Detection of a new hybrid α2 globin gene among American Blacks

Summary

We have examined the α globin gene complex for 49 individuals with α-thalassemia-2 (−α^3.7). Crossovers resulting in α-thalassemia-2 (type I) were observed in all 57 chromosomes with the −α^3.7 defect. Except for one α-thalassemia-2 chromosome, all were linked to the absence of an Rsa I restriction site located 0.7 kb 5′ to the α2-globin gene; this polymorphic site was observed for 10 of 38 non-α-thalassemia chromosomes from Black Americans. In four Black families with a heterozygous α-thalassemia-2 [−α^3.7 (I)], an Apa I restriction site has been identified in the IVS-2 of the α2 gene of the normal chromosome (labeled the α^*2 gene). The α^*2 gene of one Black subject was cloned and a segment located 5′ to the Cap site as well as the IVS-2, exon 3, and a 3′ segment were sequenced. The data show that the α^*2 gene is an α2 gene except for a segment between nucleotides (nts) 580–81 and nt 509 (Cap site=nt 1), and perhaps as far upstream as nt-634, which has an α1 sequence. This α^*2 hybrid gene probably originated through a double crossover; the structural identity of its IVS-2 with that of the α1 gene adequately explains the presence of the Apa I restriction site.