Interpretação da patogenicidade e estabelecimento de um banco de dados de variações de número de cópias (cnvs) em uma amostra da população brasileira

• Ano de defesa: 2019
• Autor(a) principal: Godoy, Victoria Cabral Silveira Monteiro De [UNIFESP]
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: CNV; Copy Number Variation; Database; Variação De Número De Cópia; Banco De Dados
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=8754207; https://repositorio.unifesp.br/handle/11600/59762

To survey and classify CNVs, previously identified from arrays performed in our laboratory, in order to build a CNV database of a Brazilian cohort. Methods: A Brazilian cohort of 284 individuals was analyzed, including patients with phenotypic alterations and their unaffected parents. The following array platforms were used: Genome-Wide Human Array 6.0 SNP array (n= 66 individuals), CytoScan High-Density SNP array (n= 163 individuals) and CytoScan 750K (n= 55 individuals), from Affymetrix. Array analyses were performed using the Chromosome Analysis Suite software (ChAS), (Affymetrix, Santa Clara, CA, USA). All arrays that met the QC parameters were included in the analysis and, by using a flowchart, the CNVs were classified according to their pathogenicity. Results: A total of 1,792 CNVs (1,380 gains and 412 losses) were classified as benign (82%), likely benign (3.1%), VUS (5.5%), likely pathogenic (0.2%) and pathogenic (9.2%). Some of the CNVs classified as likely benign or VUS were recurrent and presented an increased frequency. These CNVs could be considered benign in our Brazilian sample, changing the interpretation of their clinical impact. Conclusions: We constructed an internal CNV database of a Brazilian cohort that will be useful for future genomic analyzes in our laboratory. Our study described a high frequency of specific CNVs classified as possibly benign and VUS, and therefore those events were reclassified as benign. In addition, our study established a novel analysis flowchart that was highly effective in classifying the CNVs, even without a phenotype-based classification method.