α-Globin gene organisation in blacks precludes the severe form of α-thalassaemia

Abstract

IN most human populations, the α-globin structural gene loci are duplicated so that each diploid cell contains four copies of α-globin genes^1–3. In α-thalassaemia, a hereditary disorder of α-globin chain synthesis, the most common molecular lesion is due to the deletion of the α-globin genes^4–7. In the Asian population, four main α-thalassaemia syndromes of increasing clinical severity are recognised: (1) the silent carrier state (α-thalassaemia-2) with no clinical manifestation; (2) α-thalassaemia trait (α-thalassaemia-1), characterised by microcytic red blood cells but little or no anaemia; (3) haemoglobin-H disease, which manifests as haemolytic anaemia; and (4) homozygous α-thalassaemia, in which the afflicted fetus dies at or around term from hydrops fetalis. These four syndromes are due to the deletion of from one to all four copies of the α-globin genes. In this study, we have characterised α-thalassaemia in people of African origin. Haemoglobin screening programmes have shown that α-thalassaemia occurs in the black population^8–10. Recently we have demonstrated by complementary DNA–DNA hybridisation that in black individuals with clinically well defined α-thalassaemia trait, two of the four normal α-globin genes were deleted¹¹. However, in this population, haemoglobin-H disease is rare and homozygous α-thalassaemia has never been found^12,13. For this study we have used the restriction endonuclease mapping technique of Southern¹⁴ to delineate the nature of the deletion of the α-globin genes.