Fig. 2. Mutations of the PrP gene are associated with prion diseases. The top rectangle represents the coding region of the human PrP gene; the hatched green areas indicate the amino- and carboxyl-terminal signal sequences, and the five dark green boxes (R) are the "octa repeats," sequences of 8 amino acids. The red arrows indicate amino acid replacements in individual mutant PrP genes. The diseases associated with these mutations are given in blue (CJD, GSS, FFI). The Met-129 to Val replacement represents a polymorphism, which in itself is not associated with disease; however, it modifies the effects of the Asp-178 to Asn mutation, such that when the latter is combined with Met-129 it is associated with FFI and when combined with Val-129 it is associated with CJD. Amplification of the number of octa repeats has been found in cases of familial CJD and GSS.
From: C. Weissmann (1999) Molecular genetics of transmissible spongiform encephalopathies. J. Biol. Chem. 274: 3-6 (html)(pdf)