Abstract
Prion diseases, including ovine scrapie, bovine spongiform encephalopathy (BSE), human kuru and Creutzfeldt–Jakob disease (CJD), originate from a conformational change of the normal cellular prion protein (PrPC) into abnormal protease-resistant prion protein (PrPSc). There is concern regarding these prion diseases because of the possibility of their zoonotic infections across species. Mutations and polymorphisms of prion sequences may influence prion-disease susceptibility through the modified expression and conformation of proteins. Rapid determination of susceptibility based on prion-sequence polymorphism information without complex structural and molecular biological analyses may be possible. Information regarding the effects of mutations and polymorphisms on prion-disease susceptibility was collected based on previous studies to classify the susceptibilities of sequences, whereas the BLOSUM62 scoring matrix and the position-specific scoring matrix were utilised to determine the distance of target sequences. The k-nearest neighbour analysis was validated with cross-validation methods. The results indicated that the number of polymorphisms did not influence prion-disease susceptibility, and three and four k-objects showed the best accuracy in identifying the susceptible group. Although sequences with negative polymorphisms showed relatively high accuracy for determination, polymorphisms may still not be an appropriate factor for estimating variation in susceptibility. Discriminant analysis of prion sequences with scoring matrices was attempted as a possible means of determining susceptibility to prion diseases. Further research is required to improve the utility of this method.
Highlights
Transmissible spongiform encephalopathy (TSE) is a mammalian prion disease associated with neurodegenerative disorders including ovine scrapie, bovine spongiform encephalopathy (BSE), cervine chronic wasting disease, feline spongiform encephalopathy, mink transmissible mink encephalopathy, human kuru, Gerstmann–Straussler–Scheinker syndrome, Creutzfeldt–Jakob disease (CJD) and fatal familial insomnia.[1]
Mutant sequences were generated according to previous studies on amino-acid substitutions that affect prion-disease susceptibility and were used to construct a test data set for the discriminant analysis
We evaluated the genetic risk for prion disease based on individual polymorphisms in the Prion protein (PrP) sequence
Summary
Transmissible spongiform encephalopathy (TSE) is a mammalian prion disease associated with neurodegenerative disorders including ovine scrapie, bovine spongiform encephalopathy (BSE), cervine chronic wasting disease, feline spongiform encephalopathy, mink transmissible mink encephalopathy, human kuru, Gerstmann–Straussler–Scheinker syndrome, Creutzfeldt–Jakob disease (CJD) and fatal familial insomnia.[1]. Prion disease is caused by the accumulation of proteaseresistant prion protein (PrPSc), which is derived from conformational conversion of normal cellular PrP (PrPC). Has neuropathological features involving the formation of amyloid plaques that develop spongiform brain tissue.[4] The structure of PrPSc contains a high proportion of b-sheets because of conformational conversion of PrPC, which is composed mainly of a-helical structures.[5] Prion protein (PrP) is encoded by the PrP gene (PRNP) and is strongly conserved among mammals.[6]. PrPC is a protein of 210 amino acids in length that resides mainly on the surface of the Correspondence: Professor HS Son, Laboratory of Computational Biology and Bioinformatics, Graduate School of Public Health, Seoul National University, 1
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
