Rhesus macaques (Macaca mulatta) are the most widely used nonhuman primates in biomedical research. This species is critically important in efforts to understand the causes and potential new treatments for many human diseases. Rhesus macaques are a premier model organism for the study of the pathogenesis of HIV-AIDS, and for development of novel treatments and new vaccines against HIV infection. In addition, rhesus macaques are commonly used in studies of basic neurobiology, risk factors for psychiatric illnesses such as anxiety disorders and depression, metabolic diseases such as diabetes and osteoporosis, and reproductive biology. This project will dramatically increase the value and impact of this laboratory primate species for all types of biomedical research by generating a substantial amount of new information about genetic variation within the species. It is well established that genetic differences among people influence their risk of developing many, probably most, diseases including those listed above. Genetic variation can also influence the progression of disease and the responses of different people to a specific treatment. We will facilitate research concerning the genetic basis of disease susceptibility and response to treatment by identifying large numbers of new DNA sequence variants in functional genes and intervening sequences within the rhesus genome. To accomplish this, we will produce high-quality whole genome DNA sequence data for 433 rhesus macaques. The sequence data will be used to identify currently unknown DNA sequence variation present in this species, including single nucleotide variants, small indels, CNVs and other variants. The study subjects will be animals already characterized for one or more disease-related phenotypes, such as vaccine protection against SIV-AIDS, neurobiological traits, behavioral traits, metabolic disorders such as diabetes or polycystic ovary syndrome, and gastrointestinal diseases. By sequencing these animals, we will generate BOTH general information about variation across the macaque genome and specific information beneficial to the investigators who have phenotypically characterized these animals and contributed these DNA samples. All the data generated will be made publicly available through appropriate NIH and NPRC databases.

Public Health Relevance

This project will advance and facilitate research in various fields by generating a large amount of novel, valuable information about genetic variation within rhesus macaques. This species is important for research related to many different human health problems. Increased knowledge of genetic variation in this species will allow researchers to conduct innovative studies of genetic effects on human health and disease using this model organism.

Agency
National Institute of Health (NIH)
Institute
Office of The Director, National Institutes of Health (OD)
Type
Resource-Related Research Projects (R24)
Project #
5R24OD011173-06
Application #
9114686
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Zou, Sige
Project Start
2011-09-01
Project End
2018-05-31
Budget Start
2016-06-01
Budget End
2017-05-31
Support Year
6
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Baylor College of Medicine
Department
Genetics
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030
Rogers, Jeffrey (2018) The behavioral genetics of nonhuman primates: Status and prospects. Am J Phys Anthropol 165 Suppl 65:23-36
Dray, Beth K; Raveendran, Muthuswamy; Harris, R Alan et al. (2018) Mismatch repair gene mutations lead to lynch syndrome colorectal cancer in rhesus macaques. Genes Cancer 9:142-152
Bimber, Benjamin N; Ramakrishnan, Ranjani; Cervera-Juanes, Rita et al. (2017) Whole genome sequencing predicts novel human disease models in rhesus macaques. Genomics 109:214-220
Xue, Cheng; Raveendran, Muthuswamy; Harris, R Alan et al. (2016) The population genomics of rhesus macaques (Macaca mulatta) based on whole-genome sequences. Genome Res 26:1651-1662
Rio Deiros, David; Gibbs, Richard A; Rogers, Jeffrey (2016) DNAism: exploring genomic datasets on the web with Horizon Charts. BMC Bioinformatics 17:49
Zhdanova, Irina V; Rogers, Jeffrey; González-Martínez, Janis et al. (2016) The ticking clock of Cayo Santiago macaques and its implications for understanding human circadian rhythm disorders. Am J Primatol 78:117-26
Xue, Cheng; Chen, Hua; Yu, Fuli (2016) Base-Biased Evolution of Disease-Associated Mutations in the Human Genome. Hum Mutat 37:1209-1214
Yuan, Bo; Liu, Pengfei; Gupta, Aditya et al. (2015) Comparative Genomic Analyses of the Human NPHP1 Locus Reveal Complex Genomic Architecture and Its Regional Evolution in Primates. PLoS Genet 11:e1005686
Rogers, Jeffrey; Gibbs, Richard A (2014) Comparative primate genomics: emerging patterns of genome content and dynamics. Nat Rev Genet 15:347-59
Phillips, Kimberley A; Bales, Karen L; Capitanio, John P et al. (2014) Why primate models matter. Am J Primatol 76:801-27

Showing the most recent 10 out of 11 publications