Characterisation of deletions which affect the expression of fetal globin genes in man

Abstract

Deletions in the DNA of individuals with hereditary persistence of fetal Hb (HPFH) and .delta..beta.-thalassemia were 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 were precisely located with respect to restriction endonuclease cleavage sites within and surrounding the .gamma.-, .delta.- and .beta.-globin genes in normal human DNA and the deletion maps were used to obtain definitive evidence for the physical linkage of the fetal and adult .beta.-like globin genes in the order 5''G.gamma.-A.gamma.-.delta.-.beta.3''. Correlation of hematological data and the location of deletions in 2 cases of HPFH and 1 case of .delta..beta.-thalassemia suggest that a region of DNA located near the 5''-end of the .delta.-globin gene may be involved in the suppression in cis of .gamma.-globin gene expression in adults. The interpretation of a 2nd case of .delta..beta.-thalassemia is complicated by the fact that the deletion removes the A.gamma.-gene in addition to the region near the 5''-end of the .delta.-globin gene.