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

Background: The Southeast Asian deletion ( - ^SEA) is the most commonly observed mutation among diverse α-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 α-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.