Genetic studies suggest a multicentric origin for Hb G-Coushatta [β22(B4)Glu→Ala]

Hb G-Coushatta [β22(B4)Glu→Ala] is found in geographically separated ethnic groups. Commonest along the Silk Road region of China but also present in the North American Coushatta, we sought to determine whether this variant had a unicentric or multicentric origin. We examined the haplotype of the β- globin gene cluster in two Chinese families and in five Louisiana Coushatta heterozygous for this mutation. Chinese and Louisiana Coushatta had different haplotypes associated with the identical Hb G mutation. These haplotypes were defined by the presence of a HindIII restriction site in the (A)γ-globin gene and AvaII restriction site in the β-globin gene in Chinese subjects and their absence in the Louisiana Coushatta. We found a CAC at codon β2 (β- globin gene framework 1 or 2) linked to the Hb G-Coushatta gene in Chinese, and a CAT(framework 3) in Louisiana Coushatta, indicating different β- globin gene frameworks. Both the Hb G-Coushatta mutation (GAA→GCA) and the codon 2 CAC→CAT polymorphism are normal δ-globin gene sequences, suggesting the possibility of gene conversion. We conclude that Hb G-Coushatta had at least two independent origins. This could be due to separate mutations at codon β22 in Chinese and Louisiana Coushatta, a mutation at this codon and a β→δ conversion, or two β→δ gene conversion events.