Academic Journal
Genetic diversity of 1,845 rhesus macaques improves genetic variation interpretation and identifies disease models
| Title: | Genetic diversity of 1,845 rhesus macaques improves genetic variation interpretation and identifies disease models |
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| Authors: | Jun Wang, Meng Wang, Ala Moshiri, R. Alan Harris, Muthuswamy Raveendran, Tracy Nguyen, Soohyun Kim, Laura Young, Keqing Wang, Roger Wiseman, David H. O’Connor, Zach Johnson, Melween Martinez, Michael J. Montague, Ken Sayers, Martha Lyke, Eric Vallender, Tim Stout, Yumei Li, Sara M. Thomasy, Jeffrey Rogers, Rui Chen |
| Source: | Nature Communications, Vol 15, Iss 1, Pp 1-12 (2024) |
| Publisher Information: | Nature Portfolio, 2024. |
| Publication Year: | 2024 |
| Collection: | LCC:Science |
| Subject Terms: | Science |
| More Details: | Abstract 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. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2041-1723 |
| Relation: | https://doaj.org/toc/2041-1723 |
| DOI: | 10.1038/s41467-024-49922-6 |
| Access URL: | https://doaj.org/article/3f3b441ea78049f683562adc440c2848 |
| Accession Number: | edsdoj.3f3b441ea78049f683562adc440c2848 |
| Database: | Directory of Open Access Journals |
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