Prion protein gene polymorphisms in natural goat scrapie

A total of 51 goats, including seven clinical cases, from the first herd in Greece reported to have scrapie was examined to discern an association between scrapie susceptibility and polymorphisms of the gene encoding the prion protein (PrP). Each animal was evaluated for clinical signs of the disease, histopathological lesions associated with scrapie, the presence of detectable protease-resistant PrP in the brain and PrP genotype. Eleven different PrP genotypes encoding at least five unique predicted mature PrP amino acid sequences were found. These genotypes included the amino acid polymorphisms at codons 143 (H --> R) and 240 (S --> P) and 'silent' nucleotide alterations at codons 42 (a --> g) and 138 (c --> t). Additionally, novel caprine amino acid polymorphisms were detected at codons 21 (V --> A), 23 (L --> P), 49 (G --> S), 154 (R --> H), 168 (P --> Q) and 220 (Q --> H) and new silent mutations were found at codons 107 (g --> a) and 207 (g --> a). The following variants were found in scrapie-affected goats: VV21, LL23, GG(49) SS49, HH143, HR143, RR154, PP168, PP240, SP240 and SS240. All scrapie-affected animals carried the HH143RR154 genotype, with the exception of two goats (HR143), both of which had detectable protease-resistant PrP but showed no clinical signs or histopathological lesions characteristic of scrapie.