Copy number variations in the human genome: their mutational mechanisms and roles in diseases

Copy number variation (CNV) is the main type of structure variation (SV) caused by genomic rearrangement, which mainly includes deletion and duplication of sub-microscopic but large (>1 kb) genomic segments. CNV has been recognized as one of the main genetic factors underlying human diseases. The mutation rate (per locus) of CNV is much higher than that of single nucleotide polymorphism (SNP). The genome-wide assays for CNV study include array-based comparative genomic hybridization (aCGH), SNP genotyping microarrays, and next-generation sequencing techniques. Various molecular mechanisms are involved in CNV formation, which can be divided into two main categories, DNA recombination-based and DNA replication-based mechanisms. CNVs can be associated with Mendelian diseases, sporadic diseases, and susceptibility to complex diseases. CNVs can convey clinical phenotypes by gene dosage, gene disruption, gene fusion, and position effects. Further studies on CNVs will shed new light on human genome structure, genetic variations between individuals, and missing heritability of human diseases.