GSE33000   Details

GSE Accession GSE33000
Title Gene expression profiles of human prefrontal cortex brain tissues
Submission Date 10/14/11
Last Update Date 12/31/13
Pubmed ID
Experiment Type Expression profiling by array
Contributor Manikandan,,Narayanan; Kai Wang; Xia Yang; Albert,V,Smith; Bin Zhang; Joshua McElwee; Chunsheng Zhang; Sigurdur Sigurdsson; John,R,Lamb; Tao Xie; Christine Suver; Oscar Puig; Cliona Molony; Hong Bao; Stacey Melquist; Andrew,D,Johnson; Lenore,J,Laurner; Ad
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Organism Homo sapiens
Organism ID 9606
Organism Synonym man; human
Summary Dissecting the shared etiology of different diseases could benefit from a systematic search for associated molecules and their interactions. We investigated genome-wide disruptions in the co-regulation of genes in two neurodegenerative diseases, Alzheimer's or Huntington's disease (AD or HD), using expression profiles from postmortem prefrontal cortex samples of 624 demented patients and non-demented control individuals with matched genotype and clinical data. A meta-analysis based screen for changes in coordinate expression patterns revealed differentially co-expressed (DC) gene pairs that either gained or lost correlation in disease cases relative to the control group, with the former being dominant for both AD and HD. Integration of disruptions common to AD and HD with large-scale data on protein-protein and protein-DNA interactions yielded a 242-gene sub-network that was enriched for proteins involved in neuronal differentiation and genetic associations to brain structural changes and dementia in subjects aged over 70 years. Replication of the AD DC network in independent human and mouse cohorts lends confidence to the comprehensive view we offer on dysregulated brain molecular pathways in AD and HD.
Overall Design DLPFC (BA9) brain tissues of AD patients, HD patients and non-demented controls samples were obtained from Harvard Brain tissue resource center (HBTRC). The HBTRC samples were primarily of Caucasian ancestry, as only eight non-Caucasian outliers were identified, and therefore excluded for further analysis. Post-mortem interval (PMI) was 17.8+8.3 hours (mean ± standard deviation), sample pH was 6.4±0.3 and RNA integrity number (RIN) was 6.8±0.8 for the average sample in the overall cohort. Tissues were profiled on a custom-made Agilent 44K array (GPL4372_1). 622 individual DLPFC sample was profiled against a common DLPFC pool constructed from the same set of samples.
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