Detecção e análise de mutações de novo em pacientes com exposição parental à radiação ionizante de Césio-137 a partir de dados de genotipagem de polimorfismos de base única de alta densidade

• Autor(a) principal: Leite Filho, Hugo Pereira
• Data de Publicação: 2020
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Repositório Institucional da UFG
• Texto Completo: http://repositorio.bc.ufg.br/tede/handle/tede/10960
• topic: Bioinformática; SNPs; Genotipagem; Desvio Mendeliano; CytoScan 750 K; SNPs; Mendelian deviation; Genotyping; CytoScan 750K; Bioinformatics; CIENCIAS BIOLOGICAS

In 1987, in the city of Goiânia, a series of unexpected events resulted in a serious radiological accident, generated by Césio-137. The mutagenic effects of ionizing radiation (IR) can lead to accumulation of mutations in children of irradiated parents. It was established that chromosomal microarray analysis (CMA), a cytogenomic technique for the detection of SNP in a wide spectrum of regions of the human genome. The use of cytogenetic assays based on high-density microarray of DNA allows identifying variations in SNPs and, consequently, genotyping them. In this study, using the GeneChip® HD® assay it was possible to establish the genotypes of SNPs in a population born from progenitors exposed to cesium-137 ionizing radiation. Mendelian germline deviations were used to estimate the rate of mutations induced by parental exposure in their offspring. The exposed group consisted of 11 families, of which at least one parent was directly exposed to Cesium-137 ionizing radiation, including a total of 37 individuals (11 couples and 15 children born after the accident). The absorbed dose for exposed individuals ranged from 0.2 to 0.5 Gray. A group of individuals not exposed to ionizing radiation was used as a control. This group consisted of 15 families from Goiás with no history of exposure to IR. The statistical tests used were: Shapiro-Wilk test, F test, regression analysis, clustering, and the main component analysis. All analyses were performed using the statistical package R, with a significance level of 5% (p<0.05). FMDM frequencies were estimated by case and control, representing 1.3x10-3, 0.9x10-3, respectively. Thus, the frequencies of FMDM showed statistically significant differences between the exposed and control groups (p<2x10-3, α = 0.5, Student-t). The F test to compare the variations of two samples (Case and Control) from populations with normal distribution showed that the variations (F=4.47; α = 0.5, p<8x10-3) between cases and controls were significantly different. In addition, the progeny of a population accidentally exposed to low doses of IR showed ~ 1.44x more de novo Mendelian deviations (MD) than healthy controls. In conclusion, the frequency of germ line/generation MD mutation may be useful to study human populations exposed to IR retrospectively, using the Mendelian deviation findings technique, it was possible to identify the origin of the parents, as well as the type of substitution and inform which variant suffered the mutation. Therefore, DM are potentially useful markers to discriminate parental exposure to IR.