The clinical implementation of copy number detection in the age of next-generation sequencing

Introduction: The role of copy number variants (CNVs) in disease is now well established. In parallel NGS technologies, such as long-read technologies, there is continual development and data analysis methods continue to be refined. Clinical exome sequencing data is now a reality for many diagnostic laboratories in both congenital genetics and oncology. This provides the ability to detect and report both SNVs and structural variants, including CNVs, using a single assay for a wide range of patient cohorts. Areas covered: Currently, whole-genome sequencing is mainly restricted to research applications and clinical utility studies. Furthermore, detecting the full-size spectrum of CNVs as well as somatic events remains difficult for both exome and whole-genome sequencing. As a result, the full extent of genomic variants in an individual's genome is still largely unknown. Recently, new sequencing technologies have been introduced which maintain the long-range genomic context, aiding the detection of CNVs and structural variants. Expert commentary: The development of long-read sequencing promises to resolve many CNV and SV detection issues but is yet to become established. The current challenge for clinical CNV detection is how to fully exploit all the data which is generated by high throughput sequencing technologies.