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Pervasive occurrence of splice-site-creating mutations and their possible involvement in genetic disorders
The search for causative mutations in human genetic disorders has mainly focused on mutations that disrupt coding regions or splice sites. Recently, however, it has been reported that mutations creating splice sites can also cause a range of genetic disorders. In this study, we identified 5656 candi...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8933504/ https://www.ncbi.nlm.nih.gov/pubmed/35304488 http://dx.doi.org/10.1038/s41525-022-00294-0 |
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author | Sakaguchi, Narumi Suyama, Mikita |
author_facet | Sakaguchi, Narumi Suyama, Mikita |
author_sort | Sakaguchi, Narumi |
collection | PubMed |
description | The search for causative mutations in human genetic disorders has mainly focused on mutations that disrupt coding regions or splice sites. Recently, however, it has been reported that mutations creating splice sites can also cause a range of genetic disorders. In this study, we identified 5656 candidate splice-site-creating mutations (SCMs), of which 3942 are likely to be pathogenic, in 4054 genes responsible for genetic disorders. Reanalysis of exome data obtained from ciliopathy patients led us to identify 38 SCMs as candidate causative mutations. We estimate that, by focusing on SCMs, the increase in diagnosis rate is approximately 5.9–8.5% compared to the number of already known pathogenic variants. This finding suggests that SCMs are mutations worth focusing on in the search for causative mutations of genetic disorders. |
format | Online Article Text |
id | pubmed-8933504 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-89335042022-04-01 Pervasive occurrence of splice-site-creating mutations and their possible involvement in genetic disorders Sakaguchi, Narumi Suyama, Mikita NPJ Genom Med Article The search for causative mutations in human genetic disorders has mainly focused on mutations that disrupt coding regions or splice sites. Recently, however, it has been reported that mutations creating splice sites can also cause a range of genetic disorders. In this study, we identified 5656 candidate splice-site-creating mutations (SCMs), of which 3942 are likely to be pathogenic, in 4054 genes responsible for genetic disorders. Reanalysis of exome data obtained from ciliopathy patients led us to identify 38 SCMs as candidate causative mutations. We estimate that, by focusing on SCMs, the increase in diagnosis rate is approximately 5.9–8.5% compared to the number of already known pathogenic variants. This finding suggests that SCMs are mutations worth focusing on in the search for causative mutations of genetic disorders. Nature Publishing Group UK 2022-03-18 /pmc/articles/PMC8933504/ /pubmed/35304488 http://dx.doi.org/10.1038/s41525-022-00294-0 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Sakaguchi, Narumi Suyama, Mikita Pervasive occurrence of splice-site-creating mutations and their possible involvement in genetic disorders |
title | Pervasive occurrence of splice-site-creating mutations and their possible involvement in genetic disorders |
title_full | Pervasive occurrence of splice-site-creating mutations and their possible involvement in genetic disorders |
title_fullStr | Pervasive occurrence of splice-site-creating mutations and their possible involvement in genetic disorders |
title_full_unstemmed | Pervasive occurrence of splice-site-creating mutations and their possible involvement in genetic disorders |
title_short | Pervasive occurrence of splice-site-creating mutations and their possible involvement in genetic disorders |
title_sort | pervasive occurrence of splice-site-creating mutations and their possible involvement in genetic disorders |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8933504/ https://www.ncbi.nlm.nih.gov/pubmed/35304488 http://dx.doi.org/10.1038/s41525-022-00294-0 |
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