Dataset Information

Positive selection of a CD36 nonsense variant in sub-Saharan Africa, but no association with severe malaria phenotypes.

ABSTRACT: The prevalence of CD36 deficiency in East Asian and African populations suggests that the causal variants are under selection by severe malaria. Previous analysis of data from the International HapMap Project indicated that a CD36 haplotype bearing a nonsense mutation (T1264G; rs3211938) had undergone recent positive selection in the Yoruba of Nigeria. To investigate the global distribution of this putative selection event, we genotyped T1264G in 3420 individuals from 66 populations. We confirmed the high frequency of 1264G in the Yoruba (26%). However, the 1264G allele is less common in other African populations and absent from all non-African populations without recent African admixture. Using long-range linkage disequilibrium, we studied two West African groups in depth. Evidence for recent positive selection at the locus was demonstrable in the Yoruba, although not in Gambians. We screened 70 variants from across CD36 for an association with severe malaria phenotypes, employing a case-control study of 1350 subjects and a family study of 1288 parent-offspring trios. No marker was significantly associated with severe malaria. We focused on T1264G, genotyping 10,922 samples from four African populations. The nonsense allele was not associated with severe malaria (pooled allelic odds ratio 1.0; 95% confidence interval 0.89-1.12; P = 0.98). These results suggest a range of possible explanations including the existence of alternative selection pressures on CD36, co-evolution between host and parasite or confounding caused by allelic heterogeneity of CD36 deficiency.

SUBMITTER: Fry AE

PROVIDER: S-EPMC2701331 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature

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Positive selection of a CD36 nonsense variant in sub-Saharan Africa, but no association with severe malaria phenotypes.

Fry Andrew E AE Ghansa Anita A Small Kerrin S KS Palma Alejandro A Auburn Sarah S Diakite Mahamadou M Green Angela A Campino Susana S Teo Yik Y YY Clark Taane G TG Jeffreys Anna E AE Wilson Jonathan J Jallow Muminatou M Sisay-Joof Fatou F Pinder Margaret M Griffiths Michael J MJ Peshu Norbert N Williams Thomas N TN Newton Charles R CR Marsh Kevin K Molyneux Malcolm E ME Taylor Terrie E TE Koram Kwadwo A KA Oduro Abraham R AR Rogers William O WO Rockett Kirk A KA Sabeti Pardis C PC Kwiatkowski Dominic P DP

Human molecular genetics 20090429 14

The prevalence of CD36 deficiency in East Asian and African populations suggests that the causal variants are under selection by severe malaria. Previous analysis of data from the International HapMap Project indicated that a CD36 haplotype bearing a nonsense mutation (T1264G; rs3211938) had undergone recent positive selection in the Yoruba of Nigeria. To investigate the global distribution of this putative selection event, we genotyped T1264G in 3420 individuals from 66 populations. We confirme ...[more]

PMID: 19403559

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Dataset Information

Positive selection of a CD36 nonsense variant in sub-Saharan Africa, but no association with severe malaria phenotypes.

Publications

Positive selection of a CD36 nonsense variant in sub-Saharan Africa, but no association with severe malaria phenotypes.

Similar Datasets

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