Shetland Sheep 2000 Conference

 


Sandy Clark (in the middle)

This article is based on the full talk held by Dr. Sandy Clark during the Shetland Sheep 2000 Conference in Lerwick late september 2000.

Sheep-Isle want to express its gratitude to Dr. Sandy Clark and the Organizers of te Shetland Sheep Conference for the permission to bring this article.

The Shetland breed, which belongs to the Nordic group of short-tailed sheep will later be portrayed by other speakers who took part in the Conference.

Sandy Clarke is Manager and Senior Veterinary Investigation Officer at the Scottish Agricultural Colleges (SAC) Laboratory at Thurso, and has played a leading role in providing diagnostic services and policy guidance in the various animal health schemes in Shetland.

 

SCRAPIE IN SHETLAND SHEEP AND THE CONTROL AND ERADICATION PROGRAMME

 Dr Sandy Clark, SAC Veterinary Science Division, Janetstown, Thurso, Caithness.

Scrapie has been present in Shetland flocks for at least 400 years probably since the time of the Spanish Armada. The intensification of the Shetland sheep industry in the latter half of the twentieth century caused the disease to spread between sheep especially when housed or kept in-bye for lambing the danger period being when sheep produce lambs and have clinical scrapie. It is at this point that the agent is most likely to be transmitted although it is suspected that there is spread through respiration and faeces when an animal has the disease.

 The control schemes in Shetland are described in another paper and it was the introduction of a blood test in 1992 to identify scrapie resistant and susceptible 

 Shetland. The scheme in Shetland has previously relied on the identification of disease and culling of the progeny of affected sheep. Accurate record keeping has benefitted many flockmasters in determining the offspring and selection of future breeding stock. The tests available now permit all flock owners to ensure that tups cannot pass on scrapie susceptibility to their offspring.

 

At present the implications for ensuring that flocks are scrapie resistant and ultimately disease free are only too obvious since public confidence in the end product is of paramount concern.  Any control programme for scrapie will encourage consumer confidence and export of sheep meat to countries outside Great Britain.

 The Disease

 Scrapie is a progressive, degenerative, wasting disease of sheep and seems to affect all breeds although some more than others.  Animals with the disease commonly lose weight and may have abnormal walking movements, changed personalities and occasionally scratch more often than normal.  Some sheep have a nibbling reflex elicited by rubbing the back of the animal and others grind their teeth more than usual.  It ultimately ends with death or humane destruction of the animal concerned.  The average age of cases is three years and the disease is seen most often at times of stress.

 The Genetics

 It is accepted that a genetic factor is involved in the control of the transmission of scrapie from sheep to sheep.  The infectious agent responsible has been partly identified, but it is known that certain families of sheep develop the disease, whereas others do not.  The offspring of a sheep which succumbed to scrapie are highly likely to develop the disease.

If a tup develops scrapie, it is likely that many of his offspring will be present in a flock and since his genetic status will have been passed on, many of these offspring will develop the disease.

 Research workers have recognised for many years that susceptibility to scrapie is genetically controlled.  The infection has occurred in related lines of sheep and some control has followed the removal of descendants of affected ewes from the flock.  Recent advances in molecular biology have enabled researchers to identify the specific gene associated with susceptibility to scrapie.  This gene is called the PrP gene because it encodes for prion protein, the protein which in a deranged or distorted form appears to be associated with the development of scrapie disease.

 Sheep genes, like those of all vertebrates, have two DNA strands, one inherited from the ram and one from the ewe.  These DNA strands are then passed on to the next generation.  Genes are composed of chains of nucleic acids which hold the genetic code for the production of amino acids, the building blocks of proteins.  The nucleic acid sequences are called codons and each chain of codons in the gene is called an allele.  Alleles of the sheep PrP gene are composed of a chain of 256 codons.  At least five alleles of the sheep PrP gene have been identified.  They show variations at codons (positions) 136, 154 and 171.  The five alleles are:-

 A136 R154 Q171 (ARQ) found in all sheep breeds

A136 R154 R171 (ARR) found in most breeds

V136 R154 Q171 (VRQ) found in many breeds but rare in some (e.g. Suffolks)

A136 H154 Q171 (AHQ) found in many breeds but not the Charollais or Bleu de Maine

A136 R154 H171 (ARH) not found in most breeds but common in Texel

 A = alanine, V = valine, R = arginine, H = histidine and Q = glutamine (the amino acids).

 Pairing of the parental alleles can generate a wide variety of genotypes e.g. AV136RR154 RQ171 (ARR/VRQ), AA136RR154QQ171 (ARQ/ARQ) etc.

 Over the past five years researchers throughout the world have investigated the links between certain PrP genotypes and scrapie susceptibility or resistance in many different breeds of sheep and their crosses.  To date, the results have shown that:-

            over of 95% of scrapie cases occur in the QQ171 genotype, the remainder were QR171 or QH171.  But not all QQ171 sheep develop scrapie.

            no cases of scrapie, with the exception of a single Japanese Suffolk, have yet been found in sheep carrying the AA136RR154RR171 (ARR/ARR) genotype.

            scrapie is most commonly found in sheep with the genotypes VV136RR154QQ171 (VRQ/VRQ) and AV136RR154QQ171 (ARQ/ARQ): this is particularly the case in breeds such as the Shetland, Swaledale, Cheviot, Welsh Mountain and Herdwick.

            In Suffolk sheep, most cases are linked to the AA136RR154QQ171 (ARQ/ARQ) genotype: this genotype is found in rare cases of scrapie in Swaledales.

            The AHQ allele has been rarely found in scrapie cases, and then only associated with the ARQ allele.

From this data, it can be seen that the VRQ allele is linked to scrapie in many breeds, whereas in the Suffolk, and to a minor extent in some other breeds, the linkage is to the ARQ allele.  R at codon 171 is dominant and is linked to scrapie resistance.  The links between the VRQ and ARQ alleles to scrapie depend on breed, and perhaps also to the strain of scrapie disease agent.  Resistance to scrapie in all breeds is also linked to the ARR allele.  The AHQ allele is linked to resistance to scrapie in breeds in which the VRQ allele occurs, such as the Cheviot.  The significance of the ARH allele in Texels (and Suffolks) remains unclear; it may be neutral.

 The Test

 A method of determining the genetic status of any single sheep has been developed using samples collected from Shetland sheep in the later nineteen eighties and processed at the Neuropathogenesis Unit in Edinburgh.  From experimental sheep kept at Edinburgh and Thurso veterinary scientists have determined the genetic sequence associated with scrapie disease.  At the same time, the genetic code which prevents the disease developing has been identified and from a blood test it is possible to state the genetic fingerprint for any single animal.  This fingerprint is unique to that animal and never changes during its lifetime.  Moreover, as an animal breeds, it always passes on some of its genetic information to its offspring.

 The Technicalities

It has been found that the presence of certain amino acids on the genetic sequence of any sheep can be associated with susceptibility or resistance to scrapie.  At one level or codon (the site being 136) VALINE is dominant for scrapie susceptibility, whereas Alanine confers resistance.  One should not breed from an animal with Valine present at this genetic site.

 At another codon (number 171) ARGININE is dominant for scrapie resistance and suppression of disease development in some codon 136 susceptible sheep.

 A third codon is examined but as yet there have been too few resistant animals to form an opinion on the benefit of using this site at present for control of disease.

 Selecting sheep which are positive for alanine alone at Codon 136 and then looking at Codon 171 for arginine gives the possibility of having resistance at two levels on the genetic sequence.

 The Control Scheme

 The scheme established in Shetland in 1996 should ensure that only tups resistant to scrapie with at least 95% resistance will be used for breeding programmes.  As time progresses more tups with a 99% status or better will be bred and identified by blood test and within a few years the disease should disappear.  Around this time, with few cases of scrapie occurring, many flocks will be scrapie free in respect of the infectious agent.

 The control scheme is operated through the veterinary surgeons and is financially aided by Shetland Island Council who subsidise the cost of testing.  A blood sample is collected from each tup and a unique microchip inserted which will ensure secure identification in the future.  The test need only be carried out once and hence future identification is important. A passport is supplied for each tup.

 A method of recording which ewes are crossed with which tup will help in the future selection of ewes and tups ensuring that a greater degree of resistance is introduced into the breed.  Nevertheless it is important that desirable characteristics are selected for in the animals used for breeding since there is little point in ridding the islands of scrapie and having a sheep which is unsaleable.

 The Advantages

 The presence of a Control Scheme will give public confidence a boost and ultimately ensure the sale and export of sheep from Shetland.  There is increasing pressure from our European neighbours to seek freedom from these spongiform diseases in food animals - scrapie, like BSE,  is one of these diseases.  Shetland is about three years ahead of the rest of Britain at the present moment and as long as there is a concerted effort to use only tested, resistant tups, by the year 2000 there should be little if any scrapie disease seen.

 Results

 The results of genotype tests for Shetland tups show that there is a steady improvement in resistance since 1993 and that there are now some 15% of ARR/ARR tups available. As stated it is important to select tups on the basic characteristics before scrapie resistance to avoid the production of undesirable sheep and it is hoped that there will be a spread of animals with ARQ/ARQ to ARR/ARR produced.

 Conclusions

 The use of scrapie resistant animals, those which have ALANINE at Codon 136, will ensure that the population of sheep in Shetland will eventually not succumb to the disease.  In addition the use of tups which have ARGININE at Codon 171 will aid in the reduction of clinical cases of the disease as well as giving some degree of resistance.  Any reduction in clinical disease is beneficial since it gives the infectious agent less chance to spread.

 The eventual aim is to declare the sheep population of Shetland scrapie free and that meat produced and exported is from a sheep population in which there is no evidence of scrapie.  Both these factors should ensure sales for breeding and finishing sheep in the future to all parts of the British Isles and Europe.

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