Novel polymorphisms in the prion protein gene (PRNP) and stability of the resultant prion protein in different horse breeds

This study investigates novel polymorphisms in the PRNP gene, which encodes the prion protein (PrP), in horses—a species considered highly resistant to prion diseases. The research analyzed 207 horses from 20 breeds, identifying three new PRNP polymorphisms. Computational tools such as PolyPhen-2, PROVEAN, PANTHER, Meta-SNP, and PredictSNP were used to predict the potential impact of these polymorphisms on PrP stability and functionality. Additional analyses using AMYCO and Swiss-PdbViewer revealed changes in amyloid aggregation propensity and electrostatic potentials, linked to the lack of hydrogen bridges caused by these polymorphisms. These findings contribute to understanding the molecular basis of prion resistance in horses and its relation to PrP structural stability.