- Wang, Jun;
- Wang, Meng;
- Moshiri, Ala;
- Harris, R Alan;
- Raveendran, Muthuswamy;
- Nguyen, Tracy;
- Kim, Soohyun;
- Young, Laura;
- Wang, Keqing;
- Wiseman, Roger;
- O’Connor, David H;
- Johnson, Zach;
- Martinez, Melween;
- Montague, Michael J;
- Sayers, Ken;
- Lyke, Martha;
- Vallender, Eric;
- Stout, Tim;
- Li, Yumei;
- Thomasy, Sara M;
- Rogers, Jeffrey;
- Chen, Rui
Understanding and treating human diseases require valid animal models. Leveraging the genetic diversity in rhesus macaque populations across eight primate centers in the United States, we conduct targeted-sequencing on 1845 individuals for 374 genes linked to inherited human retinal and neurodevelopmental diseases. We identify over 47,000 single nucleotide variants, a substantial proportion of which are shared with human populations. By combining rhesus and human allele frequencies with established variant prediction methods, we develop a machine learning-based score that outperforms established methods in predicting missense variant pathogenicity. Remarkably, we find a marked number of loss-of-function variants and putative deleterious variants, which may lead to the development of rhesus disease models. Through phenotyping of macaques carrying a pathogenic OPA1:p.A8S variant, we identify a genetic model of autosomal dominant optic atrophy. Finally, we present a public website housing variant and genotype data from over two thousand rhesus macaques.