Physical mapping of the globin gene deletion in hereditary persistence of foetal haemoglobin (HPFH)

Abstract

We have mapped the globin gene region in the DNA of two HPFH patients. In a patient homozygous for the GγAγ type of HPFH at least 24 kb of DNA in the globin gene region has been deleted to remove most of the γ - δ intergenic region and the δ and β globin genes. The 5' break point of the deletion is located about 9 kb upstream from the δ globin gene. The 3' break point has not been precisely located but is at least 7 kb past the β globin gene. DNA from an individual heterozygous for the Greek (Aγ) type of HPFH, however, shows no detectable deletion in the entire γδβ-globin gene region. HPFH, therefore, appears to occur in different molecular forms. These results are discussed in terms of a model for the regulation of globin gene expression in man.