Investigation of parents de novo risk variants in Autism Spectrum Disorder (ASD)

• Grant number: 17/05824-2
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: June 01, 2017
• End date: July 31, 2019
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Maria Rita dos Santos e Passos Bueno
• Grantee: Eduarda Morgana da Silva Montenegro Malaguti de Souza
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center, AP.CEPID
• Associated scholarship(s): 18/13743-5 - Big data analysis of genomic variants in ASD individuals and validation of new candidate genes, BE.EP.DR

Abstract

Autism spectrum disorder (ASD) is mainly characterized through: persistent deficit in social communication and interaction, repetitive and restricted patterns of behavior and interests. It is estimate that nearly 1% of global population could receive ASD diagnosis. Studies demonstrate a high genetics contribution in ASD, the heritability is about 90%. A current and important challenge in ASD genetics field is to determine how many and which are the pathogenic variants that contribute to phenotype. It is well establish that ASD individuals present a higher rate of new variants (de novo) compared to general population. However, there are few cases wherein one de novo variant is enough penetrant to lead ASD phenotype. Thus, it is consider that inherited variants can contribute to phenotype, although to rank and to relate these variants to clinical case still challenging. Therefore, we hypothesize that among inherited variants the probably related to phenotype are de novo in parents and may occur mainly in ASD genes. For this purpose, exome sequencing will be performed in 30 ASD families (210 individuals), which consist in probands, parents and grandparents, wherein it is expected to detect de novo variants in approximately 20% of parents. Additionally, we expect to detect possible differences among de novo rates in parents, compared to probands and general population. This familial search for de novo variants in parents has never been done, and probably it will allow establishing the relevance of these variants to ASD phenotype, as well to expand the current knowledge about genes and pathways in ASD etiology. (AU)

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)

DA SILVA MONTENEGRO, EDUARDA MORGANA; COSTA, CLAUDIA SAMOGY; CAMPOS, GABRIELE; SCLIAR, MARILIA; DE ALMEIDA, TATIANA FERREIRA; ZACHI, ELAINE CRISTINA; WAHYS SILVA, ISABELA MAYA; CHAN, ADA J. S.; ZARREI, MEHDI; LOURENCO, V, NAILA C.; et al. Meta-Analyses Support Previous and Novel Autism Candidate Genes: Outcomes of an Unexplored Brazilian Cohort. Autism Research, v. 13, n. 2, p. 199-206, FEB 2020. (17/05824-2, 13/08028-1)

COSTA, CLAUDIA I. SAMOGY; CAMPOS, GABRIELE DA SILVA; MONTENEGRO, EDUARDA MORGANA DA SILVA; WANG, JAQUELINE YU TING; SCLIAR, MARILIA; MONFARDINI, FREDERICO; ZACHI, ELAINE CRISTINA; LOURENCO, NAILA C. V.; CHAN, ADA J. S.; PEREIRA, SERGIO L.; et al. Three generation families: Analysis of de novo variants in autism. European Journal of Human Genetics, v. 31, n. 9, p. 6-pg., 2023-06-06. (13/08028-1, 18/13743-5, 17/05824-2)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SOUZA, Eduarda Morgana da Silva Montenegro Malaguti de. Investigation of de novo variants and copy number variantions in autism spectrum disorder etiology. 2020. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Biociências (IBIOC/SB) São Paulo.