Significant differences in incubation times in sheep infected with bovine spongiform encephalopathy result from variation at codon 141 in the PRNP gene
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<sub>136</sub>R<sub>154</sub>Q<sub>171</sub> 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 LL141 sheep, whilst incubation periods in FF<sub>141</sub> and LF<sub>141</sub> 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
