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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Negative epistasis between the malaria-protective effects of α
+
-thalassemia and the sickle cell trait
Nature Genetics, Volume 37, No. 11, Year 2005
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Description
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. © 2005 Nature Publishing Group.
Authors & Co-Authors
Williams, Thomas Neil
Kenya, Kilifi
Centre for Geographic Medicine Research
United Kingdom, Oxford
John Radcliffe Hospital
Mwangi, Tabitha Wanja
Kenya, Kilifi
Centre for Geographic Medicine Research
United Kingdom, Oxford
John Radcliffe Hospital
Wambua, Sammy
Kenya, Kilifi
Centre for Geographic Medicine Research
Peto, Timothy E.A.
United Kingdom, Oxford
John Radcliffe Hospital
Weatherall, David J.
United Kingdom, Oxford
John Radcliffe Hospital
Gupta, Sunetra
United Kingdom, Oxford
University of Oxford
Recker, Mario
United Kingdom, Oxford
University of Oxford
Penman, Bridget S.
United Kingdom, Oxford
University of Oxford
Uyoga, Sophie M.
Kenya, Kilifi
Centre for Geographic Medicine Research
Macharia, Alex W.
Kenya, Kilifi
Centre for Geographic Medicine Research
Mwacharo, Jedidah K.
Kenya, Kilifi
Centre for Geographic Medicine Research
Snow, Robert William
Kenya, Kilifi
Centre for Geographic Medicine Research
United Kingdom, Oxford
John Radcliffe Hospital
Marsh, Kevin
Kenya, Kilifi
Centre for Geographic Medicine Research
United Kingdom, Oxford
John Radcliffe Hospital
Statistics
Citations: 255
Authors: 13
Affiliations: 3
Identifiers
Doi:
10.1038/ng1660
ISSN:
10614036
e-ISSN:
15461718
Research Areas
Cancer
Genetics And Genomics
Infectious Diseases
Maternal And Child Health
Study Design
Cross Sectional Study
Cohort Study
Study Locations
Kenya