EXCEED THE SPACE PROVIDED. Ascaris lumbricoides infection is a major international health problem. During the initial funding period of this project, we determined that between 30% and 50% of the variation in roundworm burden in the Jirel population is attributable to genetic factors. In addition, we found suggestive evidence for potential host-parasite genetic interactions. Since the last submission of this renewal application, we have completed a lOcM genome scan of 444 members of the Jirel population. This scan provided clear evidence of two linkage signals for genes influencing susceptibility to Ascaris infection on chromosomes 1and 13,and one suggestive signal on chromosome 8. This renewal application will follow up on these exciting findings by testing for linkage with candidate genes to identify the specific host genes involved in determining differential susceptibility to infection with A. lumbricoides, assessing genetic variation in the parasite populations, and examining the interactions between host genetic variation and parasite genetic variation influencing differential worm loads in the host population. We propose to sample 2000 individuals belonging to a single pedigree in the Jirel population. Power analyses indicate that this large and complex pedigree sample will have ample statistical power to resolve host-parasite interaction effects. All 2000 indiv:duals will be sampled over a 4 year period to collect blood samples and 96 hour fecal samples following treatment with albendazole for assessment of worm burdens. Genetic polymorphisms will be typed in about seven positional candidate gene regions selected on the basis of genome scan results in the human population, and at 60 loci in the parasite population. This study will be the first explicit evaluation of the simultaneous effects of host and parasite genetic factors on variation in worm burden traits associated with Ascaris lumbricoides infection. PERFORMANCE SITE ========================================Section End===========================================
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