NR AURB
AU Kashkevich,K.; Orlicz-Welcz,B.; Henz,I.; Becker,C.M.; Schiebel,K.
TI DNA polymorphisms in the promoter region of the prion protein gene PRNP modulate gene expression
QU TSE-Forum, 6. Kongress - Nationale TSE-Forschungsplattform, Greifswald 26.6.-28.6.2006, Vortrag V-20
PT Konferenz-Vortrag
AB
Modulation of susceptibility to prion infection by host genetic factors was initially reported in sheep and humans, where polymorphisms within the coding sequence of the prion protein gene (PRNP) have been shown to lead to either an increase or a decrease in susceptibility. However, within the bovine PRNP coding region no polymorphism has yet 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 control and BSE affected animals. Furthermore, the functionality of identified polymorphic sites was assessed using a luciferase reporter gene assay and the binding of different transcription factors to DNA fragments in which polymorphisms were detected was examined.
Comparative sequencing 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 in that they exhibit different allele frequencies for the 12 bp indel polymorphism in both control and BSE animals. The 12 bp indel in intron 1 affects an Sp1/Sp3-binding site that is destroyed by the deletion of this polymorphism. A significantly higher 12 bp deletion allele frequency was observed in Braunvieh BSE cattle and this can be explained by the deletion of a transcription repressor binding site. Promoter constructs containing different combinations of polymorphisms revealed that the influence of SNP combinations (haplotypes) is more important than the 12 bp indel polymorphism for PRNP expression in neuronal cells.
AD Kseniya Kashkevich, Barbara Orlicz-Welcz, Ingmar Henz, Cord-Michael Becker and Katrin Schiebel, Institut für Biochemie, Emil-Fischer-Zentrum, Universität Erlangen-Nürnberg, Fahrstr. 17, 91054 Erlangen
SP englisch
PO Deutschland
OR Tagungsband