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Neurogenetics

, Volume 7, Issue 1, pp 1–11 | Cite as

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

  • L. B. Moran
  • D. C. Duke
  • M. Deprez
  • D. T. Dexter
  • R. K. B. Pearce
  • M. B. Graeber
Original Article

Abstract

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.

Keywords

GC-RMA algorithm Microarrays Neurodegeneration Pathway definition Transcriptome signature 

Notes

Acknowledgements

We are grateful to the brain donors and their families for the provision of brain tissue for research. This work was funded through a programme grant from the UK Parkinson’s Disease Society. We are grateful to the Parkinson’s Disease Society Tissue Bank at Imperial College London, funded by the Parkinson’s Disease Society of the UK, registered charity 948776. We would also like to thank the UK Multiple Sclerosis Tissue Bank at Imperial College London. Use of an Affymetrix node in the Department of Neuropathology, funded by the Trustees of the Corsellis Collection, is gratefully acknowledged. The authors would like to thank Dr. Stuart Peirson for his expert advice on the qRT-PCR analysis and Dr. Geraint Barton from the Bioinformatics Support Service, Imperial College London, for his advice and for the reading of the manuscript.

Supplementary material

10048_2005_20_MOESM1_ESM.rtf (16 kb)
Supplemental Table 1 (PDF 61 kb)
10048_2005_20_MOESM2_ESM.ppt (690 kb)
Supplemental Figure (PDF 374 kb): Pathway relationships of the genes listed in Table 3. Green/red, positive/negative regulatory influence. Lilac, binding
10048_2005_20_MOESM3_ESM.html.
Common targets pathway reference summary (HTML 24 kb)
10048_2005_20_MOESM4_ESM.html (29 kb)
Direct interactions pathway reference summary (HTML 31 kb)
10048_2005_20_MOESM5_ESM.html.
Shortest paths pathway reference summary (HTML 482 kb)
10048_2005_20_MOESM6_ESM.html.
Common regulators pathway reference summary (HTML 125 kb)

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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • L. B. Moran
    • 1
  • D. C. Duke
    • 1
  • M. Deprez
    • 2
  • D. T. Dexter
    • 3
  • R. K. B. Pearce
    • 1
  • M. B. Graeber
    • 1
  1. 1.University Department of Neuropathology, Division of Neuroscience and Mental HealthImperial College London and Hammersmith Hospitals TrustLondonUK
  2. 2.Laboratory of Neuropathology, University HospitalUniversity of LiègeLiègeBelgium
  3. 3.Department of Cellular and Molecular Neuroscience, Division of Neuroscience and Mental HealthImperial College LondonLondonUK

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