Temporal dynamics of PRNP haplotype frequencies and optimization of selection strategies for scrapie resistance in the Valle del Belìce sheep breed.

Scrapie is a fatal transmissible spongiform encephalopathy affecting small ruminants, with susceptibility strongly influenced by polymorphisms in the prion protein gene (PRNP). The aim of this study was to evaluate trends in PRNP haplotype and genotype frequencies in the Valle del Belìce sheep breed before and after the implementation of the Sicilian scrapie Resistance Plan. Furthermore, a simulation analysis was performed to assess the expected genetic response under a revised selection strategy. A total of 4,341 animals were genotyped for the PRNP gene. In the overall population, ARR (0.543) and ARQ (0.406) were the most frequent haplotypes. In animals born before the implementation of the selection plan (pre-2016), the frequency of the ARR haplotype was 0.462 (females = 0.459; males = 0.537). In animals born after the introduction of the plan, ARR frequency increased to 0.589 (females = 0.566; males = 0.774), reflecting the greater selection intensity applied to breeding rams. These results support the effectiveness of targeted genetic selection in increasing the frequency of the resistant ARR haplotype, while emphasizing the often-overlooked role of ewes as a reservoir of susceptible genotypes. Simulation results suggest that extending selection to ewes and implementing controlled mating schemes could accelerate genetic progress, leading to near-fixation of the ARR haplotype within approximately seven to eight years. This study demonstrates that the inclusion of the entire breeding population is essential to optimize scrapie resistance programs. The findings provide a quantitative basis for revising current regional guidelines and offer broader insights for the design of sustainable genetic control strategies.