Significant differences in incubation times in sheep infected with bovine spongiform encephalopathy result from variation at codon 141 in the PRNP gene

Autor: Tan, B. C., Blanco, A. R. A., Houston, E.F., Stewart, P., Goldmann, W., Gill, A. C., de Wolf, C., Manson, J. C., McCutcheon, S.
Jazyk: angličtina
Rok vydání: 2012
Předmět:
ISSN: 0022-1317
Popis: The susceptibility of sheep to prion infection is linked to variation in the PRNP gene, which\ud encodes the prion protein. Common polymorphisms occur at codons 136, 154 and 171. Sheep\ud which are homozygous for the A136R154Q171 allele are the most susceptible to bovine spongiform\ud encephalopathy (BSE). The effect of other polymorphisms on BSE susceptibility is unknown. We\ud orally infected ARQ/ARQ Cheviot sheep with equal amounts of BSE brain homogenate and a\ud range of incubation periods was observed. When we segregated sheep according to the amino\ud acid (L or F) encoded at codon 141 of the PRNP gene, the shortest incubation period was\ud observed in LL141 sheep, whilst incubation periods in FF141 and LF141 sheep were significantly\ud longer. No statistically significant differences existed in the expression of total prion protein or the\ud disease-associated isoform in BSE-infected sheep within each genotype subgroup. This\ud suggested that the amino acid encoded at codon 141 probably affects incubation times through\ud direct effects on protein misfolding rates.
Databáze: OpenAIRE