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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
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: |
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| 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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