PUBLICATION
Systems Analysis Implicates WAVE2 Complex in the Pathogenesis of Developmental Left-Sided Obstructive Heart Defects
- Authors
- Edwards, J.J., Rouillard, A.D., Fernandez, N.F., Wang, Z., Lachmann, A., Shankaran, S.S., Bisgrove, B.W., Demarest, B., Turan, N., Srivastava, D., Bernstein, D., Deanfield, J., Giardini, A., Porter, G., Kim, R., Roberts, A.E., Newburger, J.W., Goldmuntz, E., Brueckner, M., Lifton, R.P., Seidman, C.E., Chung, W.K., Tristani-Firouzi, M., Yost, H.J., Ma'ayan, A., Gelb, B.D.
- ID
- ZDB-PUB-200506-13
- Date
- 2020
- Source
- JACC. Basic to translational science 5: 376-386 (Journal)
- Registered Authors
- Bisgrove, Brent, Demarest, Bradley, Shankaran, Sunita Sathy, Yost, H. Joseph
- Keywords
- CHD, congenital heart disease, CORUM, Comprehensive Resource of Mammalian Protein Complexes, CRISPR, clustered regularly interspaced short palindromic repeats, CTD, conotruncal defect, GOBP, Gene Ontology biological processes, HHE, high heart expression, HLHS, hypoplastic left heart syndrome, HTX, heterotaxy, LVOTO, left ventricular outflow tract obstruction, MGI, Mouse Genome Informatics, PCGC, Pediatric Cardiac Genomics Consortium, PPI, protein-protein interaction, congenital heart disease, systems biology, translational genomics
- MeSH Terms
- none
- PubMed
- 32368696 Full text @ JACC Basic Transl Sci
Citation
Edwards, J.J., Rouillard, A.D., Fernandez, N.F., Wang, Z., Lachmann, A., Shankaran, S.S., Bisgrove, B.W., Demarest, B., Turan, N., Srivastava, D., Bernstein, D., Deanfield, J., Giardini, A., Porter, G., Kim, R., Roberts, A.E., Newburger, J.W., Goldmuntz, E., Brueckner, M., Lifton, R.P., Seidman, C.E., Chung, W.K., Tristani-Firouzi, M., Yost, H.J., Ma'ayan, A., Gelb, B.D. (2020) Systems Analysis Implicates WAVE2 Complex in the Pathogenesis of Developmental Left-Sided Obstructive Heart Defects. JACC. Basic to translational science. 5:376-386.
Abstract
Genetic variants are the primary driver of congenital heart disease (CHD) pathogenesis. However, our ability to identify causative variants is limited. To identify causal CHD genes that are associated with specific molecular functions, the study used prior knowledge to filter de novo variants from 2,881 probands with sporadic severe CHD. This approach enabled the authors to identify an association between left ventricular outflow tract obstruction lesions and genes associated with the WAVE2 complex and regulation of small GTPase-mediated signal transduction. Using CRISPR zebrafish knockdowns, the study confirmed that WAVE2 complex proteins brk1, nckap1, and wasf2 and the regulators of small GTPase signaling cul3a and racgap1 are critical to cardiac development.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping