Copy number variation at 22q11.2: from rare variants to common mechanisms of developmental neuropsychiatric disorders

Mol Psychiatry. 2013 Nov;18(11):1153-65. doi: 10.1038/mp.2013.92. Epub 2013 Aug 6.


Recently discovered genome-wide rare copy number variants (CNVs) have unprecedented levels of statistical association with many developmental neuropsychiatric disorders, including schizophrenia, autism spectrum disorders, intellectual disability and attention deficit hyperactivity disorder. However, as CNVs often include multiple genes, causal genes responsible for CNV-associated diagnoses and traits are still poorly understood. Mouse models of CNVs are in use to delve into the precise mechanisms through which CNVs contribute to disorders and associated traits. Based on human and mouse model studies on rare CNVs within human chromosome 22q11.2, we propose that alterations of a distinct set of multiple, noncontiguous genes encoded in this chromosomal region, in concert with modulatory impacts of genetic background and environmental factors, variably shift the probabilities of phenotypes along a predetermined developmental trajectory. This model can be further extended to the study of other CNVs and may serve as a guide to help characterize the impact of genes in developmental neuropsychiatric disorders.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Chromosomes, Human, Pair 22 / genetics*
  • DNA Copy Number Variations / genetics*
  • Gene-Environment Interaction
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Male
  • Mental Disorders / genetics*