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

Noboru Hiroi, T. Takahashi, A. Hishimoto, T. Izumi, S. Boku, Takeshi Hiramoto

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1153-1165
Number of pages13
JournalMolecular Psychiatry
Volume18
Issue number11
DOIs
StatePublished - Nov 2013

Fingerprint

Developmental Genes
Gene Dosage
Human Chromosomes
Attention Deficit Disorder with Hyperactivity
Intellectual Disability
Genes
Schizophrenia
Genome
Phenotype
Genetic Background
Autism Spectrum Disorder

Keywords

  • ADHD
  • Autism
  • Copy number variant
  • Intellectual disability
  • Mouse model
  • Schizophrenia

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Copy number variation at 22q11.2 : From rare variants to common mechanisms of developmental neuropsychiatric disorders. / Hiroi, Noboru; Takahashi, T.; Hishimoto, A.; Izumi, T.; Boku, S.; Hiramoto, Takeshi.

In: Molecular Psychiatry, Vol. 18, No. 11, 11.2013, p. 1153-1165.

Research output: Contribution to journalArticle

Hiroi, N, Takahashi, T, Hishimoto, A, Izumi, T, Boku, S & Hiramoto, T 2013, 'Copy number variation at 22q11.2: From rare variants to common mechanisms of developmental neuropsychiatric disorders', Molecular Psychiatry, vol. 18, no. 11, pp. 1153-1165. https://doi.org/10.1038/mp.2013.92
Hiroi, Noboru ; Takahashi, T. ; Hishimoto, A. ; Izumi, T. ; Boku, S. ; Hiramoto, Takeshi. / Copy number variation at 22q11.2 : From rare variants to common mechanisms of developmental neuropsychiatric disorders. In: Molecular Psychiatry. 2013 ; Vol. 18, No. 11. pp. 1153-1165.
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