title: The enhancer-like sequence 3' to the A gamma gene is polymorphic in human populations.
abstract: Cloning and sequencing of the enhancer 3' of the A gamma globin gene of a particularly low G gamma and HbF sickle cell anemia (SCA) patient unexpectedly revealed three base changes (T----C, C----A, and A----G at sites +2285, +2460, and +2676) previously associated with the Seattle-type HPFH, thus leading the authors to suspect that the three mutations were polymorphic. The determination of the incidence of the mutations among various ethnic groups allowed the authors to conclude that this is a widely spread polymorphism, thus excluding any role of these base changes in the determination of the hereditary persistence of fetal hemoglobin (HPFH) phenotype. The origin of these three mutations is not clear because they appear linked, and the same bases (C, A, G) are found in homologous position in the 3' of the normal G gamma gene. As C, A, G at positions +2285, +2460, and +2676 are found with a 100% frequency in African SS patients and presumably among normal Africans (to explain the extremely high frequency among normal American blacks), it is likely that this was the sequence preceding the division of races. The presence of T, C, and A at the same positions apparently occurred after the divergence between blacks and the other races, that is, within the last 1 million years.
authors.affiliation: Division of Hematology, Albert Einstein College of Medicine, Bronx, NY 10461.
authors.forename: E E
authors.initials: EE
authors.lastname: Bouhassira
authors.forename: R
authors.initials: R
authors.lastname: Krishnamoorthy
authors.forename: A
authors.initials: A
authors.lastname: Ragusa
authors.forename: C
authors.initials: C
authors.lastname: Driscoll
authors.forename: D
authors.initials: D
authors.lastname: Labie
authors.forename: R L
authors.initials: RL
authors.lastname: Nagel
mesh_terms: D001483:Base Sequence; D002874:Chromosome Mapping; D004742:Enhancer Elements, Genetic; D005006:Ethnicity; D005796:Genes; D005914:Globins / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D011110:Polymorphism, Genetic
chemical_list: D005914:Globins