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Letter

Nature Genetics 37, 1253–1257 (1 November 2005) | doi:10.1038/ng1660

Negative epistasis between the malaria-protective effects of |[alpha]|+-thalassemia and the sickle cell trait

Thomas N Williams , Tabitha W Mwangi , Sammy Wambua , Timothy E A Peto , David J Weatherall , Sunetra Gupta , Mario Recker , Bridget S Penman , Sophie Uyoga , Alex Macharia , Jedidah K Mwacharo , Robert W Snow & Kevin Marsh

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.