[Jacob-list] Primitive breeds, genotype, scrapie

[Jacobflock at aol.com]

Fred Horak here.  I am not sure this is as simple as it seems on the surface. 
 I assume that the posting "that two Jacob rams tested RR at codon 171" is 
actually ARR/ARR; the number of alleles is known and both Jacobs and Tunis 
(ARQ/ARQ) have the same number of alleles for the comparison.

Natural scrapie in sheep, based on studies I've read so far, have zeroed in 
on three amino acid codons in the sheep PrP gene (a protein encoding gene) 
that are important.  The codons (a triplet sequence of DNA that identifies 
each of the 20 amino acids) are 136, 154 and 171.  The number of alleles is 
important because they may interact and how they interact is not clearly 
understood.

There are breed differences in the frequency of the PrP alleles and in the 
involved scrapie alleles.  However, in general, studies for some breeds which 
encode two PrP alleles (e.g., Suffolks, Hampshires, and some other breeds 
including the Soay) the coding is normally ARQ and ARR.  Thus a ARQ/ARQ 
Suffolk breeding would be very susceptible to natural scrapie.  On the other 
hand, natural scrapie would not be expected to be found in ARR/ARR sheep.

What the heck is ARR at 136,154, 171?  Maybe this table will help.

Amino acid          Codon           Abbreviation            Allele
136                 valine          V                   VRQ
                    alanine         A                   ARQ,AHQ,ARR
154                 arginine            R                   ARR
                    histidine       H                   AHQ
171                 arginine            R                   ARR
                    glutamine       Q                   VRQ,ARQ,AHQ

Thus at codon 171, an ARR sequence is Alanine/Arginine/Arginine.  
There are other "complex breeds" which have complex PrP genetics: Swaledale 
and Shetlands, for example, have 4 PrP gene alleles: VRQ, ARQ, ARR, AHQ.  In 
this case the VRQs seem to be extremely susceptible.  Texels are thought to 
have 5 PrP gene alleles and thus even more complicated.

If resistance to natural scrapie were bred solely on genotype an absolute 
disaster could occur:  a Suffolk ARQ/ARQ is a scrapie high risk; a Swaledale 
ARQ/ARQ is "resistant".  That is, selecting on an allele without regard to 
the number of alleles and genotype susceptibility, could be chaos.  Studies 
(?) suggest that ARR/ARR at codon 171 is thought to be "resistant" to scrapie 
and BSE for most genotypes.  There are also strains of prion diseases and I 
don't know if "resistance" means resistance to all strains.

Scrapie is usually a post-mortem finding.  Catherine O'Rourke and the people 
at Washington State have been working on a third eye-lid test which may 
indicate the presence  of the prion protein disease that casuses natural 
scrapie.  There are many prion diseases (natural scrapie being one): BSE 
(bovine spongiform/mad cow), CWD (chronic wasting) and even humans 
(Creutzfeld-Jacob) for a few "commonly known" ones.  There are strains of 
scrapie and scrapie can be evidenced at various ages.  

Scrapie "resistance" has been based on the conclusion that no scrapie was 
identified during the normal life of the sheep/flock.  But "resistance" has 
not been tested for possible latent scrapie.  I think that some "resistance" 
is being tested by infecting disease "resistant" breeds to see if it is truly 
resistant or a latent carrier.

How many PrP alleles does a Jacob have and is there a level of confidence 
that is associated with that number?  Suppose that 100 Jacobs were tested; 
say they had just two PrP alleles and they all tested as ARR+ARR.  Would that 
be a test of scrapie resistance?  ... or ... reistance to a "strain" of 
scrapie by a "line" of Jacobs?

Fred Horak