Genetic studies suggest a multicentric origin for Hb G-Coushatta [beta 22(B4)Glu -> Ala]

Hb G-Coushatta [beta 22(B4)Glu-->Ala] is found in geographically separated ethnic groups. Commonest along the Silk Road region of China but also prese nt in the North American Coushatta, we sought to determine whether this var iant had a unicentric or multicentric origin. We examined the haplotype of the beta-globin gene cluster in two Chinese families and in five Louisiana Coushatta heterozygous for this mutation. Chinese and Louisiana Coushatta h ad different haplotypes associated with the identical Hb G mutation. These haplotypes were defined by the presence of a HindIII restriction site in th e (A)gamma-globin gene and AvaII restriction site in the beta-globin gene i n Chinese subjects and their absence in the Louisiana Coushatta. We found a CA (C) under bar at codon beta 2 (beta-globin gene framework 1 or 2) linke d to the Hb G-Coushatta gene in Chinese, and a CA (T) under bar (framework 3) in Louisiana Coushatta, indicating different beta-globin gene frameworks . Both the Hb G-Coushatta mutation (G (A) under bar A-->G (C) under bar A) and the codon 2 CA (C) under bar-->CA (T) under bar polymorphism are normal delta-globin gene sequences, suggesting the possibility of gene conversion . We conclude that Hb G-Coushatta had at least two independent origins. Thi s could be due to separate mutations at codon beta 22 in Chinese and Louisi ana Coushatta, a mutation at this codon and a beta-->delta conversion, or t wo beta-->delta gene conversion events.