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Systematic meta-analysis and replication of genome-wide expression studies of Parkinson's disease: 3

ABSTRACT: Systematic meta-analysis and replication of genome-wide expression studies identifies molecular pathways of Parkinson's disease. Analysis of substantia nigrae from postmortem brains of 6 patients with Parkinson's disease (PD). Results provide insight into the molecular processes perturbed in the PD substantia nigra. Substantia nigra samples from 6 PD and 5 control subjects were obtained. At autopsy, brain hemispheres were frozen in liquid nitrogen and stored at -80C in the Kathleen Price Bryan Brain Bank in the Alzheimer's Disease Research Center at Duke University. Using the RNAgents kit (Promega, Madison, Wis), RNA was extracted from SN and adjacent midbrain tissues. Double-stranded complementary DNA was made with a biotinylated T7(dT)-24 primer. Twenty micrograms of biotinylated complementary RNA was fragmented and hybridized to Affymetrix human genome U133A microarrays. The Affymetrix .CEL files were normalized to "all probe sets" in a standardized matter, and scaled to 100 by the MAS5 algorithm implemented in the Bioconductor package.

ORGANISM(S): Homo sapiens

SUBMITTER: Bin Zheng 

PROVIDER: E-GEOD-20164 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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PGC-1α, a potential therapeutic target for early intervention in Parkinson's disease.

Zheng Bin B   Liao Zhixiang Z   Locascio Joseph J JJ   Lesniak Kristen A KA   Roderick Sarah S SS   Watt Marla L ML   Eklund Aron C AC   Zhang-James Yanli Y   Kim Peter D PD   Hauser Michael A MA   Grünblatt Edna E   Moran Linda B LB   Mandel Silvia A SA   Riederer Peter P   Miller Renee M RM   Federoff Howard J HJ   Wüllner Ullrich U   Papapetropoulos Spyridon S   Youdim Moussa B MB   Cantuti-Castelvetri Ippolita I   Young Anne B AB   Vance Jeffery M JM   Davis Richard L RL   Hedreen John C JC   Adler Charles H CH   Beach Thomas G TG   Graeber Manuel B MB   Middleton Frank A FA   Rochet Jean-Christophe JC   Scherzer Clemens R CR  

Science translational medicine 20101001 52

Parkinson's disease affects 5 million people worldwide, but the molecular mechanisms underlying its pathogenesis are still unclear. Here, we report a genome-wide meta-analysis of gene sets (groups of genes that encode the same biological pathway or process) in 410 samples from patients with symptomatic Parkinson's and subclinical disease and healthy controls. We analyzed 6.8 million raw data points from nine genome-wide expression studies, and 185 laser-captured human dopaminergic neuron and sub  ...[more]

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