First Report of Polymorphisms and Genetic Characteristics of Protein Gene () in Cats.

Prion diseases are fatal neurodegenerative disorders caused by the misfolding of the normal cellular prion protein (PrP) into its infectious isoform (PrP). 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 () and protein gene (), have been linked to prion disease susceptibility in various species. However, no studies have yet investigated the gene in cats with respect to prion diseases. Therefore, we investigated polymorphisms in the feline and analyzed their genetic characteristics. We sequenced the coding region of the gene using samples from 210 domestic cats and determined the genotype and allele frequencies of polymorphisms. We identified thirteen novel single nucleotide polymorphisms (SNPs), including six non-synonymous variants and one insertion/deletion (InDel) in the feline 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 SNPs and the InDel, suggesting linkage between these loci in cats. This study identifies novel polymorphisms in domestic cats and provides new insights into the genetic factors underlying feline susceptibility to prion diseases. The strong genetic linkage between and polymorphisms, coupled with predictions of detrimental effects on Doppel protein structure, suggests that gene variants could influence prion disease progression in cats. These findings provide a foundational framework for future studies on the functional implications of polymorphisms in FSE. To the best of our knowledge, this study is the first report on the genetic characteristics of polymorphisms in cats.