A phenomenal human infectious disease prevention mechanism through animal genotyping
Makaleler > Tam Makale · 2020
Yazarlar: E. Teferedegn, Y. Yaman, Cemal ÜN
International Journal of Infectious Diseases, SCI Expanded İndekslerine Giren Dergi, Uluslararası, Wos, 2020, cilt 101, ss 536-537
DOI: 10.1016/j.ijid.2020.09.1391
Özet
Background: Prion disease is a lethal infectious neurodegenerative disease. This non-curable disease of animals and humans is caused by the misfolding of prion protein which can potentially integrate into the food chain. To date, amino acid variants were defined in relation to prion disease. Some of the variants were described as protective against prion infection, replication, and propagation. The present study aimed to identify variations in the PRNP protein-coding gene of sheep that are critical in cellular prion conversion to infections form in animals and extrapolate the importance of the variants in human prion disease infection prevention. Methods & Materials: Genomic DNA was isolated from the EDTA treated blood using a commercial kit (Geneaid).PCR was carried out to amplify the coding region of the PRNP After incubation with 1 U Exo-SAP, a chain termination reaction was performed with BigDye™ Terminator v3.1 Cycle Sequencing Kit (Thermo Fisher Scientific Inc., USA). At the final stage, all samples were purified by ethanol precipitation method and sequenced by Applied Biosystems 3500 genetic analyzer (Thermo Fisher Scientific Inc, USA) Results: In this study, novel variants H99Q (Heterozygous), H99L (Heterozygous), N103N, A116E (Heterozygous), and A116T (Heterozygous), were identified in the sheep population. H99X and N103N variants were detected closer to the first cleavage site of the prion protein. The other variant A116X was observed in the hydrophobic palindrome region. The highly polymorphic variant G127X was also spotted in the highly conserved Glycine repeat region. These motifs are described as critical regions especially in the PrPc to PrPSc conversion, replication, and propagation. These polymorphic regions are also well conserved in humans. Conclusion: Novel variations detected in the critical regions of prion protein may have a significant effect on prion susceptibility in humans as well. Thus, controlling human prion disease infection shall be integrated with the production of prion disease-resistant animals.