Evidence Of Recent Natural Selection On The Southeast Asian Deletion (-(Sea)) Causing Alpha-Thalassemia In South China

Background: The Southeast Asian deletion (-(SEA)) is the most commonly observed mutation among diverse alpha-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 alpha-globin cluster, covering a genomic region spanning similar to 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.