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

In-Soon Roh,Ji-Yong Hwang,Hyun-Joo Sohn,Sae-Young Won,Hae-Eun Kang,Byung-Hoon Jeong,Kyung-Je Park,Hoo-Chang Park,Yong-Chan Kim

doi:10.3389/fvets.2021.804325

Abstract

Chronic wasting disease (CWD) is a deleterious brain proteinopathy caused by a pathogenic form of prion protein (PrPSc), which is converted from a benign form of prion protein (PrPC) encoded by the prion protein gene (PRNP). In elk, the M132L single nucleotide polymorphism (SNP) of the PRNP gene likely plays a pivotal role in susceptibility to CWD. However, the association of the M132L SNP with susceptibility to CWD has not been evaluated in Korean elk to date. To estimate the association of the M132L SNP with susceptibility to CWD in Korean elk, we investigated the genotype and allele frequencies of the M132L SNP by amplicon sequencing and performed association analysis between CWD-positive and CWD-negative elk. In addition, we performed a meta-analysis to evaluate the association between the M132L SNP and susceptibility to CWD in quantitatively synthesized elk populations. Furthermore, we estimated the effect of the M132L SNP on elk PrP using in silico programs, including PolyPhen-2, PROVEAN, AMYCO and Swiss-PdbViewer. We did not identify a significant association between the M132L SNP of PRNP and susceptibility to CWD in Korean elk. The meta-analysis also did not identify a strong association between the M132L SNP of PRNP and susceptibility to CWD in quantitatively synthesized elk populations. Furthermore, we did not observe significant changes in structure, amyloid propensity or electrostatic potential based on the M132L SNP in elk PrP. To the best of our knowledge, this was the first report of an association analysis and meta-analysis in Korean elk and quantitatively synthesized elk populations, respectively.

Highlights

Prion diseases are infectious brain proteinopathies caused by a pathogenic form of prion protein (PrPSc) converted from an endogenous form of prion protein (PrPC) 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; The M132L single nucleotide polymorphism (SNP) in Korean CWD Elk bovine spongiform encephalopathy (BSE) in cattle; and chronic wasting disease (CWD) in the Cervidae family [1,2,3,4,5,6,7]
We investigated the M132L SNP of the elk prion protein gene (PRNP) gene in Korean elk and performed association analysis between CWD-positive and CWD-negative elk for the first time
We did not observe a significant association between the M132L SNP of the PRNP gene and susceptibility to CWD in Korean elk

Summary

Introduction

Prion diseases are infectious brain proteinopathies caused by a pathogenic form of prion protein (PrPSc) converted from an endogenous form of prion protein (PrPC) 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; The M132L SNP in Korean CWD Elk bovine spongiform encephalopathy (BSE) in cattle; and chronic wasting disease (CWD) in the Cervidae family [1,2,3,4,5,6,7]. A previous case-control study reported that the M132L SNP of the PRNP gene is associated with vulnerability to CWD in elk in the USA [13]. CWDinoculated elk PrP transgenic mice with the L132 allele showed resistance to CWD compared to elk PrP transgenic mice with M132 allele [14]. Experimentally CWDinfected elk carrying the 132LL genotype showed extended survival times compared to elk carrying the 132MM and 132ML genotypes [15]. Another case-control study did not report the association between the M132L SNP and susceptibility to CWD in the USA [16]. The effect of the PRNP M132L SNP on the risk of CWD remains controversial

Methods

Results

Discussion

Conclusion