title: 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.
authors: Department of Zoology, University of Oxford, South Parks Road Oxford, OX1 3PS, United Kingdom. bridget.penman@zoo.ox.ac.uk
authors: Bridget S
authors: BS
authors: Penman
authors: Saman
authors: S
authors: Habib
authors: Kanika
authors: K
authors: Kanchan
authors: Sunetra
authors: S
authors: Gupta
mesh_terms: D001208:Asia / Q000453:epidemiology; D005075:Biological Evolution; D060467:Disease Resistance / Q000235:genetics*; D004843:Epistasis, Genetic; D006801:Humans; D008288:Malaria / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D012641:Selection, Genetic; D012805:Sickle Cell Trait / Q000150:complications / Q000235:genetics*; D017085:alpha-Thalassemia / Q000150:complications / Q000235:genetics*