{"doi":"10.1016/j.gim.2022.11.013","title":"Optical genome mapping and revisiting short-read genome sequencing data reveal previously overlooked structural variants disrupting retinal disease−associated genes","abstract":null,"journal":"Genetics in Medicine","year":2023,"id":620001,"datarank":0.5606504427425053,"base_score":3.7376696182833684,"endowment":3.7376696182833684,"self_citation_contribution":0.5606504427425053,"citation_network_contribution":0.0,"self_endowment_contribution":0.5606504427425053,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":41,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":56933,"name":"Kim Rodenburg","orcid":"0000-0003-0389-1518","position":1,"is_corresponding":false},{"id":474262,"name":"Jordi Corominas","orcid":null,"position":2,"is_corresponding":false},{"id":56963,"name":"Tamar Ben-Yosef","orcid":null,"position":3,"is_corresponding":false},{"id":211265,"name":"Janine Reurink","orcid":"0000-0002-5677-9258","position":4,"is_corresponding":false},{"id":211271,"name":"Hannie Kremer","orcid":"0000-0002-0841-8693","position":5,"is_corresponding":false},{"id":57096,"name":"Laura Whelan","orcid":"0000-0002-0537-4349","position":6,"is_corresponding":false},{"id":673354,"name":"Astrid S. 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Although the identification of SVs significantly improved upon the availability of genome sequencing, it is expected that involvement of SVs in IRDs is higher than anticipated. We revisited short-read genome sequencing data to enhance the identification of gene-disruptive SVs. METHODS: Optical genome mapping was performed to improve SV detection in short-read genome sequencing-negative cases. In addition, reanalysis of short-read genome sequencing data was performed to improve the interpretation of SVs and to re-establish SV prioritization criteria. RESULTS: In a monoallelic USH2A case, optical genome mapping identified a pericentric inversion (173 megabase), with 1 breakpoint disrupting USH2A. Retrospectively, the variant could be observed in genome sequencing data but was previously deemed false positive. Reanalysis of short-read genome sequencing data (427 IRD cases) was performed which yielded 30 pathogenic SVs affecting, among other genes, USH2A (n = 15), PRPF31 (n = 3), and EYS (n = 2). Eight of these (>25%) were overlooked during previous analyses. CONCLUSION: Critical evaluation of our findings allowed us to re-establish and improve our SV prioritization and interpretation guidelines, which will prevent missing pathogenic events in future analyses. Our data suggest that more attention should be paid to SV interpretation and the current contribution of SVs in IRDs is still underestimated.","is_dataset_classified":null,"base_score":3.7376696182833684,"endowment":3.7376696182833684,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"36524988","pmcid":null,"openalex_id":"https://openalex.org/W4311679045","authors":[],"funders":[{"funder_name":"Health Research Board","grant_id":"MRCG-2016-14","title":"Application of Next Generation Sequencing for the Genetic Characterisation of Irish Retinal Degeneration Patients"},{"funder_name":"European Commission","grant_id":"779257","title":"Solving the unsolved Rare Diseases"},{"funder_name":"Irish Research Council","grant_id":"unidentified","title":"unidentified"},{"funder_name":"European Commission","grant_id":"825575","title":"European Joint Programme on Rare Diseases"}],"total_grants":4,"fwci":6.3897,"citation_percentile":0.9731772,"influential_citations":0,"citation_trend":[{"year":2022,"count":1},{"year":2023,"count":9},{"year":2024,"count":19},{"year":2025,"count":9},{"year":2026,"count":3}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"https://doi.org/10.1016/j.gim.2022.11.013","host_type":"journal"},{"url":"https://doi.org/10.1016/j.gim.2022.11.013","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S1098360022010292?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S1098360022010292?httpAccept=text/plain","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/36524988","host_type":"repository"},{"url":"https://research.vumc.nl/en/publications/ea12c632-a942-4fda-8480-f17435d7e6c8","host_type":"repository"},{"url":"https://www.zora.uzh.ch/id/eprint/225540/1/1_s2.0_S1098360022010292_main.pdf","host_type":"repository"},{"url":"https://pure.amsterdamumc.nl/en/publications/549fb0af-5e52-49ba-ad3f-a3dac723f8a2","host_type":"repository"},{"url":"https://hdl.handle.net/2066/291280","host_type":"repository"},{"url":"http://hdl.handle.net/2262/102709","host_type":"repository"},{"url":"https://pure.amc.nl/en/publications/optical-genome-mapping-and-revisiting-shortread-genome-sequencing-data-reveal-previously-overlooked-structural-variants-disrupting-retinal-diseaseassociated-genes(b2b88fa0-a4a9-41a9-b28f-bcd99c6a5e7e).html","host_type":"repository"},{"url":"http://hdl.handle.net/20.500.11850/601190","host_type":"repository"},{"url":"https://doi.org/10.3929/ethz-b-000601190","host_type":"repository"},{"url":"https://doi.org/10.5167/uzh-225540","host_type":""},{"url":"https://pure.amsterdamumc.nl/files/160584993/Optical-genome-mapping-and-revisiting-short-read-genome-sequencing-data-reveal-previously-overlooked-structural-variants.pdf","host_type":"repository"},{"url":"https://repository.ubn.ru.nl//bitstream/handle/2066/291280/291280.pdf","host_type":"repository"},{"url":"https://www.tara.tcd.ie/bitstream/2262/102709/1/1-s2.0-S1098360022010292-main.pdf","host_type":"repository"},{"url":"https://dx.doi.org/10.3929/ethz-b-000601190","host_type":""},{"url":"https://hdl.handle.net/https://repository.ubn.ru.nl/handle/2066/291280","host_type":""},{"url":"https://www.scopus.com/pages/publications/85144381092","host_type":""},{"url":"http://dx.doi.org/10.1016/j.gim.2022.11.013","host_type":""},{"url":"http://people.tcd.ie/gjfarrar","host_type":""},{"url":"https://doi.org/https://doi.org/10.1016/j.gim.2022.11.013","host_type":""},{"url":"https://doi.org/https://doi.org/10.15496/publikation-94682","host_type":""}],"fields_of_study":["Genomics and Rare Diseases","Genomic variations and chromosomal abnormalities","Retinal Development and Disorders","0301 basic medicine","03 medical and health sciences","0303 health sciences"],"mesh_terms":["Chromosome Mapping","Eye Proteins","Humans","Retinal Diseases","Retrospective Studies","Genome, Human","Sequence Analysis","Genomic Structural Variation"],"keywords":["Genome","Biology","Genetics","Whole genome sequencing","Computational biology","DNA sequencing","Cancer genome sequencing","Gene","Structural variation","Prioritization","Next-generation Sequencing","Structural Variants","Inherited Retinal Diseases","Optical Genome Mapping","Short-read Genome Sequencing","Structural variants (SVs)","570","Radboudumc 4: lnfectious Diseases and Global Health Internal Medicine","Inherited retinal diseases; 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