The 84th Annual Meeting of the American Association of Physical Anthropologists (2015)


Immunogenetic regulatory variation associated with parasite infection in the Ugandan red colobus

NOAH D. SIMONS1, MARIA J. RUIZ-LOPEZ2, COLIN A. CHAPMAN3,4, TONY L. GOLDBERG4,5, KIRSTIN N. STERNER1 and NELSON TING1,2.

1Department of Anthropology, University of Oregon, 2Institute of Ecology and Evolution, University of Oregon, 3Department of Anthropology and School of Environment, McGill University, 4Makerere University Biological Field Station, Makerere University, Uganda, 5Department of Pathobiological Sciences, University of Wisconsin-Madison

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Primates have co-evolved with their pathogens, and this is evident in immune processes. While research in this area has primarily focused on protein-coding regions of the genome, the role of regulatory genetic variation in controlling an organism’s immune response to infection remains largely unstudied. We tested associations between the core promoters of two immune-related genes and gastro-intestinal helminth infection intensity in the Ugandan red colobus at Kibale National Park, Uganda. Our two candidate genes were IL-4 and MHC-DQA1, both of which have known associations with gastro-intestinal helminth infection, and we focused on the whipworm parasite (Trichuris), which has known fitness consequences in humans. We sequenced core promoters of both genes in 31 Ugandan red colobus and reconstructed individual haplotypes. While the core promoter of IL-4 contained no variation, fifteen individual regulatory variants were identified in the functionally important transcription factor binding sites of the MHC-DQA1 core promoter. Genotypes for each SNP were tested for associations with shedding of whipworm (Trichuris sp) eggs in feces using a generalized linear model. Our results identified two functional regulatory variants associated with increased shedding for the heterozygote genotype (SNP-121, p = 0.007, and SNP-197, p = 0.012). This pattern of heterozygote disadvantage is consistent with allelic expression imbalance, whereby differential expression of alleles in heterozygotes is associated with a deleterious disease phenotype. This work highlights the importance of regulatory genetic variation in determining disease susceptibility in primates, as well as the underlying role of gene expression in explaining variation in parasite shedding intensity.