Absence of Strong Genetic Linkage Disequilibrium between Single Nucleotide Polymorphisms (SNPs) in the Prion Protein Gene () and the Prion-Like Protein Gene () in the Horse, a Prion-Resistant Species.

Prion disease is a fatal neurodegenerative disorder caused by a deleterious prion protein (PrP). However, prion disease has not been reported in horses during outbreaks of transmissible spongiform encephalopathies (TSEs) in various animals in the UK. In previous studies, single nucleotide polymorphisms (SNPs) in the prion protein gene () have been significantly associated with susceptibility to prion disease, and strong linkage disequilibrium (LD) between and prion-like protein gene () SNPs has been identified in prion disease-susceptible species. On the other hand, weak LD values have been reported in dogs, a prion disease-resistant species. In this study, we investigated SNPs in the gene and measured the LD values between the and SNPs and the impact of a nonsynonymous SNP found in the horse gene. To identify SNPs in the gene, we performed direct sequencing of the gene. In addition, to assess whether the weak LD value between the and SNPs is a characteristic of prion disease-resistant animals, we measured the LD value between the and SNPs using D' and values. Furthermore, we evaluated the impact of a nonsynonymous SNP in the Doppel protein with PolyPhen-2, PROVEAN, and PANTHER. We observed two novel SNPs, c.331G > A (A111T) and c.411G > C. The genotype and allele frequencies of the c.331G > A (A111T) and c.411G > C SNPs were significantly different between Jeju, Halla, and Thoroughbred horses. In addition, we found a total of three haplotypes: GG, AG, and GC. The GG haplotype was the most frequently observed in Jeju and Halla horses. Furthermore, the impact of A111T on the Doppel protein was predicted to be benign by PolyPhen-2, PROVEAN, and PANTHER. Interestingly, a weak LD value between the and SNPs was found in the horse, a prion disease-resistant animal. To the best of our knowledge, these results suggest that a weak LD value could be one feature of prion disease-resistant animals.