NR AOTI
AU Goldmann,W.; Baylis,M.; Houston,E.F.; Chihota,C.M.; Smith,A.J.; Stevenson,E.; O'Neill,G.; Kirby,L.; Manson,J.; Hunter,N.
TI PrP genetics: A means to successfully eradicate prion diseases in animals?
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - DG-31
PT Konferenz-Poster
AB
The UK National Scrapie Plan aims to increase the level of resistance to scrapie in the national sheep flock to eventually eradicate all prion diseases (TSEs). This plan and similar strategies used in other European countries are based on the association of PrP genetics with TSE susceptibility. The level of susceptibility to prion diseases is a function of the strain of agent and the route of infection combined with the primary sequence of the PrP protein and its expression level. In sheep, several PrP polymorphisms, especially arginine in codon 171, reduce the risk of disease incidence for individual sheep and sheep populations. In contrast, only the change to valine in codon 136 increases substantially the disease risk in sheep. Unfortunately, not all sheep breeds and populations have significant frequencies of the known resistance alleles for breeding.
We have therefore investigated (I) the association of new dimorphisms with disease resistance, (II) the distribution of amino acid changes in the PrP secondary structures, (III) the occurrence of pathogenic mutations in natural scrapie and (IV) the role of ovine PrP promoter dimorphisms. Evidence will be presented from natural scrapie genetics, experimental BSE challenges and in vitro PrP conversion assays, that supports the association of a codon 168 dimorphism (Pro to Leu) with resistance. We will show that there appears to be a distinct difference between the location in PrP of resistance-associated polymorphisms in sheep and disease-linked mutations of humans. Our analysis of sheep affected by natural scrapie will confirm that pathogenic mutations are not the cause of scrapie. We will present data on the subdivision of the PrP wildtype alleles into novel haplotypes based on promoter polymorphisms. This may enable us to link gene expression and prion disease. Understanding the general principles of prion genetics will help to eradicate scrapie and emerging prion diseases, such as Chronic Wasting Disease in deer.
AD W. Goldmann (wilfred.goldmann@bbsrc.ac.uk), A.J. Smith, G. O'Neill, J. Manson, N. Hunter, Institute for Animal Health, Neuropathogenesis Unit, West Mains Rd. Edinburgh, EH9 3JF, UK; M. Baylis (matthew.baylis@bbsrc.ac.uk), F. Houston, C. Chihota, E. Stevenson, L. Kirby, Institute for Animal Health, Compton, Berkshire, RG20 7NN, UK
SP englisch
PO Deutschland