The long-term interest of this laboratory has been to gain understanding of factors affecting differential regulation of hemoglobin biosynthesis in health and disease. We are particularly interested in those processes in human erythrocyte precursors which regulate the levels of different hemoglobins in certain hereditary disorders such as thalassemia and the hemoglobinopathies. A dysfunctional human Alpha-globin gene has been cloned in E. coli. A 10 kilobase fragment of DNA containing this gene will be isolated and the gene and flanking sequences analysed to determine the structural basis of the thalassemia. A triple Alpha-gene chromosome has been discovered which appears to have arisen from a previously undescribed crossover. The DNA encompassing the crossover region will be cloned and sequenced to determine whether sequences likely to be sites of frequent crossing-over can be detected. An ATP-dependent proteolytic system is in soluble form in reticulocytes; studies with primative erythroid precursors, Friend-MEL and K562 (human) erythroleukemia cells have the proteolytic activity linked to particles. Human RBC precursors will be studied to establish the importance of the system in disposing of excess globin chains in thalassemia and other hemoglobinopathies.
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| Safaya, S; Ibrahim, A; Rieder, R F (1994) Augmentation of gamma-globin gene promoter activity by carboxylic acids and components of the human beta-globin locus control region. Blood 84:3929-35 |
| Safaya, S; Trauber, D R; Rieder, R F (1992) Studies on the in vitro and in vivo expression of a dysfunctional alpha-globin gene. Am J Hematol 39:188-93 |
| Safaya, S; Rieder, R F; Dowling, C E et al. (1989) Homozygous beta-thalassemia without anemia. Blood 73:324-8 |
