%0 Journal Article %1 Penman:09 %A Penman, B S %A Pybus, O G %A Weatherall, D J %A Gupta, S %D 2009 %J Proc Natl Acad Sci U S A %K epistasis malaria parallel_adaptation %N 50 %P 21242-21246 %R 10.1073/pnas.0910840106 %T Epistatic interactions between genetic disorders of hemoglobin can explain why the sickle-cell gene is uncommon in the Mediterranean %U http://www.ncbi.nlm.nih.gov/pubmed/19955437 %V 106 %X 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.

@article{Penman:09, abstract = {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.}, added-at = {2010-04-01T19:41:32.000+0200}, author = {Penman, B S and Pybus, O G and Weatherall, D J and Gupta, S}, biburl = {https://www.bibsonomy.org/bibtex/25bf99dd8c70ed1c6545bbcaf48f8e8d4/peter.ralph}, description = {Epistatic interactions between genetic disorders o... [Proc Natl Acad Sci U S A. 2009] - PubMed result}, doi = {10.1073/pnas.0910840106}, interhash = {4e3b5e4317107c338b542c6bbb1dc679}, intrahash = {5bf99dd8c70ed1c6545bbcaf48f8e8d4}, journal = {Proc Natl Acad Sci U S A}, keywords = {epistasis malaria parallel_adaptation}, month = dec, number = 50, pages = {21242-21246}, pmid = {19955437}, timestamp = {2011-04-27T22:03:57.000+0200}, title = {Epistatic interactions between genetic disorders of hemoglobin can explain why the sickle-cell gene is uncommon in the Mediterranean}, url = {http://www.ncbi.nlm.nih.gov/pubmed/19955437}, volume = 106, year = 2009 }