Genetic diversity of 1,845 rhesus macaques improves genetic variation interpretation and identifies disease models.

Autor: Wang J; Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA., Wang M; Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA., Moshiri A; Department of Ophthalmology & Vision Science, School of Medicine, UC Davis, Sacramento, California, USA., Harris RA; Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA., Raveendran M; Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA., Nguyen T; Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, California, USA., Kim S; Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, California, USA., Young L; Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, California, USA., Wang K; Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA., Wiseman R; Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin, USA., O'Connor DH; Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin, USA., Johnson Z; Emory National Primate Research Center, Emory University, Atlanta, Georgia, USA., Martinez M; Caribbean Primate Research Center, University of Puerto Rico, Punta Santiago, Humacao, Puerto Rico., Montague MJ; Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Sayers K; Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, Texas, USA., Lyke M; Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, Texas, USA., Vallender E; Tulane National Primate Research Center, Tulane university, Covington, Louisiana, USA., Stout T; Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, Texas, USA., Li Y; Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA., Thomasy SM; Department of Ophthalmology & Vision Science, School of Medicine, UC Davis, Sacramento, California, USA.; Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, California, USA.; California National Primate Research Center, University of California-Davis, Davis, California, USA., Rogers J; Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA., Chen R; Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA. ruichen@bcm.edu.; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA. ruichen@bcm.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Jul 05; Vol. 15 (1), pp. 5658. Date of Electronic Publication: 2024 Jul 05.
DOI: 10.1038/s41467-024-49922-6
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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