Cellular prion protein gene polymorphisms linked to differential scrapie susceptibility correlate with distinct residue connectivity between secondary structure elements.

The conformational conversion of the cellular prion protein (PrP) to the misfolded and aggregated isoform, termed scrapie prion protein (PrP), is key to the development of a group of neurodegenerative diseases known as transmissible spongiform encephalopathies (TSEs). Although the conversion mechanism is not fully understood, the role of gene polymorphisms in varying susceptibilities to prion diseases is well established. In ovine, specific gene polymorphisms in PrP alter prion disease susceptibility: the Valine136-Glutamine171 variant ( structure) displays high susceptibility to classical scrapie while the Alanine136-Arginine171 variant ( structure) displays reduced susceptibility.