Implications of Conflicting Associations of the Prion Protein (PrP) Gene with Scrapie Susceptibility and Fitness on the Persistence of Scrapie
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{"title"=>"Implications of conflicting associations of the prion protein (PrP) gene with scrapie susceptibility and fitness on the persistence of scrapie", "type"=>"journal", "authors"=>[{"first_name"=>"Andrea", "last_name"=>"Doeschl-Wilson", "scopus_author_id"=>"16244902100"}, {"first_name"=>"Rami", "last_name"=>"Sawalha", "scopus_author_id"=>"16053506400"}, {"first_name"=>"Simon", "last_name"=>"Gubbins", "scopus_author_id"=>"6701521156"}, {"first_name"=>"Beatriz", "last_name"=>"Villanueva", "scopus_author_id"=>"56054662400"}], "year"=>2009, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"19956715", "sgr"=>"71049127475", "doi"=>"10.1371/journal.pone.0007970", "scopus"=>"2-s2.0-71049127475", "pui"=>"355735309", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "issn"=>"19326203"}, "id"=>"62e86060-eb9d-3605-bef1-25534e6ddb7d", "abstract"=>"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. 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.", "link"=>"http://www.mendeley.com/research/implications-conflicting-associations-prion-protein-prp-gene-scrapie-susceptibility-fitness-persiste", "reader_count"=>12, "reader_count_by_academic_status"=>{"Researcher"=>4, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>4, "Other"=>1, "Professor"=>2}, "reader_count_by_user_role"=>{"Researcher"=>4, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>4, "Other"=>1, "Professor"=>2}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>3, "Agricultural and Biological Sciences"=>8, "Medicine and Dentistry"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>8}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}}, "reader_count_by_country"=>{"Spain"=>1}, "group_count"=>1}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/874113"], "description"=>"<p>Top graphs show predictions for 2500 years, whereas the bottom graphs illustrate the behavior up to the endemic equilibrium. Other parameter choices are <i>ε</i><sub>1</sub> = <i>ε</i><sub>2</sub> = 0, <i>ε</i><sub>3</sub> = 0.05, <i>β</i><sub>1</sub> = 4.93 and <i>β</i><sub>2</sub> = <i>β</i><sub>3</sub> = 0. For description of the parameters and other parameter values see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007970#pone-0007970-t001\" target=\"_blank\">table 1</a>. Long-term persistence was only observed for 0.532≤<i>p<sub>0</sub></i>≤0.540.</p>", "links"=>[], "tags"=>["scrapie", "prevalence", "sl", "haplotype", "parameter"], "article_id"=>544571, "categories"=>["Medicine", "Genetics"], "users"=>["Andrea Doeschl-Wilson", "Rami Sawalha", "Simon Gubbins", "Beatriz Villanueva"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0007970.g003", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Predicted_scrapie_prevalence_left_and_frequency_of_the_SL_haplotype_right_for_different_values_of_the_parameter_p_0_/544571", "title"=>"Predicted scrapie prevalence (left) and frequency of the SL haplotype (right) for different values of the parameter <i>p</i><sub>0</sub>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-11-24 01:16:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/874224"], "description"=>"(a)<p>Subscripts <i>i</i> = 1,2,3 refer to the genotypes SL/SL, SL/RH and RH/RH, respectively.</p>(b)<p>Subscripts <i>i</i> = 1,2,3 refer to the genotypes ARQ/ARQ, ARQ/ARR and ARR/ARR, respectively.</p>(c)<p>The values in the table refer to the results presented in this paper. Model results were also generated for (<i>μ</i><sub>2</sub>, <i>σ</i><sub>2</sub>) = (1.54, 0.38), <i>β</i><sub>2</sub> = 2.0–10.0 (<i>β</i><sub>2</sub>≤<i>β</i><sub>1</sub>), <i>ε</i><sub>2</sub> = 0.0–1.0 (ε<sub>2</sub>≤ε<sub>3</sub>).</p>(d)<p>Corresponds to an average life expectancy of 4 years.</p>", "links"=>[], "tags"=>["parameters", "empirical"], "article_id"=>544681, "categories"=>["Medicine", "Genetics"], "users"=>["Andrea Doeschl-Wilson", "Rami Sawalha", "Simon Gubbins", "Beatriz Villanueva"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0007970.t001", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Values_for_model_parameters_and_empirical_estimates_/544681", "title"=>"Values for model parameters and empirical estimates.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-11-24 01:18:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/433783", "https://ndownloader.figshare.com/files/433839"], "description"=>"<div><h3>Background</h3><p>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. 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.</p><h3>Methodology/Principal Findings</h3><p>A 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.</p><h3>Conclusions/Significance</h3><p>The 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.</p></div>", "links"=>[], "tags"=>["implications", "conflicting", "associations", "prion", "scrapie", "susceptibility", "persistence"], "article_id"=>145579, "categories"=>["Medicine", "Genetics"], "users"=>["Andrea Doeschl-Wilson", "Rami Sawalha", "Simon Gubbins", "Beatriz Villanueva"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0007970.s001", "https://dx.doi.org/10.1371/journal.pone.0007970.s002"], "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Implications_of_Conflicting_Associations_of_the_Prion_Protein_PrP_Gene_with_Scrapie_Susceptibility_and_Fitness_on_the_Persistence_of_Scrapie/145579", "title"=>"Implications of Conflicting Associations of the Prion Protein (PrP) Gene with Scrapie Susceptibility and Fitness on the Persistence of Scrapie", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2009-11-24 01:32:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/874021"], "description"=>"<p>Top graphs show predictions for 2500 years, whereas the bottom graphs illustrate the behavior up to the endemic equilibrium. Other parameter choices are <i>ε</i><sub>1</sub> = <i>ε</i><sub>2</sub> = 0, <i>ε</i><sub>3</sub> = 0.05, <i>p</i><sub>0</sub> = 0.54, and <i>β</i><sub>2</sub> = <i>β</i><sub>3</sub> = 0. For description of the parameters and other parameter values see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007970#pone-0007970-t001\" target=\"_blank\">table 1</a>. Long-term persistence was only observed for 4.80≤<i>β</i><sub>1</sub>≤4.93.</p>", "links"=>[], "tags"=>["scrapie", "prevalence", "sl", "haplotype", "parameter"], "article_id"=>544476, "categories"=>["Medicine", "Genetics"], "users"=>["Andrea Doeschl-Wilson", "Rami Sawalha", "Simon Gubbins", "Beatriz Villanueva"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0007970.g002", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Predicted_scrapie_prevalence_left_and_frequency_of_the_SL_haplotype_right_for_different_values_of_the_parameter_946_1_/544476", "title"=>"Predicted scrapie prevalence (left) and frequency of the SL haplotype (right) for different values of the parameter <i>β</i><sub>1</sub>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-11-24 01:14:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/873918"], "description"=>"<p>Top graphs show predictions for 2500 years, whereas the bottom graphs illustrate the behavior up to the endemic equilibrium. Other parameter choices are <i>ε</i><sub>1</sub> = <i>ε</i><sub>2</sub> = 0, <i>p</i><sub>0</sub> = 0.54, <i>β</i><sub>1</sub> = 4.93 and <i>β</i><sub>2</sub> = <i>β</i><sub>3</sub> = 0. For description of the parameters and other parameter values see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007970#pone-0007970-t001\" target=\"_blank\">table 1</a>.</p>", "links"=>[], "tags"=>["scrapie", "prevalence", "susceptible", "sl", "haplotype", "parameter"], "article_id"=>544371, "categories"=>["Medicine", "Genetics"], "users"=>["Andrea Doeschl-Wilson", "Rami Sawalha", "Simon Gubbins", "Beatriz Villanueva"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0007970.g001", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Predicted_scrapie_prevalence_and_frequency_of_the_susceptible_SL_haplotype_for_different_values_of_the_parameter_3_/544371", "title"=>"Predicted scrapie prevalence and frequency of the susceptible SL haplotype for different values of the parameter ε<sub>3</sub>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-11-24 01:12:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/874197"], "description"=>"(a)<p>No long-term persistence was observed for <i>ε</i><sub>3</sub><0.01.</p>(b)<p>The values <i>β</i><sub>1</sub> = 2.80 and <i>β</i><sub>1</sub> = 4.93 were the lower and upper bound estimates of Gubbins and Roden <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007970#pone.0007970-Gubbins1\" target=\"_blank\">[6]</a>.</p><p>For a full description of the parameters and of other parameter values used see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007970#pone-0007970-t001\" target=\"_blank\">table 1</a>.</p>", "links"=>[], "tags"=>["susceptible", "sl", "haplotype", "corresponding", "persistence", "scrapie", "parameter", "non-scrapie", "coefficient"], "article_id"=>544644, "categories"=>["Medicine", "Genetics"], "users"=>["Andrea Doeschl-Wilson", "Rami Sawalha", "Simon Gubbins", "Beatriz Villanueva"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0007970.t002", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Range_of_the_initial_frequency_of_the_susceptible_SL_haplotype_p_0_corresponding_to_long_term_persistence_of_scrapie_for_different_values_of_the_scrapie_transmission_parameter_946_1_and_the_non_scrapie_mortality_rate_coefficient_949_3_/544644", "title"=>"Range of the initial frequency of the susceptible SL haplotype (<i>p</i><sub>0</sub>) corresponding to long-term persistence of scrapie for different values of the scrapie transmission parameter <i>β</i><sub>1</sub> and the non-scrapie mortality rate coefficient <i>ε</i><sub>3</sub>.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-11-24 01:17:24"}

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