Genomic convergence analysis of schizophrenia: mRNA sequencing reveals altered synaptic vesicular transport in post-mortem cerebellum.

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 co...

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Main Authors: 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 Beavis, Faye D Schilkey, Selene M Virk, C Forrest Black, M Kathy Myers, Lar C Mader, Ray J Langley, 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 Perrone-Bizzozero, Gary P Schroth, Stephen F Kingsmore
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2008-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC2576459?pdf=render
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author 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 Beavis
Faye D Schilkey
Selene M Virk
C Forrest Black
M Kathy Myers
Lar C Mader
Ray J Langley
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 Perrone-Bizzozero
Gary P Schroth
Stephen F Kingsmore
Stephen F Kingsmore
author_facet 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 Beavis
Faye D Schilkey
Selene M Virk
C Forrest Black
M Kathy Myers
Lar C Mader
Ray J Langley
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 Perrone-Bizzozero
Gary P Schroth
Stephen F Kingsmore
Stephen F Kingsmore
author_sort Joann Mudge
collection DOAJ
description 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.
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spelling doaj.art-4360517c74a24c5291d58ba756a00d2d2022-12-21T19:41:52ZengPublic Library of Science (PLoS)PLoS ONE1932-62032008-01-01311e362510.1371/journal.pone.0003625Genomic convergence analysis of schizophrenia: mRNA sequencing reveals altered synaptic vesicular transport in post-mortem cerebellum.Joann MudgeNeil A MillerIrina KhrebtukovaIngrid E LindquistGregory D MayJim J HuntleyShujun LuoLu ZhangJennifer C van VelkinburghAndrew D FarmerSharon LewisWilliam D BeavisFaye D SchilkeySelene M VirkC Forrest BlackM Kathy MyersLar C MaderRay J LangleyJohn P UtseyRyan W KimRosalinda C RobertsSat Kirpal KhalsaMeredith GarciaVictoria Ambriz-GriffithRichard HarlanWendy CzikaStanton MartinRussell D WolfingerNora I Perrone-BizzozeroGary P SchrothStephen F KingsmoreStephen F KingsmoreSchizophrenia (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.http://europepmc.org/articles/PMC2576459?pdf=render
spellingShingle 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 Beavis
Faye D Schilkey
Selene M Virk
C Forrest Black
M Kathy Myers
Lar C Mader
Ray J Langley
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 Perrone-Bizzozero
Gary P Schroth
Stephen F Kingsmore
Stephen F Kingsmore
Genomic convergence analysis of schizophrenia: mRNA sequencing reveals altered synaptic vesicular transport in post-mortem cerebellum.
PLoS ONE
title Genomic convergence analysis of schizophrenia: mRNA sequencing reveals altered synaptic vesicular transport in post-mortem cerebellum.
title_full Genomic convergence analysis of schizophrenia: mRNA sequencing reveals altered synaptic vesicular transport in post-mortem cerebellum.
title_fullStr Genomic convergence analysis of schizophrenia: mRNA sequencing reveals altered synaptic vesicular transport in post-mortem cerebellum.
title_full_unstemmed Genomic convergence analysis of schizophrenia: mRNA sequencing reveals altered synaptic vesicular transport in post-mortem cerebellum.
title_short Genomic convergence analysis of schizophrenia: mRNA sequencing reveals altered synaptic vesicular transport in post-mortem cerebellum.
title_sort genomic convergence analysis of schizophrenia mrna sequencing reveals altered synaptic vesicular transport in post mortem cerebellum
url http://europepmc.org/articles/PMC2576459?pdf=render
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