Mapping the genomic landscape of inherited retinal disease genes prioritizes genes prone to coding and noncoding copy-number variations
| العنوان: | Mapping the genomic landscape of inherited retinal disease genes prioritizes genes prone to coding and noncoding copy-number variations |
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| المؤلفون: | Kristof Van Schil, Sarah Naessens, Stijn Van de Sompele, Marjolein Carron, Alexander Aslanidis, Caroline Van Cauwenbergh, Anja K. Mayer, Mattias Van Heetvelde, Miriam Bauwens, Hannah Verdin, Frauke Coppieters, Michael E. Greenberg, Marty G. Yang, Marcus Karlstetter, Thomas Langmann, Katleen De Preter, Susanne Kohl, Timothy J. Cherry, Bart P. Leroy, James R. Lupski, Claudia Carvalho, Max van Min, Petra Klous, Sarah De Jaegere, Sally Hooghe, Elfride De Baere |
| المصدر: | GENETICS IN MEDICINE Genetics in Medicine |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Genomics, Genome-wide association study, Computational biology, Biology, VARIANTS, Genome, 03 medical and health sciences, 0302 clinical medicine, Gene mapping, MEDIATED DELETION, parasitic diseases, RETINITIS-PIGMENTOSA, Medicine and Health Sciences, genomic features, Original Research Article, Copy-number variation, TRANSCRIPTION, Gene, Genetics (clinical), Genetics, Disease gene, DIAGNOSTIC YIELD, MUTATIONS, copy-number variations, Biology and Life Sciences, DYSTROPHY, DEGENERATIONS, inherited retinal disease genes, ENHANCERS, 030104 developmental biology, predisposition, targeted locus amplification (TLA), Human genome, EXOME SEQUENCING DATA, 030217 neurology & neurosurgery |
| الوصف: | Purpose: Part of the hidden genetic variation in heterogeneous genetic conditions such as inherited retinal diseases (IRDs) can be explained by copy-number variations (CNVs). Here, we explored the genomic landscape of IRD genes listed in RetNet to identify and prioritize those genes susceptible to CNV formation. Methods: RetNet genes underwent an assessment of genomic features and of CNV occurrence in the Database of Genomic Variants and literature. CNVs identified in an IRD cohort were characterized using targeted locus amplification (TLA) on extracted genomic DNA. Results: Exhaustive literature mining revealed 1,345 reported CNVs in 81 different IRD genes. Correlation analysis between rankings of genomic features and CNV occurrence demonstrated the strongest correlation between gene size and CNV occurrence of IRD genes. Moreover, we identified and delineated 30 new CNVs in IRD cases, 13 of which are novel and three of which affect noncoding, putative cis-regulatory regions. Finally, the breakpoints of six complex CNVs were determined using TLA in a hypothesis-neutral manner. Conclusion: We propose a ranking of CNV-prone IRD genes and demonstrate the efficacy of TLA for the characterization of CNVs on extracted DNA. Finally, this IRD-oriented CNV study can serve as a paradigm for other genetically heterogeneous Mendelian diseases with hidden genetic variation. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1098-3600 1530-0366 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c9afc86b76ee1eb917ae11e695592fc3Test https://biblio.ugent.be/publication/8529931Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c9afc86b76ee1eb917ae11e695592fc3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10983600 15300366 |
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