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Negative epistasis between the malaria-protective effects of α+-thalassemia and the sickle cell trait

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Williams, Thomas N., Mwangi, Tabitha W., Wambua, Sammy, Peto, Timothy E. A., Weatherall, David J., Gupta, Sunetra, Recker, Mario, Penman, Bridget S., Uyoga, Sophie, Macharia, Alex, Mwacharo, Jedidah K., Snow, Robert W. and Marsh, Kevin. (2005) Negative epistasis between the malaria-protective effects of α+-thalassemia and the sickle cell trait. Nature Genetics, 37 (11). pp. 1253-1257. doi:10.1038/ng1660

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Official URL: http://dx.doi.org/10.1038/ng1660

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Abstract

The hemoglobinopathies, disorders of hemoglobin structure and production, protect against death from malaria1. In sub-Saharan Africa, two such conditions occur at particularly high frequencies: presence of the structural variant hemoglobin S and alpha+-thalassemia, a condition characterized by reduced production of the normal alpha-globin component of hemoglobin. Individually, each is protective against severe Plasmodium falciparum malaria2, 3, 4, but little is known about their malaria-protective effects when inherited in combination. We investigated this question by studying a population on the coast of Kenya and found that the protection afforded by each condition inherited alone was lost when the two conditions were inherited together, to such a degree that the incidence of both uncomplicated and severe P. falciparum malaria was close to baseline in children heterozygous with respect to the mutation underlying the hemoglobin S variant and homozygous with respect to the mutation underlying alpha+-thalassemia. Negative epistasis could explain the failure of alpha+-thalassemia to reach fixation in any population in sub-Saharan Africa.

Item Type: Journal Article
Divisions: Faculty of Science > Mathematics
Journal or Publication Title: Nature Genetics
Publisher: Nature Publishing Group
ISSN: 1061-4036
Official Date: 2005
Dates:
DateEvent
2005Published
Volume: 37
Number: 11
Page Range: pp. 1253-1257
DOI: 10.1038/ng1660
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Restricted or Subscription Access

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