title: Separating the environmental and genetic factors that may be causes of bovine spongiform encephalopathy.
abstract: The initial cause of the bovine spongiform encephalopathy (BSE) epidemic is generally accepted to have been the feeding of infected animal protein to cattle. The proportion of animals affected in any year in a particular herd has generally been low. This suggests either considerable variation in the extent of challenge of the individual animals or variation in their susceptibility to challenge or both. There is known to be genetic variation in susceptibility in other spongiform encephalopathies, such as scrapie in sheep. However, earlier indications that there may be associations between the incidence of BSE in cattle and polymorphisms and mutations in the PrP gene have not been confirmed (Hunter et al. 1994). Here, we attempt to model the likely extent of challenge of the individual animals in five Holstein Friesian pedigree herds and also the distribution of incubation times to the date of clinical onset. By studying the incidence of the disease in related animals we first found that single locus genetic models fitted the data much better than a non-genetic model. This was the first statistical evidence found of genetic variation in susceptibility to BSE. A check on the model in which individual animals were randomly allocated to 'parents' showed that the result was due to the lack of allowance in the non-genetic model for those animals insufficiently challenged or, for non-genetic reasons, resistant to their level of challenge. Thus there is still no evidence, molecular or statistical, for genetic variation in susceptibility. The importance of checking the attribution of genetic effects in complex models by the random allocation of progeny to parents is clear.
authors.affiliation: Department of Epidemiology and Public Health, Ninewells Hospital and Medical School, Dundee, U.K.
authors.forename: C M
authors.initials: CM
authors.lastname: Hau
authors.forename: R N
authors.initials: RN
authors.lastname: Curnow
mesh_terms: D000818:Animals; D002417:Cattle; D002418:Cattle Diseases / Q000235:genetics*; D016643:Encephalopathy, Bovine Spongiform / Q000235:genetics*; D008957:Models, Genetic; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D011328:Prions / Q000235:genetics*
chemical_list: D009419:Nerve Tissue Proteins; D011328:Prions