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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Positive selection of a CD36 nonsense variant in sub-Saharan Africa, but no association with severe malaria phenotypes
Human Molecular Genetics, Volume 18, No. 14, Year 2009
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Description
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. © 2009 The Author(s).
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC2701331/bin/ddp192_index.html
https://efashare.b-cdn.net/share/pmc/articles/PMC2701331/bin/ddp192_1.pdf
Authors & Co-Authors
Fry, Andrew E.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Ghansa, Anita
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Ghana, Accra
Noguchi Memorial Institute for Medical Research
Small, Kerrin S.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Palma, Alejandro A.
United States, Cambridge
Broad Institute
Auburn, Sarah A.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
United Kingdom, London
Wellcome Trust
Diakité, Mahamadou L.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Green, Angie L.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Campino, Susana G.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
United Kingdom, London
Wellcome Trust
Teo, Yik Ying
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Clark, Taane Gregory
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
United Kingdom, London
Wellcome Trust
Jeffreys, Anna E.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Wilson, Jonathan N.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Jallow, Muminatou
Gambia, Banjul
Medical Research Council Laboratories Gambia
Sisay-Joof, Fatoumatta
Gambia, Banjul
Medical Research Council Laboratories Gambia
Pinder, Margaret
Gambia, Banjul
Medical Research Council Laboratories Gambia
Griffiths, Michael John
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Kenya, Nairobi
Kenya Medical Research Institute
Peshu, Norbert M.
Kenya, Nairobi
Kenya Medical Research Institute
Williams, Thomas Neil
Kenya, Nairobi
Kenya Medical Research Institute
United Kingdom, Oxford
John Radcliffe Hospital
Newton, Charles R.J.C.
Kenya, Nairobi
Kenya Medical Research Institute
United Kingdom, London
Ucl Great Ormond Street Institute of Child Health
Marsh, Kevin
Kenya, Nairobi
Kenya Medical Research Institute
United Kingdom, Oxford
John Radcliffe Hospital
Molyneux, Malcolm Edward
Malawi, Blantyre
Malawi-liverpool-wellcome Trust Clinical Research Programme
United Kingdom, Liverpool
Liverpool School of Tropical Medicine
Taylor, Terrie Ellen
Malawi, Zomba
University of Malawi
United States, East Lansing
Msu College of Osteopathic Medicine
Koram, Kwadwo A.
Ghana, Accra
Noguchi Memorial Institute for Medical Research
Oduro, Abraham Rexford
Ghana, Navrongo
Navrongo Health Research Center
Rogers, William Oscar
Indonesia, Jakarta
U.s. Naval Medical Research Unit No. 2, Jakarta
Rockett, Kirk A.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Sabeti., Pardis C.
United States, Cambridge
Broad Institute
United States, Cambridge
Harvard University
Kwiatkowski, Dominic P.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
United Kingdom, London
Wellcome Trust
Statistics
Citations: 79
Authors: 28
Affiliations: 15
Identifiers
Doi:
10.1093/hmg/ddp192
ISSN:
09646906
e-ISSN:
14602083
Research Areas
Cancer
Genetics And Genomics
Infectious Diseases
Study Design
Cross Sectional Study
Case-Control Study
Study Locations
Nigeria