Abstract
The sequence 5′ TTGGPyCAAT 3′ (the ‘CCAAT box’) is a constituent of the promoter region of many eukaryotic and prokaryotic genes1,2 and is believed to play a part in promoter function3,4. A characteristic of the two fetal human globin genes (Aγ and Gγ) 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 Aγ-globin gene in an individual with the Aγ (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 Aγ gene in adult life suggests that the CCAAT box (or its surrounding sequences) may have a role in the developmental control of γ-globin genes.
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Gelinas, R., Endlich, B., Pfeiffer, C. et al. G to A substitution in the distal CCAAT box of the Aγ-globin gene in Greek hereditary persistence of fetal haemoglobin. Nature 313, 323–325 (1985). https://doi.org/10.1038/313323a0
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DOI: https://doi.org/10.1038/313323a0
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