Polymorphism at human PrP residue 129 places constraints upon the propagation of distinct human PrPSc types and these data provide a molecular basis for this polymorphism acting as a major factor influencing both prion disease susceptibility and phenotype in humans (Collinge 2001, 2005; Mead et al. 2003; Wadsworth & Collinge 2007). This evidence concerns the gene PRNP and prion disease.