NR AXXF
AU Stewart,P.; Perucchini,M.; Goldmann,W.
TI Speculations on PrP Protein Sequence Variation and Transmission Barriers
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Epidemiology, Risk Assessment and Transmission P04.111
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
PrP misfolding is a key molecular mechanism in prion diseases. Amino acid polymorphisms become an important factor in this process because the primary sequence may provide a constraint on the number of conformations that PrP will be able to adopt. This conformational barrier through allelic variation may also lead to a barrier in transmission of prion disease within and between species.
Extensive studies into the genetics of the ovine PrP gene have established that the three polymorphic amino acid codons at positions 136, 154 and 171 are central to determining susceptibility to TSE disease. The revelation that atypical scrapie susceptibility is associated with a codon 141 polymorphism now highlights the shortfall of a PrP genetics system based on only three polymorphic codons and 15 PrP genotypes as used in the UK National Scrapie Plan (NSP).
To answer the question what the true extent of polymorphisms in the ovine PrP gene is we have continued to apply DNA sequencing analysis in the open reading frame of all major PrP alleles in sheep and other species. Most additional amino acid polymorphisms have so far been found on the ARQ allele, considered to be the ancestral allele. In addition we report here variants of the AHQ, ARR and VRQ alleles. We will provide a comparison of the PrP variation of new and previously published sequences from over 100 species to argue that detailed sequence analyses may help to predicted key amino acid positions with relevance for species barriers and normal protein function.
AD P. Stewart, M. Perucchini, W. Goldmann, Roslin Institute, Neuropathogenesis Unit, UK
SP englisch
PO Schottland