CNV

Copy number variation (CNV) refers to a type of structural variation in the genome where the number of copies of a particular DNA segment differs between individuals or populations from what is typical. CNVs range in size from about one kilobase to several megabases and can involve deletions, duplications, or more complex rearrangements. They can encompass whole genes, portions of genes, or regulatory regions, and may affect gene dosage, disrupt coding sequence, or alter gene expression.

CNVs can be inherited or arise de novo during gametogenesis or early development. Mechanisms generating CNVs include non-allelic homologous recombination and replication-based errors such as fork stalling and template switching. The functional impact of a CNV depends on the genes or regulatory elements it affects, as well as dosage sensitivity, penetrance, and genetic background. Most CNVs are benign, but some contribute to disease risk or phenotypic variation.

Detection and characterization rely on array-based methods such as array comparative genomic hybridization (array CGH) and SNP arrays, as well as sequencing-based approaches that use read depth, split-read, and paired-end mapping signals. Bioinformatic analyses integrate multiple lines of evidence to identify CNVs and estimate copy number. Reference resources such as the Database of Genomic Variants (DGV) and population SV catalogs in gnomAD aid interpretation, while ClinGen provides dosage sensitivity information relevant to clinical assessment.

Clinically, CNVs are associated with developmental disorders, neuropsychiatric conditions, congenital anomalies, and cancer, where gains or losses of copy number can alter gene dosage. Many CNVs, however, are benign and contribute to normal genetic diversity and adaptation. Interpreting CNVs involves integrating phenotype, inheritance, and functional evidence.