Optical genome mapping and revisiting short-read genome sequencing data reveal previously overlooked structural variants disrupting retinal disease−associated genes
| Autor: | Suzanne E. de Bruijn, Kim Rodenburg, Jordi Corominas, Tamar Ben-Yosef, Janine Reurink, Hannie Kremer, Laura Whelan, Astrid S. Plomp, Wolfgang Berger, G. Jane Farrar, Árpád Ferenc Kovács, Isabelle Fajardy, Rebekkah J. Hitti-Malin, Nicole Weisschuh, Marianna E. Weener, Dror Sharon, Ronald J.E. Pennings, Lonneke Haer-Wigman, Carel B. Hoyng, Marcel R. Nelen, Lisenka E.L.M. Vissers, L. Ingeborgh van den Born, Christian Gilissen, Frans P.M. Cremers, Alexander Hoischen, Kornelia Neveling, Susanne Roosing |
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| Přispěvatelé: | Human Genetics, Human genetics, Amsterdam Reproduction & Development (AR&D) |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
All institutes and research themes of the Radboud University Medical Center
Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7] Inherited retinal diseases Optical genome mapping Next-generation sequencing Short-read genome sequencing Structural variants Other Research Radboud Institute for Health Sciences [Radboudumc 0] lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6] Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12] Genetics (clinical) |
| Zdroj: | Genetics in medicine. Lippincott Williams and Wilkins Genetics in Medicine, 25, 3 Genetics in Medicine. Lippincott Williams and Wilkins de Bruijn, S E, Rodenburg, K, Corominas, J, Ben-Yosef, T, Reurink, J, Kremer, H, Whelan, L, Plomp, A S, Berger, W, Farrar, G J, Ferenc Kovács, Á, Fajardy, I, Hitti-Malin, R J, Weisschuh, N, Weener, M E, Sharon, D, Pennings, R J E, Haer-Wigman, L, Hoyng, C B, Nelen, M R, Vissers, L E L M, van den Born, L I, Gilissen, C, Cremers, F P M, Hoischen, A, Neveling, K & Roosing, S 2022, ' Optical genome mapping and revisiting short-read genome sequencing data reveal previously overlooked structural variants disrupting retinal disease−associated genes ', Genetics in Medicine . https://doi.org/10.1016/j.gim.2022.11.013 Genetics in Medicine, 25 Genetics in Medicine, 25 (3) |
| ISSN: | 1098-3600 |
| DOI: | 10.1016/j.gim.2022.11.013 |
| Popis: | Purpose: Structural variants (SVs) play an important role in inherited retinal diseases (IRD). 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. Genetics in Medicine, 25 (3) |
| Databáze: | OpenAIRE |
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