Evidence of differential selection for the −α 3.7 and −α 4.2 single‐α‐globin gene deletions within the same population

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 ( HBA 1 ) and α2 ( HBA 2 ) 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.