Using Systems Genetics to Probe for Gene Interactions in Congenital Heart Disease
Abstract
In this project we tried 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 planned to use a two-pronged strategy to systematically identify cardiac gene networks: comprehensively identifying genetic interactors of cardiogenic genesNKX2-5/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 (aim 2). During year one and two, we identified ~163 regions in the fly genome that display either synthetic lethality or cardiac phenotypes in conjunction with tinman/pannier with about 80% 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. Surprisingly, we found many loci that ameliorated the tin/pnr double-heterozygous phenotypes in transheterozygous condition. The next steps are to follow up with identification of 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 will process these cells for mass-screening using our collaborators high-throughput assay.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2023
- Accession Number
- AD1225087
Entities
People
- Georg Vogler