Shetland Sheep 2000 Conference

Sandy
Clark (in the middle)
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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.
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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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