NR AOYA
AU Preuss,S.; He,H.; Eckert,J.; Melchinger,E.; Kuss,A.W.; Geldermann,H.
TI New DNA variants associated with transmissible spongiform encephalopathy (TSE) in cattle and sheep
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - DG-53
PT Konferenz-Poster
AB Forms of TSE that occur in man and other mammalian species are associated with an increase in protease resistant scrapie isoform of the prion protein (PrPsc). Among other factors, the pathogenesis is influenced by DNA variants in the prion protein encoding gene (PRNP) of the host genome. The objective of the study was the analysis of new DNA variants outside the coding PRNP regions. Variable sites were analysed by automated screening procedures. Based on the GenBank sequences, suitable sites were selected and sequenced for cattle and sheep from genetically different breeds. Bovine and ovine PRNP sequences showed similar positions for most of the polymorphic sites. Allelic variants were observed for eight out of 24 sites in cattle and six out of 23 sites in sheep. Because a number of polymorphic sites were newly detected within a short physical distance of each other their haplotypes are in linkage disequilibrium and can be efficiently applied for association studies on prion disease. For cattle, the alleles at polymorphic PRNP sites are compared between genomic DNA of 262 BSE cattle and DNA of control animals. Data evaluation is in progress. In sheep, the polymorphic sites were genotyped for 623 animals of eight German breeds and analysed for their combinations with PRNP ORF variants at the codons 136, 154 and 171. We found highly significant associations between PRNP genotypes/alleles and scrapie risk groups as deduced from the ORF variants. For further studies a number of sheep carrying different PRNP genotypes are infected with scrapie. The few, hitherto available DNA markers in the bovine and ovine PRNP have limited variability and do not allow efficient genotyping. Thus the new, highly polymorphic PRNP microsatellite sites markedly improve the analysis of phylogenetic origin of different PRNP alleles and trait association studies for TSE.
AD S. Preuss, H. He, J. Eckert, E. Melchinger, A.W. Kuss, H. Geldermann, Department of Animal Breeding and Biotechnology, University of Hohenheim, Stuttgart, Germany
SP englisch
PO Deutschland