Restriction endonuclease mapping of the human γ globin gene loci

The restriction endonuclease sites in and around the human γ globin gene loci have been mapped using the gel blotting technique of Southern, in both normal DNA and DNA from an individual with hereditary persistence of fetal hemoglobin (HPFH). In normal DNA, the _γ genes are linked to the δ (and β) globin genes, and the orientation of these genes with respect to transcription is (5′) G_γ→A_γ→γ→β (3′). The distance between the G_γ and A_γ genes is 3.5 kb and that between the A_γ and δ genes is 16 kb. In both normal DNA and HPFH DNA, the γ genes are interrupted by an intervening sequence, approximately 1 kb in length that is situated between codon positions 99 and 121 of the coding sequence. In different DNA samples, there is polymorphism for the presence or absence of a Hind III site in the intervening sequence of either _γ globin gene. In HPFH DNA, a deletion of at least 16 kb of DNA has been detected. This deletion starts at a point approximately 12.5 kb from the 3′-end of A_gamma; gene and extends through the δ and β globin genes to a point at least 3 kb beyond the 3′-end of β globin gene.