Original Scientific Article
Evaluation of resistance and susceptibility to prion diseases in Pelibuey sheep from Mexico
Fabiola Rodríguez-Andrade ,
Arnulfo Villanueva-Castillo * ,
Cesar Feliciano Pastelin-Rojas ,
Raymundo Avila-Benitez ,
Ruby Sandy Moreno-Mejía ,
José Alfredo Galicia-Domínguez

Mac Vet Rev 2023; 46 (1): 17 - 26

10.2478/macvetrev-2022-0030

Received: 26 April 2022

Received in revised form: 28 November 2022

Accepted: 01 December 2022

Available Online First: 28 December 2022

Published on: 15 March 2023

Correspondence: Arnulfo Villanueva-Castillo, arnulfo.villanueva@correo.buap.mx
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Abstract

Transmissible spongiform encephalopathies (TSEs) are a group of neurodegenerative diseases with a chronic and fatal course, which are caused by a misfolded form of the cellular prion protein that is encoded by the host. The purpose of this work was to evaluate the resistance and genetic susceptibility to prion diseases in Pelibuey sheep from Mexico. The sequences of 99 Pelibuey sheep from the central and southwestern regions of Mexico were analyzed to determine the polymorphisms related to resistance and genetic susceptibility to scrapie, the Hardy-Weinberg equilibrium test and the D-Tajima test was used to identify the effect of evolutionary forces on the PRNP gene. Twelve non-synonymous polymorphisms Q101R, M112T, A116P, G127A, A136V, M137T, L141F, H143R, R154H, Q171R, Q171H, N176K were detected, in addition two synonymous substitutions 231R (agg/cgg) and 237L (ctc/ctg) were found. As a result of the sequence analysis, the ARR allele was not  under the Hardy-Weinberg equilibrium, indicating that there is an evolutionary force at work, and the D-Tajima suggest the existence of purifying genetic selection. In conclusion, Pelibuey sheep exhibit genotypes for the PRNP gene that make them resistant to developing classic scrapie; at least 98% of the population is a carrier of an allele related to scrapie resistance; while for atypical scrapie there is a very high probability that an outbreak occurred in the herds, since the ARQ allele in combination with the L substitution at codon 141 confers susceptibility to carrier sheep.

Keywords: PRNP gene, polymorphisms, genetic susceptibility, genetic selection, Pelibuey


References

1. O’Neill, G.T., Donnelly, K., Marshall, E., Cairns, D., Goldmann, W., Hunter, N. (2003). Characterization of ovine PrP gene promoter activity in N2a neuroblastoma and ovine foetal brain cell lines. J Anim Breed Genet. 120,  14-123. https://doi.org/10.1046/j.1439-0388.2003.00381.x
2. Goldmann, W., Baylis, M., Chihota, C., Stevenson, E., Hunter, N. (2005). Frequencies of PrP gene haplotypes in British sheep flocks and the implications for breeding programmes. J Appl Microbiol. 98, 1294-1302. https://doi.org/10.1111/j.1365-2672.2005.02568.x PMid:15916643
3. Baylis, M., Goldmann, W. (2004). The genetics of scrapie in sheep and goats. Curr Mol Med. 4, 385- 396. https://doi.org/10.2174/1566524043360672 PMid:15354869
4. Meydan, Özkan, M.M., Yildiz, M.A. (2013). Genetic risk assessment for atypical scrapie in Turkish native sheep breeds. Small Rumin Res. 111, 16-22. https://doi.org/10.1016/j.smallrumres.2012.08.013
5. Paludi, D., Thellung, S., Chiovitti, K., Corsaro, A., Villa, V., Russo, C., et al. (2007). Different structural stability and toxicity of PrP(ARR) and PrP(ARQ) sheep prion protein variants. J Neurochem. 103, 2291- 300. https://doi.org/10.1111/j.1471-4159.2007.04934.x  PMid:17919292
6. Saunders, G.C., Lantier, I., Cawthraw, S., Berthon, P., Moore, S.J., Arnold, M.E., et al. (2009). Protective effect of the T112 PrP variant in sheep challenged with bovine spongiform encephalopathy. J Gen Virol. 90, 2569-574. https://doi.org/10.1099/vir.0.012724-0 PMid:19587133
7. McIntyre, K.M., Trewby, H., Gubbins, S., Baylis, M. (2010). The impact of sheep breed on the risk of classical scrapie. Epidemiol Infect. 138, 384-392. https://doi.org/10.1017/S0950268809990537 PMid:19678970
8. Drogemuller, C., Leeb, T., Distl, O. (2001). PrP genotype frequencies in German breeding sheep and the potential to breed for resistance to scrapie. Vet Rec. 149, 349-352. https://doi.org/10.1136/vr.149.12.349 PMid:11594380
9. Guan, F., Pan, L., Li J., Tang, H., Zhu, C., Shi, G. (2011). Polymorphisms of the prion protein gene and their effects on litter size and risk evaluation for scrapie in Chinese Hu sheep. Virus Genes. 43, 147-152. https://doi.org/10.1007/s11262-011-0609-5 PMid:21556743 PMCid:PMC3124648 
10. Sartore, S., Rasero, R., Colussi, S., Acutis, P.L., Peletto, S., Soglia, D., et al. (2013). Effect of selection for scrapie resistance on genetic diversity in a rare and locally adapted sheep breed: The case of Sambucana. Livest Sci. 157, 75-80. https://doi.org/10.1016/j.livsci.2013.08.006 
11. Brandsma, J.H., Janss, L.L.G., Visscher, A.H. (2005). Association between PrP genotypes and performance traits in an experimental Dutch Texel herd. Livest Prod Sci. 95, 89-94. https://doi.org/10.1016/j.livprodsci.2004.12.011 
12. Casellas, J., Caja, G., Bach, R., Francino, O., Piedrafita, J. (2007). Association analyses between the prion protein locus and reproductive and lamb weight traits in Ripollesa sheep. J Anim Sci. 85, 592-597. https://doi.org/10.2527/jas.2006-308 PMid:17060422
13. Woolhouse, M.E., Coen, P., Matthews, L., Foster, J.D., Elsen, J.M., Lewis, R.M., et al. (2001). A centuries-long epidemic of scrapie in British sheep? Trends Microbiol. 9, 67-70. https://doi.org/10.1016/S0966-842X(00)01912-0 PMid:11173245
14. Gubbins, S., Cook, C.J., Hyder, K., Boulton, K., Davis, C., Thomas, E., et al. (2009). Associations between lamb survival and prion protein genotype: analysis of data for ten sheep breeds in Great Britain. BMC Vet Res. 5, 3. https://doi.org/10.1186/1746-6148-5-3 PMid:19159456 PMCid:PMC2637852
15. Alfonso, L., Parada, A., Legarra, A., Ugarte, E., Arana, A. (2006). The effects of selective breeding against scrapie susceptibility on the genetic variability of the Latxa Black-Faced sheep breed. Genet Sel Evol. 38, 495-511. https://doi.org/10.1186/1297-9686-38-5-495 PMid:16954042 PMCid:PMC2689259
16. Aguilar-Martínez, C.U., Berruecos-Villalobos, J.M., Espinoza-Gutiérrez, B., Segura-Correa, J.C., Valencia-Méndez, J., Roldán-Roldán, A. (2017). Origen, historia y situacion actual de la oveja pelibuey en Mexico. Tropical and Subtropical Agroecosystems 20, 429-439. 
17. OIE (2005) Sampling methods. OIE Manual on Terrestrial Animals. 3-15. 
18. Acin, C., Martin-Burriel, I., Goldmann, W., Lyahyai, J., Monzon, M., Bolea, R., et al. (2004). Prion protein gene polymorphisms in healthy and scrapie-affected Spanish sheep. J Gen Virol. 85, 2103-2110. https://doi.org/10.1099/vir.0.80047-0 PMid:15218196
19. Seabury, C.M., Derr, J.N. (2003). Identification of a novel ovine PrP polymorphism and scrapie-resistant genotypes for St. Croix White and a related composite breed. Cytogenet Genome Res. 102, 85-88. https://doi.org/10.1159/000075730 PMid:14970684
20. Heaton, Leymaster, K.A., Freking, B.A., Hawk, D.A., Smith, T.L.P., Keele, J.W., et al. (2003). Prion gene sequence variation within diverse groups of U.S. sheep, beef cattle, and deer. Mamm Genome. 14, 765-777. https://doi.org/10.1007/s00335-003-2283-y PMid:14722726
21. Saunders, G.C., Cawthraw, S., Mountjoy, S.J., Hope, J., Windl, O. (2006). PrP genotypes of atypical scrapie cases in Great Britain. J Gen Virol. 87, 3141-3149. https://doi.org/10.1099/vir.0.81779-0 PMid:17030846
22. Vaccari, G., Scavia, G., Sala, M., Cosseddu, G., Chiappini, B., Conte, M., et al. (2009). Protective effect of the AT137RQ and ARQK176 PrP allele against classical scrapie in Sarda breed sheep. Vet Res. 40, 19. https://doi.org/10.1051/vetres/2009002 PMid:19171116 PMCid:PMC2695041
23. Hautaniemi, M., Tapiovaara, H., Korpenfelt, S.L., Sihvonen, L. (2012). Genotyping and surveillance for scrapie in Finnish sheep. BMC Vet Res. 8, 122. https://doi.org/10.1186/1746-6148-8-122 PMid:22831168 PMCid:PMC3414783 
24. DeSilva U., Guo X., Kupfer D.M., Fernando S.C., Pillai A.T., Najar F.Z., et al. (2003). Allelic variants of ovine prion protein gene (PRNP) in Oklahoma sheep. Cytogenet Genome Res. 102, 89-94. https://doi.org/10.1159/000075731 PMid:14970685
25. Lan, Li J., Sun, C., Liu, Y., Zhao, Y., Chi, T., et al. (2014). Allelic variants of PRNP in 16 Chinese local sheep breeds. Arch Virol. 159, 2141-2144. https://doi.org/10.1007/s00705-014-2048-9 PMid:24643335
26. Alvarez, Gutierrez-Gil, B., Uzun, M., Primitivo, F.S., Arranz, J.J. (2011). Genetic variability in the prion protein gene in five indigenous Turkish sheep breeds. Small Rumin Res. 99, 93-98. https://doi.org/10.1016/j.smallrumres.2011.03.043 
27. Ün, C., Oztabak, K., Ozdemir, N., Akıs, I., Mengi, A. (2008). Genotyping of PrP gene in native Turkish sheep breeds. Small Rumin Res. 74, 260-264. https://doi.org/10.1016/j.smallrumres.2007.06.002 
28. Teferedegn, E.Y., Yaman, Y., Un, C. (2020). Five novel PRNP gene polymorphisms and their potential effect on Scrapie susceptibility in three native Ethiopian sheep breeds. BMC Vet Res. 16, 122. https://doi.org/10.1186/s12917-020-02336-0 PMid:32349749 PMCid:PMC7189463 
29. Hunter, N., Moore, L., Hosie, B.D., Dingwall, W.S., Greig, A. (1997). Association between natural scrapie and PrP genotype in a flock of Suffolk sheep in Scotland. Vet Rec. 140, 59-63. https://doi.org/10.1136/vr.140.3.59 PMid:9023905 
30. Sirakov, I., Peshev, R., Christova, L. (2011). Genetic predisposition of some Bulgarian sheep breeds to the scrapie disease. Virus Genes. 43, 153-159. https://doi.org/10.1007/s11262-011-0615-7 PMid:21533749 
31. Meydan Yuceer, B., Degirmenci, R., Ozkan, M.M., Yildiz, M.A. (2012). Prion protein gene polymorphism and genetic risk evaluation for scrapie in all Turkish native sheep breeds. Virus Genes. 45, 169-175. https://doi.org/10.1007/s11262-012-0744-7 PMid:22528641 
32. Ianella, P., McManus, C.M., Caetano, A.R., Paiva, S.R. (2012). PRNP haplotype and genotype frequencies in Brazilian sheep: issues for conservation and breeding programs. Res Vet Sci. 93, 219-225. https://doi.org/10.1016/j.rvsc.2011.06.025 PMid:21816449
33. Lühken, G., Lipsky, S., Peter, C., Erhardt, G. (2008). Prion protein polymorphisms in autochthonous European sheep breeds in respect to scrapie eradication in affected flocks. Small Rumin Res. 75, 43-47. https://doi.org/10.1016/j.smallrumres.2007.07.010 
34. Slate, J. (2005). Molecular evolution of the sheep prion protein gene. Proc Biol Sci. 272, 2371-2377. https://doi.org/10.1098/rspb.2005.3259 PMid:16243700 PMCid:PMC1559970 
35. Glatt, C.E., DeYoung, J.A., Delgado, S., Service, S.K., Giacomini, K.M., Edwards, R.H., et al. (2001). Screening a large reference sample to identify very low frequency sequence variants: comparisons between two genes. Nat Genet. 27, 435-438. https://doi.org/10.1038/86948 PMid:11279528 
36. SIAP (2021). Sheep, Livestock population, 2012-2021. https://www.gob.mx/cms/uploads/attachment/file/744954/Inventario_2021_ovino.pdf 
37. van Rheede, T., Smolenaars ,M.M., Madsen, O., de Jong, W.W. (2003). Molecular evolution of the mammalian prion protein. Mol Biol Evol. 20, 111-121. https://doi.org/10.1093/molbev/msg014 PMid:12519913 
38. Seabury, C.M., Honeycutt, R.L., Rooney, A.P., Halbert, N.D., Derr, J.N. (2004). Prion protein gene (PRNP) variants and evidence for strong purifying selection in functionally important regions of bovine exon 3. Proc Natl Acad Sci U S A. 101, 15142-15147. https://doi.org/10.1073/pnas.0406403101 PMid:15477588 PMCid:PMC524052 
39. Tsangaras, K., Kolokotronis, S.O., Ulrich, R.G., Morand, S., Michaux, J., Greenwood, A.D. (2014). Negative purifying selection drives prion and doppel protein evolution. J Mol Evol. 79, 12-20. https://doi.org/10.1007/s00239-014-9632-1 PMid:25038839 
40. Sezgin, E., Teferedegn, E.Y., Un, C., Yaman, Y. (2022). Excessive replacement changes drive evolution of global sheep prion protein (PRNP) sequences. Heredity (Edinb). 128, 377-385. https://doi.org/10.1038/s41437-022-00520-6 PMid:35273383


Copyright

© 2022 Rodríguez-Andrade F. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Conflict of Interest Statement

The authors declared that they have no potential lict of interest with respect to the authorship and/or publication of this article.

Citation Information

Macedonian Veterinary Review. Volume 46, Issue 1, Pages 17-26, e-ISSN 1857-7415, p-ISSN 1409-7621, DOI: 10.2478/macvetrev-2022-0030, 2022