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 ?-like globin mRNA (Lepore-globin mRNA sequences) compared with ?-globin mRNA by molecular hybridization. The relative amounts of ?- and Lepore mRNA are similar to the amounts of ?- 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 ?-globin specific complementary DNA and protect it from nuclease digestion, indicating close homology between the ?-mRNA sequences present in Lepore mRNA and the ?-complementary-DNA probe. The authors have also quantitated the numbers of ?-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 ??-gene fusion product.