MOLECULAR GENETICS OP THE β-THALASSEMIA (β-THAL) SYNDROMES

Abstract

Globin messenger RNA (mRNA) from reticulocytes of several patients with various β-thal syndromes was studied in two ways: I. partially purified globin mRNA preparations from β-thal reticulocytes were tested for their capacity to promote α and βA globin chain synthesis in a heterologous cell-free system which preferentially synthesized βA chains when incubated with normal human globin mRNA (βA/α = 2-4). In this system, globin mRNA preparations from each of 10 patients with β-thal (βA/α = 0.1-0.3); 2 patients with homozygous β0-thal (βA/α = 0); and 4 patients doubly heterozygous for β0-thal and an abnormal hemoglobin (βA/α = 0) reproduced in every case the defect in β chain synthesis occurring in their intact reticulocytes. II. The actual chemical amounts of β chain specific mRNA sequences (relative to α chain sequences) in the β-thal mRNA's were measured by re-annealing β-thal mRNA, in separate experiments, with synthetic radioactive DMA (cDNA) complementary to purified normal α chain specific or β chain specific mRNA. When measured by these hybridization techniques, β chain mRNA was reduced to 10-30% of normal in the 4 patients tested with β+-thal and was absent in 4 patients with β0-thal. All of the β-thal syndromes studied to date are thus characterized by β chain mRNA which is diminished (β+-thal) or absent (β0-thal) not only in terms of template activity but also in absolute chemical amounts.