Viewpoint: Before progressing from “exomes" to “genomes”… don't forget splicing mutations
| cam.issuedOnline | 2018-07-12 | |
| dc.contributor.author | Woods, CG | |
| dc.contributor.author | Shaikh, samiha | |
| dc.contributor.author | Nahorski, michael | |
| dc.contributor.author | raj, harjeet | |
| dc.contributor.orcid | Woods, Geoff [0000-0002-8077-2101] | |
| dc.date.accessioned | 2018-09-08T06:32:09Z | |
| dc.date.available | 2018-09-08T06:32:09Z | |
| dc.description.abstract | Splicing mutations are less commonly reported than other mutation types1-3. However, despite most being functional nulls, previous reports suggested that they are under-recognized2. Our recent experience of investigating a cohort of 38 individuals with a severe, genetically heterogeneous Mendelian phenotype shows that this continues to be a problem; three mutations that affected splicing were initially “missed” because they were not detected by current splice site detection algorithms. Our concern is that splicing mutations will continue to be overlooked in clinical laboratory settings because the quantity of data generated per person by “exomes” and “genomes” necessitates the use of splice site detection programs. Our cases highlight significant deficiencies in current standard programs, where variants at the U2 canonical AG (acceptor) and GT (donor) splice sites are reliably detected, but variants at other positions with more loosely defined consensus sequences, or U12 splice sites, are rarely detected4. | |
| dc.description.sponsorship | MRC CASE and Wellcome Trust Coll.award | |
| dc.identifier.doi | 10.17863/CAM.27209 | |
| dc.identifier.issn | 1018-4813 | |
| dc.identifier.uri | https://www.repository.cam.ac.uk/handle/1810/279841 | |
| dc.language.iso | eng | |
| dc.publisher | Springer Nature | |
| dc.publisher.url | https://www.nature.com/articles/s41431-018-0214-3#article-info | |
| dc.rights | Attribution 4.0 International (CC BY 4.0) | |
| dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
| dc.title | Viewpoint: Before progressing from “exomes" to “genomes”… don't forget splicing mutations | |
| dc.type | Article | |
| dcterms.dateAccepted | 2018-06-15 | |
| prism.publicationName | European Journal of Human Genetics | |
| pubs.funder-project-id | MRC (MR/K017551/1) | |
| pubs.funder-project-id | Wellcome Trust (via University College London (UCL)) (532344) | |
| rioxxterms.licenseref.startdate | 2018-06-15 | |
| rioxxterms.licenseref.uri | http://www.rioxx.net/licenses/all-rights-reserved | |
| rioxxterms.type | Journal Article/Review | |
| rioxxterms.version | VoR | |
| rioxxterms.versionofrecord | 10.1038/s41431-018-0214-3 |
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