Identification and characterization of genes controlling blood pressure by the ENU methodology

• Grant number: 17/14448-4
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: October 01, 2017
• End date: September 30, 2018
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: José Eduardo Krieger
• Grantee: Roberto Braz Pontes Junior
• Supervisor: Bruce Alan Beutler
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Institution abroad: University of Texas Southwestern Medical Center, Dallas (UT Southwestern), United States
• Associated to the scholarship: 17/05352-3 - Blood pressure control genes characterization and localization through the ENU methodology, BP.PD

Abstract

Hypertension affects one billion people worldwide and in 95% of the cases, patients present essential hypertension which causes remain unknown. Studies in human population demonstrated that the heritability of the systolic and diastolic blood pressure varies from 25 to 68%, according to the population.Moreover, studies using genomic approaches to identify the genetic causes for human hypertension revealed more than 100 genetic variants associated with blood pressure. However, these variants account for only 1-2% of the variation in blood pressure in humans. Contributing to the difficulty of identifying the cause of essential hypertension, studies of mapping and refinement of quantitative traits in rats have shown limited results despite the great time and resources expended. Recently, Wang and coworkers described a methodology using forward-genetic screen based on next-generation sequencing and bioinformatics tools capable of quickly analyzing the genotypic and phenotypic data, in order to provide a robust association between the results. The aim of this work is to identify and characterize blood pressure regulating genes using the forward-genetic approach described by Wang et al. Thus,we believe that this strategy will enable systematic characterization of blood pressure regulating genes in mice in a unique way.