Classic and atypical scrapie - a genetic perspective

Scrapie was the first prion disease to be recognised and the study of this disease in sheep and goats has provided a wealth of information not only for scrapie but also for the other prion diseases. All prion diseases are under strong genetic control of the prion gene PRNP, independent of whether they are typical or atypical scrapie and which of the different prion strains is causing infection. Decades of studies using experimental disease challenges and field surveys have established disease association models, in which species-specific amino acid variations in the prion or PrP protein, encoded by the PRNP gene, can predict disease susceptibility or resistance. PRNP genetics represents an important and successful basis for implementing scrapie eradication strategies in sheep and goats. In general terms these studies have revealed that there appear to be many more amino acid changes in PrP leading to increased resistance than to higher susceptibility. Most changes are in the globular part of PrP protein and three regions appear to have major influence. This knowledge can be transferred into prion diseases of other species to facilitate genetic control strategies. However, an obstacle remains with the lack of fully understanding the underlying molecular mechanism, impeding our ability to deal with the difference in the genetic control between typical and atypical forms of scrapie or to predict association in newly infected species. This chapter will discuss the advances in both typical and atypical scrapie from a genetic perspective.