DEFECTS IN DNA AND GLOBIN MESSENGER-RNA IN HOMOZYGOTES FOR HEMOGLOBIN LEPORE

Globin messenger RNA (mRNA) isolated from 3 patients homozygous for hemoglobin Lepore is shown to have a marked reduction of the amount of β-like globin mRNA (Lepore-globin mRNA sequences) compared with α-globin mRNA by molecular hybridization. The relative amounts of α- and Lepore mRNA are similar to the amounts of α- and Lepore globin synthesized in intact cells and by isolated mRNA in a cell-free system. It is also demonstrated that Lepore-globin mRNA can completely hybridize to full-length or nearly full-length β-globin specific complementary DNA and protect it from nuclease digestion, indicating close homology between the δ-mRNA sequences present in Lepore mRNA and the β-complementary-DNA probe. The authors have also quantitated the numbers of β-like globin gene sequences in genomic Lepore DNA by molecular hybridization and demonstrated a reduction in their number consistent with the Lepore gene being a δβ-gene fusion product.