A study of the conformational impacts in products of genes with non-synonymous variants in cis

• Grant number: 22/15941-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2023
• End date: April 30, 2025
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Michel Satya Naslavsky
• Grantee: Camila Hosoe Takase
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Variants in gene regions can have functional effects over its products, often with consequences to clinical phenotypes. Coding non-synonymous variants, to which amino acids are substituted, can impact protein structure and, as a consequence, its function. The analysis and assessment of the effects of the presence of simultaneous non-synonymous coding variants in cis configuration (across a single homologous chromosome) concerning the structure of the resulting protein and the phenotypic consequences to the carrier are commonly dismissed in comparison to the study of implications that occur due to isolated non-synonym coding variants. The project aims to investigate the occurrence of cis non-synonymous coding variants in a Brazilian population sample utilizing the whole-genome sequencing dataset obtained from the SABE (Saúde, Bem-estar e Envelhecimento) cohort as a basis to filter the non-synonym variants. Knowing the existence of a significant abundance of cis configurations of coding variants in diploid human genomes, filters will be used to identify potential cis variants. Based on the genes obtained in the last phase, the ones with resolved and available tridimensional protein structures will be sought, to enable evaluation and comparison with the impacts caused by the co-occurrence of cis variants and the occurrence of a single isolated variant, seeking to elucidate its effects and promote a bigger focus on this sphere. This project is expected to contribute in understanding the combined effect of more than a single variant occurring at a given gene product as compared to the effects of each individual variant.