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- Title
Negative epistasis between the malaria-protective effects of α<sup>+</sup>-thalassemia and the sickle cell trait.
- Authors
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.; Marsh, Kevin
- Abstract
The hemoglobinopathies, disorders of hemoglobin structure and production, protect against death from malaria. In sub-Saharan Africa, two such conditions occur at particularly high frequencies: presence of the structural variant hemoglobin S and α+-thalassemia, a condition characterized by reduced production of the normal α-globin component of hemoglobin. Individually, each is protective against severe Plasmodium falciparum malaria, 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 α+-thalassemia. Negative epistasis could explain the failure of α+-thalassemia to reach fixation in any population in sub-Saharan Africa.
- Publication
Nature Genetics, 2005, Vol 37, Issue 11, p1253
- ISSN
1061-4036
- Publication type
Academic Journal
- DOI
10.1038/ng1660