IDENTIFICATION OF DIFFERENTIALLY EXPRESSED GENES IN TWO CORTICAL REGIONS OF PATIENTS WITH MOOD DISORDERS BY SERIAL ANALYSIS OF GENE EXPRESSION (SAGE).
J.Li; P.V.Choudary; S.J.Evans; M.P.Vawter; H.Tomita; M.O.Lopez-Figueroa; E.G.Jones; W.E.Bunney; H.Akil; S.J.Watson; R.M.Myers
Society for Neuroscience 33rd Annual Meeting. 2003.
We have constructed and analyzed six SAGE libraries to characterize gene expression changes in post-mortem brains of individuals suffering from severe mood disorders. The libraries were made from total RNA samples representing two brain regions, anterior cingulate gyrus and dorsolateral prefrontal cortex, from three pooled subject groups: 5 normal controls (CTRL), 5 patients of bipolar disorder (BP) and 5 patients of major depressive disorder (MDD). Each library was sequenced to generate 200,000-300,000 10-base tags. We have identified ~200 unique tags differentially expressed between BP and CTRL, and ~300 tags between MDD and CTRL. Approximately 32% of these tags can be assigned to a Unigene cluster, about half of which correspond to genes of some known function. Another 25% of the tags cannot be assigned to a gene; and the remaining 43% can be assigned to multiple genes. We are currently using tag-specific PCR to isolate and ascertain the cognate transcripts that generated these unknown tags as potentially novel candidate genes for mood disorders. We are using quantitative Reverse Transcription-PCR to validate the putative differentially expressed genes in a larger sample set of 20 CTRLs, 11 MDDs and 9 BPs. The SAGE and RT-PCR results are being compared and integrated with the Affymetrix Oligonucleotide arrays data on the same samples. Supported by the Pritzker Neuropsychiatric Disorder Research Consortium Fund and NIH Conte grant MH60398-03.