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.

Original publication

DOI

10.1073/pnas.0910840106

Type

Journal article

Journal

Proc Natl Acad Sci U S A

Publication Date

15/12/2009

Volume

106

Pages

21242 - 21246

Keywords

Africa, Anemia, Sickle Cell, Epistasis, Genetic, Gene Frequency, Hemoglobins, Abnormal, Humans, Malaria, Mediterranean Islands, Thalassemia