Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI.
Human Genome Sequencing Center and Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX.
J Immunol. 2024 Jun 1;212(11):1754-1765. doi: 10.4049/jimmunol.2300856.
Mauritian-origin cynomolgus macaques (MCMs) serve as a powerful nonhuman primate model in biomedical research due to their unique genetic homogeneity, which simplifies experimental designs. Despite their extensive use, a comprehensive understanding of crucial immune-regulating gene families, particularly killer Ig-like receptors (KIR) and NK group 2 (NKG2), has been hindered by the lack of detailed genomic reference assemblies. In this study, we employ advanced long-read sequencing techniques to completely assemble eight KIR and seven NKG2 genomic haplotypes, providing an extensive insight into the structural and allelic diversity of these immunoregulatory gene clusters. Leveraging these genomic resources, we prototype a strategy for genotyping KIR and NKG2 using short-read, whole-exome capture data, illustrating the potential for cost-effective multilocus genotyping at colony scale. These results mark a significant enhancement for biomedical research in MCMs and underscore the feasibility of broad-scale genetic investigations.
毛里求斯长尾猕猴(MCMs)由于其独特的遗传同质性,简化了实验设计,成为生物医学研究中强有力的非人类灵长类动物模型。尽管它们被广泛使用,但由于缺乏详细的基因组参考组装,对关键免疫调节基因家族,特别是杀伤细胞免疫球蛋白样受体(KIR)和自然杀伤细胞组 2(NKG2)的全面了解受到了阻碍。在这项研究中,我们采用先进的长读测序技术,完全组装了 8 个 KIR 和 7 个 NKG2 基因组单倍型,深入了解了这些免疫调节基因簇的结构和等位基因多样性。利用这些基因组资源,我们提出了一种使用短读、全外显子捕获数据进行 KIR 和 NKG2 基因分型的策略,展示了在群体水平上进行经济高效的多位点基因分型的潜力。这些结果标志着 MCMs 生物医学研究的重大进展,并强调了广泛遗传研究的可行性。