Effectivity of whole-exome sequencing in copy number variant detection in children with neurodevelopmental disorders
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| Year of publication | 2021 |
| Type | Conference abstract |
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| Description | Copy number variants (CNVs) are a common source of genetic variation in neurodevelopmental disorders (NDDs). Chromosomal microarray analysis (CMA) is currently regarded as the gold standard for its detection. Whole-exome sequencing (WES) is widely accepted as a powerful tool for exome-wide detection of single-nucleotide variants (SNVs) and small insertions and deletions (InDels). Detection of CNVs using WES have also recently become possible through the development of special algorithms and software. Our study evaluated two WES read-depth based CNV detection pipelines using high-resolution CMA as a standard in 20 families (trios or quatros) of children with severe NDDs and associated congenital abnormalities. A total of 15 CNVs in 8 families (384–3025 kb) identified using Agilent CGH+SNP array platform were compared to CNVs identified using WES by Human Core Exome (Twist Biosciences) on Illumina NovaSeq 6000. Using two WES in-house CNV detection pipelines developed by Masaryk University and Newcastle University, respectively, we confirmed and specified all 15 CNVs previously detected by CMA. All length variabilities in findings were verified using qPCR and manually curated. Both pipelines detected an elevated proportion of small variants compared to CMA, however, no clinically relevant findings were newly discovered. Our pilot study confirmed that combined identi?cation of SNVs, InDels, and CNVs would increase the versatility of WES in diagnostics of NDDs in children. Supported by Ministry of Health of the Czech Republic, grant nr. NU20-07-00145. All rights reserved. |
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