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===========================================

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI037091-08
Application #
6896778
Study Section
Genome Study Section (GNM)
Program Officer
Rao, Malla R
Project Start
1995-08-01
Project End
2007-05-31
Budget Start
2005-06-01
Budget End
2007-05-31
Support Year
8
Fiscal Year
2005
Total Cost
$667,685
Indirect Cost
Name
Texas Biomedical Research Institute
Department
Type
DUNS #
007936834
City
San Antonio
State
TX
Country
United States
Zip Code
78245
Williams, Kimberly D; Blangero, John; Subedi, Janardan et al. (2013) Nonsyndromic brachydactyly type D and type E mapped to 7p15 in healthy children and adults from the Jirel ethnic group in eastern Nepal. Am J Hum Biol 25:743-50
Williams-Blangero, Sarah; Criscione, Charles D; VandeBerg, John L et al. (2012) Host genetics and population structure effects on parasitic disease. Philos Trans R Soc Lond B Biol Sci 367:887-94
Williams, Kimberly D; Nahhas, Ramzi W; Cottom, Carol R et al. (2012) Evaluation of qualitative methods for phenotyping brachymesophalangia-V from radiographs of children. Am J Hum Biol 24:68-73
Criscione, Charles D; Anderson, Joel D; Sudimack, Dan et al. (2010) Landscape genetics reveals focal transmission of a human macroparasite. PLoS Negl Trop Dis 4:e665
Williams-Blangero, Sarah; Vandeberg, John L; Subedi, Janardan et al. (2008) Two quantitative trait loci influence whipworm (Trichuris trichiura) infection in a Nepalese population. J Infect Dis 197:1198-203
Williams-Blangero, Sarah; Vandeberg, John L; Subedi, Janardan et al. (2008) Localization of multiple quantitative trait loci influencing susceptibility to infection with Ascaris lumbricoides. J Infect Dis 197:66-71
Criscione, Charles D; Anderson, Joel D; Sudimack, Dan et al. (2007) Disentangling hybridization and host colonization in parasitic roundworms of humans and pigs. Proc Biol Sci 274:2669-77
Criscione, Charles D; Anderson, Joel D; Raby, Kyle et al. (2007) Microsatellite markers for the human nematode parasite Ascaris lumbricoides: development and assessment of utility. J Parasitol 93:704-8
Williams-Blangero, Sarah; Blangero, John (2006) Collection of pedigree data for genetic analysis in isolate populations. Hum Biol 78:89-101
Kunwar, C B; Chapagain, R H; Subba, B et al. (2006) Occurrence of soil-transmitted helminths in women at the Himalayan region of Nepal. Kathmandu Univ Med J (KUMJ) 4:444-7

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