Copy Number Variant Detection Using Next-Generation Sequencing

摘要: Copy number variation refers to imbalanced structural resulting in gain or loss of genomic DNA a region ranging from tens millions bases long. variants (CNVs) are critical class genetic clinical next-generation sequencing (NGS) due their wide-ranging impacts human disease. The variety and complexity methods used detect CNVs NGS data can be daunting. This chapter will summarize general approaches CNV detection data, application such across diverse applications, screening identify causal We briefly describe the origins functional significance review non-NGS technologies. Considerations various contexts discussed, including candidate gene, exome, whole genome, cell-free applications. main conceptual discovery reviewed detail, mate pair alignment, relative depth coverage, direct assembly sequence-based evidence split reads. highly design- platform-dependent, requiring customization trade-offs for specific approaches. discuss strengths weaknesses different context both capture-based genome platforms, highlighting considerations germline DNA, tumor tissue, fetal DNA. availability reference standards benchmarking by methods. Finally, we cover orthogonal validation technologies toward goal incorporating clinically actionable NGS-based patient care.