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Brain Advance Access published online on December 21, 2007
Brain, doi:10.1093/brain/awm312
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© The Author (2007). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Chromosomal profiles of gene expression in Huntington's disease

Alexander N. Anderson1, Federico Roncaroli2, Angela Hodges3, Manuel Deprez4 and Federico E. Turkheimer1,2

1MRC Clinical Sciences Centre, Hammersmith Hospital, London, 2Department of Clinical Neuroscience, Division of Neuroscience & Mental Health, Imperial College London, 3MRC Centre for Neurodegeneration Research, Institute of Psychiatry, London, UK and 4Laboratory of Neuropathology, Department of Pathology, University Hospital of Liège, Belgium

Correspondence to: Dr Federico E. Turkheimer, Department of Clinical Neuroscience, Division of Neuroscience and Mental Health, Cyclotron Building, Room 236, Hammersmith Hospital, DuCane Road, London W12 0NN, UK E-mail: federico.turkheimer{at}imperial.ac.uk

Recent studies suggested that Huntington's disease is due to aberrant interactions between mutant huntingtin protein, transcription factors and transcriptional co-activators resulting in widespread transcriptional dysregulation. Mutant huntingtin also interacts with histone acetyltransferases, consequently interfering with the acetylation and deacetylation states of histones. Because histone modifications and chromatin structure coordinate the expression of gene clusters, we have applied a novel mathematical approach, Chromowave, to analyse microarray datasets of brain tissue and whole blood to understand how genomic regions are altered by the effects of mutated huntingtin on chromatin structure. Results show that, in samples of caudate and whole blood from Huntington's disease patients, transcription is indeed deregulated in large genomic regions in coordinated fashion, that transcription in these regions is associated with disease progression and that altered chromosomal clusters in the two tissues are remarkably similar. These findings support the notion of a common genome-wide mechanism of disruption of RNA transcription in the brain and periphery of Huntington's disease patients.

Key Words: Huntington's disease; microarrays; histone deacetylase; chromosomal expression; Chromowave

Abbreviations: HD, Huntington's disease; HDAC, histone deacetylase

Received August 15, 2007. Revised October 21, 2007. Accepted November 30, 2007.


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