Transcriptional changes in Huntington disease identified using genome-wide expression profiling and cross-platform analysis.
Evaluation of transcriptional changes in the striatum may be an effective approach to understanding the natural history of changes in expression contributing to the pathogenesis of Huntington disease (HD). We have performed genome-wide expression profiling of the YAC128 transgenic mouse model of HD at 12 and 24 months of age using two platforms in parallel: Affymetrix and Illumina. The data from these two powerful platforms were integrated to create a combined rank list, thereby revealing the identity of additional genes that proved to be differentially expressed between YAC128 and control mice. Using this approach, we identified 13 genes to be differentially expressed between YAC128 and controls which were validated by quantitative real-time PCR in independent cohorts of animals. In addition, we analyzed additional time points relevant to disease pathology: 3, 6 and 9 months of age. Here we present data showing the evolution of changes in the expression of selected genes: Wt1, Pcdh20 and Actn2 RNA levels change as early as 3 months of age, whereas Gsg1l, Sfmbt2, Acy3, Polr2a and Ppp1r9a RNA expression levels are affected later, at 12 and 24 months of age. We also analyzed the expression of these 13 genes in human HD and control brain, thereby revealing changes in SLC45A3, PCDH20, ACTN2, DDAH1 and PPP1R9A RNA expression. Further study of these genes may unravel novel pathways contributing to HD pathogenesis. DDBJ/EMBL/GenBank accession no: GSE19677.
Becanovic
Kristina
K
Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada V5Z 4H4.
Pouladi
Mahmoud A
MA
Lim
Raymond S
RS
Kuhn
Alexandre
A
Pavlidis
Paul
P
Luthi-Carter
Ruth
R
Hayden
Michael R
MR
Leavitt
Blair R
BR
D000367:Age Factors; D000818:Animals; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D016678:Genome; D015894:Genome, Human; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D014158:Transcription, Genetic
C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins