Epistatic interactions between genetic disorders o... [Proc Natl Acad Sci U S A. 2009] - PubMed result

Proc Natl Acad Sci U S A. 2009 Dec 1. [Epub ahead of print]

Epistatic interactions between genetic disorders of hemoglobin can explain why the sickle-cell gene is uncommon in the Mediterranean.
Penman BS, Pybus OG, Weatherall DJ, Gupta S.

Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, United Kingdom.

Several human genetic disorders of hemoglobin have risen in frequency because of the protection they offer against death from malaria, sickle-cell anemia being a canonical example. Here we address the issue of why this highly protective mutant, present at high frequencies in subSaharan Africa, is uncommon in Mediterranean populations that instead harbor a diverse range of thalassemic hemoglobin disorders. We demonstrate that these contrasting profiles of malaria-protective alleles can arise and be stably maintained by two well-documented phenomena: an alleviation of the clinical severity of alpha- and beta-thalassemia in compound thalassemic genotypes and a cancellation of malaria protection when alpha-thalassemia and the sickle-cell trait are coinherited. The complex distribution of globin mutants across Africa and the Mediterranean can therefore be explained by their specific intracellular interactions.

PMID: 19955437 [PubMed - as supplied by publisher]

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Epistatic interactions between genetic disorders o... [Proc Natl Acad Sci U S A. 2009] - PubMed result