Chagas' disease is a zoonotic disease found throughout Central and South America. The protozoan parasite T. cruzi, the causative agent of Chagas' disease, is estimated to infect 16-18 million people, and approximately 100 million are at risk of infection. Chagas' disease is the leading cause of heart disease in Latin America-about 30-40% of those infected will ultimately have some degree of cardiac involvement. There are no vaccines and no safe and effective drugs for prophylaxis or therapy. It is estimated that at least 100,00 infected persons reside in the United States raising public health concerns regarding the safety of blood and tissue banks. A critical problem for research on Chagas' disease is the lack of a suitable model organism that mimics the disease process in humans. At the Southwest Regional Primate Research Center (SRPRC) a large, pedigreed colony of baboons, many of which are naturally infected with T. cruzi, provides an ideal model system for investigating the genetics of susceptibility to infection with T. cruzi. It is proposed to develop the baboon as a primate model for studying the genetics of Chagas' disease in humans. The effect of environmental and genetic factors in determining seropositivity to T. cruzi in the pedigreed colony of baboons will be quantified. How genetic effects interact with aspects of the host environment such as shared sire environment, common cage environment, and cage cohabitation history will be determined. Age- and sex-specific prevalence of seropositivity to T. cruzi in caged and corralled baboons in the same macroenvironment will be contrasted to determine if these caging practices affect the rare infection. A genome linkage scan will be performed to identify regions of the baboon genome that effect susceptibility to infection by T. cruzi as evidenced by seroconversion. Finally, a novel method will be used for joint linkage and linkage disequilibrium analysis to fine-map linkage regions and identify specific candidate genes that affect infection with T. cruzi.
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