Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
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SHR Neuro Krebs Kardio Lipid Stoffw Microb
Royer-Bertrand, B; Cisarova, K; Niel-Butschi, F; Mittaz-Crettol, L; Fodstad, H; Superti-Furga, A.
CNV Detection from Exome Sequencing Data in Routine Diagnostics of Rare Genetic Disorders: Opportunities and Limitations.
Genes (Basel). 2021; 12(9):
Doi: 10.3390/genes12091427
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- Abstract:
- To assess the potential of detecting copy number variations (CNVs) directly from exome sequencing (ES) data in diagnostic settings, we developed a CNV-detection pipeline based on ExomeDepth software and applied it to ES data of 450 individuals. Initially, only CNVs affecting genes in the requested diagnostic gene panels were scored and tested against arrayCGH results. Pathogenic CNVs were detected in 18 individuals. Most detected CNVs were larger than 400 kb (11/18), but three individuals had small CNVs impacting one or a few exons only and were thus not detectable by arrayCGH. Conversely, two pathogenic CNVs were initially missed, as they impacted genes not included in the original gene panel analysed, and a third one was missed as it was in a poorly covered region. The overall combined diagnostic rate (SNVs + CNVs) in our cohort was 36%, with wide differences between clinical domains. We conclude that (1) the ES-based CNV pipeline detects efficiently large and small pathogenic CNVs, (2) the detection of CNV relies on uniformity of sequencing and good coverage, and (3) in patients who remain unsolved by the gene panel analysis, CNV analysis should be extended to all captured genes, as diagnostically relevant CNVs may occur everywhere in the genome.
- Find related publications in this database (using NLM MeSH Indexing)
- Adolescent - administration & dosage
- Adult - administration & dosage
- Aged - administration & dosage
- Aged, 80 and over - administration & dosage
- Child - administration & dosage
- Child, Preschool - administration & dosage
- Cohort Studies - administration & dosage
- DNA Copy Number Variations - administration & dosage
- Diagnostic Tests, Routine - administration & dosage
- Female - administration & dosage
- Genetic Testing - methods
- High-Throughput Nucleotide Sequencing - methods
- Humans - administration & dosage
- Infant - administration & dosage
- Male - administration & dosage
- Middle Aged - administration & dosage
- Rare Diseases - diagnosis, epidemiology, genetics
- Sequence Analysis, DNA - methods
- Switzerland - epidemiology
- Exome Sequencing - methods
- Young Adult - administration & dosage
- Find related publications in this database (Keywords)
- arrayCGH (aCGH)
- copy number variations (CNVs)
- exome sequencing (ES)
- MLPA
- next-generation sequencing (NGS)
- rare and undiagnosed disease
- structural variation (SV)