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Regulatory elements and microRNAs involved in the modulation of fetal hemoglobin levels in patients with beta-hemoglobinopathies

Grant number: 11/15570-1
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): December 01, 2011
Effective date (End): February 28, 2015
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Claudia Regina Bonini Domingos
Grantee:Gisele Cristine de Souza Carrocini
Home Institution: Instituto de Biociências, Letras e Ciências Exatas (IBILCE). Universidade Estadual Paulista (UNESP). Campus de São José do Rio Preto. São José do Rio Preto , SP, Brazil

Abstract

The normal values for fetal hemoglobin (Hb F) in adults without hemoglobin alterations ranging from 0% to 1%. However, polymorphisms in certain regions of the genome are known to influence the Hb F concentration. Findings in the literature indicated the participation of micro-RNAs in erythropoiesis, and recent studies suggest that these elements appear to be related to the process of expression exchange that occurs between Hb F and Hb A. This process is important in the pathophysiology development of sickle cell anemia and beta thalassemia homozygous. Individuals with these diseases have genetic phenotype and variable Hb F levels. It is estimated that the regulatory elements and micro-RNAs involved in ³-globin genes expression control are expressed differently in those with hemoglobin alterations compared to negative control group, consisting of individuals with Hb AA, and positive control group, composed of heterozygous for mutations Hereditary Persistence of Fetal Hemoglobin. The objectives of this study are to screening specific genomic regions to find putative regulation elements and micro-RNAs that influence the ³A and ³G gene expression in individuals with sickle cell anemia, homozygote beta thalassemia negative and positive control group in relation to increased levels of Hb F. The peripheral blood samples will be submitted to the classical tests to hemoglobinopathies diagnostic, chromatographic analysis by HPLC and molecular analysis to confirm the mutations. Initially a pilot project will be conducted with samples from individuals with beta-hemoglobinopathies and control subjects. The sample group will be screened for regulatory elements and micro-RNAs previously selected by bioinformatics tools. Expression of micro-RNAs will be analyzed by qPCR and RT-PCR. The results of the elements that were expressed in this pilot test will be assessed in patients with beta-hemoglobinopathies undergoing specific treatment, with the aim of evaluate the drugs response.

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
CARROCINI, GISELE C. S.; VENANCIO, LARISSA P. R.; PESSOA, VIVIANI L. R.; LOBO, CLARISSE L. C.; BONINI-DOMINGOS, CLAUDIA R. Mutational Profile of Homozygous -Thalassemia in Rio de Janeiro, Brazil. HEMOGLOBIN, v. 41, n. 1, p. 12-15, 2017. Web of Science Citations: 1.
DE SOUZA CARROCINI, GISELE CRISTINE; RODRIGUES VENANCIO, LARISSA PAOLA; BONINI-DOMINGOS, CLAUDIA REGINA. Screening of Transcription Factors Involved in Fetal Hemoglobin Regulation Using Phylogenetic Footprinting. EVOLUTIONARY BIOINFORMATICS, v. 11, p. 239-244, 2015. Web of Science Citations: 2.
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
CARROCINI, Gisele Cristine de Souza. Elementos de regulação e microRNAs envolvidos na modulação dos níveis de hemoglobina fetal em indivíduos portadores de beta-hemoglobinopatias. 2015. 134 f. Doctoral Thesis - Universidade Estadual Paulista "Júlio de Mesquita Filho" Instituto de Biociências, Letras e Ciências Exatas..

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