Whole genome expression profiling of the medial and lateral substantia nigra in Parkinson's disease

被引:185
作者
Moran, LB
Duke, DC
Deprez, M
Dexter, DT
Pearce, RKB
Graeber, MB
机构
[1] Imperial Coll London & Hammersmith Hosp Trust, Div Neurosci & Mental Hlth, Univ Dept Neuropathol, London W6 8RF, England
[2] Univ Liege, Univ Hosp, Neuropathol Lab, Liege, Belgium
[3] Imperial Coll London, Div Neurosci & Mental Hlth, Dept Cellular & Mol Neurosci, London, England
关键词
GC-RMA algorithm; microarrays; neurodegeneration; pathway definition; transcriptome signature;
D O I
10.1007/s10048-005-0020-2
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
We have used brain tissue from clinically well-documented and neuropathologically confirmed cases of sporadic Parkinson's disease to establish the transcriptomic expression profile of the medial and lateral substantia nigra. In addition, the superior frontal cortex was analyzed in a subset of the same cases. DNA oligonucleotide microarrays were employed, which provide whole human genome coverage. A total of 570 genes were found to be differentially regulated at a high level of significance. A large number of differentially regulated expressed sequence tags were also identified. Levels of mRNA sequences encoded by genes of key interest were validated by means of quantitative real-time polymerase chain reaction (PCR). Comparing three different normalization procedures, results based on the recently published GeneChip Robust Multi Array algorithm were found to be the most accurate predictor of real-time PCR results. Several new candidate genes which map to PARK loci are reported. In addition, the DNAJ family of chaperones is discussed in the context of Parkinson's disease pathogenesis.
引用
收藏
页码:1 / 11
页数:11
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