Copy number variation and susceptibility to human disorders (Review)

A large number of analyses of a new form of genetic variation, known as copy number variation (CNV), have been published recently as a new tool for understanding the genetic basis of complex traits such as diabetes, asthma, Crohn's disease, autism and bipolar disorder. Through the use of different types of genome-wide scanning procedures, CNVs have been shown to be associated with several complex and common disorders, including nervous system disorders. One of the common features of the regions associated with the complex and common disorders identified thus far is the presence of CNVs and segmental duplications. Segmental duplications lead to genome instability. Because of their location and nature (several contain genes), many CNVs have functional consequences, such as gene dosage alteration, the disruption of genes and the modulation of the activities of other genes. Therefore, these genetic variations have an influence on phenotypes, the susceptibility of an individual to disease, drug response and human genome evolution. These types of variants (gain and loss of DNA) are not restricted to humans, having also been identified in other organisms. Our current knowledge regarding CNVs and their heritability is still rudimentary, due to their location in regions of complex genomic structure and to the technical limitations of association studies. Future advances in the technology will aid in the construction of a new CNV map, used to find the genes underlying common diseases and to understand familial genetic conditions, severe developmental defects in humans and other organisms, and genome evolution.