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- Title
Genomic Convergence Analysis of Schizophrenia: mRNA Sequencing Reveals Altered Synaptic Vesicular Transport in Post-Mortem Cerebellum.
- Authors
Mudge, Joann; Miller, Neil A.; Khrebtukova, Irina; Lindquist, Ingrid E.; May, Gregory D.; Huntley, Jim J.; Shujun Luo; Lu Zhang; van Velkinburgh, Jennifer C.; Farmer, Andrew D.; Lewis, Sharon; Beavis^1, William D.; Schilkey, Faye D.; Virk, Selene M.; Black, C. Forrest; Myers, M. Kathy; Mader, Lar C.; Langley, Ray J.; Utsey, John P.; Kim, Ryan W.
- Abstract
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 for dysfunction in cerebellar cortex in SCZ.
- Subjects
SCHIZOPHRENIA; MENTAL illness; HERITABILITY; NUCLEOTIDES; GENE expression; GOLGI apparatus; GENETIC regulation; MENTAL health; NEURAL transmission
- Publication
PLoS ONE, 2008, Vol 3, Issue 11, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0003625