These studies are designed to define and precisely characterize various molecular lesions occurring in the beta-globin gene cluster in patients with beta thalassemia or with syndromes associated with increased HbF production in adult life, such as delta-beta thalassemia or hereditary persistence of fetal hemoglobin (HPFH). To investigate the mechanism by which premature termination codons cause a quantitative deficiency of beta globin mRNA, precursor and spliced mRNA molecules are generated in vitro and in vivo. The processing and nuclear to cytoplasmic transport of these RNA molecules are studied by microinjection into nuclei of Xenopus oocytes.
