b6c3c29b-5d03-4091-b551-e0bc1a8c5ea7
title
Extended linkage disequilibrium surrounding the  hemoglobin E  variant due to malarial selection.
31ddf594-b2a8-48cd-b7c3-b26898efa6da
abstract
The  hemoglobin E variant (HbE; ( beta )26Glu-->Lys)  is concentrated in parts of Southeast Asia where malaria is endemic, and  HbE  carrier status has been shown to confer some protection against Plasmodium falciparum malaria. To examine the effect of natural selection on the pattern of linkage disequilibrium (LD) and to infer the evolutionary history of the  HbE  variant, we analyzed biallelic markers surrounding the  HbE  variant in a Thai population. Pairwise LD analysis of  HbE  and 43 surrounding biallelic markers revealed LD of  HbE  extending beyond 100 kb, whereas no LD was observed between non- HbE  variants and the same markers. The inferred haplotype network suggests a single origin of the  HbE  variant in the Thai population. Forward-in-time computer simulations under a variety of selection models indicate that the  HbE  variant arose 1,240-4,440 years ago. These results support the conjecture that the  HbE  mutation occurred recently, and the allele frequency has increased rapidly. Our study provides another clear demonstration that a high-resolution LD map across the human genome can detect recent variants that have been subjected to positive selection.