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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Format: | Article |
Language: | English |
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Public Library of Science (PLoS)
2008-01-01
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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. |
first_indexed | 2024-12-20T11:46:04Z |
format | Article |
id | doaj.art-4360517c74a24c5291d58ba756a00d2d |
institution | Directory Open Access Journal |
issn | 1932-6203 |
language | English |
last_indexed | 2024-12-20T11:46:04Z |
publishDate | 2008-01-01 |
publisher | Public Library of Science (PLoS) |
record_format | Article |
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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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