Abstract
BackgroundExisting mathematical models for scrapie dynamics in sheep populations assume that the PrP gene is only associated with scrapie susceptibility and with no other fitness related traits. This assumption contrasts recent findings of PrP gene associations with post-natal lamb survival in scrapie free Scottish Blackface populations. Lambs with scrapie resistant genotypes were found to have significantly lower survival rates than those with susceptible genotypes. The present study aimed to investigate how these conflicting PrP gene associations may affect the dynamic patterns of PrP haplotype frequencies and disease prevalence.Methodology/Principal FindingsA deterministic mathematical model was developed to explore how the associations between PrP genotype and both scrapie susceptibility and postnatal lamb mortality affect the prevalence of scrapie and the associated change in PrP gene frequencies in a closed flock of sheep. The model incorporates empirical evidence on epidemiological and biological characteristics of scrapie and on mortality rates induced by causes other than scrapie. The model results indicate that unfavorable associations of the scrapie resistant PrP haplotypes with post-natal lamb mortality, if sufficiently strong, can increase scrapie prevalence during an epidemic, and result in scrapie persisting in the population. The range of model parameters, for which such effects were observed, is realistic but relatively narrow.Conclusions/SignificanceThe results of the present model suggest that for most parameter combinations an unfavourable association between PrP genotype and post-natal lamb mortality does not greatly alter the dynamics of scrapie and, hence, would not have an adverse impact on a breeding programme. There were, however, a range of scenarios, narrow, but realistic, in which such an unfavourable association resulted in an increased prevalence and in the persistence of infection. Consequently, associations between PrP genotypes and fitness traits should be taken into account when designing future models and breeding programmes.
Highlights
Incidences of scrapie, a fatal transmissible spongiform encephalopathy (TSE) of sheep and goats, have been reported in European countries for several centuries [1], but progress on the control of this disease was long inhibited by the restricted understanding of the causes of infection and modes of transmission
The scrapie eradication policies were strongly influenced by the predictions of mathematical models, which incorporated emerging information on host genetics and scrapie epidemiology and predicted the impact of selection on changes in prion protein (PrP) gene frequencies and scrapie prevalence over time (e.g. [5,6])
Assuming first that the PrP genotype is only associated with scrapie susceptibility, so that changes in PrP haplotype frequencies are exclusively caused by scrapie related mortality, our model predicts that scrapie eventually disappears from the population within a few decades or centuries (Figures 1a, 1c)
Summary
Incidences of scrapie, a fatal transmissible spongiform encephalopathy (TSE) of sheep and goats, have been reported in European countries for several centuries [1], but progress on the control of this disease was long inhibited by the restricted understanding of the causes of infection and modes of transmission. The numerous mathematical models and policies vary widely in their approach and underlying assumptions, they unanimously build upon the assumption that polymorphisms of the PrP gene are associated only with scrapie susceptibility and not with any other trait such as fitness or performance. Under this assumption, models predict that scrapie will eventually disappear from a closed population as a result of natural selection Existing mathematical models for scrapie dynamics in sheep populations assume that the PrP gene is only associated with scrapie susceptibility and with no other fitness related traits. The present study aimed to investigate how these conflicting PrP gene associations may affect the dynamic patterns of PrP haplotype frequencies and disease prevalence
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