NR AWHO

AU Johnson,C.; Johnson,J.; Vanderloo,J.P.; Keane,D.; Bochsler,P.; Aiken,J.M.; McKenzie,D.

TI Prion protein gene expression is modulated by DNA polymorphisms in the promoter region

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-13

PT Konferenz-Poster

AB The primary sequence of the prion protein affects susceptibility to transmissible spongiform encephalopathies (TSE; prion disease) in mice, sheep and humans. The Prnp sequence of freeranging, Wisconsin white-tailed deer was determined and the Prnp genotypes of CWD-positive and negative deer compared. Six amino acid (AA) changes were identified; two of which were located in pseudogenes. Two alleles, a glutamine to lysine polymorphism at codon 226 and a single octapeptide repeat insertion into the pseudogene, have not been previously reported. The predominant alleles, wild-type (glutamine at AA95, glycine at AA96 and glutamine at AA226) and a glycine to serine polymorphism at AA96 (G96S), comprise almost 98% of the Prnp alleles in the Wisconsin white-tailed deer population. Comparison of the allelic frequencies in the CWD-positive and -negative deer suggests that G96S and a glutamine to histidine polymorphism at AA 95 (Q95H) are linked to a reduced susceptibility to CWD. The G96S allele does not, however, provide complete resistance, as a CWD-positive G96S/G96S deer was identified. The G96S allele is also linked to slower progression of disease in CWD-positive deer based on the deposition of PRPcwd in the obex region of the medulla oblongata. To further determine the effect of variations of the cervid Prnp alleles on susceptibility, deer with known Prnp genotypes were orally dosed with CWD inocula prepared from wild-type/wild-type homozygous animals. The experimentally infected wild-type/wild-type animals have succumbed to disease, animals heterozygous for Prnp alleles have not.

AD C. Johnson, J. Johnson, J.P. Vanderloo, J.M. Aiken, D. McKenzie: 1Department of Animal Health and Biomedical Sciences, University of Wisconsin, Madison, WI, USA; D. Keane, P. Bochsler: Wisconsin Veterinary Diagnostic Laboratory, University of Wisconsin, Madison, WI, USA. E-mail: mckenzie@svm.vetmed.wisc.edu

SP englisch

PO Italien

EA Poster

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