NR AWHV
AU Kashkevich,K.; Orlicz-Welcz,B.; Henz,I.; Fischer,C.; Becker,C.M.; Schiebel,K.
TI Prion protein gene expression is modulated by DNA polymorphisms in the promoter region
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Poster sessions GEN-14
PT Konferenz-Poster
AB The phenomenon that host genetic factors modulate the susceptibility to prion infection was initially reported in sheep and human, where polymorphisms within the coding sequence of the prion protein gene (PRNP) have been shown to lead to an increase or decrease in susceptibility. However, no polymorphism within the bovine PRNP coding region has been shown to be associated with bovine spongiform encephalopathy (BSE). To determine whether polymorphisms within the promoter region are involved in susceptibility or resistance to BSE, DNA polymorphisms of the promoter region of the bovine PRNP gene were identified and genotyped in breeding bulls as control and animals tested positive for BSE. Furthermore, the functional relevance of identified polymorphic sites was assessed using a luciferase reporter gene assay. The binding of different transcription factors to DNA fragments in which polymorphisms were detected, was examined. Comparative sequencing and MALDI-TOF based SNP analysis between control and BSE affected animals from 4 different bovine breeds (namely Schwarzbunt, Rotbunt, Braunvieh and Fleckvieh) showed that Braunvieh animals are significantly different from other breeds, exhibiting different allele frequencies for the 12 bp indel polymorphism in control and BSE animals. Genotyping and haplotype calculation of nine polymorphisms in the promoter region resulted in significantly different haplotype distribution in control and BSE animals. Promoter constructs of main haplotypes containing different combinations of polymorphisms revealed that the influence of SNP combinations (haplotypes) is more important for PRNP expression in neuronal cells than the 12 bp indel polymorphism alone. The haplotype resulting in the lowest expression level is underrepresented in BSE animals compared to controls and therefore supports the hypothesis that expression level is correlated to susceptibility to TSE.
AD K. Kashkevich, B. Orlicz-Welcz, I. Henz, C.-M. Becker, K. Schiebel: Institute of Biochemistry, Emil-Fischer-Center, University Erlangen-Nürnberg, Erlangen, Germany; C. Fischer: Institute of Human Genetics, University Heidelberg, Heidelberg, Germany. E-mail: katrin.schiebel@biochem.uni-erlangen.de
SP englisch
PO Italien