Whole Exome Sequencing in oral clefts selected from the Brazilian Database on Craniofacial Anomalies

• Grant number: 18/21370-4
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2019
• End date: November 30, 2021
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Vera Lúcia Gil da Silva Lopes
• Grantee: Vera Lúcia Gil da Silva Lopes
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Ilária Cristina Sgardioli ; Társis Antônio Paiva Vieira

Abstract

The implementation of databases is a worldwide strategy for epidemiological recognition and its impact - individual and collective - on prevention, diagnosis and treatment. The Brazilian Database on Craniofacial Anomalies (BDCA) collects sociodemographic and genetic information and performs the clinical follow-up of craniofacial anomalies, with major contribution of cases of oral clefts. This project aims to investigate the etiology of familial non-syndromic oral clefts (FNSOC) and unusual syndromic conditions with oral clefts as a cardinal signal (Syndromic Oral Cleft - SOC) through Whole Exome Sequencing. The cases were selected from a set of 2000 individuals registered with BDCA. Of 48 families with NSOC and vertical transmission, 18 were chosen for investigation, in addition to 08 individuals with unusual conditions in which Chromosomal Microarray Analysis (CMA) presents regions of homozygozity suggesting autosomal recessive inheritance.From total DNA and whole exome sequencing, the analysis will be performed through an algorithm developed for craniofacial anomalies by the University of Nijmegen, which cooperates in this study. In cases without mutations previously associated with craniofacial anomalies, the whole exome will be analyzed, seeking for new genes related to the oral clefts. Confirmation of the variants and investigation of other members of the families will be carried out by Sanger technique. In addition to the training of human resources, scientific results would include identification of genetic component on FNSOC and clinical and etiological characterization of new syndromic pictures with oral clefts, including theirs natural histories and clinical management, as well as their participation in Brazilian population. All data would be part of the BDCA and the Brazilian Initiative on Precision Medicine (BIPMed). After the laboratory investigation, the transmission of the results to the families will be part of genetic counselling. (AU)