Regulation of human alpha-globin gene expression and alpha-thalassemia

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Hemoglobin and globin genes are important models for studying protein and gene structure, function and regulation. We reviewed the main aspects of regulation of human alpha-globin synthesis, encoded by two adjacent genes (alpha 2 and alpha 1) clustered on chromosome 16. Their expression is controlled mainly by a regulatory element located 40 kb upstream on the same chromosome, the alpha-major regulatory element, whose activity is restricted to a core fragment of 350 bp, within which several regulatory protein binding sites have been found. Natural deletions involving alpha-major regulatory element constitute a particular category of alpha-thalassemia determinants in which the alpha-globin genes are physically intact but functionally inactive.7410451053Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)FAPESP [02/13801-7, 03/07412-0]CNPq [475481/2006-2

Hematological phenotype and the type of beta thalassemia mutation in Brazil

The type of beta thalassemia mutation found in heterozygous individuals is believed to influence hematological symptoms. Our data demonstrated that patients with the mild mutation (beta IVSI-nt 6) have a higher mean corpuscular hemoglobin (MCH) than those with the severe forms (beta(0)039 or beta IVSI-nt 1), and the hemoglobin A(2) levels were lower in beta(0) mutations than in the beta IVSI-nt 6 mutation. However, in contrast to previous studies, we were not able to indicate MCH as a clear discriminator between the beta(0) and beta(+) mutations.20231932

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