Origin of the beta S-globin gene in blacks: the contribution of recurrent mutation or gene conversion or both.

Abstract

To investigate the origin(s) of the mutation(s) leading to the .beta.S-globin gene in North American populations of African ancestry, DNA polymorphisms were analyzed in the .beta.-globin gene cluster in a large number of .beta.A- and .beta.S-globin gene-bearing chromosomes in USA and Jamaican Blacks. Sixteen different haplotypes were found of polymorphic sites associated with 170 .beta.S-globin gene-bearing chromosomes. The three most common .beta.S haplotypes, which account for 151/170 of the .beta.S-globin gene-bearing chromosomes, are only rarely seen in the chromosomes bearing the .beta.A-globin gene in these populations (6/47). Two observations suggest multiple origins or interallelic gene conversion, or both, of the .beta.S mutation; the mutation is present in all 3 .beta.-globin gene frameworks; .beta.S haplotypes can be divided into 4 groups, each of which cannot be derived from any other by less two crossing-over events. Observation of the .beta.S mutation on 16 different haplotypes in African populations can be best explained by a number of simple recombination events 5'' to the .beta.-globin gene and up to 4 independent mutations and/or interallelic gene conversions.