Breaking enhancers to gain insights into developmental defects
Despite ground-breaking genetic studies that have identified thousands of risk variants for developmental diseases, how these variants lead to molecular and cellular phenotypes remains a gap in knowledge. Many of these variants are non-coding and occur at enhancers, which orchestrate key regulatory...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2023-07-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/88187 |
| _version_ | 1797771273271508992 |
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| author | Daniel A Armendariz Anjana Sundarrajan Gary C Hon |
| author_facet | Daniel A Armendariz Anjana Sundarrajan Gary C Hon |
| author_sort | Daniel A Armendariz |
| collection | DOAJ |
| description | Despite ground-breaking genetic studies that have identified thousands of risk variants for developmental diseases, how these variants lead to molecular and cellular phenotypes remains a gap in knowledge. Many of these variants are non-coding and occur at enhancers, which orchestrate key regulatory programs during development. The prevailing paradigm is that non-coding variants alter the activity of enhancers, impacting gene expression programs, and ultimately contributing to disease risk. A key obstacle to progress is the systematic functional characterization of non-coding variants at scale, especially since enhancer activity is highly specific to cell type and developmental stage. Here, we review the foundational studies of enhancers in developmental disease and current genomic approaches to functionally characterize developmental enhancers and their variants at scale. In the coming decade, we anticipate systematic enhancer perturbation studies to link non-coding variants to molecular mechanisms, changes in cell state, and disease phenotypes. |
| first_indexed | 2024-03-12T21:35:08Z |
| format | Article |
| id | doaj.art-0d17fa6c60924513bd9e05f393634d0d |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-03-12T21:35:08Z |
| publishDate | 2023-07-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-0d17fa6c60924513bd9e05f393634d0d2023-07-27T10:06:53ZengeLife Sciences Publications LtdeLife2050-084X2023-07-011210.7554/eLife.88187Breaking enhancers to gain insights into developmental defectsDaniel A Armendariz0https://orcid.org/0000-0002-5857-1282Anjana Sundarrajan1https://orcid.org/0000-0003-0231-8090Gary C Hon2https://orcid.org/0000-0002-1615-0391Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, United StatesCecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, United StatesCecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, United States; Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, United States; Lyda Hill Department of Bioinformatics, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, United StatesDespite ground-breaking genetic studies that have identified thousands of risk variants for developmental diseases, how these variants lead to molecular and cellular phenotypes remains a gap in knowledge. Many of these variants are non-coding and occur at enhancers, which orchestrate key regulatory programs during development. The prevailing paradigm is that non-coding variants alter the activity of enhancers, impacting gene expression programs, and ultimately contributing to disease risk. A key obstacle to progress is the systematic functional characterization of non-coding variants at scale, especially since enhancer activity is highly specific to cell type and developmental stage. Here, we review the foundational studies of enhancers in developmental disease and current genomic approaches to functionally characterize developmental enhancers and their variants at scale. In the coming decade, we anticipate systematic enhancer perturbation studies to link non-coding variants to molecular mechanisms, changes in cell state, and disease phenotypes.https://elifesciences.org/articles/88187genomicsgenetic diseasesCRISPRdevelopment |
| spellingShingle | Daniel A Armendariz Anjana Sundarrajan Gary C Hon Breaking enhancers to gain insights into developmental defects eLife genomics genetic diseases CRISPR development |
| title | Breaking enhancers to gain insights into developmental defects |
| title_full | Breaking enhancers to gain insights into developmental defects |
| title_fullStr | Breaking enhancers to gain insights into developmental defects |
| title_full_unstemmed | Breaking enhancers to gain insights into developmental defects |
| title_short | Breaking enhancers to gain insights into developmental defects |
| title_sort | breaking enhancers to gain insights into developmental defects |
| topic | genomics genetic diseases CRISPR development |
| url | https://elifesciences.org/articles/88187 |
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