The molecular basis of alpha thalassaemia in a South African population.

We have investigated the molecular basis of alpha thalassaemia in the so-called 'Cape Coloured' population of Cape Town. DNA from 17 cases was analysed by Southern blotting and hybridization with an alpha globin complementary DNA probe. Three types of alpha thalassaemia genetic determinants were detected: the 3.5 kb deletion which inactivates one alpha globin gene per chromosome (-alpha/haplotype), a much larger deletion which removes both alpha globin genes (- -/haplotype), and a non-deletion determinant which leaves both alpha globin genes intact. The interaction of these determinants with each other or with the normal chromosome (alpha alpha/) produced the phenotypes alpha thalassaemia silent carrier, alpha thalassaemia trait and Hb H disease. All cases of the -alpha/haplotype result from the rightward deletion which removes the Bgl II site between the duplicated alpha globin genes. The predominance of the -alpha/haplotype (21 out of the 28 alpha thalassaemia determinants) over the - -/haplotype is consistent with the low incidence of Hb H disease and the apparent absence of Hb Bart's hydrops fetalis in this population group.