Detection and characterization of structural variants in the human genome using new technologies

• Grant number: 22/16766-1
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2023
• End date: May 31, 2025
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Társis Antônio Paiva Vieira
• Grantee: Társis Antônio Paiva Vieira
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Cláudia Márcia Benedetto de Carvalho Fonseca ; Vera Lúcia Gil da Silva Lopes

Abstract

Structural variants (SVs) are rearrangements of the DNA in a genome resulting in novel breakpoint junctional events, including all structural chromosomal rearrangements, and can be disease causing. Balanced chromosomal rearrangements (BCRs), complex chromosomal rearrangements (CCRs) and ring chromosomes are rare and can cause abnormal phenotypes through different mechanisms. New technologies such as next generation sequencing and optical genome mapping (OGM) allow SVs characterization with an unprecedented level of resolution, contributing to the discovery of new disease genes and to the knowledge of mechanisms of origin of SVs. The aims of this study are: (a) characterizing BCRs in individuals with abnormal phenotypes; (b) characterizing CCRs; and (c) investigating the instability of ring chromosomes and characterize its breakpoints. It will be done using whole genomic sequencing with 30X and low-pass genomic sequencing, OGM, chromosomal microarray analysis (CMA) and fluorescent in situ hybridization (FISH). Genome sequencing and OGM will be performed at laboratory facilities and will be analysed with the support of Professor Claudia Carvalho from the Pacific Northwest Research Institute (PNRI), US, who is experienced in these methods to solve structural rearrangements. FISH and CMA will be performed at the Laboratory of Human Cytogenetics and Cytogenomics (LHCC) - Unicamp. This research project will contribute to the characterization of structural variants in the human genome, at the level of base pairs of DNA, and may contribute to the identification of new disease genes and to the knowledge of mechanisms of origin of the studied alterations. (AU)