All 76 vCJD patients examined (DNA sequence for PrP determined) as of early 2001 are homozygous for M129 (i.e. both genes encode for a Methionine in this position of the protein). Either, M129 is necessary for transmission of BSE to humans or V129 delays the clinical onset of the disease (thus V129 vCJD patients may not have developed symptoms at this time). In either case, it is interesting that both bovine, ovine and even mouse PrP have a M at this position (highlighed M in the figure).
The very high sequence conservation between bovine (cattle) and ovine (sheep) PrPs and the ability of BSE but not Scrapie to infect humans, indicates that the species specificity for disease transmission does not depend completely on the PrP sequence itself.
There are several single amino acid mutations within PrP that can cause TSE in humans. This fact has supported the probability that BSE arose from a PrP mutation in a single cattle in the UK that eventually spread the condition during the now illegal ruminant to ruminant feeding program. Unluckily the founder BSE animal is required to identify the original mutation.
There is an octapeptide insert (PHGGGWGQ) in the bovine sequence shown above. The presence or absence of the octarepeat is the only known specific polymorphism in the sequence of bovine PrP. Its presence or absence is not linked to BSE and only once such insert has been found in bovine PrP. Humans have similar octarepeat inserts, although much more varied. The presence of two or more additional repeats may cause CJD.
click
on image for additional information about genetics and TSE