O papel das duplicações segmentares na formação de variação do número de cópias de novo após a exposição parental a doses baixas de radiação ionizante observadas na geração F1 de indivíduos acidentalmente expostos ao Césio-137

• Ano de defesa: 2018
• Autor(a) principal: Oliveira, Lorraynne Guimarães
• Orientador(a): Cruz, Aparecido Divino da
• Banca de defesa: Silva, Cláudio Carlos da , Santos, Eliane Eugenia dos
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Pontifícia Universidade Católica de Goiás
• Programa de Pós-Graduação: Programa de Pós-Graduação STRICTO SENSU em Genética
• Departamento: Escola de Ciências Agrárias e Biológicas::Curso de Biologia Bacharelado
• País: Brasil
• Palavras-chave em Português: Mutação. SNP Array. Transgeracional. Radiação.
• Palavras-chave em Inglês: Mutation. SNP Array. Transgenerational. Radiation.
• Área do conhecimento CNPq: CIENCIAS BIOLOGICAS::GENETICA
• Link de acesso: https://tede2.pucgoias.edu.br/handle/tede/3999

At the end of 1987 was one of the most serious radiological accidents in history, occurred in Goiânia-Goiás-Brazil, causing the contamination of the environment, succeending in the external irradiation and the internal contamination of several people. The direct and indirect effects of radiation initiate a series of biochemical and molecular signaling events that can repair the damage or culminate in permanent physiological changes or cell death. Mammalian cells have integrated response systems that detect DNA damage, activate signaling cascades, and realize repair. Chromosomal rearrangements induced by exposure to ionizing radiation can occur by Double Strand Break in the DNA (DSB). The main DNA repair mechanism responsible for the repair of DSBs is Nonallelic Homologous Recombination (NAHR). Through the NAHR process, the Low Copy Repeats known also with Segmental Duplications (LCRs / SDs) can lead to DNA rearrangements, such: deletions, duplications, inversions and translocations. Chromosomal Microarray Analysis (CMA) based on SNP array, is established on the identification of Copy Number Variantion (CNV), including gains and losses. The goal of this study was to investigate the effect of the presence of LCRs in the formation of new CNVs observed in the offspring of individuals exposed to low doses of IR of Cesium-137. The exposed group consisted of 12 families, of which at least one parent was directly exposed to IR Césio-137, including a total of 40 individuals (12 couples and 16 children born after the accident). The absorbed dose for the exposed individuals was estimated at ≤0.2 Gray. A group with 8 families of individuals not exposed to IR was used as control. The statistical tests used were Chi-Square, Pearson's Chi-Square, ANOVA, Spearman's Correlation, Kruskal Wallis, Likelihood Ratio and Linear Linear Association. All analyzes were performed with a significance level of 5% (p <0.05). We identified 50 (10.6%) and 23 (9.7%) CNVs that were being flanked by LCRs for the case and control groups, respectively. The test showed no significant difference. The comparison of gain and loss CNVs flanked by LCRs showed a significant difference where LCRs were significantly more associated with gain CNVs. The presence of LCRs was often associated with more longer CNVs, suggesting that CNVs originating from NAHR tend to be bigger. The CNV rates mutation and paternal meiosis in F1 generation of the case and control groups showed a significant difference. Men exposed to IR transmit more CNVs again small when compared to transmission based on maternal exposure and between controls. The estimation of rate mutation in LCR-mediated CNVs analyzed in F1 generation and in their biological parents was a useful biomarker in the retrospective evaluation of parental exposure to IR in human populations, especially for Burden mutation rate estimation.