한빛사 논문
In-Soon Roh1, Yong-Chan Kim2,3, Sae-Young Won2,3, Min-Ju Jeong2,3, Kyung-Je Park1, Hoo-Chang Park1, Yu-Ran Lee1, Hae-Eun Kang1, Hyun-Joo Sohn1, Byung-Hoon Jeong2,3
1Reference Laboratory for Chronic Wasting Disease(CWD), Foreign Animal Disease Division, Animal and Plant Quarantine Agency, Gimcheon, Republic of Korea
2Korea Zoonosis Research Institute, Jeonbuk National University, Iksan, Republic of Korea
3Department of Bioactive Material Sciences and Institute for Molecular Biology and Genetics, Jeonbuk National University, Jeonju, Republic of Korea
Correspondence Byung-HoonJeong, Hyun-JooSohn
In-Soon Roh and Yong-Chan Kim have contributed equally to this work.
Abstract
Prion diseases are incurable neurodegenerative disorders caused by proteinase K-resistant prion protein (PrPSc) derived from normal prion protein (PrPC) encoded by the prion protein gene (PRNP). Although the cervid PRNP gene plays a pivotal role in the pathological mechanism of chronic wasting disease (CWD), there is no existing association analysis between susceptibility to CWD and genetic polymorphisms of the PRNP gene in sika deer. We investigated genetic polymorphisms of the PRNP gene using amplicon sequencing in sika deer. In addition, to identify a genetic susceptibility factor, we compared the genotype, allele and haplotype frequencies of the PRNP gene between CWD-positive and CWD-negative sika deer. Furthermore, to assess the effect of the genetic polymorphisms on sika deer prion protein (PrP), we performed in silico analysis using PolyPhen-2, PROVEAN and AMYCO. Finally, we analysed the tertiary structure and electrostatic potential of sika deer PrP based on single nucleotide polymorphisms (SNPs) using the SWISS-MODEL and Swiss-PdbViewer programs. We found a total of 24 SNPs of the PRNP gene, including 22 novel SNPs (10 synonymous SNPs and 12 nonsynonymous SNPs), in sika deer. Among the nonsynonymous SNPs, we found a strong association of susceptibility to CWD with c.56G > A (Ser19Asn). In addition, we found that c.56G > A (Ser19Asn), c.296A > T (His99Leu) and c.560T > A (Val187Asp) were predicted to have damaging effects on sika deer PrP. Furthermore, we observed significant alterations in the electrostatic potential of sika deer PrP by genetic polymorphisms of the 187Asp allele. To the best of our knowledge, this was the first association study between genetic polymorphisms of the PRNP gene and susceptibility to CWD in sika deer.
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