«Mapping PRNP Polymorhisms in Portuguese Serra da Estrela Ovine Populations: Insights into Scrapie Susceptibility and Farm Animal Improvement»

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.To assess scrapie susceptibility of Serra da Estrela sheep breed, the full coding region of PRNP gene of a 92 Serra da Estrela sheep cohort was sequenced, and subsequent SNP frequencies were analysed.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 (ARR/ARR).In contrast, the VRQ allele, associated with scrapie susceptibility, was absent.Several previously unreported SNPs were identified in this study, and their impact on prion protein aggregation propensity and structure was explored using PolyPhen-2 and AMYCO.Earlier Portuguese surveys in this breed reported similar ARR/ARR (17%) and ARR/ARQ (42-44%) frequencies.Across other native and regional breeds, ARR is often rarer (e.g., 0.02-0.05 in Ethiopian sheep; low in many African and Indonesian populations), while ARQ predominates and VRQ may still be present.Thus, Serra da Estrela compares favourably for classical scrapie risk.The high frequency of the ARR allele without full ARR fixation suggests that no selective breeding for scrapie resistance has been applied.Serra da Estrela sheep already carry a high frequency of the protective ARR allele and lack VRQ but maintain rich PRNP diversity and novel variants.These results support the implementation of a gradual ARR-focused selection that strengthens resistance to classical (and better manages atypical) scrapie while consciously preserving genetic variability to ensure long-term breed sustainability.