Edwards, JJ;
Rouillard, AD;
Fernandez, NF;
Wang, Z;
Lachmann, A;
Shankaran, SS;
Bisgrove, BW;
... Gelb, BD; + view all
(2020)
Systems Analysis Implicates WAVE2 Complex in the Pathogenesis of Developmental Left-Sided Obstructive Heart Defects.
JACC: Basic to Translational Science
, 5
(4)
pp. 376-386.
10.1016/j.jacbts.2020.01.012.
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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.
| Type: | Article |
|---|---|
| Title: | Systems Analysis Implicates WAVE2 Complex in the Pathogenesis of Developmental Left-Sided Obstructive Heart Defects |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.jacbts.2020.01.012 |
| Publisher version: | https://doi.org/10.1016/j.jacbts.2020.01.012 |
| Language: | English |
| Additional information: | © 2020 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation under a Creative Commons license (https://creativecommons.org/licenses/by-nc-nd/4.0/). |
| Keywords: | congenital heart disease, systems biology, translational genomics |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Clinical Science |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10096332 |
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