The genetics and molecular basis of alpha thalassaemia in association with Hb S in Jamaican Negroes

ABSTRACT

We have studied seven Jamaican Negro families in whom the genes for O thalassaemia and the sickle cell mutation (ás) were independently segretated. Using a combination of techniques we identified two O thalassaemia phenotypes which resemble the reserve (O thalassaemia 1) and mild (O thalassaemia 2) determinants previously described in Orientals. This study has enabled us to clearly correlate the phenotype of O thalassaemia with the genotype in this population. Furthermore, since in each family O 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 OO/OO, -O/-O genotype who are also heterozygous for the ás mutation. Genetic analysis in these families shows that in each case subjects with the O thalassaemia 1 phenotype are homozygous for the O thalassaemia 2 defect (-O/-O). We have found no instances of the genotype --/OO in this population which may explain the rarity of the severe O thalassaemia 2 homozygotes from this population shows that the (-O/) haplotype results from a deletion of one of the linked pair of O globin and that this had probably arisen by an unequal crossover between non-homologous O genes (AU)