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Title: Extended linkage disequilibrium surrounding the hemoglobin E variant due to malarial selection
Authors: Jun Ohashi
Izumi Naka
Jintana Patarapotikul
Hathairad Hananantachai
Gary Brittenham
Sornchai Looareesuwan
Andrew G. Clark
Katsushi Tokunaga
University of Tokyo
Cornell University
Mahidol University
Columbia University, College of Physicians and Surgeons
Keywords: Biochemistry, Genetics and Molecular Biology;Medicine
Issue Date: 1-Jan-2004
Citation: American Journal of Human Genetics. Vol.74, No.6 (2004), 1198-1208
Abstract: The hemoglobin E variant (HbE;β26Glu→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.
ISSN: 00029297
Appears in Collections:Scopus 2001-2005

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