GENETIC MANAGEMENT OF CHIMPANZEES IN BIOMEDICAL RESEARCH

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Chimpanzees are important animal models in biomedical research. Genetic management can be used to maximize the value of these animals for both breeding and research. To date, genetic management programs have assessed genetic variation from genetic markers. However, quantitative traits also can be used to estimate underlying genetic variability. Almost every colony has a wealth of quantitative trait data in the form of routinely collected clinical measures that could be used in genetic management. The goal of the proposed project is to develop techniques for research-oriented genetic management using the Southwest Foundation for Biomedical Research (SFBR) chimpanzee colony as a model population. These techniques could be readily applied to other colonies of nonhuman primates. The objectives of the research are 1) to develop and evaluate techniques of quantitative genetics as tools for managing primate colonies, 2) to search for the influence of major gene loci on clinical measurements commonly made on primates used in biomedical research, and 3) to use the generated data to develop management strategies that will maximize production of animals suitable for research while minimizing loss of genetic variability. Specifically, the colony will be characterized for 15-20 polymorphic markers. These data will be used to validate pedigrees and directly assess genetic variability in the colony. Quantitative genetic analysis, complex segregation analysis, and measured genotype analysis will be performed on serial clinical chemistry data, hematological measures, and body weights to assess quantitative genetic variation. Methods will be developed to utilize heritable quantitative trait information in management decision making. As an example of the relevance of these techniques for research, the genetic components of liver function response to hepatitis C infection will be determined. Based on data generated in previous steps, new methods will be developed to include pedigree relationships and genetic information in experimental animal selection procedures. Computer simulation will be used to assess the impact of such selection strategies on the future viability of the colony. This project will provide new general tools for using widely available quantitative trait and pedigree data in the genetic management of nonhuman primate colonies, and will extend our knowledge of the genetic determinants of physiological variation.