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

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

doi:10.3389/fvets.2021.804325

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

Front Vet Sci. 2022 Jan 14:8:804325. doi: 10.3389/fvets.2021.804325. eCollection 2021.

Authors

In-Soon Roh¹, Yong-Chan Kim^{2

3}, Sae-Young Won^{2

3}, Kyung-Je Park¹, Hoo-Chang Park¹, Ji-Yong Hwang¹, Hae-Eun Kang¹, Hyun-Joo Sohn¹, Byung-Hoon Jeong^{2

3}

Affiliations

¹ Reference Laboratory for Chronic Wasting Disease (CWD), Foreign Animal Disease Division, Animal and Plant Quarantine Agency, Gimcheon, South Korea.
² Korea Zoonosis Research Institute, Jeonbuk National University, Iksan, South Korea.
³ Department of Bioactive Material Sciences and Institute for Molecular Biology and Genetics, Jeonbuk National University, Jeonju, South Korea.

Abstract

Chronic wasting disease (CWD) is a deleterious brain proteinopathy caused by a pathogenic form of prion protein (PrP^Sc), which is converted from a benign form of prion protein (PrP^C) 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.

Keywords: CWD; Elk (Cervus canadensis); M132L; PRNP; SNP; meta-analysis; polymorphism; prion.