The enhancer-like sequence 3' to the A gamma gene is polymorphic in human
populations
EE Bouhassira, R Krishnamoorthy, A Ragusa, C Driscoll, D Labie and RL Nagel
Division of Hematology, Albert Einstein College of Medicine, Bronx, NY
10461.
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.
Volume 73,
Issue 4,
pp. 1050-1053,
03/01/1989
Copyright © 1989 by The American Society of Hematology
