title: Significant differences in incubation times in sheep infected with bovine spongiform encephalopathy result from variation at codon 141 in the PRNP gene.
abstract: The susceptibility of sheep to prion infection is linked to variation in the PRNP gene, which encodes the prion protein. Common polymorphisms occur at codons 136, 154 and 171. Sheep which are homozygous for the A(136)R(154)Q(171) allele are the most susceptible to bovine spongiform encephalopathy (BSE). The effect of other polymorphisms on BSE susceptibility is unknown. We orally infected ARQ/ARQ Cheviot sheep with equal amounts of BSE brain homogenate and a range of incubation periods was observed. When we segregated sheep according to the amino acid (L or F) encoded at codon 141 of the PRNP gene, the shortest incubation period was observed in LL(141) sheep, whilst incubation periods in FF(141) and LF(141) sheep were significantly longer. No statistically significant differences existed in the expression of total prion protein or the disease-associated isoform in BSE-infected sheep within each genotype subgroup. This suggested that the amino acid encoded at codon 141 probably affects incubation times through direct effects on protein misfolding rates.
authors.affiliation: Neurobiology Division, The Roslin Institute and R(D)SVS, University of Edinburgh, Easter Bush, Midlothian, Edinburgh EH25 9RG, UK.
authors.forename: Boon Chin
authors.initials: BC
authors.lastname: Tan
authors.affiliation: Neurobiology Division, The Roslin Institute and R(D)SVS, University of Edinburgh, Easter Bush, Midlothian, Edinburgh EH25 9RG, UK.
authors.forename: Anthony R Alejo
authors.initials: ARA
authors.lastname: Blanco
authors.affiliation: School of Veterinary Medicine, The University of Glasgow, Glasgow G61 1QH, UK.
authors.forename: E Fiona
authors.initials: EF
authors.lastname: Houston
authors.affiliation: Neurobiology Division, The Roslin Institute and R(D)SVS, University of Edinburgh, Easter Bush, Midlothian, Edinburgh EH25 9RG, UK.
authors.forename: Paula
authors.initials: P
authors.lastname: Stewart
authors.affiliation: Neurobiology Division, The Roslin Institute and R(D)SVS, University of Edinburgh, Easter Bush, Midlothian, Edinburgh EH25 9RG, UK.
authors.forename: Wilfred
authors.initials: W
authors.lastname: Goldmann
authors.affiliation: Neurobiology Division, The Roslin Institute and R(D)SVS, University of Edinburgh, Easter Bush, Midlothian, Edinburgh EH25 9RG, UK.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Gill
authors.affiliation: Neurobiology Division, The Roslin Institute and R(D)SVS, University of Edinburgh, Easter Bush, Midlothian, Edinburgh EH25 9RG, UK.
authors.forename: Christopher
authors.initials: C
authors.lastname: de Wolf
authors.affiliation: Neurobiology Division, The Roslin Institute and R(D)SVS, University of Edinburgh, Easter Bush, Midlothian, Edinburgh EH25 9RG, UK.
authors.forename: Jean C
authors.initials: JC
authors.lastname: Manson
authors.affiliation: Neurobiology Division, The Roslin Institute and R(D)SVS, University of Edinburgh, Easter Bush, Midlothian, Edinburgh EH25 9RG, UK.
authors.forename: Sandra
authors.initials: S
authors.lastname: McCutcheon
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001483:Base Sequence; D001923:Brain Chemistry; D002417:Cattle; D003062:Codon / Q000235:genetics; D004247:DNA / Q000235:genetics; D016643:Encephalopathy, Bovine Spongiform / Q000209:etiology* / Q000235:genetics / Q000635:transmission; D014644:Genetic Variation; D018621:PrPC Proteins / Q000032:analysis; D018620:PrPSc Proteins / Q000235:genetics / Q000472:pathogenicity; D011328:Prions / Q000235:genetics* / Q000472:pathogenicity*; D012756:Sheep / Q000235:genetics; D012757:Sheep Diseases / Q000209:etiology* / Q000235:genetics / Q000635:transmission; D013997:Time Factors; D014774:Virulence / Q000235:genetics
chemical_list: D003062:Codon; D018621:PrPC Proteins; D018620:PrPSc Proteins; D011328:Prions; D004247:DNA