Population genetics of marmosets in Asian primate research centers and loci associated with epileptic risk revealed by whole-genome sequencing

Abstract

The common marmoset ( Callithrix jacchus ) has emerged as a valuable nonhuman primate model in biomedical research with the recent release of high-quality reference genome assemblies. Epileptic marmosets have been independently reported in two Asian primate research centers. Nevertheless, the population genetics within these primate centers and the specific genetic variants associated with epilepsy in marmosets have not yet been elucidated. Here, we characterized the genetic relationships and risk variants for epilepsy in 41 samples from two epileptic marmoset pedigrees using whole-genome sequencing. We identified 14 558 184 single nucleotide polymorphisms (SNPs) from the 41 samples and found higher chimerism levels in blood samples than in fingernail samples. Genetic analysis showed fourth-degree of relatedness among marmosets at the primate centers. In addition, SNP and copy number variation (CNV) analyses suggested that the WW domain-containing oxidoreductase ( WWOX ) and Tyrosine-protein phosphatase nonreceptor type 21 ( PTPN21 ) genes may be associated with epilepsy in marmosets. Notably, KCTD18-like gene deletion was more common in epileptic marmosets than control marmosets. This study provides valuable population genomic resources for marmosets in two Asian primate centers. Genetic analyses identified a reasonable breeding strategy for genetic diversity maintenance in the two centers, while the case-control study revealed potential risk genes/variants associated with epilepsy in marmosets.

Comparative transcriptome analysis between rhesus macaques (<i>Macaca mulatta</i>) and crab-eating macaques (<i>M. fascicularis</i>)

“…The overlapping brain-specific genes included many critical human neurological disease-associated genes (e.g., DCC , EPHA3 , and STXBP1 ) ( Figure 4D ). Notably, DCC guides axonal growth during neural development and is associated with various neurological diseases ( Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders, 2019 ), while STXBP1 is crucial for neurotransmitter release, with MFA carrying STXBP1 mutations showing focal epilepsy as a primate model of human genetic disorders ( Lu et al, 2022 ; Yang et al, 2023 ). These findings further underscore the relevance of macaques as models for studying neurological diseases and advancing our understanding of human health.…”