1887

Abstract

Data from 4049 Romanov sheep belonging to a flock affected by natural scrapie were analysed by using survival-analysis techniques. Failure time was defined as the period of time between first exposure to infection and the date that animals left the flock with scrapie signs. Four hundred and forty-seven sheep were identified as ‘scrapie animals’. Several models, including level of exposure as a time-dependent effect, PrP genotype, sex, age at first exposure, litter size and factors related to vertical transmission, were tested. The best model was extended to a sire–dam frailty model, in order to estimate the polygenic variation in addition to that in the Prnp gene. A combined effect of rearing type and the dam's disease status was detected. Thus, only sheep with a low degree of exposure to infection as lambs (lambs reared artificially and born out of a healthy dam) showed less risk than others. Animals first exposed to infection at older ages seemed to be less susceptible to scrapie. In this Romanov population, new genotypes (AHQ/AHQ, AHQ/VRQ, ARR/VRQ and ARR/ARQ) were associated with risk, suggesting the effect of genotypes on the incubation period of animals. Polygenic variance was responsible for 21 % of the total genetic variability that was related to susceptibility to scrapie. Therefore, the genetic susceptibility to scrapie may be explained by the joint effect of point mutations at the Prnp major gene and a number of genes that modulate its effect.

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2005-03-01
2024-03-28
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References

  1. Andréoletti O., Berthon P., Levavasseur E., Marc D., Lantier F., Monks E., Elsen J.-M., Schelcher F. 2002a; Phenotyping of protein–prion (PrPsc)-accumulating cells in lymphoid and neural tissues of naturally scrapie-affected sheep by double-labeling immunohistochemistry. J Histochem Cytochem 50:1357–1370 [CrossRef]
    [Google Scholar]
  2. Andréoletti O., Lacroux C., Chabert A. 8 other authors 2002b; PrPSc accumulation in placentas of ewes exposed to natural scrapie: influence of foetal PrP genotype and effect on ewe-to-lamb transmission. J Gen Virol 83:2607–2616
    [Google Scholar]
  3. Barron R. M., Thomson V., King D., Shaw J., Melton D. W., Manson J. C. 2003; Transmission of murine scrapie to P101L transgenic mice. J Gen Virol 84:3165–3172 [CrossRef]
    [Google Scholar]
  4. Baylis M., Goldmann W., Houston F., Cairns D., Chong A., Ross A., Smith A., Hunter N., McLean A. R. 2002; Scrapie endemic in a fully PrP-genotyped sheep flock. J Gen Virol 83:2907–2914
    [Google Scholar]
  5. Belt P. B. G. M., Muileman I. H., Schreuder B. E. C., Bos-de Ruijter J., Gielkens A. L. J., Smits M. A. 1995; Identification of five allelic variants of the sheep PrP gene and their association with natural scrapie. J Gen Virol 76:509–517 [CrossRef]
    [Google Scholar]
  6. Billinis C., Psychas V., Leontides L., Spyrou V., Argyroudis S., Vlemmas I., Leontides S., Sklaviadis T., Papadopoulos O. 2004; Prion protein gene polymorphisms in healthy and scrapie-affected sheep in Greece. J Gen Virol 85:547–554 [CrossRef]
    [Google Scholar]
  7. Bruce M. E., McConnell I., Fraser H., Dickinson A. G. 1991; The disease characteristics of different strains of scrapie in Sinc congenic mouse lines: implications for the nature of the agent and host control of pathogenesis. J Gen Virol 72:595–603 [CrossRef]
    [Google Scholar]
  8. Damgaard L. H., Korsgaard I. R., Simonsen J., Dalsgaard O., Andersen A. H. 2003; Genetic versus non-genetic Weibull log-normal sire frailty models: a simulation study. Interbull Bulletin 30:35–42
    [Google Scholar]
  9. Díaz C., Vitezica Z. G., Rupp R., Elsen J. M. 2003; El uso de la prediccion de genotipos en el análisis de supervivencia: un caso de scrapie. ITEA 24:456–458 (in Spanish)
    [Google Scholar]
  10. Ducrocq V., Casella G. 1996; A Bayesian analysis of mixed survival models. Genet Sel Evol 28:505–529 [CrossRef]
    [Google Scholar]
  11. Ducrocq V., Sölkner J. 1998; ‘The Survival Kit’. A fortran package for the analysis of survival data. In Proceedings of the Sixth World Congress on Genetics Applied to Livestock Production Armidale, Australia: Issue 27: pp  447–448
    [Google Scholar]
  12. Ducrocq V., Besbes B., Protais M. 2000; Genetic improvement of laying hens viability using survival analysis. Genet Sel Evol 32:23–40 [CrossRef]
    [Google Scholar]
  13. Elsen J.-M., Amigues Y., Schelcher F. 7 other authors 1999; Genetic susceptibility and transmission factors in scrapie: detailed analysis of an epidemic in a closed flock of Romanov. Arch Virol 144:431–445 [CrossRef]
    [Google Scholar]
  14. Fernando R. L., Gianola D. 1990; Statistical inferences in populations undergoing selection or non-random mating. In Advances in Statistical Methods for Genetic Improvement of Livestock pp  437–453 Edited by Gianola D., Hammond K. Berlin: Springer;
    [Google Scholar]
  15. Fernando R. L., Stricker C., Elston R. C. 1993; An efficient algorithm to compute the posterior genotypic distribution for every member of a pedigree without loops. Theor Appl Genet 87:89–93
    [Google Scholar]
  16. Goldmann W., Hunter N., Smith G., Foster J., Hope J. 1994; PrP genotype and agent effects in scrapie: change in allelic interaction with different isolates of agent in sheep, a natural host of scrapie. J Gen Virol 75:989–995 [CrossRef]
    [Google Scholar]
  17. Gravenor M. B., Stallard N., Curnow R., McLean A. R. 2003; Repeated challenge with prion disease: the risk of infection and impact on incubation period. Proc Natl Acad Sci U S A 100:10960–10965 [CrossRef]
    [Google Scholar]
  18. Gruner L., Bouix J., Vu Tien Kang J., Mandonnet N., Eychenne F., Cortet J., Sauvé C., Limouzin C. 2004; A short-term divergent selection for resistance to Teladorsagia circumcincta in Romanov sheep using natural or artificial challenge. Genet Sel Evol 36:217–242 [CrossRef]
    [Google Scholar]
  19. Houston E. F., Halliday S. I., Jeffrey M., Goldmann W., Hunter N. 2002; New Zealand sheep with scrapie-susceptible PrP genotypes succumb to experimental challenge with a sheep-passaged scrapie isolate (SSBP/1. J Gen Virol 83:1247–1250
    [Google Scholar]
  20. Hunter N. 1997; Molecular biology and genetics of scrapie in sheep. In The Genetics of Sheep pp  225–240 Edited by Piper L., Ruvinsky A. Wallingford, UK: CAB International;
    [Google Scholar]
  21. Hunter N., Foster J. D., Dickinson A. G., Hope J. 1989; Linkage of the gene for the scrapie-associated fibril protein (PrP) to the Sip gene in Cheviot sheep. Vet Rec 124:364–366 [CrossRef]
    [Google Scholar]
  22. Hunter N., Foster J. D., Goldmann W., Stear M. J., Hope J., Bostock C. 1996; Natural scrapie in a closed flock of Cheviot sheep occurs in specific PrP genotypes. Arch Virol 141:809–824 [CrossRef]
    [Google Scholar]
  23. Laplanche J. L., Elsen J. M., Eychenne F., Schelcher F., Richard S., Amigues Y., Launay J. M. 1996; Scrapie outbreak in sheep after oral exposure to infective gastrointestinal nematode larvae. In Transmissible Subacute Spongiform Encephalopathies: Prion Diseases pp  41–46 Edited by Court L., Dodet B. Paris: Elsevier;
    [Google Scholar]
  24. Lloyd S. E., Onwuazor O. N., Beck J. A., Mallinson G., Farrall M., Targonski P., Collinge J., Fisher E. M. C. 2001; Identification of multiple quantitative trait loci linked to prion disease incubation period in mice. Proc Natl Acad Sci U S A 98:6279–6283 [CrossRef]
    [Google Scholar]
  25. Lloyd S. E., Uphill J. B., Targonski P. V., Fisher E. M., Collinge J. 2002; Identification of genetic loci affecting mouse-adapted bovine spongiform encephalopathy incubation time in mice. Neurogenetics 4:77–81 [CrossRef]
    [Google Scholar]
  26. Manolakou K., Beaton J., McConnell I., Farquar C., Manson J., Hastie N. D., Bruce M., Jackson I. J. 2001; Genetic and environmental factors modify bovine spongiform encephalopathy incubation period in mice. Proc Natl Acad Sci U S A 98:7402–7407 [CrossRef]
    [Google Scholar]
  27. Matthews L., Coen P. G., Foster J. D., Hunter N., Woolhouse M. E. J. 2001; Population dynamics of a scrapie outbreak. Arch Virol 146:1173–1186 [CrossRef]
    [Google Scholar]
  28. Meuwissen T. H. E., Goddard M. E. 1997; Estimation of effects of quantitative trait loci in large complex pedigrees. Genetics 146:409–416
    [Google Scholar]
  29. Moore R. C., Hope J., McBride P. A., McConnell I., Selfridge J., Melton D. W., Manson J. C. 1998; Mice with gene targetted prion protein alterations show that Prnp, Sine and Prni are congruent. Nat Genet 18:118–125 [CrossRef]
    [Google Scholar]
  30. Moreno C. R., Lantier I., Lantier F. 7 other authors 2002; Transposition to sheep of mouse quantitative trait loci (QTL) influencing susceptibility to prion diseases. In Proceedings of the Seventh World Congress on Genetics Applied to Livestock Production Montpellier, France: 19–23 August 2002 No. 13–21
    [Google Scholar]
  31. Moreno C. R., Cosseddu G., Andréoletti O. 9 other authors 2003a; Identification of quantitative trait loci (QTL) modulating prion incubation period in sheep. In Proceedings of International Workshop on Major Genes and QTL in Sheep and Goats Toulouse, France: 8–11 December 2003
    [Google Scholar]
  32. Moreno C. R., Lantier F., Lantier I., Sarradin P., Elsen J.-M. 2003b; Detection of new quantitative trait loci for susceptibility to transmissible spongiform encephalopathies in mice. Genetics 165:2085–2091
    [Google Scholar]
  33. O'Rourke K. I., Holyoak G. R., Clark W. W., Mickelson J. R., Wang S., Melco R. P., Besser T. E., Foote W. C. 1997; PrP genotypes and experimental scrapie in orally inoculated Suffolk sheep in the United States. J Gen Virol 78:975–978
    [Google Scholar]
  34. Post K., Riesner D., Walldorf V., Mehlhorn H. 1999; Fly larvae and pupae as vectors for scrapie. Lancet 354:1969–1970 [CrossRef]
    [Google Scholar]
  35. Prusiner S. B., Scott M. R. 1997; Genetics of prions. Annu Rev Genet 31:139–175 [CrossRef]
    [Google Scholar]
  36. Soller M., Andersson L. 1998; Genomic approaches to the improvement of disease resistance in farm animals. Rev Sci Tech 17:329–345
    [Google Scholar]
  37. Stephenson D. A., Chiotti K., Ebeling C., Groth D., DeArmond S. J., Prusiner S. B., Carlson G. A. 2000; Quantitative trait loci affecting prion incubation time in mice. Genomics 69:47–53 [CrossRef]
    [Google Scholar]
  38. Stringer S. M., Hunter N., Woolhouse M. E. J. 1998; A mathematical model of the dynamics of scrapie in a sheep flock. Math Biosci 153:79–98 [CrossRef]
    [Google Scholar]
  39. Thorgeirsdottir S., Sigurdarson S., Thorisson H. M., Georgsson G., Palsdottir A. 1999; PrP gene polymorphism and natural scrapie in Icelandic sheep. J Gen Virol 80:2527–2534
    [Google Scholar]
  40. Thorgeirsdottir S., Georgsson G., Reynisson E., Sigurdarson S., Palsdottir A. 2002; Search for healthy carriers of scrapie: an assessment of subclinical infection of sheep in an Icelandic scrapie flock by three diagnostic methods and correlation with PrP genotypes. Arch Virol 147:709–722 [CrossRef]
    [Google Scholar]
  41. Tranulis M. A., Osland A., Bratberg B., Ulvund M. J. 1999; Prion protein gene polymorphisms in sheep with natural scrapie and healthy controls in Norway. J Gen Virol 80:1073–1077
    [Google Scholar]
  42. Tuo W., O'Rourke K. I., Zhuang D., Cheevers W. P., Spraker T. R., Knowles D. P. 2002; Pregnancy status and fetal prion genetics determine PrPSc in placentomes of scrapie-infected sheep. Proc Natl Acad Sci U S A 99:6310–6315 [CrossRef]
    [Google Scholar]
  43. Vitezica Z. G. 2003; Analysis of complex pedigrees for estimating genotypes. Application to the study of genetic resistance to scrapie . PhD thesis Institut National Agronomique Paris-Grignon; France:
  44. Vitezica Z. G., Elsen J. M., Rupp R., Díaz C. 2005; The use of genotype probabilities to estimate risk factors: a scrapie case. Genet Sel Evol (in press
    [Google Scholar]
  45. Wisniewski H. M., Sigurdarson S., Rubenstein R., Kascsak R. J., Carp R. I. 1996; Mites as vectors for scrapie. Lancet 347:1114
    [Google Scholar]
  46. Woolhouse M. E. J., Stringer S. M., Matthews L., Hunter N., Anderson R. M. 1998; Epidemiology and control of scrapie within a sheep flock. Proc R Soc Lond B Biol Sci 265:1205–1210 [CrossRef]
    [Google Scholar]
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