The frequency of the gamma chain variant A gamma T in different populations, and its use in evaluating gamma gene expression in association with thalassemia.

The occurrence of the A gamma T chain (i.e. A gamma 75 Ile----Thr) in different populations was evaluated through a study of 4250 cord blood samples and blood samples from more than 350 SS patients. High frequencies were observed in Italy, Yugoslavia, Turkey, Holland, but also in Japan, Vietnam, and India. The chain is (nearly) absent in the Black population of Ghana and Kenya, and low frequencies were observed in China and Australian aborigines. Only a few adult SS patients (18 out of 357) were A gamma T heterozygotes. The chromosomes with the A gamma T globin gene were mapped through an evaluation of the presence of 10 different restriction sites. The A gamma T chromosomes from different populations were closely related and had the same subhaplotypes of [- - + + T - +] (Hinc II 5' to epsilon; Xmn I 5' to G gamma; Hind III in G gamma and A gamma; Hinc II in and 3' to psi beta), quite different from the subhaplotypes seen for A gamma T negative chromosomes. This suggests a common ancestor which may have originated in Southern Europe. An evaluation of the gamma chain production by both chromosomes in SS patients and beta-thalassemia heterozygotes was possible for subjects with an A gamma T heterozygosity. It was concluded that in beta-thalassemia trait, the gamma chain synthesis is directed for about two-thirds by the thalassemic chromosome and for about one-third by the normal chromosome; the contribution by the normal chromosome decreases with a decrease in total gamma chain production.