1. Understanding α-Globin Gene Regulation: Aiming to Improve the Management of Thalassemia
- Author
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Doug Higgs, Marie-Alice Deville, M De Gobbi, M Muers, Martin J. Law, Karen M. Lower, A Argentaro, Douglas Vernimmen, Jim R. Hughes, David Garrick, Richard J. Gibbons, and Eduardo Anguita
- Subjects
X-linked Nuclear Protein ,Thalassemia ,Management of thalassemia ,biosynthesis/genetics ,Alpha-thalassemia ,Regulatory Sequences, Nucleic Acid ,Biology ,medicine.disease_cause ,Chromosomes ,General Biochemistry, Genetics and Molecular Biology ,Human ,Pair 11 ,genetics, Chromosomes ,Pair 16 ,genetics, DNA Helicases ,genetics/physiology, Epigenesis ,Genetic ,genetics, Gene Expression Regulation, Gene Expression Regulation ,Developmental, Globins ,biosynthesis/genetics, Hematologic Neoplasms ,genetics, Hematopoiesis ,genetics, Humans, Mutation, Myelodysplastic Syndromes ,genetics, Nuclear Proteins ,genetics/physiology, Regulatory Sequences ,Nucleic Acid, Telomere ,genetics, Thalassemia ,genetics/therapy, alpha-Thalassemia ,genetics ,Epigenesis, Genetic ,alpha-Thalassemia ,History and Philosophy of Science ,hemic and lymphatic diseases ,medicine ,Humans ,Developmental ,Globin ,genetics/physiology ,Gene ,Regulation of gene expression ,Genetics ,Mutation ,Nucleic Acid ,Chromosomes, Human, Pair 11 ,General Neuroscience ,DNA Helicases ,Gene Expression Regulation, Developmental ,Nuclear Proteins ,Telomere ,medicine.disease ,Globins ,Hematopoiesis ,genetics/therapy ,Gene Expression Regulation ,Regulatory sequence ,Hematologic Neoplasms ,Myelodysplastic Syndromes ,Regulatory Sequences ,Chromosomes, Human, Pair 16 ,Epigenesis - Abstract
Over the past 50 years, many advances in our understanding of the general principles controlling gene expression during hematopoiesis have come from studying the synthesis of hemoglobin. Discovering how the alpha- and beta-globin genes are normally regulated and documenting the effects of inherited mutations that cause thalassemia have played a major role in establishing our current understanding of how genes are switched on or off in hematopoietic cells. Previously, nearly all mutations causing thalassemia have been found in or around the globin loci, but rare inherited and acquired trans-acting mutations are being found more often. Such mutations have demonstrated new mechanisms underlying human genetic disease. Furthermore, they are revealing new pathways in the regulation of globin gene expression that, in turn, may open up new avenues for improving the management of patients with common types of thalassemia.
- Published
- 2005