Advancements in chimerism estimation and SNV genotyping in common marmosets: Enhancing genetic diversity analysis using next-generation sequencing

Abstract

While marmosets are crucial in biomedical research, genetic research into these species using next-generation sequencing (NGS) has proven significantly challenging due to chimerism. We have developed an innovative method to estimate chimerism ratios and correct single nucleotide variant (SNV) genotypes in marmoset NGS data. This advancement has enabled the construction of a comprehensive variome for 56 Korean common marmosets (Callithrix jacchus) that were cultivated at Osong Medical Innovation Foundation and 18 public Callitrichidae specimens, altogether encompassing about 200 million of SNVs. Using our method, we achieved a 5% chimerism ratio in hair follicles, allowing for the adjustment of homozygous SNVs from chimerism reads. However, this was not successful in blood with high chimerism. Analysis of this extensive variome data revealed the existence of a positive association between genetic diversity and conservation status, and it also showed signs of inbreeding in our specimens. The genetic structure analysis of C. jacchus and its related species holds significant potential for enhancing genetic diversity through inter-species admixture. These findings provide crucial insights into marmoset genetic diversity that are expected to offer valuable guidance for conservation strategies and the enhancement of genetic health in marmoset research populations.