Is codon 129 of prion protein polymorphic in human beings but not in animals?

Abstract

In human beings, there is a polymorphism at aminoacid position 129 of the prion protein which influences susceptibility to prion infection. In European populations, the usual distribution pattern is about 50% heterozygosity for methionine/valine (Met/Val), 40% homozygosity for methionine (Met/Met), and 10% for valine (Val/Val). Methionine homozygosity predisposes to sporadic Creutzfeldt Jakob disease (CJD) as well as acquired CJD. 1 Palmer MS Dryden AJ Hughes JT et al. Homozygous prion protein genotype predisposes to sporadic Creutzfeldt-Jacob disease. Nature. 1991; 352: 340-342 Crossref PubMed Scopus (737) Google Scholar In patients with new variant CJD (nvCJD) Met/Met has been invariably found. 2 Will RG Ironside JW Zeidler M et al. A new variant of Creutzfeldt-Jakob disease in the UK. Lancet. 1996; 347: 921-925 Summary PubMed Scopus (1877) Google Scholar Structural models ascribe importance to position 129 in stabilising the conformation of PrP by interaction with other aminoacid residues. Conformational change from α-helical to β-sheet structure is thought to be a primary event in prion diseases. The figure shows the location of the α-helical regions revealed by computer-assisted structure prediction and of structural regions determined by a nuclear magnetic resonance-based model of murine PrP (121–231). 3 Riek R Hornemann S Wider G Billeter M Glockshuber R Wüthrich K NMR structure of the mouse protein domain PrP (121–231). Nature. 1996; 382: 180-182 Crossref PubMed Scopus (1114) Google Scholar