Negative epistasis between α + thalassaemia and sickle cell trait can explain interpopulation variation in South Asia

Abstract

Recent studies in Kenya and Ghana have shown that individuals who inherit two malaria-protective genetic disorders of haemoglobin-α + thalassaemia and sickle cell trait-experience a much lower level of malaria protection than those who inherit sickle cell trait alone. We have previously demonstrated that this can limit the frequency of α + thalassaemia in a population in which sickle cell is present, which may account for the frequency of α + thalassaemia in sub-Saharan Africa not exceeding 50%. Here we consider the relationship between α + thalassaemia and sickle cell in South Asian populations, and show that very high levels of α + thalassaemia combined with varying levels of malaria selection can explain why sickle cell has penetrated certain South Asian populations but not others. © 2011 The Author(s). Evolution © 2011 The Society for the Study of Evolution..