Polymorphisms of the prion‐related protein gene are strongly associated with cervids’ susceptibility to chronic wasting disease

Abstract

Background: Chronic wasting disease (CWD) is a cervid prion disease that is caused by abnormal prion protein (PrP Sc ). Recent studies have reported that prion family genes showed a strong association with the susceptibility of several types of prion diseases. To date, an association study of the prionrelated protein gene (PRNT) has not been performed in any type of cervid prion disease. Methods: In the present study, we investigated PRNT polymorphisms in large deer, including 235 elk, 257 red deer and 150 sika deer. We compared genotype, allele and haplotype frequencies of PRNT polymorphisms between CWD-negative animals and CWD-positive animals to find an association of PRNT polymorphisms with the susceptibility of CWD. Results: We found a total of five novel single nucleotide polymorphisms (SNPs) in the cervid PRNT gene. Interestingly, we observed significantly different distributions of genotypes and allele frequencies of three PRNT SNPs, including c.108C>T, c.159+30C>T and c.159+32A>C, between CWDnegative and CWD-positive red deer. In addition, significant differences of two haplotype frequencies in red deer were found between the CWD-negative and CWD-positive groups. However, the association identified in the red deer was not found in elk and sika deer. Conclusion:To the best of our knowledge, this report is the first to describe the strong association of PRNT SNPs with the susceptibility of CWD.

First report of a strong association between genetic polymorphisms of the prion protein gene ( PRNP ) and susceptibility to chronic wasting disease in sika deer ( Cervus nippon )

“…Sika deer (Cervus nippon) is a deer species native to East Asia and is also widespread throughout North America and Europe (Roh et al, 2021).…”

“…In addition, mule deer carrying the 225F allele of the PRNP gene showed a prolonged incubation period against CWD infection. Furthermore, the M132L single nucleotide polymorphism (SNP) of the PRNP gene, which is homologous to the M129V SNP of the human PRNP gene, modulates the conversion efficiency of PrP Sc according to the coincidence of donor and acceptor genotypes (Arifin et al, 2021;Roh et al, 2021;White et al, 2010).…”

“…In addition, mule deer carrying the 225F allele of the PRNP gene showed a prolonged incubation period against CWD infection. Furthermore, the M132L single nucleotide polymorphism (SNP) of the PRNP gene, which is homologous to the M129V SNP of the human PRNP gene, modulates the conversion efficiency of PrP Sc according to the coincidence of donor and acceptor genotypes (Arifin et al., 2021; Kim & Jeong, 2021; Roh et al., 2021; White et al., 2010). Although several studies have found that the cervid PRNP gene plays a key role in genetic characteristics related to CWD infection, there is no prior study of an association between susceptibility to CWD and genetic polymorphisms of the PRNP gene in sika deer.…”

Association Study of the M132L Single Nucleotide Polymorphism With Susceptibility to Chronic Wasting Disease in Korean Elk: A Meta-Analysis

“…Prion diseases are infectious brain proteinopathies caused by a pathogenic form of prion protein (PrP Sc ) converted from an endogenous form of prion protein (PrP C ) and are classified into several types in a wide range of mammalian hosts: Creutzfeldt-Jakob disease (CJD), fatal familial insomnia (FFI) and Gerstmann-Sträussler-Scheinker syndrome (GSS) in humans; scrapie in sheep and goats; bovine spongiform encephalopathy (BSE) in cattle; and chronic wasting disease (CWD) in the Cervidae family (1)(2)(3)(4)(5)(6)(7). After CWD was first reported in mule deer in the USA in the 1967, CWD has been reported globally, including in North America, South Korea and Scandinavia, in variable cervid species, such as white-tailed deer, elk, moose, red deer and reindeer (8)(9)(10)(11). To date, CWD is a fatal and incurable disorder, and its exact origin has not been elucidated to date.…”

Novel Polymorphisms and Genetic Characteristics of the Prion Protein Gene in Pheasants

“…In goats, 9 polymorphisms including codons T110P, G127S, M142I, G145D, N146D,S, R154H, R211Q and Q222K are associated with scrapie (5,(9)(10)(11). In addition, the M132L SNP of the PRNP gene in elk plays a pivotal role in the conversion of PrP Sc in CWD (12)(13)(14). Conversely, representative prion disease-resistant animals, including dogs and horses have specific amino acids related to resistance in the conversion of PrP C to PrP Sc .…”