Detection of clinically relevant copy-number variants by exome sequencing in a large cohort of genetic disorders.
Genet Med
; 19(6): 667-675, 2017 06.
Article
in En
| MEDLINE
| ID: mdl-28574513
ABSTRACT
PURPOSE:
Copy-number variation is a common source of genomic variation and an important genetic cause of disease. Microarray-based analysis of copy-number variants (CNVs) has become a first-tier 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 exome-based CNV profiling results in an increase in the diagnostic yield without additional testing, bringing us closer to single-test genomics.Genet Med advance online publication 27 October 2016.
Full text:
1
Database:
MEDLINE
Main subject:
DNA Copy Number Variations
/
Exome
/
Whole Genome Sequencing
/
Genetic Diseases, Inborn
Type of study:
Diagnostic_studies
/
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Risk_factors_studies
Limits:
Humans
/
Male
Language:
En
Journal:
Genet Med
Journal subject:
GENETICA MEDICA
Year:
2017
Type:
Article
Affiliation country:
Netherlands