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Functional interrogation of autoimmune disease genetics using CRISPR/Cas9 technologies and massively parallel reporter assays

Genetic studies, including genome-wide association studies, have identified many common variants that are associated with autoimmune diseases. Strikingly, in addition to being frequently observed in healthy individuals, a number of these variants are shared across diseases with diverse clinical pres...

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Autores principales: Ding, James, Frantzeskos, Antonios, Orozco, Gisela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8837574/
https://www.ncbi.nlm.nih.gov/pubmed/34508276
http://dx.doi.org/10.1007/s00281-021-00887-4
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author Ding, James
Frantzeskos, Antonios
Orozco, Gisela
author_facet Ding, James
Frantzeskos, Antonios
Orozco, Gisela
author_sort Ding, James
collection PubMed
description Genetic studies, including genome-wide association studies, have identified many common variants that are associated with autoimmune diseases. Strikingly, in addition to being frequently observed in healthy individuals, a number of these variants are shared across diseases with diverse clinical presentations. This highlights the potential for improved autoimmune disease understanding which could be achieved by characterising the mechanism by which variants lead to increased risk of disease. Of particular interest is the potential for identifying novel drug targets or of repositioning drugs currently used in other diseases. The majority of autoimmune disease variants do not alter coding regions and it is often difficult to generate a plausible hypothetical mechanism by which variants affect disease-relevant genes and pathways. Given the interest in this area, considerable effort has been invested in developing and applying appropriate methodologies. Two of the most important technologies in this space include both low- and high-throughput genomic perturbation using the CRISPR/Cas9 system and massively parallel reporter assays. In this review, we introduce the field of autoimmune disease functional genomics and use numerous examples to demonstrate the recent and potential future impact of these technologies.
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spelling pubmed-88375742022-02-23 Functional interrogation of autoimmune disease genetics using CRISPR/Cas9 technologies and massively parallel reporter assays Ding, James Frantzeskos, Antonios Orozco, Gisela Semin Immunopathol Review Genetic studies, including genome-wide association studies, have identified many common variants that are associated with autoimmune diseases. Strikingly, in addition to being frequently observed in healthy individuals, a number of these variants are shared across diseases with diverse clinical presentations. This highlights the potential for improved autoimmune disease understanding which could be achieved by characterising the mechanism by which variants lead to increased risk of disease. Of particular interest is the potential for identifying novel drug targets or of repositioning drugs currently used in other diseases. The majority of autoimmune disease variants do not alter coding regions and it is often difficult to generate a plausible hypothetical mechanism by which variants affect disease-relevant genes and pathways. Given the interest in this area, considerable effort has been invested in developing and applying appropriate methodologies. Two of the most important technologies in this space include both low- and high-throughput genomic perturbation using the CRISPR/Cas9 system and massively parallel reporter assays. In this review, we introduce the field of autoimmune disease functional genomics and use numerous examples to demonstrate the recent and potential future impact of these technologies. Springer Berlin Heidelberg 2021-09-10 2022 /pmc/articles/PMC8837574/ /pubmed/34508276 http://dx.doi.org/10.1007/s00281-021-00887-4 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Review
Ding, James
Frantzeskos, Antonios
Orozco, Gisela
Functional interrogation of autoimmune disease genetics using CRISPR/Cas9 technologies and massively parallel reporter assays
title Functional interrogation of autoimmune disease genetics using CRISPR/Cas9 technologies and massively parallel reporter assays
title_full Functional interrogation of autoimmune disease genetics using CRISPR/Cas9 technologies and massively parallel reporter assays
title_fullStr Functional interrogation of autoimmune disease genetics using CRISPR/Cas9 technologies and massively parallel reporter assays
title_full_unstemmed Functional interrogation of autoimmune disease genetics using CRISPR/Cas9 technologies and massively parallel reporter assays
title_short Functional interrogation of autoimmune disease genetics using CRISPR/Cas9 technologies and massively parallel reporter assays
title_sort functional interrogation of autoimmune disease genetics using crispr/cas9 technologies and massively parallel reporter assays
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8837574/
https://www.ncbi.nlm.nih.gov/pubmed/34508276
http://dx.doi.org/10.1007/s00281-021-00887-4
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