Universität zu Köln

Van Schil, Kristof, Naessens, Sarah, Van de Sompele, Stijn ORCID: 0000-0002-3294-0668, Carron, Marjolein, Aslanidis, Alexander, Van Cauwenbergh, Caroline ORCID: 0000-0002-1948-9091, Mayer, Anja Kathrin, Van Heetvelde, Mattias, Bauwens, Miriam, Verdin, Hannah, Coppieters, Frauke ORCID: 0000-0001-7224-0992, Greenberg, Michael E., Yang, Marty G., Karlstetter, Marcus, Langmann, Thomas, De Preter, Katleen, Kohl, Susanne, Cherry, Timothy J., Leroy, Bart P. and De Baere, Elfride ORCID: 0000-0002-5609-6895 (2018). Mapping the genomic landscape of inherited retinal disease genes prioritizes genes prone to coding and noncoding copy-number variations. Genet. Med., 20 (2). S. 202 - 214. NEW YORK: NATURE PUBLISHING GROUP. ISSN 1530-0366

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Van Schil, Kristof UNSPECIFIED UNSPECIFIED UNSPECIFIED Naessens, Sarah UNSPECIFIED UNSPECIFIED UNSPECIFIED Van de Sompele, Stijn UNSPECIFIED orcid.org/0000-0002-3294-0668 UNSPECIFIED Carron, Marjolein UNSPECIFIED UNSPECIFIED UNSPECIFIED Aslanidis, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Van Cauwenbergh, Caroline UNSPECIFIED orcid.org/0000-0002-1948-9091 UNSPECIFIED Mayer, Anja Kathrin UNSPECIFIED UNSPECIFIED UNSPECIFIED Van Heetvelde, Mattias UNSPECIFIED UNSPECIFIED UNSPECIFIED Bauwens, Miriam UNSPECIFIED UNSPECIFIED UNSPECIFIED Verdin, Hannah UNSPECIFIED UNSPECIFIED UNSPECIFIED Coppieters, Frauke UNSPECIFIED orcid.org/0000-0001-7224-0992 UNSPECIFIED Greenberg, Michael E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Yang, Marty G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Karlstetter, Marcus UNSPECIFIED UNSPECIFIED UNSPECIFIED Langmann, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED De Preter, Katleen UNSPECIFIED UNSPECIFIED UNSPECIFIED Kohl, Susanne UNSPECIFIED UNSPECIFIED UNSPECIFIED Cherry, Timothy J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Leroy, Bart P. UNSPECIFIED UNSPECIFIED UNSPECIFIED De Baere, Elfride UNSPECIFIED orcid.org/0000-0002-5609-6895 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-197370
DOI:	10.1038/gim.2017.97
Journal or Publication Title:	Genet. Med.
Volume:	20
Number:	2
Page Range:	S. 202 - 214
Date:	2018
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	NEW YORK
ISSN:	1530-0366
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language EXOME SEQUENCING DATA; RETINITIS-PIGMENTOSA; MEDIATED DELETION; DIAGNOSTIC YIELD; MUTATIONS; DYSTROPHY; DEGENERATIONS; TRANSCRIPTION; ENHANCERS; VARIANTS Multiple languages Genetics & Heredity Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/19737