Novel polymorphisms and genetic studies of the shadow of prion protein gene () in pheasants.

Abstract

BACKGROUND: Prion diseases in mammals are caused by the structural conversion of the natural prion protein (PrP) to a pathogenic isoform, the "scrapie form of prion protein (PrP)." Several studies reported that the shadow of prion protein (Sho), encoded by the shadow of prion protein gene (), is involved in prion disease development by accelerating the conformational conversion of PrPto PrP. Until now, genetic polymorphisms of thegene and the protein structure of Sho related to fragility to prion disease have not been investigated in pheasants, which are a species of poultry. METHODS: Here, we identified thegene sequence by polymerase chain reaction (PCR) and compared thegene 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 thegene in pheasants and analyzed genotype, allele, and haplotype frequencies, as well as linkage disequilibrium among the genetic polymorphisms. Furthermore, we usedprograms, 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. RESULTS: In the present study, we reported pheasantgene 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. CONCLUSION: To the best of our knowledge, this is the first report of the genetic and structural features of the pheasantgene.