Effects of DNA degradation and genotype imputation on high-density SNP microarray in pairwise kinship analysis

• Published in: Legal medicine (Tokyo, Japan) Japan), 2023-02, Vol.60, p.102158-102158, Article 102158
• Main Authors: Chu, Ming-Chieh, Morimoto, Chie, Kawai, Chihiro, Miyao, Masashi, Tamaki, Keiji
• Format: Article
• Language: English
• Subjects: Chromosomes; DNA - genetics; DNA microarray; Genotype; high-density SNPs; Humans; Imputation; Oligonucleotide Array Sequence Analysis; Pairwise kinship analysis; Polymorphism, Single Nucleotide - genetics
• ISSN: 1344-6223; 1873-4162
• DOI: 10.1016/j.legalmed.2022.102158

•We examined the effect of DNA sample density and quality on pairwise kinship analysis using DNA microarray.•Poor DNA quality had a more serious effect than small DNA quantity on SNP typing.•Genotype imputation could complement no-called SNPs in the case of mild degradation.•DNA microarray with imputation is promising method for analysis of forensic DNA samples. High-density single nucleotide polymorphisms (SNPs) can detect distant relatives even in the context of pairwise kinship analysis. Although DNA microarrays conveniently generate genome-wide SNP data, they require large quantities of high-quality DNA. Genotyping data obtained from low-quantity and low-quality samples are likely unreliable owing to the incidence of no-called or mistyped SNPs. In this study, we examined the effects of insufficient sample densities and sample degradation on the efficacy of kinship analysis. While low DNA amounts had a minor effect, DNA degradation led to a significant increase in no-call rates and error rates. Posterior probabilities of kinship determination, calculated using the index of chromosomal sharing, were markedly lower in proportion to the no-call rates and error rates. We also investigated the effect of genotype imputation to complement the no-called genome data utilizing SNPs reference panels. We found that the posterior probability of the relative-assumed person increased with genotype complementation in case of mild degradation, even with mistyped genotypes. Therefore, DNA microarray with imputation is a promising method for analyzing forensic DNA samples taken from situations where DNA quantity and quality may be compromised, such as disaster victim identification using pairwise kinship analysis.