Transcriptome sequencing revealed significant alteration of cortical promoter usage and splicing in schizophrenia.
While hybridization based analysis of the cortical transcriptome has provided important insight into the neuropathology of schizophrenia, it represents a restricted view of disease-associated gene activity based on predetermined probes. By contrast, sequencing technology can provide un-biased analys...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2012-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC3338678?pdf=render |
id |
doaj-15fd9a3708a34ff49966ce029ce2b3b7 |
---|---|
record_format |
Article |
spelling |
doaj-15fd9a3708a34ff49966ce029ce2b3b72020-11-25T01:53:29ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0174e3635110.1371/journal.pone.0036351Transcriptome sequencing revealed significant alteration of cortical promoter usage and splicing in schizophrenia.Jing Qin WuXi WangNatalie J BeveridgePaul A TooneyRodney J ScottVaughan J CarrMurray J CairnsWhile hybridization based analysis of the cortical transcriptome has provided important insight into the neuropathology of schizophrenia, it represents a restricted view of disease-associated gene activity based on predetermined probes. By contrast, sequencing technology can provide un-biased analysis of transcription at nucleotide resolution. Here we use this approach to investigate schizophrenia-associated cortical gene expression.The data was generated from 76 bp reads of RNA-Seq, aligned to the reference genome and assembled into transcripts for quantification of exons, splice variants and alternative promoters in postmortem superior temporal gyrus (STG/BA22) from 9 male subjects with schizophrenia and 9 matched non-psychiatric controls. Differentially expressed genes were then subjected to further sequence and functional group analysis. The output, amounting to more than 38 Gb of sequence, revealed significant alteration of gene expression including many previously shown to be associated with schizophrenia. Gene ontology enrichment analysis followed by functional map construction identified three functional clusters highly relevant to schizophrenia including neurotransmission related functions, synaptic vesicle trafficking, and neural development. Significantly, more than 2000 genes displayed schizophrenia-associated alternative promoter usage and more than 1000 genes showed differential splicing (FDR<0.05). Both types of transcriptional isoforms were exemplified by reads aligned to the neurodevelopmentally significant doublecortin-like kinase 1 (DCLK1) gene.This study provided the first deep and un-biased analysis of schizophrenia-associated transcriptional diversity within the STG, and revealed variants with important implications for the complex pathophysiology of schizophrenia.http://europepmc.org/articles/PMC3338678?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jing Qin Wu Xi Wang Natalie J Beveridge Paul A Tooney Rodney J Scott Vaughan J Carr Murray J Cairns |
spellingShingle |
Jing Qin Wu Xi Wang Natalie J Beveridge Paul A Tooney Rodney J Scott Vaughan J Carr Murray J Cairns Transcriptome sequencing revealed significant alteration of cortical promoter usage and splicing in schizophrenia. PLoS ONE |
author_facet |
Jing Qin Wu Xi Wang Natalie J Beveridge Paul A Tooney Rodney J Scott Vaughan J Carr Murray J Cairns |
author_sort |
Jing Qin Wu |
title |
Transcriptome sequencing revealed significant alteration of cortical promoter usage and splicing in schizophrenia. |
title_short |
Transcriptome sequencing revealed significant alteration of cortical promoter usage and splicing in schizophrenia. |
title_full |
Transcriptome sequencing revealed significant alteration of cortical promoter usage and splicing in schizophrenia. |
title_fullStr |
Transcriptome sequencing revealed significant alteration of cortical promoter usage and splicing in schizophrenia. |
title_full_unstemmed |
Transcriptome sequencing revealed significant alteration of cortical promoter usage and splicing in schizophrenia. |
title_sort |
transcriptome sequencing revealed significant alteration of cortical promoter usage and splicing in schizophrenia. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2012-01-01 |
description |
While hybridization based analysis of the cortical transcriptome has provided important insight into the neuropathology of schizophrenia, it represents a restricted view of disease-associated gene activity based on predetermined probes. By contrast, sequencing technology can provide un-biased analysis of transcription at nucleotide resolution. Here we use this approach to investigate schizophrenia-associated cortical gene expression.The data was generated from 76 bp reads of RNA-Seq, aligned to the reference genome and assembled into transcripts for quantification of exons, splice variants and alternative promoters in postmortem superior temporal gyrus (STG/BA22) from 9 male subjects with schizophrenia and 9 matched non-psychiatric controls. Differentially expressed genes were then subjected to further sequence and functional group analysis. The output, amounting to more than 38 Gb of sequence, revealed significant alteration of gene expression including many previously shown to be associated with schizophrenia. Gene ontology enrichment analysis followed by functional map construction identified three functional clusters highly relevant to schizophrenia including neurotransmission related functions, synaptic vesicle trafficking, and neural development. Significantly, more than 2000 genes displayed schizophrenia-associated alternative promoter usage and more than 1000 genes showed differential splicing (FDR<0.05). Both types of transcriptional isoforms were exemplified by reads aligned to the neurodevelopmentally significant doublecortin-like kinase 1 (DCLK1) gene.This study provided the first deep and un-biased analysis of schizophrenia-associated transcriptional diversity within the STG, and revealed variants with important implications for the complex pathophysiology of schizophrenia. |
url |
http://europepmc.org/articles/PMC3338678?pdf=render |
work_keys_str_mv |
AT jingqinwu transcriptomesequencingrevealedsignificantalterationofcorticalpromoterusageandsplicinginschizophrenia AT xiwang transcriptomesequencingrevealedsignificantalterationofcorticalpromoterusageandsplicinginschizophrenia AT nataliejbeveridge transcriptomesequencingrevealedsignificantalterationofcorticalpromoterusageandsplicinginschizophrenia AT paulatooney transcriptomesequencingrevealedsignificantalterationofcorticalpromoterusageandsplicinginschizophrenia AT rodneyjscott transcriptomesequencingrevealedsignificantalterationofcorticalpromoterusageandsplicinginschizophrenia AT vaughanjcarr transcriptomesequencingrevealedsignificantalterationofcorticalpromoterusageandsplicinginschizophrenia AT murrayjcairns transcriptomesequencingrevealedsignificantalterationofcorticalpromoterusageandsplicinginschizophrenia |
_version_ |
1724990677962457088 |