Origin of the beta 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 beta S-globin gene in North American populations of African ancestry, we analyzed DNA polymorphisms in the beta-globin gene cluster in a large number of both beta A- and beta S-globin gene-bearing chromosomes in U.S. and Jamaican Blacks. We found 16 different haplotypes 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. First, the mutation is present in all three beta-globin gene frameworks. Second, the beta S haplotypes can be divided into four groups, each of which cannot be derived from any other by less than two crossing-over events. In summary, our observation of the beta S mutation on 16 different haplotypes in African populations can be best explained by (i) a number of simple recombination events 5' to the beta-globin gene and (ii) up to four independent mutations and/or interallelic gene conversions.
D000483:Alleles; D000755:Anemia, Sickle Cell / Q000235:genetics*; D044383:Black People; D005785:Gene Conversion; D005796:Genes; D005914:Globins / Q000235:genetics*; D006451:Hemoglobin, Sickle / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007563:Jamaica / Q000208:ethnology; D009154:Mutation; D011110:Polymorphism, Genetic; D014481:United States; D001741:Black or African American
D006451:Hemoglobin, Sickle; D005914:Globins