Evaluating the effects of silent genes on pairwise kinship testing

Abstract

Short tandem repeat (STR) loci are frequently utilized in kinship testing, and mutations of a single base occurring in the primer-binding region of the STR locus can result in the failure of allelic amplification and the emergence of silent genes. Silent genes are not observable and, therefore, are excluded from the genotypes assessed. Pedigree likelihood ratios (LRs) are often employed in kinship testing to determine the likelihood of different kinship scenarios. LR values are derived from various types of genotypes. LR_exact values are based on the exact or actual genotypes, which may include silent genes. Conversely, LR_observe values are based on observed genotypes that exclude silent genes, while LR_adjust values incorporate all potential genotypes, including both observed and those with silent genes. Initially, the formulae for LRs in 1st degree, 2nd degree, and 3rd degree kinship testing are presented according to different genotype forms of pairwise individuals. The correctness of these formulae is then verified using the Familias software, and the results are compared with those from the GeneVisa software (www.genevisa.net). Lastly, the simulation modules of GeneVisa are used to assess the impact of silent genes on pairwise kinship testing. The findings indicate that the overall impact of silent genes is minimal, although in some cases, the effects can be relatively significant. The influence of silent genes generally decreases as the kinship relationship becomes more distant. In specific kinship tests, the effect of silent genes is reduced when the individuals are unrelated compared to when there is a kinship relationship. Utilizing the LR_adjust value for 1st degree and 2nd degree kinship testing can substantially mitigate the effects of silent genes.