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 identif...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2017-01-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/22617 |
| _version_ | 1811202623003426816 |
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| author | Jun-yi Zhu Yulong Fu Margaret Nettleton Adam Richman Zhe Han |
| author_facet | Jun-yi Zhu Yulong Fu Margaret Nettleton Adam Richman Zhe Han |
| author_sort | Jun-yi Zhu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T02:41:54Z |
| format | Article |
| id | doaj.art-45ad8aa5151945ba84f52313dccd7cf9 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:41:54Z |
| publishDate | 2017-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-45ad8aa5151945ba84f52313dccd7cf92022-12-22T03:51:17ZengeLife Sciences Publications LtdeLife2050-084X2017-01-01610.7554/eLife.22617High throughput in vivo functional validation of candidate congenital heart disease genes in DrosophilaJun-yi Zhu0Yulong Fu1Margaret Nettleton2Adam Richman3Zhe Han4https://orcid.org/0000-0002-5177-7798Center for Cancer and Immunology Research, Children's National Medical Center, Washington, United StatesCenter for Cancer and Immunology Research, Children's National Medical Center, Washington, United StatesCenter for Cancer and Immunology Research, Children's National Medical Center, Washington, United StatesCenter for Cancer and Immunology Research, Children's National Medical Center, Washington, United StatesCenter for Cancer and Immunology Research, Children's National Medical Center, Washington, United States; Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, United StatesGenomic 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.https://elifesciences.org/articles/22617congenital heart diseaseheart developmentin vivo validationhistone modificationDrosophila |
| spellingShingle | Jun-yi Zhu Yulong Fu Margaret Nettleton Adam Richman Zhe Han High throughput in vivo functional validation of candidate congenital heart disease genes in Drosophila eLife congenital heart disease heart development in vivo validation histone modification Drosophila |
| title | High throughput in vivo functional validation of candidate congenital heart disease genes in Drosophila |
| title_full | High throughput in vivo functional validation of candidate congenital heart disease genes in Drosophila |
| title_fullStr | High throughput in vivo functional validation of candidate congenital heart disease genes in Drosophila |
| title_full_unstemmed | High throughput in vivo functional validation of candidate congenital heart disease genes in Drosophila |
| title_short | High throughput in vivo functional validation of candidate congenital heart disease genes in Drosophila |
| title_sort | high throughput in vivo functional validation of candidate congenital heart disease genes in drosophila |
| topic | congenital heart disease heart development in vivo validation histone modification Drosophila |
| url | https://elifesciences.org/articles/22617 |
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