Whole transcriptome sequencing reveals gene expression and splicing differences in brain regions affected by Alzheimer's disease.

Recent studies strongly indicate that aberrations in the control of gene expression might contribute to the initiation and progression of Alzheimer's disease (AD). In particular, alternative splicing has been suggested to play a role in spontaneous cases of AD. Previous transcriptome profiling...

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Autores principales:	Natalie A Twine, Karolina Janitz, Marc R Wilkins, Michal Janitz
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/74e71787791a44eea75014f5219ba1b2
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spelling	oai:doaj.org-article:74e71787791a44eea75014f5219ba1b22021-11-18T07:00:07ZWhole transcriptome sequencing reveals gene expression and splicing differences in brain regions affected by Alzheimer's disease.1932-620310.1371/journal.pone.0016266https://doaj.org/article/74e71787791a44eea75014f5219ba1b22011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21283692/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Recent studies strongly indicate that aberrations in the control of gene expression might contribute to the initiation and progression of Alzheimer's disease (AD). In particular, alternative splicing has been suggested to play a role in spontaneous cases of AD. Previous transcriptome profiling of AD models and patient samples using microarrays delivered conflicting results. This study provides, for the first time, transcriptomic analysis for distinct regions of the AD brain using RNA-Seq next-generation sequencing technology. Illumina RNA-Seq analysis was used to survey transcriptome profiles from total brain, frontal and temporal lobe of healthy and AD post-mortem tissue. We quantified gene expression levels, splicing isoforms and alternative transcript start sites. Gene Ontology term enrichment analysis revealed an overrepresentation of genes associated with a neuron's cytological structure and synapse function in AD brain samples. Analysis of the temporal lobe with the Cufflinks tool revealed that transcriptional isoforms of the apolipoprotein E gene, APOE-001, -002 and -005, are under the control of different promoters in normal and AD brain tissue. We also observed differing expression levels of APOE-001 and -002 splice variants in the AD temporal lobe. Our results indicate that alternative splicing and promoter usage of the APOE gene in AD brain tissue might reflect the progression of neurodegeneration.Natalie A TwineKarolina JanitzMarc R WilkinsMichal JanitzPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 1, p e16266 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Natalie A Twine Karolina Janitz Marc R Wilkins Michal Janitz Whole transcriptome sequencing reveals gene expression and splicing differences in brain regions affected by Alzheimer's disease.
description	Recent studies strongly indicate that aberrations in the control of gene expression might contribute to the initiation and progression of Alzheimer's disease (AD). In particular, alternative splicing has been suggested to play a role in spontaneous cases of AD. Previous transcriptome profiling of AD models and patient samples using microarrays delivered conflicting results. This study provides, for the first time, transcriptomic analysis for distinct regions of the AD brain using RNA-Seq next-generation sequencing technology. Illumina RNA-Seq analysis was used to survey transcriptome profiles from total brain, frontal and temporal lobe of healthy and AD post-mortem tissue. We quantified gene expression levels, splicing isoforms and alternative transcript start sites. Gene Ontology term enrichment analysis revealed an overrepresentation of genes associated with a neuron's cytological structure and synapse function in AD brain samples. Analysis of the temporal lobe with the Cufflinks tool revealed that transcriptional isoforms of the apolipoprotein E gene, APOE-001, -002 and -005, are under the control of different promoters in normal and AD brain tissue. We also observed differing expression levels of APOE-001 and -002 splice variants in the AD temporal lobe. Our results indicate that alternative splicing and promoter usage of the APOE gene in AD brain tissue might reflect the progression of neurodegeneration.
format	article
author	Natalie A Twine Karolina Janitz Marc R Wilkins Michal Janitz
author_facet	Natalie A Twine Karolina Janitz Marc R Wilkins Michal Janitz
author_sort	Natalie A Twine
title	Whole transcriptome sequencing reveals gene expression and splicing differences in brain regions affected by Alzheimer's disease.
title_short	Whole transcriptome sequencing reveals gene expression and splicing differences in brain regions affected by Alzheimer's disease.
title_full	Whole transcriptome sequencing reveals gene expression and splicing differences in brain regions affected by Alzheimer's disease.
title_fullStr	Whole transcriptome sequencing reveals gene expression and splicing differences in brain regions affected by Alzheimer's disease.
title_full_unstemmed	Whole transcriptome sequencing reveals gene expression and splicing differences in brain regions affected by Alzheimer's disease.
title_sort	whole transcriptome sequencing reveals gene expression and splicing differences in brain regions affected by alzheimer's disease.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/74e71787791a44eea75014f5219ba1b2
work_keys_str_mv	AT natalieatwine wholetranscriptomesequencingrevealsgeneexpressionandsplicingdifferencesinbrainregionsaffectedbyalzheimersdisease AT karolinajanitz wholetranscriptomesequencingrevealsgeneexpressionandsplicingdifferencesinbrainregionsaffectedbyalzheimersdisease AT marcrwilkins wholetranscriptomesequencingrevealsgeneexpressionandsplicingdifferencesinbrainregionsaffectedbyalzheimersdisease AT michaljanitz wholetranscriptomesequencingrevealsgeneexpressionandsplicingdifferencesinbrainregionsaffectedbyalzheimersdisease
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Whole transcriptome sequencing reveals gene expression and splicing differences in brain regions affected by Alzheimer's disease.

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