title: Evidence of differential selection for the -α(3.7)  and -α(4.2)  single-α-globin gene deletions within the same population.
abstract: Since the 1950s, a strong correlation between high carrier rates for β-thalassemia mutations and selective survival advantage in tropical and subtropical 'malarial belt' regions has been established. Due to the relatively more complex genetics of α-thalassemia, a similar relationship was demonstrated for α-globin gene mutations only from the 1980s, with both single- and double-α-globin gene deletions prevalent in the malarial belt. Mechanistically, the single-α-globin gene deletions arise from non-allelic recombination between the homologous α1 (HBA1) and α2 (HBA2) globin genes. Compared to the -α(3.7)  and ααα(anti3.7)  rightward crossover alleles, much less is known about the -α(4.2)  and ααα(anti4.2)  leftward crossover alleles. We performed a survey of 1,285 unselected cord blood samples from the 3 major ethnic groups in Singapore. Overall, the frequency of the -α(3.7)  deletion was significantly higher than its reciprocal ααα(anti3.7)  triplication, consistent with positive selection for the -α(3.7)  single-gene deletion. In marked contrast, there was no significant difference in frequency between the -α(4.2)  and reciprocal ααα(anti4.2)  alleles, suggesting the absence of positive selection for the -α(4.2)  single-gene deletion. The similar ααα(anti3.7)  and ααα(anti4.2)  allele frequencies also suggested that the crossover rates at X and Z homology boxes are similar. Taken together, these observations suggest a differential positive selection for the -α(3.7)  and -α(4.2)  alleles within the same population. Further population and biological studies may be required to explain these current observations.
authors.affiliation: University College London Medical School, University College London, London, UK.
authors.forename: Zhi Min
authors.initials: ZM
authors.lastname: Yap
authors.forename: Kar Mun
authors.initials: KM
authors.lastname: Sun
authors.forename: Clara R L
authors.initials: CR
authors.lastname: Teo
authors.forename: Arnold S C
authors.initials: AS
authors.lastname: Tan
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Chong
mesh_terms: D000483:Alleles; D003434:Crossing Over, Genetic; D005006:Ethnicity; D005312:Fetal Blood / Q000378:metabolism; D017353:Gene Deletion; D005787:Gene Frequency; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D015995:Prevalence; D012641:Selection, Genetic; D012846:Singapore / Q000453:epidemiology; D055542:alpha-Globins / Q000235:genetics*; D017085:alpha-Thalassemia / Q000097:blood / Q000208:ethnology* / Q000235:genetics*
chemical_list: D055542:alpha-Globins