Origin and spread of beta-globin gene mutations in India, Africa, and Mediterranea: analysis of the 5' flanking and intragenic sequences of beta S and beta C genes.
Nucleotide polymorphisms of both the 5' flanking and intragenic regions of the human beta-globin gene were investigated by directly sequencing genomic DNA after amplification by the polymerase chain reaction in 47 subjects homozygous for the beta S or the beta C mutation. The sickle-cell mutation was found in the context of five different haplotypes defined by eight nucleotide substitutions and various structures of a region of the simple repeated sequence (AT) chi Ty. All subjects from the same geographic origin bear an identical chromosomal structure, defining the Senegal-, Bantu-, Benin-, Cameroon-, and Indian-type chromosomes. These results strengthen our previous conclusions about the multiple occurrence of the sickle-cell mutation. The Benin-type chromosome was also found among Algerian and Sicilian sickle-cell patients, whereas the Indian-type chromosome was observed in two geographically distant tribes, illustrating the spread of these sickle-cell genes. We also found that the intragenic sequence polymorphisms (frameworks) are not always in linkage disequilibrium with the BamH I polymorphism downstream from the beta-globin gene, as had been previously observed. Finally, we present a tentative phylogenetic tree of the different alleles at this locus. Some polymorphisms of this sequence might be contemporary with our last common ancestor, the great apes, that is, about 4-6 millions years old.
Trabuchet
G
G
Laboratoire de Biologie Cellulaire, CNRS UMR 106, Université Claude Bernard Lyon I, Villeurbanne, France.
Elion
J
J
Baudot
G
G
Pagnier
J
J
Bouhass
R
R
Nigon
V M
VM
Labie
D
D
Krishnamoorthy
R
R
D000349:Africa / Q000453:epidemiology; D000483:Alleles; D000755:Anemia, Sickle Cell / Q000453:epidemiology / Q000235:genetics*; D001483:Base Sequence; D005075:Biological Evolution; D008040:Genetic Linkage; D005914:Globins / Q000235:genetics*; D006801:Humans; D007194:India / Q000453:epidemiology; D008522:Mediterranean Sea; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D016415:Sequence Alignment
D005914:Globins