Molecular analysis of PRNP gene in sheep (scrapie)

Spongiform encephalopathies are a class of fatal neurological diseases. Clinical signs are characteristic of a progressive degeneration of the central nervous system; death is inevitable. On post-mortem, brain histopathology shows a characteristic spongy appearance. The infectious agent is a modified form of a protein encoded by a gene in the host.

The name given to this infectious particle is prion. The host gene is called the prion protein (PrP) gene, which is a normal part of the genome of mammals and chickens. Its polypeptide product, called cellular PrP(superscript C), is a naturally-occurring protein attached to the outer surface of neurones and some other cells. PrP(superscript C) appears to play a role in maintaining the Purkinje cells of the cerebellum, which are essential for balance and muscular function.

The infectious agent, called scrapie PrP(superscript Sc), is a modifed form of PrP(superscript C). It is important to realise that these modifications involve no change in amino acid sequence. When PrP(superscript Sc) molecules enter a previously uninfected host, they convert the naturally occurring PrP(superscript C) molecules, produced by the host gene, into infectious PrP(superscript Sc) particles, which ultimately cause clinical signs in that animal, and which can spread to other animals, both horizontally (by infection) and vertically (by maternal transmission). (OMIA)

This disease has been recognised in sheep for many centuries. Extensive polymorphism has been discovered in codons 136, 154 and 171, giving rise to amino-acid substitutions at these sites. There is substantial evidence that at least some of this polymorphism is strongly associated with susceptibility/resistance to scrapie. Of note, the presence of arginine at codon 171 on both alleles of the PrP gene may confer resistance to the development of clinical TSE disease.

Codon 136: Val/Ala (GTC/GCC)

Codon 154: Arg/His (CGT/CAT)

Codon 171: Arg/Gln/His (CGG/CAG/CAT)