Document Type

Journal Article

Publication Date

1-20-2017

Journal

Elife

Volume

6

DOI

10.7554/eLife.22617

Abstract

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.

Comments

Reproduced with permission of eLife Sciences Publications Ltd. eLife

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

Peer Reviewed

1

Open Access

1

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