@article{8529931,
  abstract     = {{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.}},
  author       = {{Van Schil, Kristof and Naessens, Sarah and Van de Sompele, Stijn and Carron, Marjolein and Aslanidis, Alexander and Van Cauwenbergh, Caroline and Mayer, Anja Kathrin and Van Heetvelde, Mattias and Bauwens, Miriam and Verdin, Hannah and Coppieters, Frauke and Greenberg, Michael E and Yang, Marty G and Karlstetter, Marcus and Langmann, Thomas and De Preter, Katleen and Kohl, Susanne and Cherry, Timothy J and Leroy, Bart and De Baere, Elfride}},
  issn         = {{1098-3600}},
  journal      = {{GENETICS IN MEDICINE}},
  keywords     = {{copy-number variations,genomic features,inherited retinal disease genes,predisposition,targeted locus amplification (TLA),EXOME SEQUENCING DATA,RETINITIS-PIGMENTOSA,MEDIATED DELETION,DIAGNOSTIC YIELD,MUTATIONS,DYSTROPHY,DEGENERATIONS,TRANSCRIPTION,ENHANCERS,VARIANTS}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{202--213}},
  title        = {{Mapping the genomic landscape of inherited retinal disease genes prioritizes genes prone to coding and noncoding copy-number variations}},
  url          = {{http://doi.org/10.1038/gim.2017.97}},
  volume       = {{20}},
  year         = {{2018}},
}

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