Copy number variants (CNVs) are genomic imbalances strongly linked to the aetiology of neuropsychiatric disorders such as schizophrenia and autism. By virtue of their large size, CNVs often contain many genes, providing a multi-genic view of disease processes that can be dissected in model systems. Thus, CNV research provides an important stepping stone towards understanding polygenic disease mechanisms, positioned between monogenic and polygenic risk models. In this review, we will outline hypothetical models for gene interactions occurring within CNVs and discuss different approaches used to study rodent and stem cell disease models. We highlight recent work showing that genetic and pharmacological strategies can be used to rescue important aspects of CNV-mediated pathophysiology, which often converges onto synaptic pathways. We propose that using a rescue approach in complete CNV models provides a new path forward for precise mechanistic understanding of complex disorders and a tangible route towards therapeutic development.
ASJC Scopus subject areas
- General Neuroscience