Data for: A systems genetics approach identifies roles for proteasome factors in heart development and congenital heart defects

In this study, we sought to take a new approach to identify genetic causes
of CHDs. By combining analyses of genes that are under strong selective
constraint along with published embryonic heart transcriptomes, we
identified over 200 new candidate genes for CHDs. We utilized
protein-protein interaction (PPI) network analysis to identify a
functionally-related subnetwork consisting of known CHD genes as well as
genes encoding proteasome factors, in particular POMP, PSMA6,
PSMA7, PSMD3, and PSMD6. We used CRISPR targeting in zebrafish embryos to
preliminarily identify roles for the PPI subnetwork genes in heart
development. We then used CRISPR to create new mutant zebrafish strains
for two of the proteasome genes in the subnetwork: pomp and psmd6. We show
that loss of proteasome gene functions leads to defects in zebrafish heart
development, including dysmorphic hearts, myocardial cell blebbing, and
reduced outflow tracts. We also identified deficits in cardiac function in
pomp and psmd6 mutants. These heart defects resemble those seen in
zebrafish mutants for known CHD genes and other critical heart development
genes. Our study provides a novel systems genetics approach to further our
understanding of the genetic causes of human CHDs.