Simultaneous Analysis of Expression Levels of Many Genes in Post-Mortem Brain Tissue From Individuals With Schizophrenia and Bipolar Disease

Simultaneous Analysis of

Expression Levels of Many Genes in Post-Mortem Brain Tissue from Individuals with Schizophrenia

and Bipolar Disease

K. Faridi*, K. Hyder, A.

Chenchik, N.L. Johnston, R.H.Yolken, and the Stanley

Neuropathology Consortium. The Stanley Division of Developmental

Neurovirology

Johns Hopkins University School of Medicine, 600 N. Wolfe

St./Blalock 1111

Baltimore, MD 21287-4933, USA

The analysis of expression levels of genes

in the post-mortem brains of individuals with schizophrenia and

bipolar disease is a potentially important method in

understanding the molecular basis of these diseases. The

simultaneous analysis of levels of a large number of genes is

particularly valuable, allowing the evaluation of functionally

related gene groups.

We used the Clontech Atlas Human I cDNA

Expression Array to simultaneously analyze levels of 588 genes.

Total RNA was extracted from cerebellar brain tissue. This RNA

was used to generate 32P-labelled cDNA probes, which

were hybridized to the membrane array. Autoradiograph images of

each array were then analyzed using ImageQuaNT software

(Molecular Dynamics) generating a value for each gene. A total of

22 samples were analyzed, including four brains from

schizophrenics, six from bipolar individuals, five from

clinically depressed individuals, and seven normal controls.

ANOVA analysis was performed to compare the levels of each gene

between the four disease groups. Several genes were found to be

significantly differentially expressed in patients and controls.

In addition, for each disease, total RNA from four samples was

pooled, and this mixture was hybridized to the array. The largest

differences were seen in levels of glutathione S-transferase

microsomal (raised in schizophrenic and bipolar) and glutathione

S-transferase theta-1 (depressed in schizophrenic).