Using Systems Genetics to Probe for Gene Interactions in Congenital Heart Disease
Abstract
In this project we are trying to understand the gene networks underlying congenital heart disease, specifically bicuspid aortic valve (BAV) and its relation to hypoplastic left heart syndrome (HLHS). Under this proposal we are using a two-pronged strategy to systematically identify cardiac gene networks: comprehensively identifying genetic interactors of cardiogenic genes NKX2-5/tinman and GATA4/pannier using the adult Drosophila (fruit fly) heart (aim 1), and iPSC-derived cardiac progenitors and cardiomyocytes from two families (parent/proband trios) with BAV+HLHS (aim2). During year one, we identified approx. 40 regions in the fly genome that display either synthetic lethality or cardiac phenotypes in conjunction with tinman/pannier with about 30 percent completion of the genetic screen. These regions include several likely candidate genes such as Muscle-specific protein 300 (Msp300/Nesprin1), as well as many new potential loci with currently unknown role in heart development and function. While we are completing the genetic screen to identify all tin/pnr interacting loci in the fly genome, we are also setting up the experiments to follow up on identifying the specific gene loci inside the candidate regions responsible for the interaction. For aim 2, we acquired the cell lines (iPSCs) necessary for conducting the proposed research and are currently processing these cells for mass-screening using our collaborators high-throughput assay.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2022
- Accession Number
- AD1169483
Entities
People
- Georg Vogler
Organizations
- Sanford Burnham Prebys Medical Discovery Institute