Evidence of differential selection for the -α(3.7) and -α(4.2) single-α-globin gene deletions within the same population

• Published in: European journal of haematology Vol. 90; no. 3; pp. 210 - 213
• Main Authors: Yap, Zhi Min, Sun, Kar Mun, Teo, Clara R L, Tan, Arnold S C, Chong, Samuel S
• Format: Journal Article
• Language: English
• Published: England 01.03.2013
• Subjects: Alleles; alpha-Globins - genetics; alpha-Thalassemia - blood; alpha-Thalassemia - ethnology; alpha-Thalassemia - genetics; Crossing Over, Genetic; Ethnic Groups; Fetal Blood - metabolism; Gene Deletion; Gene Frequency; Genotype; Heterozygote; Humans; Prevalence; Selection, Genetic; Singapore - epidemiology; Singapore
• ISSN: 1600-0609
• DOI: 10.1111/ejh.12058

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.