DNA copy-number analysis in bipolar disorder and schizophrenia reveals aberrations in genes involved in glutamate signaling

Hum Mol Genet. 2006 Mar 1;15(5):743-9. doi: 10.1093/hmg/ddi489. Epub 2006 Jan 24.

Abstract

Using bacterial artificial chromosome (BAC) array comparative genome hybridization (aCGH) at approximately 1.4 Mbp resolution, we screened post-mortem brain DNA from bipolar disorder cases, schizophrenia cases and control individuals (n=35 each) for DNA copy-number aberrations. DNA copy number is a largely unexplored source of human genetic variation that may contribute risk for complex disease. We report aberrations at four loci which were seen in affected but not control individuals, and which were verified by quantitative real-time PCR. These aberrant loci contained the genes encoding EFNA5, GLUR7, CACNG2 and AKAP5; all brain-expressed proteins with known or postulated roles in neuronal function, and three of which (GLUR7, CACNG2 and AKAP5) are involved in glutamate signaling. A second cohort of psychiatric samples was also tested by quantitative PCR using the primer/probe sets for EFNA5, GLUR7, CACNG2 and AKAP5, and samples with aberrant copy number were found at three of the four loci (GLUR7, CACNG2 and AKAP5). Further scrutiny of these regions may reveal insights into the etiology and genetic risk factors for these complex psychiatric disorders.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • A Kinase Anchor Proteins
  • Adaptor Proteins, Signal Transducing / genetics
  • Bipolar Disorder / genetics*
  • Calcium Channels / genetics
  • Chromosome Aberrations*
  • Chromosomes, Artificial, Bacterial
  • Cohort Studies
  • DNA Primers
  • Frontal Lobe / chemistry
  • Gene Dosage*
  • Genetic Variation
  • Genome, Human
  • GluK3 Kainate Receptor
  • Glutamic Acid / genetics
  • Glutamic Acid / metabolism*
  • Humans
  • Nucleic Acid Hybridization
  • Receptors, Kainic Acid / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Schizophrenia / genetics*
  • Signal Transduction / genetics*

Substances

  • A Kinase Anchor Proteins
  • AKAP5 protein, human
  • Adaptor Proteins, Signal Transducing
  • CACNG2 protein, human
  • Calcium Channels
  • DNA Primers
  • Receptors, Kainic Acid
  • Glutamic Acid