Deletions in the DNA of individuals with hereditary persistence of fetal haemoglobin (HPFH) and δβ-thalassaemia have been mapped as a means of identifying regulatory sequences involved in the switch from fetal to adult globin gene expression. The end points of these deletions have been precisely located with respect to restriction endonuclease cleavage sites within and surrounding the γ-, δ- and β-globin genes in normal human DNA and the deletion maps were used to obtain definitive evidence f or the physical linkage of the fetal and adult β-like globin genes in the order 5′Gγ-Aγ-δ-β3′. Correlation of haematological data and the location of deletions in two cases of HPFH and one case of δβ-thalassaemia suggest that a region of DNA located near the 5′-end of the δ-globin gene may be involved in the suppression in cis of γ-globin gene expression in adults. The interpretation of a second case of δβ-thalassaemia is complicated by the fact that the deletion removes the Aγ-gene in addition to the region near the 5′-end of the δ-globin gene.
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Fritsch, E., Lawn, R. & Maniatis, T. Characterisation of deletions which affect the expression of fetal globin genes in man. Nature 279, 598–603 (1979). https://doi.org/10.1038/279598a0
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