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

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