CNVs

Copy number variations (CNVs) are segments of DNA in which the number of copies varies between individuals of a species. They include deletions and duplications and can range from about 1 kilobase to several megabases in length. Multi-allelic CNVs, with more than two possible copy numbers, also occur in the human genome.

CNVs are a major source of genetic diversity in humans. While many CNVs are benign and present in healthy populations, others alter gene dosage or disrupt genes and regulatory regions, contributing to phenotypic variation and disease risk.

CNVs arise through several mechanisms, most notably non-allelic homologous recombination (NAHR) during meiosis, replication-based processes such as FoSTeS/MMBIR, and activity of transposable elements. Genomic architecture, including segmental duplications, predisposes regions to CNV formation.

Detection and interpretation: CNVs are detected with array-based comparative genomic hybridization and SNP microarrays, and increasingly by DNA sequencing using read depth, split-read, and discordant paired-end signals. Interpretation relies on CNV size, gene content, inheritance pattern, and comparison to population CNV catalogs; many CNVs are benign, some are likely pathogenic, and others are of uncertain significance.

Clinical relevance: Pathogenic CNVs are associated with developmental disorders, congenital anomalies, and neuropsychiatric conditions. Most CNVs are inherited, but some arise de novo. Genetic counseling, parental testing, and reference resources such as the Database of Genomic Variants, ClinVar, and DECIPHER support assessment of clinical significance.