Assuntos
Globinas/genética , Talassemia/genética , Alelos , Pool Gênico , Humanos , México/etnologiaRESUMO
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.
Assuntos
Alelos , Anemia Falciforme/genética , População Negra , Conversão Gênica , Genes , Globinas/genética , Hemoglobina Falciforme/genética , Mutação , Polimorfismo Genético , Homozigoto , Humanos , Jamaica/etnologia , Estados UnidosRESUMO
In order to investigate the origin(s) of the mutation(s) leading to the beta S-globin gene in North American populations of African ancestory, we analysed 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 halotypes 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. (AU)
Assuntos
Humanos , Alelos , Anemia Falciforme/genética , Conversão Gênica , Genes , Globinas/genética , Hemoglobina Falciforme/genética , Mutação , Polimorfismo Genético , Homozigoto , Jamaica/etnologiaRESUMO
We have summarized a number of different genetic disorders which can be diagnosed at the DNA level using restriction endonuclease fragment analysis. A whole spectrum of defects can be recognized: point mutations, deletions, additions, and crossing-over products or hybrid genes. These same restriction endonuclease techniques can enable different genes to be marked by polymorphism patterns. Thus, abnormal genes can be identified even if their exact DNA lesion is unknown or cannot be directly detected. The progress that has been made with the hemoglobinopathies and the experience from this group of single gene disorders should find application to other diseases as soon as specific probes become available.