An Extended Targeted Copy Number Variation Detection Array Including 187 Genes for the Diagnostics of Neuromuscular Disorders

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Sagath , L , Lehtokari , V-L , Välipakka , S , Udd , B , Wallgren-Pettersson , C , Pelin , K & Kiiski , K 2018 , ' An Extended Targeted Copy Number Variation Detection Array Including 187 Genes for the Diagnostics of Neuromuscular Disorders ' , Journal of Neuromuscular Diseases , vol. 5 , no. 3 , pp. 307-314 . https://doi.org/10.3233/JND-170298

Title: An Extended Targeted Copy Number Variation Detection Array Including 187 Genes for the Diagnostics of Neuromuscular Disorders
Author: Sagath, L.; Lehtokari, V.-L.; Välipakka, S.; Udd, B.; Wallgren-Pettersson, C.; Pelin, K.; Kiiski, K.
Contributor: University of Helsinki, Department of Medical and Clinical Genetics
University of Helsinki, Medicum
University of Helsinki, Department of Medical and Clinical Genetics
University of Helsinki, Medicum
University of Helsinki, Medicum
University of Helsinki, Molecular and Integrative Biosciences Research Programme
University of Helsinki, Medicum
Date: 2018
Language: eng
Number of pages: 8
Belongs to series: Journal of Neuromuscular Diseases
ISSN: 2214-3599
URI: http://hdl.handle.net/10138/299668
Abstract: Background: Our previous array, the Comparative Genomic Hybridisation design (CGH-array) for nemaline myopathy (NM), named the NM-CGH array, revealed pathogenic copy number variation (CNV) in the genes for nebulin (NEB) and tropomyosin 3 (TPM3), as well as recurrent CNVs in the segmental duplication (SD), i.e. triplicate, region of NEB (TRI, exons 82-89, 90-97, 98-105). In the light of this knowledge, we have designed and validated an extended CGH array, which includes a selection of 187 genes known to cause neuromuscular disorders (NMDs). Objective: Our aim was to develop a reliable method for CNV detection in genes related to neuromuscular disorders for routine mutation detection and analysis, as a much-needed complement to sequencing methods. Methods: We have developed a novel custom-made 4×180 k CGH array for the diagnostics of NMDs. It includes the same tiled ultra-high density coverage of the 12 known or putative NM genes as our 8×60 k NM-CGH-array but also comprises a selection of 175 additional genes associated with NMDs, including titin (TTN), at a high to very high coverage. The genes were divided into three coverage groups according to known and potential pathogenicity in neuromuscular disorders. Results: The array detected known and putative CNVs in all three gene coverage groups, including the repetitive regions of NEB and TTN. Conclusions: The targeted neuromuscular disorder 4×180 k array-CGH (NMD-CGH-array v1.0) design allows CNV detection for a broader spectrum of neuromuscular disorders at a high resolution. © 2018 - IOS Press and the authors. All rights reserved.
Subject: connectin
DNA
muscle protein
nebulin
TTN protein, human, Article
clinical article
comparative genomic hybridization
controlled study
copy number variation
gene deletion
gene duplication
gene loss
genetic association
genetic gain
human
mutational analysis
NEB gene
neuromuscular disease
pathogenicity
priority journal
reliability
TTN gene
adult
DNA microarray
female
genetics
genomics
male
microarray analysis
mutation
nemaline myopathy
procedures
reproducibility, Adult
Connectin
DNA Copy Number Variations
Female
Genomics
Humans
Male
Microarray Analysis
Muscle Proteins
Mutation
Myopathies, Nemaline
Neuromuscular Diseases
Oligonucleotide Array Sequence Analysis
Reproducibility of Results
1184 Genetics, developmental biology, physiology
3112 Neurosciences
3121 General medicine, internal medicine and other clinical medicine
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