Using hiPSCs to model neuropsychiatric copy number variations (CNVs) has potential to reveal underlying disease mechanisms

Brain Res. 2017 Jan 15;1655:283-293. doi: 10.1016/j.brainres.2015.11.009. Epub 2015 Nov 12.


Schizophrenia is a neuropsychological disorder with a strong heritable component; genetic risk for schizophrenia is conferred by both common variants of relatively small effect and rare variants with high penetrance. Genetically engineered mouse models can recapitulate rare variants, displaying some behavioral defects associated with schizophrenia; however, these mouse models cannot recapitulate the full genetic architecture underlying the disorder. Patient-derived human induced pluripotent stem cells (hiPSCs) present an alternative approach for studying rare variants, in the context of all other risk alleles. Genome editing technologies, such as CRISPR-Cas9, enable the generation of isogenic hiPSC lines with which to examine the functional contribution of single variants within any genetic background. Studies of these rare variants using hiPSCs have the potential to identify commonly disrupted pathways in schizophrenia and allow for the identification of new therapeutic targets. This article is part of a Special Issue entitled SI:StemsCellsinPsychiatry.

Keywords: CNV; Hipsc models; Mouse models; Schizophrenia.

Publication types

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

MeSH terms

  • Animals
  • DNA Copy Number Variations*
  • Humans
  • Induced Pluripotent Stem Cells / physiology*
  • Mental Disorders / genetics*
  • Mental Disorders / physiopathology*