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Genomic Convergence Analysis of Schizophrenia: mRNA Sequencing Reveals Altered Synaptic Vesicular Transport in Post-Mortem Cerebellum

By Joann Mudge, Neil A. Miller, Irina Khrebtukova, Ingrid E. Lindquist, Gregory D. May, Jim J. Huntley, Shujun Luo, Lu Zhang, Jennifer C. Van Velkinburgh, Andrew D. Farmer, Sharon Lewis, William D, Faye D. Schilkey, Selene M. Virk, C. Forrest Black, M. Kathy Myers, Lar C. Mader, Ray J, John P. Utsey, Ryan W. Kim, Rosalinda C. Roberts, Sat Kirpal Khalsa, Meredith Garcia, Victoria Ambriz-griffith, Richard Harlan, Wendy Czika, Stanton Martin, Russell D. Wolfinger, Nora I and Perrone-bizzozero Gary P. Schroth


Schizophrenia (SCZ) is a common, disabling mental illness with high heritability but complex, poorly understood genetic etiology. As the first phase of a genomic convergence analysis of SCZ, we generated 16.7 billion nucleotides of short read, shotgun sequences of cDNA from post-mortem cerebellar cortices of 14 patients and six, matched controls. A rigorous analysis pipeline was developed for analysis of digital gene expression studies. Sequences aligned to approximately 33,200 transcripts in each sample, with average coverage of 450 reads per gene. Following adjustments for confounding clinical, sample and experimental sources of variation, 215 genes differed significantly in expression between cases and controls. Golgi apparatus, vesicular transport, membrane association, Zinc binding and regulation of transcription were overrepresented among differentially expressed genes. Twenty three genes with altered expression and involvement in presynaptic vesicular transport, Golgi function and GABAergic neurotransmission define a unifying molecular hypothesis fo

Year: 2011
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