title: Genomic convergence analysis of schizophrenia: mRNA sequencing reveals altered synaptic vesicular transport in post-mortem cerebellum.
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 over-represented 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.
authors.affiliation: National Center for Genome Resources, Santa Fe, NM, USA.
authors.forename: Joann
authors.initials: J
authors.lastname: Mudge
authors.forename: Neil A
authors.initials: NA
authors.lastname: Miller
authors.forename: Irina
authors.initials: I
authors.lastname: Khrebtukova
authors.forename: Ingrid E
authors.initials: IE
authors.lastname: Lindquist
authors.forename: Gregory D
authors.initials: GD
authors.lastname: May
authors.forename: Jim J
authors.initials: JJ
authors.lastname: Huntley
authors.forename: Shujun
authors.initials: S
authors.lastname: Luo
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: van Velkinburgh
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Farmer
authors.forename: Sharon
authors.initials: S
authors.lastname: Lewis
authors.forename: William D
authors.initials: WD
authors.lastname: Beavis
authors.forename: Faye D
authors.initials: FD
authors.lastname: Schilkey
authors.forename: Selene M
authors.initials: SM
authors.lastname: Virk
authors.forename: C Forrest
authors.initials: CF
authors.lastname: Black
authors.forename: M Kathy
authors.initials: MK
authors.lastname: Myers
authors.forename: Lar C
authors.initials: LC
authors.lastname: Mader
authors.forename: Ray J
authors.initials: RJ
authors.lastname: Langley
authors.forename: John P
authors.initials: JP
authors.lastname: Utsey
authors.forename: Ryan W
authors.initials: RW
authors.lastname: Kim
authors.forename: Rosalinda C
authors.initials: RC
authors.lastname: Roberts
authors.forename: Sat Kirpal
authors.initials: SK
authors.lastname: Khalsa
authors.forename: Meredith
authors.initials: M
authors.lastname: Garcia
authors.forename: Victoria
authors.initials: V
authors.lastname: Ambriz-Griffith
authors.forename: Richard
authors.initials: R
authors.lastname: Harlan
authors.forename: Wendy
authors.initials: W
authors.lastname: Czika
authors.forename: Stanton
authors.initials: S
authors.lastname: Martin
authors.forename: Russell D
authors.initials: RD
authors.lastname: Wolfinger
authors.forename: Nora I
authors.initials: NI
authors.lastname: Perrone-Bizzozero
authors.forename: Gary P
authors.initials: GP
authors.lastname: Schroth
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Kingsmore
mesh_terms: D000328:Adult; D000368:Aged; D001344:Autopsy; D016022:Case-Control Studies; D002531:Cerebellum / Q000378:metabolism / Q000473:pathology*; D020869:Gene Expression Profiling; D015894:Genome, Human; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology; D017422:Sequence Analysis, DNA / Q000379:methods*; D013572:Synaptic Vesicles / Q000235:genetics* / Q000378:metabolism
chemical_list: D012333:RNA, Messenger