Origin of the β(S) globin gene in Blacks: The contribution of recurrent mutation or gene conversion or both

In order to investigate the origin(s) of the mutation(s) leading to the β(S)-globin gene in North American populations of African ancestry, we analyzed DNA polymorphisms in the β-globulin gene cluster in a large number of both β(A) and β(S) globin gene-bearing chromosomes in U.S. and Jamaican Blacks. We found 16 different haplotypes of polymorphic sites associated with 170 β(S) globin gene-bearing chromosomes. The three most common β(S) haplotypes, which account for 151/170 of the β(S) globin gene-bearing chromosomes, are only rarely seen in the chromosomes bearing the β(A) globin gene in these populations (6/47). Two observations suggest multiple origins or interallelic gene conversion, or both, of the β(S) mutation. First, the mutation is present in all three β-globin gene frameworks. Second, the β(S) haplotypes can be divided into four groups, each of which cannot be derived from any other by less than two cross-over events. In summary, our observation of the β(S) mutation on 16 different haplotypes in African populations can be explained by (i) a number of simple recombination events 5' to the β-globin gene and (ii) up to four independent mutations and/or interallelic gene conversions.