ORIGINAL_SCIENTIFIC_ARTICLE 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 https://macvetrev.mk/LoadArticlePdf/356 2022-3-15 17 26 10.2478/macvetrev-2022-0030 PRNP gene polymorphisms genetic susceptibility genetic selection Pelibuey Fabiola Rodríguez-Andrade false 1 1Facultad de Medicina Veterinaria y Zootecnia, Benemérita Universidad Autónoma de Puebla, 4 Sur 304 Col. Centro, CP 75482, Tecamachalco Puebla, México AUTHOR Arnulfo Villanueva-Castillo false 2 1Facultad de Medicina Veterinaria y Zootecnia, Benemérita Universidad Autónoma de Puebla, 4 Sur 304 Col. Centro, CP 75482, Tecamachalco Puebla, México; 2Cuerpo Académico de Enfermedades Emergentes, Bioinformática y Modelado, Facultad de Medicina Veterinaria y Zootecnia, Benemérita Universidad Autónoma de Puebla, 4 Sur 304 Col. Centro, CP 75482, Tecamachalco Puebla, México AUTHOR Cesar Feliciano Pastelin-Rojas false 3 1Facultad de Medicina Veterinaria y Zootecnia, Benemérita Universidad Autónoma de Puebla, 4 Sur 304 Col. Centro, CP 75482, Tecamachalco Puebla, México; 2Cuerpo Académico de Enfermedades Emergentes, Bioinformática y Modelado, Facultad de Medicina Veterinaria y Zootecnia, Benemérita Universidad Autónoma de Puebla, 4 Sur 304 Col. Centro, CP 75482, Tecamachalco Puebla, México AUTHOR Raymundo Avila-Benitez false 4 1Facultad de Medicina Veterinaria y Zootecnia, Benemérita Universidad Autónoma de Puebla, 4 Sur 304 Col. Centro, CP 75482, Tecamachalco Puebla, México; 2Cuerpo Académico de Enfermedades Emergentes, Bioinformática y Modelado, Facultad de Medicina Veterinaria y Zootecnia, Benemérita Universidad Autónoma de Puebla, 4 Sur 304 Col. Centro, CP 75482, Tecamachalco Puebla, México AUTHOR Ruby Sandy Moreno-Mejía false 5 1Facultad de Medicina Veterinaria y Zootecnia, Benemérita Universidad Autónoma de Puebla, 4 Sur 304 Col. Centro, CP 75482, Tecamachalco Puebla, México AUTHOR José Alfredo Galicia-Domínguez false 6 1Facultad de Medicina Veterinaria y Zootecnia, Benemérita Universidad Autónoma de Puebla, 4 Sur 304 Col. Centro, CP 75482, Tecamachalco Puebla, México AUTHOR O’Neill, G.T., Donnelly, K., Marshall, E., Cairns, D., Goldmann, W., Hunter, N. (2003). 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