identification single nucleotide polymorphisms (IISNP), found that the ratio of mismatch loci to total SNPs was 1.78-6.95% in close relatives compared with 10.93-13.49% in unrelated pairs. Last, we reported three real cases with undetermined paternity by STRs and rectified them by dissecting with our IISNP panel. These results suggested that high-density IISNP panel can be used to identify and rectify misjudged cases effectively.

Keywords: ambiguous STR result; close relative; deficiency case; misjudged paternity; random false match; single nucleotide polymorphism.

FIGURE 1

Mismatch ratio for relative and non-relative pairs based on SNP data. Mismatch ratio means the fraction of genetic incompatible SNPs in total detected loci. Tested relative types including full sibling (n = 14), grandparent-grandchild (n = 27), uncle/aunt-niece/nephew (n = 9), and non-relative (n = 60).

FIGURE 2

Mismatch loci number under different total detected SNPs in simulation between full sibling pair. For each violin, we randomly selected the corresponding number of SNPs and counted the mismatch loci number for 100 times. Minimum of mismatch loci were labeled for each violin.