SOUTHWEST FOUNDATION FOR BIOMEDICAL RESEARCH
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Baboon Model for the Genetics of Chagas Disease

 Chagas disease is a zoonotic disease found throughout Central and South America. The protozoan parasite Trypanosoma 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 e ective drugs for prophylaxis or therapy. It is estimated that at least 100,000 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 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. We propose to develop the baboon as a primate model for studying the genetics of Chagas disease in humans. We will quantify the effect of environmental and genetic factors in determining seropositivity to T.cruzi in the pedigreed colony of baboons. We will determine how genetic effects interact with aspects of the host environment such as shared sire environment, common cage environment, and cage cohabitation history. We will contrast age- and sex-specific prevalences of seropositivity to T. cruzi in caged and corraled baboons in the same macroenvironment to determine if these caging practices a ect the rate of infection. We will perform a genome linkage scan to identify regions of the baboon genome that affect susceptibility to infection by T.cruzi as evidenced by seroconversion. Finally, we will use a novel method for joint linkage and linkage disequilibrium analysis to fine-map linkage regions and identify specific candidate genes that affect infection with T.cruzi.