An interaction-based model for neuropsychiatric features of copy-number variants

PLoS Genet. 2019 Jan 17;15(1):e1007879. doi: 10.1371/journal.pgen.1007879. eCollection 2019 Jan.


Variably expressive copy-number variants (CNVs) are characterized by extensive phenotypic heterogeneity of neuropsychiatric phenotypes. Approaches to identify single causative genes for these phenotypes within each CNV have not been successful. Here, we posit using multiple lines of evidence, including pathogenicity metrics, functional assays of model organisms, and gene expression data, that multiple genes within each CNV region are likely responsible for the observed phenotypes. We propose that candidate genes within each region likely interact with each other through shared pathways to modulate the individual gene phenotypes, emphasizing the genetic complexity of CNV-associated neuropsychiatric features.

Publication types

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

MeSH terms

  • Abnormalities, Multiple / genetics
  • Abnormalities, Multiple / physiopathology
  • Chromosome Disorders / genetics
  • Chromosome Disorders / physiopathology
  • Chromosome Duplication / genetics
  • DNA Copy Number Variations / genetics*
  • Gene Expression Regulation
  • Genetic Association Studies*
  • Genetic Heterogeneity*
  • Genetic Predisposition to Disease*
  • Humans
  • Phenotype
  • Smith-Magenis Syndrome / genetics
  • Smith-Magenis Syndrome / physiopathology
  • Sotos Syndrome / genetics
  • Sotos Syndrome / physiopathology
  • Williams Syndrome / genetics
  • Williams Syndrome / physiopathology

Supplementary concepts

  • Potocki-Lupski syndrome
  • Williams-Beuren Region Duplication Syndrome