a cross-study transcriptional analysis of parkinsons diseasecross-study转录分析帕金森病.pdfVIP

A Cross-Study Transcriptional Analysis of Parkinson’s Disease 1. 1. 1 1 Greg T. Sutherland , Nicholas A. Matigian , Alistair M. Chalk , Matthew J. Anderson , Peter A. 1,2 1 1 1,3,4 Silburn , Alan Mackay-Sim , Christine A. Wells , George D. Mellick * 1 National Centre for Adult Stem Cell Research, Eskitis Institute for Cell and Molecular Therapies, Griffith University, Brisbane, Queensland, Australia, 2 The School of Medicine, University of Queensland, Brisbane, Queensland, Australia, 3 Department of Neurology, Princess Alexandra Hospital, Brisbane, Queensland, Australia, 4 Department of Neurology, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia Abstract The study of Parkinson’s disease (PD), like other complex neurodegenerative disorders, is limited by access to brain tissue from patients with a confirmed diagnosis. Alternatively the study of peripheral tissues may offer some insight into the molecular basis of disease susceptibility and progression, but this approach still relies on brain tissue to benchmark relevant molecular changes against. Several studies have reported whole-genome expression profiling in post-mortem brain but reported concordance between these analyses is lacking. Here we apply a standardised pathway analysis to seven independent case-control studies, and demonstrate increased concordance between data sets. Moreover data convergence increased when the analysis was limited to the five substantia nigra (SN) data sets; this highlighted the down regulation of dopamine