First Report of Polymorphisms and Genetic Characteristics of <i>Prion-like</i> Protein Gene (<i>PRND</i>) in Cats

Prion diseases are fatal neurodegenerative disorders caused by the misfolding of the normal cellular prion protein (PrP^C) into its infectious isoform (PrP^Sc). Although prion diseases in humans, sheep, goats, and cattle have been extensively studied, feline spongiform encephalopathy (FSE) remains poorly understood. Genetic factors, particularly polymorphisms in the prion protein gene (<i>PRNP</i>) and <i>prion-like</i> protein gene (<i>PRND</i>), have been linked to prion disease susceptibility in various species. However, no studies have yet investigated the <i>PRND</i> gene in cats with respect to prion diseases. Therefore, we investigated polymorphisms in the feline <i>PRND gene</i> and analyzed their genetic characteristics. We sequenced the coding region of the <i>PRND</i> gene using samples from 210 domestic cats and determined the genotype and allele frequencies of <i>PRND</i> polymorphisms. We identified thirteen novel single nucleotide polymorphisms (SNPs), including six non-synonymous variants and one insertion/deletion (InDel) in the feline <i>PRND</i> gene. Four of the non-synonymous SNPs were predicted to have deleterious effects on the Doppel protein’s structure and function. Notably, the SNP c.97A>G (I33V) showed potential structural clashes, and the others formed additional hydrogen bonds. The LD analysis revealed strong genetic associations between the <i>PRND</i> SNPs and the <i>PRNP</i> InDel, suggesting linkage between these loci in cats. This study identifies novel <i>PRND</i> polymorphisms in domestic cats and provides new insights into the genetic factors underlying feline susceptibility to prion diseases. The strong genetic linkage between <i>PRND</i> and <i>PRNP</i> polymorphisms, coupled with predictions of detrimental effects on Doppel protein structure, suggests that <i>PRND</i> gene variants could influence prion disease progression in cats. These findings provide a foundational framework for future studies on the functional implications of <i>PRND</i> polymorphisms in FSE. To the best of our knowledge, this study is the first report on the genetic characteristics of <i>PRND</i> polymorphisms in cats.