AUTHOR=Choi Da-In , Zayed Mohammed , Kim Yong-Chan , Jeong Byung-Hoon 

TITLE=Novel polymorphisms and genetic studies of the shadow of prion protein gene (SPRN) in pheasants

JOURNAL=Frontiers in Veterinary Science

VOLUME=11

YEAR=2024

URL=https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2024.1399548

DOI=10.3389/fvets.2024.1399548

ISSN=2297-1769

ABSTRACT=<sec id="sec1"><title>Background</title><p>Prion diseases in mammals are caused by the structural conversion of the natural prion protein (PrP<sup>C</sup>) to a pathogenic isoform, the “scrapie form of prion protein (PrP<sup>Sc</sup>).” Several studies reported that the shadow of prion protein (Sho), encoded by the shadow of prion protein gene (<italic>SPRN</italic>), is involved in prion disease development by accelerating the conformational conversion of PrP<sup>C</sup> to PrP<sup>Sc</sup>. Until now, genetic polymorphisms of the <italic>SPRN</italic> gene and the protein structure of Sho related to fragility to prion disease have not been investigated in pheasants, which are a species of poultry.</p></sec><sec id="sec2"><title>Methods</title><p>Here, we identified the <italic>SPRN</italic> gene sequence by polymerase chain reaction (PCR) and compared the <italic>SPRN</italic> gene and Sho protein sequences among various prion disease-susceptible and -resistant species to identify the distinctive genetic features of pheasant Sho using Clustal Omega. In addition, we investigated genetic polymorphisms of the <italic>SPRN</italic> gene in pheasants and analyzed genotype, allele, and haplotype frequencies, as well as linkage disequilibrium among the genetic polymorphisms. Furthermore, we used <italic>in silico</italic> programs, namely Mutpred2, MUpro and AMYCO, to investigate the effect of non-synonymous single nucleotide polymorphisms (SNPs). Finally, the predicted secondary and tertiary structures of Sho proteins from various species were analyzed by Alphafold2.</p></sec><sec id="sec3"><title>Results</title><p>In the present study, we reported pheasant <italic>SPRN</italic> gene sequences for the first time and identified a total of 14 novel SNPs, including 7 non-synonymous and 4 synonymous SNPs. In addition, the pheasant Sho protein sequence showed 100% identity with the chicken Sho protein sequence. Furthermore, amino acid substitutions were predicted to affect the hydrogen bond distribution in the 3D structure of the pheasant Sho protein.</p></sec><sec id="sec4"><title>Conclusion</title><p>To the best of our knowledge, this is the first report of the genetic and structural features of the pheasant <italic>SPRN</italic> gene.</p></sec>