Academic Journal
Detection and characterization of copy-number variants from exome sequencing in the DDD study
| العنوان: | Detection and characterization of copy-number variants from exome sequencing in the DDD study |
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| المؤلفون: | Petr Danecek, Eugene J. Gardner, Tomas W. Fitzgerald, Giuseppe Gallone, Joanna Kaplanis, Ruth Y. Eberhardt, Caroline F. Wright, Helen V. Firth, Matthew E. Hurles |
| المصدر: | Genetics in Medicine Open, Vol 2, Iss , Pp 101818- (2024) |
| بيانات النشر: | Elsevier, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Genetics LCC:Medicine |
| مصطلحات موضوعية: | Chromosomal microarrays, Copy-number variation, Exome sequencing, Neurodovelopmental disease, Rare disease, Genetics, QH426-470, Medicine |
| الوصف: | Purpose: Structural variants such as multiexon deletions and duplications are an important cause of disease but are often overlooked in standard exome/genome sequencing analysis. We aimed to evaluate the detection of copy-number variants (CNVs) from exome sequencing (ES) in comparison with genome-wide low-resolution and exon-resolution chromosomal microarrays (CMAs) and to characterize the properties of de novo CNVs in a large clinical cohort. Methods: We performed CNV detection using ES of 9859 parent-offspring trios in the Deciphering Developmental Disorders (DDD) study and compared them with CNVs detected from exon-resolution array comparative genomic hybridization in 5197 probands from the DDD study. Results: Integrating calls from multiple ES-based CNV algorithms using random forest machine learning generated a higher quality data set than using individual algorithms. Both ES- and array comparative genomic hybridization–based approaches had the same sensitivity of 89% and detected the same number of unique pathogenic CNVs not called by the other approach. Of DDD probands prescreened with low-resolution CMAs, 2.6% had a pathogenic CNV detected by higher-resolution assays. De novo CNVs were strongly enriched in known DD-associated genes and exhibited no bias in parental age or sex. Conclusion: ES-based CNV calling has higher sensitivity than low-resolution CMAs currently in clinical use and comparable sensitivity to exon-resolution CMA. With sufficient investment in bioinformatic analysis, exome-based CNV detection could replace low-resolution CMA for detecting pathogenic CNVs. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2949-7744 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S2949774424009646; https://doaj.org/toc/2949-7744 |
| DOI: | 10.1016/j.gimo.2024.101818 |
| URL الوصول: | https://doaj.org/article/8e0772a2bdbe41f584339b04b2c8e9ed |
| رقم الانضمام: | edsdoj.8e0772a2bdbe41f584339b04b2c8e9ed |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 29497744 |
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| DOI: | 10.1016/j.gimo.2024.101818 |