Faculty Opinions recommendation of Detection of clinically relevant copy-number variants by exome sequencing in a large cohort of genetic disorders.
Year: 2020
Type: peer-review
Abstract: Purpose: Copy-number variation is a common source of genomic variation and an important genetic cause of disease.Microarraybased analysis of copy-number variants (CNVs) has become a firsttier diagnostic test for patients with neurodevelopmental disorders, with a diagnostic yield of 10-20%.However, for most other genetic disorders, the role of CNVs is less clear and most diagnostic genetic studies are generally limited to the study of single-nucleotide variants (SNVs) and other small variants.With the introduction of exome and genome sequencing, it is now possible to detect both SNVs and CNVs using an exome-or genome-wide approach with a single test.Methods: We performed exome-based read-depth CNV screening on data from 2,603 patients affected by a range of genetic disorders for which exome sequencing was performed in a diagnostic setting.Results: In total, 123 clinically relevant CNVs ranging in size from 727 bp to 15.3 Mb were detected, which resulted in 51 conclusive diagnoses and an overall increase in diagnostic yield of ~2% (ranging from 0 to -5.8% per disorder).Conclusions: This study shows that CNVs play an important role in a broad range of genetic disorders and that detection via exomebased CNV profiling results in an increase in the diagnostic yield without additional testing, bringing us closer to single-test genomics.
Author: Heather Mefford
Institution: University of Washington
Language: English
Topic: Genomics and Rare Diseases
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4242893802