title: A common gene expression signature in Huntington's disease patient brain regions.
abstract: BACKGROUND
  Gene expression data provide invaluable insights into disease mechanisms. In Huntington's disease (HD), a neurodegenerative disease caused by a tri-nucleotide repeat expansion in the huntingtin gene, extensive transcriptional dysregulation has been reported. Conventional dysregulation analysis has shown that e.g. in the caudate nucleus of the post mortem HD brain the gene expression level of about a third of all genes was altered. Owing to this large number of dysregulated genes, the underlying relevance of expression changes is often lost in huge gene lists that are difficult to comprehend.
  
  
  METHODS
  To alleviate this problem, we employed weighted correlation network analysis to archival gene expression datasets of HD post mortem brain regions.
  
  
  RESULTS
  We were able to uncover previously unidentified transcription dysregulation in the HD cerebellum that contained a gene expression signature in common with the caudate nucleus and the BA4 region of the frontal cortex. Furthermore, we found that yet unassociated pathways, e.g. global mRNA processing, were dysregulated in HD. We provide evidence to show that, contrary to previous findings, mutant huntingtin is sufficient to induce a subset of stress response genes in the cerebellum and frontal cortex BA4 region. The comparison of HD with other neurodegenerative disorders showed that the immune system, in particular the complement system, is generally activated. We also demonstrate that HD mouse models mimic some aspects of the disease very well, while others, e.g. the activation of the immune system are inadequately reflected.
  
  
  CONCLUSIONS
  Our analysis provides novel insights into the molecular pathogenesis in HD and identifies genes and pathways as potential therapeutic targets.
authors.affiliation: Department of Medical and Molecular Genetics, King's College London, London, SE1 9RT, UK. andreas.neueder@kcl.ac.uk.
authors.forename: Andreas
authors.initials: A
authors.lastname: Neueder
authors.affiliation: Department of Medical and Molecular Genetics, King's College London, London, SE1 9RT, UK. gillian.bates@kcl.ac.uk.
authors.forename: Gillian P
authors.initials: GP
authors.lastname: Bates
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D006801:Humans; D006816:Huntington Disease / Q000235:genetics*; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: D015415:Biomarkers