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dc.contributor.authorLabadorf, Adam
dc.contributor.authorHoss, Andrew
dc.contributor.authorLagomarsino, Valentina
dc.contributor.authorLatourelle, Jeanne C.
dc.contributor.authorHadzi, Tiffany C.
dc.contributor.authorBregu, Joli
dc.contributor.authorMacDonald, Marcy E.
dc.contributor.authorGusella, James F.
dc.contributor.authorChen, Jiang-Fan
dc.contributor.authorAkbarian, Schahram
dc.contributor.authorWeng, Zhiping
dc.contributor.authorMyers, Richard H.
dc.date2022-08-11T08:09:44.000
dc.date.accessioned2022-08-23T16:41:26Z
dc.date.available2022-08-23T16:41:26Z
dc.date.issued2015-12-04
dc.date.submitted2016-01-15
dc.identifier.citationPLoS One. 2015 Dec 4;10(12):e0143563. doi: 10.1371/journal.pone.0143563. eCollection 2015. <a href="http://dx.doi.org/10.1371/journal.pone.0143563">Link to article on publisher's site</a>
dc.identifier.issn1932-6203 (Linking)
dc.identifier.doi10.1371/journal.pone.0143563
dc.identifier.pmid26636579
dc.identifier.urihttp://hdl.handle.net/20.500.14038/39882
dc.description.abstractHuntington's Disease (HD) is a devastating neurodegenerative disorder that is caused by an expanded CAG trinucleotide repeat in the Huntingtin (HTT) gene. Transcriptional dysregulation in the human HD brain has been documented but is incompletely understood. Here we present a genome-wide analysis of mRNA expression in human prefrontal cortex from 20 HD and 49 neuropathologically normal controls using next generation high-throughput sequencing. Surprisingly, 19% (5,480) of the 28,087 confidently detected genes are differentially expressed (FDR < 0.05) and are predominantly up-regulated. A novel hypothesis-free geneset enrichment method that dissects large gene lists into functionally and transcriptionally related groups discovers that the differentially expressed genes are enriched for immune response, neuroinflammation, and developmental genes. Markers for all major brain cell types are observed, suggesting that HD invokes a systemic response in the brain area studied. Unexpectedly, the most strongly differentially expressed genes are a homeotic gene set (represented by Hox and other homeobox genes), that are almost exclusively expressed in HD, a profile not widely implicated in HD pathogenesis. The significance of transcriptional changes of developmental processes in the HD brain is poorly understood and warrants further investigation. The role of inflammation and the significance of non-neuronal involvement in HD pathogenesis suggest anti-inflammatory therapeutics may offer important opportunities in treating HD.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=26636579&dopt=Abstract">Link to Article in PubMed</a>
dc.rights<p>Copyright: 2015 Labadorf et al. This is an open access article distributed under the terms of the <a href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</a>, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited</p>
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectBioinformatics
dc.subjectComputational Biology
dc.subjectComputational Neuroscience
dc.subjectDevelopmental Biology
dc.subjectDevelopmental Neuroscience
dc.subjectGenetics
dc.subjectNervous System Diseases
dc.subjectNeurology
dc.titleRNA Sequence Analysis of Human Huntington Disease Brain Reveals an Extensive Increase in Inflammatory and Developmental Gene Expression
dc.typeArticle
dc.source.journaltitlePloS one
dc.source.volume10
dc.source.issue12
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=3688&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/2684
dc.identifier.contextkey8015337
refterms.dateFOA2022-08-23T16:41:26Z
html.description.abstract<p>Huntington's Disease (HD) is a devastating neurodegenerative disorder that is caused by an expanded CAG trinucleotide repeat in the Huntingtin (HTT) gene. Transcriptional dysregulation in the human HD brain has been documented but is incompletely understood. Here we present a genome-wide analysis of mRNA expression in human prefrontal cortex from 20 HD and 49 neuropathologically normal controls using next generation high-throughput sequencing. Surprisingly, 19% (5,480) of the 28,087 confidently detected genes are differentially expressed (FDR < 0.05) and are predominantly up-regulated. A novel hypothesis-free geneset enrichment method that dissects large gene lists into functionally and transcriptionally related groups discovers that the differentially expressed genes are enriched for immune response, neuroinflammation, and developmental genes. Markers for all major brain cell types are observed, suggesting that HD invokes a systemic response in the brain area studied. Unexpectedly, the most strongly differentially expressed genes are a homeotic gene set (represented by Hox and other homeobox genes), that are almost exclusively expressed in HD, a profile not widely implicated in HD pathogenesis. The significance of transcriptional changes of developmental processes in the HD brain is poorly understood and warrants further investigation. The role of inflammation and the significance of non-neuronal involvement in HD pathogenesis suggest anti-inflammatory therapeutics may offer important opportunities in treating HD.</p>
dc.identifier.submissionpathoapubs/2684
dc.contributor.departmentProgram in Bioinformatics and Integrative Biology
dc.source.pagese0143563


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<p>Copyright: 2015 Labadorf et al. This is an open access article distributed under the terms of the <a href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</a>, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited</p>
Except where otherwise noted, this item's license is described as <p>Copyright: 2015 Labadorf et al. This is an open access article distributed under the terms of the <a href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</a>, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited</p>