NR APAQ
AU Xiang,W.; Windl,O.; Dugas,M.; Kohlmann,A.; Westner,I.; Neumann,M.; Kretzschmar,H.A.
TI Expression profiling in sporadic Creutzfeldt-Jakob disease
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - BR-41
PT Konferenz-Poster
AB
Sporadic Creutzfeldt-Jakob disease (sCJD) is the most common form of the human prion disease worldwide. The cause of sCJD is still unclear. The sole described genetic factor influencing the susceptibility to sCJD is a common polymorphism in the coding region of the prion protein gene (PRNP) at the codon 129 (M129V). So far, the major predisposing factors aside from the codon 129 of the PRNP are still not clear. Several subtypes of sCJD associated with distinct clinicopathological features can be classified by the genotype at codon 129 and the biochemical properties of the protease-resistant prion protein in the diseased brain. However, it is currently not known whether particular subtypes of sCJD are reflected by distinct gene expression profiles.
The aim of this study is to identify dysregulated genes in the diseased brain by expression profiling using the high-density oligonucleotide probe arrays (U133A, Affymetrix(r)). Gene expression profiles associated with sCJD or with a particular subtype of sCJD will be defined for a better understanding of the pathogenesis of this disease and its variability. Furthermore, this study might help to identify predisposing genes aside from PRNP.
Frontal cortices of post-mortem human brains of sCJD and frontal cortices from unaffected controls were studied. Total RNA derived from brain tissues was used to generate biotinylated antisense RNA, which was hybridized to the high-density oligonucleotide probe arrays. The significantly upregulated and downregulated genes in sCJD were identified by FDR (false discovery rate) analysis. Some of them are involved in signal transduction, apoptosis or cell cycle. Most of the identified genes in this study were not previously associated with sCJD. In addition, dysregulated genes associated with a particular subtype of sCJD were identified by using signal-to-noise statistics. The findings of this study generated several novel insights into patterns of genetic activity correlated with sCJD.
AD W. Xiang, O. Windl, I. Westner, M. Neumann, H.A. Kretzschmar, Institute of Neuropathology, Ludwig-Maximilians-University, 81377 Munich, Germany; M. Dugas, Department of Medical Informatics, Biometrics, and Epidemiology, Ludwig-Maximilians-University, 81377 Munich, Germany; A. Kohlmann, Laboratory for Leukemia Diagnostics, Department of Internal Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University, 81377 Munich, Germany
SP englisch
PO Deutschland