Evolutionary history of sickle-cell mutation: implications for global genetic medicine.

摘要: Resistance afforded by the sickle-cell trait against severe malaria has led to high frequencies of mutation [HBB; c.20T>A, p.Glu6Val; OMIM: 141900 (HBB-βS)] in most parts Africa. High-coverage sequencing and genotype data have now confirmed single African origin gene variant (HBB-βS)]. Nevertheless, classical HBB-like genes cluster haplotypes remain a rich source HBB-βS evolutionary information. The overlapping distribution other disease-associated variants means that their genetics must be investigated concurrently. In this review: (1) we explore history its implications understanding human migration within out Africa: e.g. HBB recent paths Bantu expansion, occurrence ~7% Senegal haplotype Angola reflecting changes population/SCD dynamics, existence all five Cameroon Egypt suggesting much longer presence these regions; (2) discuss time estimates emergence Africa finally, (3) for genetic medicine complex epistatic interactions between selected under environmental pressure HBB, HBA, G6PD, APOL1, APOE, OSBPL10 RXRA.