Forward and reverse genomic screens enhance the understanding of phenotypic variation in a large Chinese rhesus macaque cohort

Bao-Lin Zhang, Yongxuan Chen, Yali Zhang, Yicheng Qiao, Yang Wu, Yi Zhang, Yizheng Lu, Xinran You, Yanling Li, Hong-Di Huang, Qiong Wang, Yijiang Li, Yun Wang, Wenxian Xiao, Hexian Duan, Ming-Hao Qiu, Nan-Hui Chen, Xiaomei Yu, Min-Min Yang, Longbao Lv, David N. Cooper, Ping Zheng, Yong-Gang Yao (), Ning Liu (), Jian-Hong Wang () and Dong-Dong Wu ()
Additional contact information
Bao-Lin Zhang: Chinese Academy of Sciences
Yongxuan Chen: Chinese Academy of Sciences
Yali Zhang: Chinese Academy of Sciences
Yicheng Qiao: University of Chinese Academy of Sciences
Yang Wu: West China Hospital of Sichuan University
Yi Zhang: Chinese Academy of Sciences
Yizheng Lu: Chinese Academy of Sciences
Xinran You: Chinese Academy of Sciences
Yanling Li: Chinese Academy of Sciences
Hong-Di Huang: Chinese Academy of Sciences
Qiong Wang: Chinese Academy of Sciences
Yijiang Li: Chinese Academy of Sciences
Yun Wang: Chinese Academy of Sciences
Wenxian Xiao: Chinese Academy of Sciences
Hexian Duan: Chinese Academy of Sciences
Ming-Hao Qiu: Chinese Academy of Sciences
Nan-Hui Chen: Chinese Academy of Sciences
Xiaomei Yu: Chinese Academy of Sciences
Min-Min Yang: Chinese Academy of Sciences
Longbao Lv: Chinese Academy of Sciences
David N. Cooper: Cardiff University
Ping Zheng: Chinese Academy of Sciences
Yong-Gang Yao: Chinese Academy of Sciences
Ning Liu: University of Chinese Academy of Sciences
Jian-Hong Wang: Chinese Academy of Sciences
Dong-Dong Wu: Chinese Academy of Sciences

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: Abstract Combining genotype and phenotype data promises to greatly increase the value of macaque as biomedical models for human disease. Here we launch the Macaque Biobank project by deeply sequencing 919 captive Chinese rhesus macaques (CRM) while assessing 52 phenotypic traits. Genomic analyses reveal the captive CRMs are a mixture of multiple wild sources and exhibit significantly lower mutational load than their Indian counterparts. We identify hundreds of loss-of-function variants linked to human inherited disease and drug targets, and at least seven exert significant effects on phenotypes using forward genomic screens. Genome-wide association analyses reveal 30 independent loci associated with phenotypic variations. Using reverse genomic approaches, we identify DISC1 (p.Arg517Trp) as a genetic risk factor for neuropsychiatric disorders, with macaques carrying this deleterious allele exhibiting impairments in working memory and cortical architecture. This study demonstrates the potential of macaque cohorts for the investigation of genotype-phenotype relationships and exploring potential spontaneous models of human genetic disease.

Date: 2025
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DOI: 10.1038/s41467-025-63747-x

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