Evidence of recent natural selection on the Southeast Asian deletion (--(SEA)) causing ?-thalassemia in South China.

ABSTRACT: BACKGROUND: The Southeast Asian deletion (--(SEA)) is the most commonly observed mutation among diverse ?-thalassemia alleles in Southeast Asia and South China. It is generally argued that mutation --(SEA), like other variants causing hemoglobin disorders, is associated with protection against malaria that is endemic in these regions. However, little evidence has been provided to support this claim. RESULTS: We first examined the genetic imprint of recent positive selection on the --(SEA) allele and flanking sequences in the human ?-globin cluster, covering a genomic region spanning ~410 kb, by genotyping 28 SNPs in a Chinese population consisting of 76 --(SEA) heterozygotes and 138 normal individuals. The pattern of linkage disequilibrium (LD) and the long-range haplotype test revealed a signature of positive selection. The network of inferred haplotypes suggested a single origin of the --(SEA) allele. CONCLUSIONS: Thus, our data support the hypothesis that the --(SEA) allele has been subjected to recent balancing selection, triggered by malaria.

SUBMITTER: Qiu QW 

PROVIDER: S-EPMC3626844 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature