{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:44:27Z","timestamp":1760060667996,"version":"build-2065373602"},"reference-count":43,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T00:00:00Z","timestamp":1758326400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"RumiRes project\u2014\u201cVigil\u00e2ncia epidemiol\u00f3gica de resist\u00eancias antimicrobianas e res\u00edduos medicamentosos em Pequenos ruminantes da Regi\u00e3o Centro\u201d","award":["PRR-C05-i03-I-000190","2021.09461.BD"],"award-info":[{"award-number":["PRR-C05-i03-I-000190","2021.09461.BD"]}]},{"name":"Maria de Sousa scholarship","award":["PRR-C05-i03-I-000190","2021.09461.BD"],"award-info":[{"award-number":["PRR-C05-i03-I-000190","2021.09461.BD"]}]},{"name":"FCT\u2014Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","award":["PRR-C05-i03-I-000190","2021.09461.BD"],"award-info":[{"award-number":["PRR-C05-i03-I-000190","2021.09461.BD"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Scrapie (classical and atypical) susceptibility in sheep is strongly influenced by PRNP gene polymorphisms. In Portugal, limited data exist for native breeds such as Serra da Estrela, despite their relevance to animal conservation and food production. The full coding region of PRNP gene of 92 Serra da Estrela sheep was sequenced and SNP frequencies were analysed. The predicted functional impact of nonsynonymous SNPs was assessed using PolyPhen-2 and AMYCO. A total of 27 SNPs were identified, including 20 nonsynonymous variants. Thirteen major haplotypes were observed. The ARR allele, which provides resistance to classical scrapie, was present in 58.7% of the population, with 18.5% of animals being homozygous. Several previously unreported SNPs were identified, and their impact on prion protein aggregation propensity and structure was explored. The high frequency of the ARR allele without full ARR fixation suggests that no selective breeding for scrapie resistance has been applied. These results support the adoption of gradual selection strategies that preserve genetic variability and promote farmer compliance, while increasing classical and atypical scrapie resistance.<\/jats:p>","DOI":"10.3390\/ani15182750","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T10:05:17Z","timestamp":1758535517000},"page":"2750","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mapping PRNP Polymorphisms in Portuguese Serra da Estrela Ovine Populations: Insights into Scrapie Susceptibility and Farm Animal Improvement"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-2191-9831","authenticated-orcid":false,"given":"Soraia","family":"Rodrigues","sequence":"first","affiliation":[{"name":"School of Medicine and Biomedical Sciences (ICBAS), Universidade do Porto (UP), 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2828-7202","authenticated-orcid":false,"given":"Guilherme","family":"Moreira","sequence":"additional","affiliation":[{"name":"School of Medicine and Biomedical Sciences (ICBAS), Universidade do Porto (UP), 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9742-5643","authenticated-orcid":false,"given":"S\u00e9rgio","family":"Santos-Silva","sequence":"additional","affiliation":[{"name":"School of Medicine and Biomedical Sciences (ICBAS), Universidade do Porto (UP), 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8374-3739","authenticated-orcid":false,"given":"Sara","family":"Gomes-Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"School of Medicine and Biomedical Sciences (ICBAS), Universidade do Porto (UP), 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4054-9124","authenticated-orcid":false,"given":"Maria","family":"Aires Pereira","sequence":"additional","affiliation":[{"name":"Escola Superior Agr\u00e1ria de Viseu, Instituto Polit\u00e9cnico de Viseu, 3500-631 Viseu, Portugal"},{"name":"CERNAS-IPV Research Centre, Instituto Polit\u00e9cnico de Viseu, Campus Polit\u00e9cnico, Repeses, 3504-510 Viseu, Portugal"},{"name":"Global Health and Tropical Medicine, GHTM, Associate Laboratory in Translation and Innovation Towards Global Health, LA-REAL, Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa, UNL, Rua da Junqueira 100, 1349-008 Lisboa, Portugal"}]},{"given":"Alexandra","family":"Baptista","sequence":"additional","affiliation":[{"name":"Escola Superior Agr\u00e1ria de Viseu, Instituto Polit\u00e9cnico de Viseu, 3500-631 Viseu, Portugal"},{"name":"CERNAS-IPV Research Centre, Instituto Polit\u00e9cnico de Viseu, Campus Polit\u00e9cnico, Repeses, 3504-510 Viseu, Portugal"},{"name":"Universidade de Tr\u00e1s-os-Montes e Alto Douro, Quinta de Prados, 5000-801 Vila Real, Portugal"}]},{"given":"Rita","family":"Cruz","sequence":"additional","affiliation":[{"name":"Escola Superior Agr\u00e1ria de Viseu, Instituto Polit\u00e9cnico de Viseu, 3500-631 Viseu, Portugal"},{"name":"Epidemiology Research Unit (EPIUnit), Instituto de Sa\u00fade P\u00fablica da Universidade do Porto, Rua das Taipas 135, 4050-600 Porto, Portugal"},{"name":"Laboratory for Integrative and Translational Research in Population Health (ITR), Rua das Taipas 135, 4050-600 Porto, Portugal"}]},{"given":"Fernando","family":"Esteves","sequence":"additional","affiliation":[{"name":"Escola Superior Agr\u00e1ria de Viseu, Instituto Polit\u00e9cnico de Viseu, 3500-631 Viseu, Portugal"},{"name":"CERNAS-IPV Research Centre, Instituto Polit\u00e9cnico de Viseu, Campus Polit\u00e9cnico, Repeses, 3504-510 Viseu, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8769-8103","authenticated-orcid":false,"given":"Jo\u00e3o R.","family":"Mesquita","sequence":"additional","affiliation":[{"name":"School of Medicine and Biomedical Sciences (ICBAS), Universidade do Porto (UP), 4050-313 Porto, Portugal"},{"name":"Associate Laboratory for Animal and Veterinary Science (AL4AnimalS), 1300-477 Lisboa, Portugal"},{"name":"Centro de Estudos de Ci\u00eancia Animal (CECA), Instituto de Ci\u00eancias, Tecnologias e Agroambiente (ICETA), Universidade do Porto (UP), 4051-401 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Cosier, V., and Daraban, S. (2016). Current Understanding of PRNP Genetics: A Tool for Molecular Assisted Selection in Sheep Populations (A Review). Bull. Univ. Agric. Sci. Vet. Med. Cluj-Napoca. Anim. Sci. Biotechnol., 73.","DOI":"10.15835\/buasvmcn-asb:11976"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5149","DOI":"10.15666\/aeer\/1804_51495173","article-title":"History of Prion Protein Gene (PRNP) Polymorphism in Sheep and Scientific Findings","volume":"18","author":"Iqbal","year":"2020","journal-title":"Appl. Ecol. Environ. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1080\/19336896.2023.2186767","article-title":"Polymorphism of Prion Protein Gene (PRNP) in Nigerian Sheep","volume":"17","author":"Adeola","year":"2023","journal-title":"Prion"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"600","DOI":"10.2460\/ajvr.81.7.600","article-title":"Pathogenesis, Detection, and Control of Scrapie in Sheep","volume":"81","author":"Cassmann","year":"2020","journal-title":"Am. J. Vet. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"372491","DOI":"10.1155\/2014\/372491","article-title":"Polymorphisms at Amino Acid Residues 141 and 154 Influence Conformational Variation in Ovine PrP","volume":"2014","author":"Yang","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1080\/19336896.2018.1467193","article-title":"Nucleotide Variants in Prion-Related Protein (Testis-Specific) Gene (PRNT) and Effects on Chinese and Mongolian Sheep Phenotypes","volume":"12","author":"Li","year":"2018","journal-title":"Prion"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1080\/19336896.2017.1405886","article-title":"Genetic Effects of PRNP Gene Insertion\/Deletion (Indel) on Phenotypic Traits in Sheep","volume":"12","author":"Li","year":"2018","journal-title":"Prion"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1007\/s00705-006-0758-3","article-title":"Prion Protein Gene (PRNP) Polymorphisms in Xinjiang Local Sheep Breeds in China","volume":"151","author":"Lan","year":"2006","journal-title":"Arch. Virol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.gene.2011.06.005","article-title":"Molecular Cloning and Polymorphism Analysis of the Prion Protein Gene in Tan Sheep of Ningxia, China","volume":"485","author":"Xu","year":"2011","journal-title":"Gene"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"6079","DOI":"10.3168\/jds.2013-6570","article-title":"Short Communication: Analysis of Association between the Prion Protein (PRNP) Locus and Milk Traits in Latxa Dairy Sheep","volume":"96","author":"Vitezica","year":"2013","journal-title":"J. Dairy Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1784","DOI":"10.3168\/jds.S0022-0302(06)72247-0","article-title":"Influence of Prion Protein Genotypes on Milk Production Traits in Spanish Churra Sheep","volume":"89","author":"Arranz","year":"2006","journal-title":"J. Dairy Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.46265\/genresj.QULD1720","article-title":"International Congress on the Breeding of Sheep and Goats","volume":"2","author":"Gerlinger","year":"2021","journal-title":"Genet. Resour."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.jcpa.2013.10.001","article-title":"Influence of Polymorphisms in the Prion Protein Gene on the Pathogenesis and Neuropathological Phenotype of Sheep Scrapie after Oral Infection","volume":"150","author":"Pitarch","year":"2014","journal-title":"J. Comp. Pathol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.1099\/vir.0.80047-0","article-title":"Prion Protein Gene Polymorphisms in Healthy and Scrapie-Affected Spanish Sheep","volume":"85","author":"Goldmann","year":"2004","journal-title":"J. Gen. Virol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"170","DOI":"10.15547\/\/bjvm.2219","article-title":"PrP Gene Polymorphism and Its Influence on Some Productive Traits of Sheepbreeds Reared in Bulgaria","volume":"23","author":"Koynarski","year":"2020","journal-title":"Bulg. J. Vet. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.12681\/jhvms.22967","article-title":"Genetic Improvement of Indigenous Greek Sheep and Goat Breeds","volume":"71","author":"Argyriadou","year":"2019","journal-title":"J. Hell. Vet. Med. Soc."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1053\/rvsc.2000.0441","article-title":"Prion Protein Gene Polymorphisms in Pedigree Sheep in Ireland","volume":"70","author":"Aherne","year":"2001","journal-title":"Res. Vet. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1177\/1040638712471343","article-title":"Development of a Real-Time Polymerase Chain Reaction Assay for Single Nucleotide Polymorphism Genotyping Codons 136, 154, and 171 of the PRNP Gene and Application to Brazilian Sheep Herds","volume":"25","author":"Driemeier","year":"2013","journal-title":"J. Vet. Diagn. Investig."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.smallrumres.2019.02.010","article-title":"Genotyping of Prion Protein in Black Merino Sheep from the Iberian Peninsula","volume":"173","year":"2019","journal-title":"Small Rumin. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.livsci.2015.10.002","article-title":"PRNP Polymorphisms in Four Italian Sheep Breeds","volume":"181","author":"Curcio","year":"2015","journal-title":"Livest. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/s12041-017-0763-1","article-title":"Prion Protein Gene Polymorphisms in Turkish Native Goat Breeds","volume":"96","author":"Meydan","year":"2017","journal-title":"J. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"261","DOI":"10.33988\/auvfd.437314","article-title":"Analysis of Prion Protein Coding Gene Polymorphisms in Palestinian Native Sheep Breeds","volume":"66","author":"Alsayed","year":"2019","journal-title":"Ank. \u00dcniversitesi Vet. Fak\u00fcltesi Derg."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/s11262-010-0549-5","article-title":"Polymorphism of Prion Protein Gene in Sheep of Inner Mongolian, China","volume":"42","author":"Han","year":"2011","journal-title":"Virus Genes"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.4238\/2012.June.21.2","article-title":"Ovine Prion Protein Genotype Frequencies in Northwestern China","volume":"11","author":"Zhao","year":"2012","journal-title":"Genet. Mol. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1007\/s12041-018-0932-x","article-title":"Biodiversity and Selection for Scrapie Resistance in Sheep: Genetic Polymorphism in Eight Breeds of Algeria","volume":"97","author":"Djaout","year":"2018","journal-title":"J. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Teferedegn, E.Y., Yaman, Y., and 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.","DOI":"10.1186\/s12917-020-02336-0"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1136\/vr.161.15.524","article-title":"Polymorphisms of the PRNP Gene in Moroccan Sheep Breeds","volume":"161","author":"Serrano","year":"2007","journal-title":"Vet. Rec."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1007\/s11250-012-0088-2","article-title":"Prion Protein Gene Polymorphism in Four West African Sheep Populations","volume":"44","author":"Royo","year":"2012","journal-title":"Trop. Anim. Health Prod."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.livprodsci.2005.06.009","article-title":"Prion Protein Genetic Polymorphisms and Breeding Strategies in Portuguese Breeds of Sheep","volume":"99","author":"Gama","year":"2006","journal-title":"Livest. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1111\/j.1365-2052.2009.01992.x","article-title":"Prion-like Doppel Gene Polymorphisms and Scrapie Susceptibility in Portuguese Sheep Breeds","volume":"41","author":"Mesquita","year":"2010","journal-title":"Anim. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1099\/vir.0.018879-0","article-title":"Putative Emergence of Classical Scrapie in a Background of Enzootic Atypical Scrapie","volume":"91","author":"Orge","year":"2010","journal-title":"J. Gen. Virol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"European Food Safety Authority (EFSA), Arnold, M., Ru, G., Simmons, M., Vidal-Diez, A., Ortiz-Pelaez, A., and Stella, P. (2021). Scientific Report on the Analysis of the 2-Year Compulsory Intensified Monitoring of Atypical Scrapie. EFSA J., 19, e06686.","DOI":"10.2903\/j.efsa.2021.6686"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1099\/vir.0.80437-0","article-title":"Polymorphisms at Codons 141 and 154 in the Ovine Prion Protein Gene Are Associated with Scrapie Nor98 Cases","volume":"86","author":"Moum","year":"2005","journal-title":"J. Gen. Virol."},{"key":"ref_34","unstructured":"CISE (2025, July 09). Centro de Interpreta\u00e7\u00e3o da Serra da Estrela. Available online: https:\/\/www.cise.pt\/pt\/."},{"key":"ref_35","unstructured":"INIAV (2025, July 16). Serra da Estrela. Available online: http:\/\/anidop.iniav.pt\/index.php\/racas\/racas-autoctones\/ovinos\/serra-da-estrela."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Rausch, T., Fritz, M.H.-Y., Untergasser, A., and Benes, V. (2020). Tracy: Basecalling, Alignment, Assembly and Deconvolution of Sanger Chromatogram Trace Files. BMC Genom., 21.","DOI":"10.1186\/s12864-020-6635-8"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nmeth0410-248","article-title":"A Method and Server for Predicting Damaging Missense Mutations","volume":"7","author":"Adzhubei","year":"2010","journal-title":"Nat. Methods"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Iglesias, V., Conchillo-Sole, O., Batlle, C., and Ventura, S. (2019). AMYCO: Evaluation of Mutational Impact on Prion-like Proteins Aggregation Propensity. BMC Bioinform., 20.","DOI":"10.1186\/s12859-019-2601-3"},{"key":"ref_39","first-page":"657","article-title":"Advances in Scrapie Research","volume":"26","author":"Cosseddu","year":"2007","journal-title":"Rev. Sci. Tech."},{"key":"ref_40","unstructured":"European Parliament, and Council of the European Union (2025). Regulation (EC) No 999\/2001 of the European Parliament and of the Council of 22 May 2001 Laying down Rules for the Prevention, Control and Eradication of Certain Transmissible Spongiform Encephalopathies, No. 999\/2001, Council of the European Union Regulation (EC)."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1051\/vetres:2008010","article-title":"PrP Genetics in Ruminant Transmissible Spongiform Encephalopathies","volume":"39","author":"Goldmann","year":"2008","journal-title":"Vet. Res."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Houston, F., Goldmann, W., Foster, J., Gonz\u00e1lez, L., Jeffrey, M., and Hunter, N. (2015). Comparative Susceptibility of Sheep of Different Origins, Breeds and PRNP Genotypes to Challenge with Bovine Spongiform Encephalopathy and Scrapie. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0143251"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3487","DOI":"10.1099\/vir.0.80246-0","article-title":"Identification of Putative Atypical Scrapie in Sheep in Portugal","volume":"85","author":"Orge","year":"2004","journal-title":"J. Gen. Virol."}],"container-title":["Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2615\/15\/18\/2750\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:46:21Z","timestamp":1760035581000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2615\/15\/18\/2750"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,20]]},"references-count":43,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["ani15182750"],"URL":"https:\/\/doi.org\/10.3390\/ani15182750","relation":{},"ISSN":["2076-2615"],"issn-type":[{"type":"electronic","value":"2076-2615"}],"subject":[],"published":{"date-parts":[[2025,9,20]]}}}