| Summary: | Prion disease has displayed large infection host ranges among several species; however, dogs have not been reported to be infected and are considered prion disease-resistant animals. Case-controlled studies in several species, including humans and cattle, indicated a potent association of prion protein gene (<i>PRNP</i>) polymorphisms in the progression of prion disease. Thus, because of the proximal location and similar structure of the <i>PRNP</i> gene among the prion gene family, the <i>prion-like</i> protein gene (<i>PRND</i>) was noted as a novel candidate gene that contributes to prion disease susceptibility. Several case-controlled studies have confirmed the relationship of the <i>PRND</i> gene with prion disease vulnerability, and strong genetic linkage disequilibrium blocks were identified in prion-susceptible species between the <i>PRNP</i> and <i>PRND</i> genes. However, to date, polymorphisms of the dog <i>PRND</i> gene have not been reported, and the genetic linkage between the <i>PRNP</i> and <i>PRND</i> genes has not been examined thus far. Here, we first investigated dog <i>PRND</i> polymorphisms in 207 dog DNA samples using direct DNA sequencing. A total of four novel single nucleotide polymorphisms (SNPs), including one nonsynonymous SNP (c.149G>A, R50H), were identified in this study. We also found two major haplotypes among the four novel SNPs. In addition, we compared the genotype and allele frequencies of the c.149G>A (R50H) SNP and found significantly different distributions among eight dog breeds. Furthermore, we annotated the c.149G>A (R50H) SNP of the dog <i>PRND</i> gene using <i>in silico</i> tools, PolyPhen-2, PROVEAN, and PANTHER. Finally, we examined linkage disequilibrium between the <i>PRNP</i> and <i>PRND</i> genes in dogs. Interestingly, we did not find a strong genetic linkage between these two genes. To the best of our knowledge, this was the first genetic study of the <i>PRND</i> gene in a prion disease-resistant animal, a dog.
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