FINDING GENES FOR COMPLEX, AGE-RELATED CHANGES IN NONHUMAN PRIMATES: THE PEDIGREED BABOON MODEL
M.C. Mahaney
Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, Texas 78245-0549, USA.
Aging is a complex, multifactorial process characterized by intrinsic, progressive, reductions in function occurring from maturity to death. Non-human primates, particularly members of the superfamily Cercopithecoidea (Old World monkeys), may represent animal models for human aging and longevity that biologically are more relevant than rodents or insects (for example) and which have life-history characteristics making them relatively tractable for genetic studies. Over 20 years of effort at the Southwest Foundation for Biomedical Research (and its recently created affiliate, the Southwest Regional Primate Research Center) has led to the establishment of the pedigreed baboon (Papio hamadryas) a model organism for detection, characterization, localization, and identification of genes influencing normal, quantitative variation in complex, multifactorial phenotypes. This work has entailed creation and management of large, non-inbred, multigenerational pedigrees of baboons who are bred randomly with respect to phenotype; development and implementation of specialized computer-based approaches for the management of pedigree data; development of efficient and reliable facilities and protocols for large-scale molecular genetics/genomics; development of innovative statistical genetic methods to facilitate the analysis and interpretation of pedigree, phenotype, genotype, and DNA sequence data; and establishment of computing resources with sufficient processing capacity and speed to implement these methods. To date, we have exploited these resources successfully to localize and characterize genes influencing variation in a wide variety of processes, including lipoprotein metabolism and dietary response, bone mineral density and turnover, platelet function and hemostasis, sodium-lithium counter-transport and blood pressure regulation, and reproductive endocrinology -- all with implications for human health and disease. In addition, we are conducting genetic studies of body composition, dental morphology and development, glucose metabolism, neurotransmitter levels and behavior, and susceptibility to infection. One of our newer endeavors is a collaborative research project that proposes to detect, characterize, and localize genes contributing to normal variation in biomarkers of aging and senescence in these pedigreed baboons. Preliminary observations of this collaboration include detection of a significant additive genetic component to longevity. We offer our work with the pedigreed baboon -- past, current, and proposed -- as one example of how colonies of nonhuman primates might be utilized to dissect the complex, multifactorial process that is aging.
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