Expression of G gamma and A gamma globin genes in human adults.
Expression of the human fetal G gamma and A gamma globin genes declines shortly after birth, and adults generally have less than 1% fetal hemoglobin or Hb F (alpha 2 gamma 2). However, some adults with hereditary persistence of fetal hemoglobin (HPFH) have elevated expression of either the G gamma or A gamma gene due to a mutation in its upstream promoter. Mutations with strong effects on expression have been found at -175 and -202 of the G gamma gene and at -117, -196, -198 and -202 of the A gamma gene. Mutations at -158 and -161 of G gamma have weaker effects, which are observable primarily as increases in the G gamma:A gamma ratio. Published data are reviewed which suggest that the -158 mutation may lead to observable elevations of Hb F in SS and beta(0)-thal patients and occasionally in normal non-anemic individuals. These data also suggest that additional high Hb F determinants are linked to Benin, Bantu and Asian beta S haplotypes in some instances. A model based on data from SV40 is presented which suggests that specific DNA sequence motifs of the gamma globin gene may bind regulatory proteins. It is proposed that the -158 and -161 mutations have weak effects because they are located on the fringe of regulatory sequence motifs.
Gilman
J G
JG
Department of Cell and Molecular Biology, Medical College of Georgia, Augusta 30912.
D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood / Q000235:genetics; D001208:Asia; D044383:Black People; D004742:Enhancer Elements, Genetic; D005319:Fetal Hemoglobin / Q000235:genetics*; D005786:Gene Expression Regulation; D005914:Globins / Q000235:genetics*; D006801:Humans; D009154:Mutation; D011401:Promoter Regions, Genetic; D013789:Thalassemia / Q000097:blood
D005914:Globins; D005319:Fetal Hemoglobin