The Genetics and Molecular Basis of Alpha Thalassaemia in Association with Hb S in Jamaican Negroes

S ummary . We have studied seven Jamaican Negro families in whom the genes for α thalassaemia and the sickle cell mutation (β s ) were independently segregated. Using a combination of techniques we identified two α thalassaemia phenotypes which resemble the severe (α thalassaemia 1) and mild (α thalassaemia 2) determinants previously described in Orientals. This study has enabled us to clearly correlate the phenotype of α thalassaemia with the genotype in this population. Furthermore, since in each family α thalassaemia was present in association with the gene for the sickle cell mutation we have determined the proportion of Hb S in the peripheral blood of individuals with the αα/αα, ‐α/αα and ‐α/‐α genotype who are also heterozygous for the β s mutation. Genetic analysis in these families shows that in each case subjects with the α thalassaemia 1 phenotype are homozygous for the α thalassaemia 2 defect (‐α/ ‐α). We have found no instances of the genotype ‐/αα in this population which may explain the rarity of the severe α thalassaemia syndromes in Jamaica. Restriction mapping data in the α thalassaemia 2 homozygotes from this population shows that the (‐α/) haplotype results from a deletion of one of the linked pair of α globin genes and that this has probably arisen by an unequal crossover between non‐homologous α genes.