Characterisation of the PRNP gene polymorphisms in Zom sheep
Abstract
Aim of study: Polymorphisms in codons 136, 154, and 171 of the prion protein gene (PRNP) are critical due to their association with susceptibility or resistance to scrapie, a fatal neurodegenerative disease in sheep. This study aimed to analyze the genetic diversity of PRNP in Zom sheep, an indigenous breed of Türkiye, and to evaluate its potential implications for scrapie resistance.
Area of study: Türkiye.
Material and methods: Genomic DNA was extracted from blood samples of 46 Zom sheep. A 662 bp region of the PRNP gene was amplified using polymerase chain reaction (PCR) and sequenced. Allele and genotype frequencies of the identified polymorphisms were calculated. The potential functional effects of missense single nucleotide polymorphisms (SNPs) were predicted using PolyPhen-2, PANTHER, and AMYCO bioinformatics tools. Haplotype analysis was also performed to assess genetic variation.
Main results: Five alleles and six genotypes were identified. The ARQ allele, ARQ/ARQ and ARR/ARQ genotypes were predominant, while resistance-associated alleles and genotypes were less frequent. Ten polymorphisms were identified, including one insertion/deletion variant and six missense SNPs leading to amino acid substitutions. PolyPhen-2 classified T195I, T196S, and N146S as benign, while T193S was predicted as possibly damaging and V179G as probably damaging. PANTHER predicted all scorable SNPs as possibly damaging, whereas AMYCO found no amyloidogenic risk. Additionally, twelve haplotypes were identified within the population.
Research highlights: This study provides population-level data on PRNP polymorphisms in Zom sheep, suggesting a potential link to partial resistance to scrapie and offering insights for future breeding approaches.
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References
Acín C, Martín-Burriel I, Goldmann W, Lyahyai J, Monzon M, Bolea R, Smith A, Rodellar C, Badiola JJ, Zaragoza P, 2004. Prion protein gene polymorphisms in healthy and scrapie-affected Spanish sheep. J Gen Virol 85(7):2103-2110. https://doi.org/10.1099/vir.0.80047-0
Alvarez L, Gutierrez-Gil B, Uzun M, San Primitivo F, Arranz JJ, 2011. Genetic variability in the prion protein gene in five indigenous Turkish sheep breeds. Small Rumin Res 99(2-3):93-98. https://doi.org/10.1016/j.smallrumres.2011.03.043
Arnold M, Ortiz-Pelaez A, 2014. The evolution of the prevalence of classical scrapie in sheep in Great Britain using surveillance data between 2005 and 2012. Prev Vet Med 117(1):242-250. https://doi.org/10.1016/j.prevetmed.2014.07.015
Babar ME, Farid A, Benkel BF, Ahmad J, Sajid IA, Imran M, Hussain T, Nadeem A, 2008. Genetic variability at seven codons of the prion protein gene in nine Pakistani sheep breeds. J Genet 87(2):187-190. https://doi.org/10.1007/s12041-008-0029-z
Bakkebø MK, Mouillet-Richard S, Espenes A, Goldmann W, Tatzelt J, Tranulis MA, 2015. The cellular prion protein: a player in immunological quiescence. Front Immunol 6:450. https://doi.org/10.3389/fimmu.2015.00450
Benarroch E, 2024. What Are the Roles of Cellular Prion Protein in Normal and Pathologic Conditions? Neurology 102(7):e209272. https://doi.org/10.1212/WNL.0000000000209272
Benestad SL, Sarradin P, Thu B, Schönheit J, Tranulis MA, Bratberg B, 2003. Cases of scrapie with unusual features in Norway and designation of a new type, Nor98. Vet Rec 153(7):202-208. https://doi.org/10.1136/vr.153.7.202
Brown P, Bradley R, 1998. 1755 and all that: a historical primer of transmissible spongiform encephalopathy. BMJ 317:1688-1692. https://doi.org/10.1136/bmj.317.7174.1688
Calzolai L, Zahn R, 2003. Influence of pH on NMR structure and stability of the human prion protein globular domain. J Biol Chem 278(37):35592-35596. https://doi.org/10.1074/jbc.M303005200
Celik R, Arserim NB, Durak MH, 2012. Some production characteristics of zom sheep types. Asian J Anim Vet Adv 7:1035-1040. https://doi.org/10.3923/ajava.2012.1035.1040
Clouscard C, Beaudry P, Elsen JM, Milan D, Dussaucy M, Bounneau C, Schelcher F, Chatelain J, Launay JM, Laplanche JL, 1995. Different allelic effects of the codons 136 and 171 of the prion protein gene in sheep with natural scrapie. J Gen Virol 76(8):2097-2101. https://doi.org/10.1099/0022-1317-76-8-2097
Collinge J, Clarke AR, 2007. A general model of prion strains and their pathogenicity. Science 318(5852):930-936. https://doi.org/10.1126/science.1138718
Dawson M, Hoinville LJ, Hosie BD, Hunter N, 1998. Guidance on the use of PrP genotyping as an aid to the control of clinical scrapie. Vet Rec 142(23):623-625.
DeSilva U, Guo X, Kupfer DM, Fernando SC, Pillai ATV, Najar FZ, So S, Fitch GQ, Roe BA, 2003. Allelic variants of ovine prion protein gene (PRNP) in Oklahoma sheep. Cytogenet Genome Res 102(1-4):89-94. https://doi.org/10.1159/000075731
Drögemüller C, De Vries F, Hamann H, Leeb T, Distl O, 2004. Breeding German sheep for resistance to scrapie. Vet Rec 154(9):257-260. https://doi.org/10.1136/vr.154.9.257
Gmür A, Gaillard C, Dolf G, 2004. Characterization of the prion protein gene (PRNP) region in Swiss sheep breeds. J Anim Breed Genet 121(3):216-220. https://doi.org/10.1111/j.1439-0388.2004.00447.x
Goldmann W, 2008. PrP genetics in ruminant transmissible spongiform encephalopathies. Vet Res 39(4):30. https://doi.org/10.1051/vetres:2008010
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
Hafi A, Eather J, Garner G, 2017. Economic consequences of a scrapie outbreak in Australia. ABARES research report 17.10, Australian Bureau of Agricultural and Resource Economics and Sciences, Canberra, Australia. 108 pp.
Hunter N, Goldmann W, Foster JD, Cairns D, Smith G, 1997. Natural scrapie and PrP genotype: case-control studies in British sheep. Vet Rec 141(6):137-140. https://doi.org/10.1136/vr.141.6.137
Ikeda T, Horiuchi M, Ishiguro N, Muramatsu Y, Kai-Uwe GD, Shinagawa M, 1995. Amino acid polymorphisms of PrP with reference to onset of scrapie in Suffolk and Corriedale sheep in Japan. J Gen Virol 76(10):2577-2581. https://doi.org/10.1099/0022-1317-76-10-2577
Ji HF, Zhang HY, 2010. β-sheet constitution of prion proteins. Trends Biochem Sci 35(3):129-134. https://doi.org/10.1016/j.tibs.2009.12.002
Karami M, Amirinia C, Kashan NEJ, Amirmozafari N, Chamani M, Banabazi MH, 2011. Polymorphisms of the prion protein gene Arabi sheep breed in Iran. Afr J Biotechnol 10(70):15819-15822. https://doi.org/10.5897/AJB10.1780
Kurar E, Bulut Z, Nizamoğlu M, 2014. Türkiye’de bulunan bazı koyun ırklarının PrP lokus polimorfizmleri yönünden incelenmesi. Eurasian J Vet Sci 30(3):145-151. https://doi.org/10.15312/EurasianJVetSci.201436514
Meydan H, Yüceer B, Degirmenci R, Özkan MM, Yildiz MA, 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
Miller SA, Dykes DD, Polesky HF, 1988. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16(3):1215. https://doi.org/10.1093/nar/16.3.1215
Minor Jr DL, Kim PS, 1994. Measurement of the β-sheet-forming propensities of amino acids. Nature 367(6464):660-663. https://doi.org/10.1038/367660a0
Moum T, Olsaker I, Hopp P, Moldal T, Valheim M, Moum T, Benestad SL, 2005. Polymorphisms at codons 141 and 154 in the ovine prion protein gene are associated with scrapie Nor98 cases. J Gen Virol 86(1):231-235. https://doi.org/10.1099/vir.0.80437-0
O’Doherty E, Aherne M, Ennis S, Weavers E, Roche JF, Sweeney T, 2001. Prion protein gene polymorphisms in pedigree sheep in Ireland. Res Vet Sci 70(1):51-56. https://doi.org/10.1053/rvsc.2000.0441
Prusiner SB, 1998. Prions. Proc Natl Acad Sci USA 95(23):13363-13383. https://doi.org/10.1073/pnas.95.23.13363
Saunders GC, Lantier I, Cawthraw S, Berthon P, Moore SJ, Arnold ME, Windl O, Simmons MM, Andréoletti O, Bellworthy S, Lantier F, 2009. Protective effect of the T112 PrP variant in sheep challenged with bovine spongiform encephalopathy. J Gen Virol 90(10):2569-2574. https://doi.org/10.1099/vir.0.012724-0
Sezgin E, Teferedegn EY, Ün C, Yaman Y, 2022. Excessive replacement changes drive evolution of global sheep prion protein (PRNP) sequences. Heredity 128(5):377-385. https://doi.org/10.1038/s41437-022-00520-6
Stepanek O, Horin P, 2017. Genetic diversity of the prion protein gene (PRNP) coding sequence in Czech sheep and evaluation of the national breeding programme for resistance to scrapie in the Czech Republic. J Appl Genet 58:111-121. https://doi.org/10.1007/s13353-016-0354-5
U.S. Department of Agriculture, Animal and Plant Health Inspection Service (APHIS), 2025. Scrapie. https://www.aphis.usda.gov/livestock-poultry-disease/sheep-goat/scrapie [11 June 2025]
Teferedegn EY, 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
Ün C, Oztabak K, Ozdemir N, Akıs I, Mengi A, 2008. Genotyping of PrP gene in native Turkish sheep breeds. Small Rumin Res 74(1):260-264. https://doi.org/10.1016/j.smallrumres.2007.06.002
Vaccari G, Petraroli R, Agrimi U, Eleni C, Perfetti MG, Di Bari MA, Morelli L, Ligios C, Busani L, Nonno R, Di Guardo G, 2001. PrP genotype in Sarda breed sheep and its relevance to scrapie. Arch Virol 146:2029-2037. https://doi.org/10.1007/s007050170050
Wang Y, Qin Z, Qiao J, Zhao D, 2008. Polymorphisms of the prion protein gene in sheep of Inner Mongolia, China. Virus Genes 37:128-130. https://doi.org/10.1007/s11262-008-0244-y
Warner R, Morris D, Dawson M, 2006. PrP genotype progression in flocks participating in the National Scrapie Plan for Great Britain. Vet Rec 159(15):473-479. https://doi.org/10.1136/vr.159.15.473
Yamaguchi KI, Matsumoto T, Kuwata K, 2008. Critical region for amyloid fibril formation of mouse prion protein: unusual amyloidogenic properties of the helix 2 peptide. Biochemistry 47(50):13242-13251. https://doi.org/10.1021/bi801562w
Zeder MA, 2008. Domestication and early agriculture in the Mediterranean Basin: Origins, diffusion, and impact. Proc Natl Acad Sci USA 105(33):11597-11604. https://doi.org/10.1073/pnas.0801317105
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