Absence of Strong Genetic Linkage Disequilibrium between Single Nucleotide Polymorphisms (SNPs) in the Prion Protein Gene (PRNP) and the Prion-Like Protein Gene (PRND) in the Horse, a Prion-Resistant Species.
Prion disease is a fatal neurodegenerative disorder caused by a deleterious prion protein (PrPSc). 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 (PRNP) have been significantly associated with susceptibility to prion disease, and strong linkage disequilibrium (LD) between PRNP and prion-like protein gene (PRND) 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 PRND gene and measured the LD values between the PRNP and PRND SNPs and the impact of a nonsynonymous SNP found in the horse PRND gene. To identify SNPs in the PRND gene, we performed direct sequencing of the PRND gene. In addition, to assess whether the weak LD value between the PRNP and PRND SNPs is a characteristic of prion disease-resistant animals, we measured the LD value between the PRNP and PRND SNPs using D' and r2 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 PRNP and PRND 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.
['Won|Sae-Young|SY|', 'Kim|Yong-Chan|YC|', 'Do|Kyoungtag|K|0000-0001-5188-7295', 'Jeong|Byung-Hoon|BH|0000-0002-4525-9994']
D000483:Alleles D000818:Animals D002874:Chromosome Mapping D060467:Disease Resistance D058851:GPI-Linked Proteins D020022:Genetic Predisposition to Disease D005838:Genotype D006239:Haplotypes D006734:Horse Diseases D006736:Horses D015810:Linkage Disequilibrium D008322:Mammals D020641:Polymorphism, Single Nucleotide D017096:Prion Diseases D011328:Prions D013045:Species Specificity
single nucleotide polymorphisms polymorphisms prion PRNP prion-like protein gene PRND Doppel