The Case for Exempting Primitive Sheep from the National Scrapie Plan


June Morris


Will scrapie genotype selection lead to loss of our pure ancient breeds of sheep?

A consultation document for a National Scrapie Plan for Great Britain has been issued by the Ministry of Agriculture, Fisheries and Food. Replies are required by October 31st 2000. Below are some arguments against implementation of scrapie genotyping for sheep breeds belonging to the Northern Short-tail group.

Three main concerns are:

1. These are unique ancient breeds where selection for a particular expression of any character would risk the loss of a unique genetic resource.

2. These are breeds where there appears to be a complete lack of the 'resistant Codon 136 154 171 genotype' AA RR RR, or it may occur infrequently in the population.

3. There is to date incomplete information about the role of the prion protein. There is, however, sufficient indication that it may have an important role in, for example, resistance to oxidative stress and possibly copper homeostasis. It may be significant when considering the Northern short-tail group of sheep that the gene coding for the prion protein is found on chromosome 13, the same chromosome on which the Agouti gene, affecting the colour of the sheep is located. The Northern short-tails are coloured sheep breeds.

Each of these points is addressed in more detail below.

1. Unique ancient breeds

In Britain we are fortunate to have the remnants of two ancient breeds of sheep.

i. The SOAY on islands in the St Kilda archipelago off the west coast of Scotland.

ii. The NORTH RONALDSDAY on the most northerly island of that name in Orkney.

I am not aware of any scrapie in either of these indigenous island sheep populations. Each of these breeds is kept in smaller numbers in flocks on mainland Britain. Archaeological settlements from 5000 years ago had skeletons of this type of sheep. Other ancient members of the Northern short-tail group of sheep include the Icelandic, Norwegian and the French Ouessant sheep. Icelandic and Ouessant sheep are also kept in Britain.

These ancient breeds remain because of minimal selection by man and it is generally agreed that selection for a particular expression, morphological, physiological or biochemical, would be inappropriate. Furthermore, there are many examples where selection for one character often has an unexpected effect on other, apparently unrelated, characters.

2. Lack of scrapie-resistant genotype in these breeds.

Codon 136 154 171 Codon 136 154 171

AA RR QQ rather than the 'desirable' AA RR RR, appears to be the prion protein genotype characteristic of many Northern short-tail breeds. Thus Thorgeirsdottir et al 1999 found that in 932 Icelandic sheep no polymorphism occurred at Codon 171, only the glutamine allele (Q) was found.

These authors mention that the prion protein ARQ background seems to be the ancestral genotype in sheep. Where we are fortunate enough to have ancient breeds, it is therefore very important to maintain this ancestral genotype.

A similar situation is seen in the Soay sheep. Hunter et al 1997 found that 92% of the 26 sheep genotyped were homozygous for ARQ. One animal was heterozygous for ARQ and only 1 Soay sheep had the AA RR RR 'resistant genotype'.

Although not published, North Ronaldsay sheep also appear to be characteristically AA RR QQ.

One could perhaps argue that if the homozygous ARQ is the ancestral sheep genotype, and therefore characteristic of the remaining ancient sheep breeds, that any deviation from this may represent inadvertent crossing with other breeds.

3. Normal role of the prion protein.

The link made by Brown et al 1997 between normal prion protein and resistance to oxidative stress has many implications for the ability of an animal to withstand disease. Free radical production is implicated with disease, stress conditions, some plant toxins, and pesticides. The ability of an animal to deal with these free radicals, using enzymes such as superoxide dismutase and glutathione peroxidase, is very important. Brown et al 1997, in studies on isolated cells, have linked levels of both these antioxidant enzymes to normal prion protein content. Brown et al also suggest that prion protein expression is associated with regulation of resistance to oxidative stress in skeletal muscle. This raises the question as to whether, by selecting for particular prion protein genotypes, we may be inadvertently altering the animal's ability to cope with disease, stress, even some toxic plants and the wide range of agrochemicals used.

Prion protein and copper.

It is of particular interest when considering North Ronaldsay sheep that a number of publications have linked copper with prion protein. The prion protein has in fact been found to bind copper. North Ronaldsay sheep are the most copper sensitive sheep. Their ability to accumulate copper has been related to their unique diet of almost completely seaweed on their native island. Seaweed contains a number of substances, which reduced the bioavailability of copper. Wadsworth et al 1999 demonstrated that copper could affect the prion protein conformation and two human types of the prion protein found in subtypes of Creutzfeldt-Jacob disease could be interconverted by binding of copper or zinc. The authors even raise the possibility that drugs which have an effect on copper metabolism may be of therapeutic value in prion disease. Waggoner et al 1999 suggest a role for the prion protein in regulating copper homeostasis at the membrane level.

To summarise: we have important ancient coloured breeds of sheep in Britain with the ancestral prion genotype at codons 136, 154, 171 of AA RR QQ. Pure bred animals with the 'scrapie resistant' genotype AA RR RR may not exist, and in terms of the continued existence of these ancient breeds it would be inappropriate to attempt any selection on this basis. These ancient breeds, unlike many highly selected modern sheep breeds, have the ability to survive outdoor conditions with minimal care by man. They are also 'gene banks' with a genetic diversity exceeding modern breeds. Indeed the suggestion of a role for prion protein in dealing with oxidative stress may be an integral part of their survival. I ask, therefore, that these ancient breeds of sheep, belonging to the Northern short-tail group, should be considered separately and should not, like many breeds in the past, become an irreversible casualty of man's selection.                                                                 

ŠJune Morris Ph.D. (September 2000)



Brown, D.R., Schmidt, B., Groschup M. H., Kretzschmar, H.A. 1998. Prion - protein expression in muscle cells and toxicity of a prion protein fragment. European Journal of Cell Biology, 75, 29-37.

Brown D. R., Schmidt, B., Kretzschmar H.A. 1997, Effects of oxidative stress on prion protein expression in PC12 cells, International Journal of Developmental Neuroscience. 15,8, 961-972.

Hunter, N., Goldmann W., Foster J.D., Cairns, D., Smith, G. 1997. Natural Scrapie and PrP genotype: case-control studies in British sheep. Veterinary Record, 141, 137-140

Thorgeirsdottir, S., Sigurdarson, S., Thorisson, H.M., Georgsson, G, Palsdottir, A. 1999. PrP gene polymorphism and natural scrapie in Icelandic sheep. Journal of General Virology, 80, 2527-2534.

Wadsworth J.D.F., Hill A.F., Joiner S., Jackson G.S., Clarke A.R. Collinge J., 1999. Strain-specific prion-protein conformation determined by metal ions. Nature Cell Biology 1, 55-59

Waggoner D.J., Bartnikas T.B., Gitlin D, 1999. The Role of Copper in Neurodegenerative Disease. Neurobiology of Disease 6, 221-230.

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