High throughput in vivo functional validation of candidate congenital heart disease genes in Drosophila
Genomic sequencing has implicated large numbers of genes and de novo mutations as potential disease risk factors. A high throughput in vivo model system is needed to validate gene associations with pathology. We developed a Drosophila-based functional system to screen candidate disease genes identified from Congenital Heart Disease (CHD) patients. 134 genes were tested in the Drosophila heart using RNAi-based gene silencing. Quantitative analyses of multiple cardiac phenotypes demonstrated essential structural, functional, and developmental roles for more than 70 genes, including a subgroup encoding histone H3K4 modifying proteins. We also demonstrated the use of Drosophila to evaluate cardiac phenotypes resulting from specific, patient-derived alleles of candidate disease genes. We describe the first high throughput in vivo validation system to screen candidate disease genes identified from patients. This approach has the potential to facilitate development of precision medicine approaches for CHD and other diseases associated with genetic factors.
Article and author information
National Heart, Lung, and Blood Institute (NIH R01)
- Zhe Han
National Institute of Diabetes and Digestive and Kidney Diseases (NIH R01)
- Zhe Han
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Richard P Harvey, Victor Chang Cardiac Research Institute, Australia
- Received: October 23, 2016
- Accepted: January 11, 2017
- Accepted Manuscript published: January 13, 2017 (version 1)
- Accepted Manuscript updated: January 20, 2017 (version 2)
- Version of Record published: February 9, 2017 (version 3)
- Version of Record updated: August 8, 2017 (version 4)
© 2017, Zhu et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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