G to A substitution in the distal CCAAT box of the A gamma-globin gene in Greek hereditary persistence of fetal haemoglobin.
The sequence 5'TTGGPyCAAT 3' (the 'CCAAT box') is a constituent of the promoter region of many eukaryotic and prokaryotic genes and is believed to play a part in promoter function. A characteristic of the two fetal human globin genes (A gamma and G gamma) is a duplication of a 12-base pair (bp) sequence containing the CCAAT box. Here we report a G----A substitution in the TTG sequence of the distal CCAAT box of the A gamma-globin gene in an individual with the A gamma (Greek) type of hereditary persistence of fetal haemoglobin (HPFH). This represents the first report of a natural mutation of the CCAAT box in a eukaryotic gene. The fact that this transition is associated with inappropriate expression of the A gamma gene in adult life suggests that the CCAAT box (or its surrounding sequences) may have a role in the developmental control of gamma-globin genes.
Gelinas
R
R
Endlich
B
B
Pfeiffer
C
C
Yagi
M
M
Stamatoyannopoulos
G
G
D001483:Base Sequence; D004247:DNA; D005260:Female; D005319:Fetal Hemoglobin; D005914:Globins / Q000235:genetics*; D006453:Hemoglobinopathies / Q000235:genetics*; D006801:Humans; D009154:Mutation; D013789:Thalassemia / Q000235:genetics; D014158:Transcription, Genetic
D005914:Globins; D004247:DNA; D005319:Fetal Hemoglobin