NR AWNG
AU Saunders,G.C.; Cawthraw,S.; Mountjoy,S.J.; Hope,J.; Windl,O.
TI PrP gene polymorphisms in atypical scrapie cases in Great Britain
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-26
PT Konferenz-Poster
AB As part of the scrapie surveillance programme in Great Britain (GB), during 2002 and 2003, rapid tests were used to screen apparently healthy sheep passing through abattoirs. This survey detected atypical scrapie infection in sheep with PrP genotypes thought to be genetically resistant to the classical form of scrapie. DNA sequencing of the PrP gene promoter, ORF and UTR from the British atypical scrapie cases (n = 69), classical scrapie cases (n = 59) and scrapie free controls (n = 138), was undertaken to identify whether PrP variants, other than the three well characterised polymorphic codons, influenced susceptibility to atypical scrapie infection. Four non-synonymous changes M112T, M137T, L141F and P241S were detected which are most probably associated with the A136R154Q171 haplotype. Only the PrP variant containing a phenylalanine residue at amino acid position 141 was found to be more commonly associated with the atypical scrapie cases. In addition to the single nucleotide polymorphisms associated with the ARQ allele, two out of nine atypical scrapie cases with the ARR/ARR genotype were found to contain a 24bp insertion leading to an additional octapeptide repeat. The 3 kb 3' UTR sequence, revealed three main haplotypes. Atypical scrapie cases were found to be associated with the most common haplotype, with all 69 samples found to carry at least 1 copy of this 3' UTR haplotype. This haplotype was however also associated with the ARR allele. Unravelling whether the UTR has an effect, independent of the ORF, in conferring susceptibility to atypical has not been possible to ascertain with the limited number of samples examined. The 5 kb promoter sequence, which included exons 1 and 2 and intron 1 revealed five main haplotypes, with no clear association with atypical scrapie cases. This study was funded by Defra, UK
AD Department of TSE Molecular Biology, Veterinary Laboratories Agency, New Haw, Addlestone, Surrey KT15 3NB, UK
SP englisch
PO Italien