DNA copy-number analysis in bipolar disorder and schizophrenia reveals aberrations in genes involved in glutamate signaling.
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.
Wilson
Gary M
GM
Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Suite 100, 570 West 7th Avenue, Vancouver, BC, Canada V5Z 4S6.
Flibotte
Stephane
S
Chopra
Vikramjit
V
Melnyk
Brianna L
BL
Honer
William G
WG
Holt
Robert A
RA
D054758:A Kinase Anchor Proteins; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D001714:Bipolar Disorder / Q000235:genetics*; D015220:Calcium Channels / Q000235:genetics; D002869:Chromosome Aberrations; D022202:Chromosomes, Artificial, Bacterial; D015331:Cohort Studies; D017931:DNA Primers; D005625:Frontal Lobe / Q000737:chemistry; D018628:Gene Dosage; D014644:Genetic Variation; D015894:Genome, Human; D018698:Glutamic Acid / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009693:Nucleic Acid Hybridization; D018092:Kainic Acid Receptors / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012559:Schizophrenia / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*; D000097808:GluK3 Kainate Receptor
D054758:A Kinase Anchor Proteins; D048868:Adaptor Proteins, Signal Transducing; D015220:Calcium Channels; D017931:DNA Primers; D018698:Glutamic Acid; D018092:Kainic Acid Receptors; D000097808:GluK3 Kainate Receptor; C487775:AKAP5 protein, human; C491912:CACNG2 protein, human