Elimination of natural scrapie in sheep by sire genotype selection

Abstract

SCRAPIE, a subacute neuromuscular disease of middle-aged sheep, has been attributed variously to an infection or to heredity^1,2. The clinical disorder follows progressive symmetrical decay of neurones in localised brain sites, notably the hypothalamo–neurophysial and olivo-pontocerebellar ‘systems’ (ref. 3), associated with a terminal axon dystrophy^4–9. An artificially transmissible spongiform encephalopathic agent (TSEPA), or ‘slow virus’, to which many attribute the disease^10,11, is commonly present in diseased animals but its aetiological role remains unclear. Based on the clinical manifestation of natural scrapie, I have proposed that the disease is controlled by an autosomal recessive gene^1,2,12. This hypothesis allowed identification of the three presumptive genotypes (ss, sS, SS), and precise prediction of attack rates^13,14, amenable to quantitative experimental verification¹⁵. The evidence summarised here, which has been compiled since 1958, provides strong support for my hypothesis.