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

Fry, A. E., Ghansa, A., Small, K. S., Palma, A., Auburn, S., Diakite, M., Green, A., Campino, S., Teo, Y. Y., Clark, T. G., Jeffreys, A. E., Wilson, J., Jallow, M., Sisay-Joof, F., Pinder, M., Griffiths, M. J., Peshu, N., Williams, T. N., Newton, C. R., Marsh, Kevin, Molyneux, Malcolm E, Taylor, T. E., Koram, K. A., Oduro, A. R., Rogers, W. O., Rockett, K. A., Sabeti, P. C. and Kwiatkowski, D. P. (2009) 'Positive selection of a CD36 nonsense variant in sub-Saharan Africa, but no association with severe malaria phenotypes'. Human Molecular Genetics, Vol 18, Issue 14, pp. 2683-2692.

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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.

Item Type: Article
Additional Information: Fry, Andrew E. Ghansa, Anita Small, Kerrin S. Palma, Alejandro Auburn, Sarah Diakite, Mahamadou Green, Angela Campino, Susana Teo, Yik Y. Clark, Taane G. Jeffreys, Anna E. Wilson, Jonathan Jallow, Muminatou Sisay-Joof, Fatou Pinder, Margaret Griffiths, Michael J. Peshu, Norbert Williams, Thomas N. Newton, Charles R. Marsh, Kevin Molyneux, Malcolm E. Taylor, Terrie E. Koram, Kwadwo A. Oduro, Abraham R. Rogers, William O. Rockett, Kirk A. Sabeti, Pardis C. Kwiatkowski, Dominic P.
Subjects: WA Public Health > WA 30 Socioeconomic factors in public health (General)
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
WA Public Health > Health Problems of Special Population Groups > WA 395 Health in developing countries
QX Parasitology > Insects. Other Parasites > QX 650 Insect vectors
QX Parasitology > Insects. Other Parasites > QX 515 Anopheles
WB Practice of Medicine > Medical Climatology > WB 710 Diseases of geographic areas
QX Parasitology > QX 4 General works
QX Parasitology > Insects. Other Parasites > QX 510 Mosquitoes
QX Parasitology > QX 45 Host-parasite relations
Faculty: Department: Groups (2002 - 2012) > Clinical Group
Digital Object Identifer (DOI): https://doi.org/10.1093/hmg/ddp192
Depositing User: Users 43 not found.
Date Deposited: 28 May 2010 15:40
Last Modified: 06 Feb 2018 12:59
URI: http://archive.lstmed.ac.uk/id/eprint/271

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