1d. Breeding a scrapie resistant international sheep flock
Submitting InstitutionsUniversity of Edinburgh,
Unit of AssessmentAgriculture, Veterinary and Food Science
Summary Impact TypeTechnological
Research Subject Area(s)
Agricultural and Veterinary Sciences: Animal Production, Veterinary Sciences
Medical and Health Sciences: Medical Microbiology
Summary of the impact
Impact: Economic, public policy and animal health and welfare:
Selective breeding based upon identification of PRNP genotypes can
eliminate animals that are susceptible to scrapie from the flock.
Significance: UK sheep meat exports are worth >£380million.
Breeding for scrapie resistance protected the sheep industry from similar
damage to that inflicted by BSE on cattle and the UK economy.
Beneficiaries: Farmers, animals, consumers
Attribution: Professor Hunter and Dr. Goldmann (Roslin Institute,
now part of UoE) identified polymorphisms of the PrP (PRNP) gene
linked to scrapie susceptibility and resistance in sheep.
Reach: International, programmes breeding for resistance to
scrapie in sheep are now used in the UK, Europe and USA.
Scrapie is a transmissible spongiform encephalopathy (TSE) of sheep and
goats. It is a disease of considerable economic consequence to the small
ruminant farming industry. Within the EU, scrapie is a notifiable disease
named in Annex B group II; affected farms will face severe trading
restrictions and may lose a significant number of animals. Scrapie is also
a listed disease in the OIE Terrestrial Animal Health Code (2008) and as
such affects wider international trade.
Following the bovine transmissible spongiform encephalopathy (BSE)
epidemic, concerns arose that a zoonotic BSE epidemic in sheep or goats
could be misdiagnosed for scrapie, this was indeed later shown to have
happened in a UK goat in the 1990s. Consequently, at the EU level, scrapie
control became a priority in both species.
Selection of sheep for scrapie resistance became a possibility after the
pioneering work by Hunter (Group Leader, Roslin Institute and UoE,
employed 1986-onwards) demonstrated strong association between prion
protein (PrP) genotype (PRNP) and scrapie susceptibility (research
from 1993 onwards). Considerable additional work with Goldmann (Group
Leader, Roslin Institute and UoE employed 1989-onwards) extended the
linkage information [3.1-3.3]. Epidemiological studies consolidated this
association for natural scrapie outbreaks [3.4].
Hunter/Goldmann demonstrated that sheep with PRNP genotype
VRQ/VRQ are highly susceptible to classical scrapie, whereas ARR/ARR
animals are resistant [3.1-3.3].
Based on the success in the reduction of sheep scrapie following the
implementation of the various sheep breeding strategies [3.5], EU and UK
research effort in ruminant TSEs since 2006 has focused on goat scrapie
genetics. This has led recently to the discovery of new resistant goat PRNP
alleles (e.g. IRK), which are currently tested in collaboration with the
goat industry for their potential in breeding programs on commercial
farms. This EU (UK) goat scrapie genetics research has been coordinated by
References to the research
3.1. Goldmann W, Hunter N, Smith G, Foster J and Hope J. (1994) PrP
genotype and agent effects in scrapie: change in allelic interaction with
different isolates of agent in sheep, a natural host of scrapie. Journal
of General Virology, 75: 989-99. http://dx.doi.org/10.1099/0022-1317-75-5-989
3.2. Hunter N, Foster JD, Goldmann W, Stear M, Hope J and Bostock C.
(1996) Natural scrapie in a closed flock of Cheviot sheep occurs only in
specific PrP genotypes. Archives of Virology 141: 809-824. http://dx.doi.org/10.1007/BF01718157
3.4. Woolhouse, MEJ; Stringer, SM; Matthews, L; Hunter, N; Anderson, RM
(1998) Epidemiology and control of scrapie within a sheep flock. In:
Proceedings of the Royal Society B-Biological Sciences, Vol. 265, No.
1402, p. 1205-1210. http://dx.doi.org/10.1098/rspb.1998.0421
3.6. Goldmann, W.,Ryan K, Stewart P, Parnham D, Xecohtencatl R, Fernandez
N, Saunders G, Windl O, Gonzalez L, Bossers A, Foster J (2011) Caprine
prion gene polymorphisms are associated with decreased scrapie
susceptibility in goat herds in the United Kingdom. Vet Res 42, 110. http://dx.doi.org/10.1186/1297-9716-42-110
Details of the impact
The research results were communicated to the sheep industry directly by
visits to agricultural shows (e.g. Royal Show, Highland Show, over several
years) with information on posters, or on stands and by giving talks to
breeders' and veterinarians groups, for example at ADAS, Redesdale,
Northumberland and at AVTRW meetings.
Impact on Policy
The findings led directly to the implementation of the National Scrapie
Plan (NSP) [5.2], which ran in the UK from 2001 to 2009 and, following the
European Commission Decision 2003/100/EC, to similar programmes throughout
the EU. These strategies were implemented with the twin aims of
controlling classical scrapie, and protecting the consumer from the
exposure to BSE via sheep meat, should the national flock have become
infected. The genotyping components of these programmes imposed breeding
strategies upon entire sheep industries, such that breeding flocks were
required to select against susceptible PRNP alleles (i.e. VRQ) in
favour of resistant alleles (e.g. ARR) [5.2].
The National Scrapie Plan, funded by the UK government, provided free
genotyping of 1.8 million sheep in 11,000 flocks in an effort to control
all TSEs, including BSE, in sheep. As a result of EU policy, sheep
breeders both within and outside the EU require (Directive 91/68/EEC)
[5.3] genotyping and health certificates in order to trade their sheep
(OIE Terrestrial Animal Health Code, 2008) [5.4]. Scrapie continues to be
a notifiable disease in the EU, trade in affected animals or animals
coming from a flock known to have the disease in the last two years is
prohibited, and genotyping for resistance remains the best means for
Selection for TSE resistance by PRNP genotyping has reduced the
reported incidence of scrapie in sheep as a result of profound impact on
the genetic structure of the entire UK sheep industry: between 2002 and
2006 the frequency of the susceptible VRQ allele decreased in ram lambs by
60% and the frequency of the ARR allele rose by 37% and as a direct
result, the reported prevalence of sheep with scrapie has also decreased
from 0.22% in 2003 to 0.04% in 2008 [5.5]. Voluntary PRNP
genotyping continues, through the industry-funded Scrapie Monitoring
Scheme (since January 2009), which issues certificates of sheep genotype
for trading purposes.
Impact on the Economy
UK sheep meat exports are worth >£380million (2011 figures) [5.5].
Breeding for resistance to scrapie and BSE, and the fact that it was being
carried out, undoubtedly protected the sheep industry from similar damage
to that inflicted by BSE on cattle and the UK economy. WHO estimates US$6
billion losses to the UK and in addition, EU paid out 4.7 billion euros in
control measures for cattle BSE.
In June 2013, the USDA followed the example of UK and the EU and
implemented a Scrapie Free Flock Certification Program [5.6].
Impact on Animal Welfare
Sheep welfare has been improved by selection against PRNP
genotypes linked to susceptibility to scrapie and subsequent reduction in
incidence of disease. There is under-reporting of scrapie but
nevertheless, Defra statistics [5.5] indicate over 200 scrapie sheep were
reported to them in 2002, and three in 2011.
Our work that established the genetic basis of scrapie resistance has
ensured continuous maintenance of the UK (and international) sheep flocks
in the face of potential disease outbreaks [5.5]. The expertise developed
has continued to attract translational research funding from Defra and UE
sources focussed specifically on modes of transmission of the disease.
PRNP gene based selection for eradication of TSEs and for the creation of
resistant populations is now an accepted approach for control of all TSEs
in livestock [3.5]. The EU regulations which were based on
Hunter's/Goldmann's research now impact worldwide and have led to many
genetic surveys of sheep and goat populations to assess their potential
for resistance breeding.
Sources to corroborate the impact
5.1 Dawson, M, Moore, R.C., Bishop, S.C. (2008). Progress and limits of
PrP gene selection policy. Veterinary Research 39, 25. http://dx.doi.org/10.1051/vetres:2007064
5.2 Defra ARCHIVE: BSE: Other TSEs — National Scrapie Plan for Great
5.3 Council Directive 91/68/EEC of 28 January 1991 on animal health
conditions governing intra-Community trade in ovine and caprine animals http://tinyurl.com/oahcnzs
5.4 The OIE Terrestrial Animal Health Code (Terrestrial Code) sets out
standards for the improvement of terrestrial animal health and welfare and
veterinary public health worldwide, including through standards for safe
international trade in terrestrial animals (mammals, birds and bees) and
their products: http://tinyurl.com/pa732qr
5.5 TSE statistics — Animal Health and Veterinary Laboratories Agency http://tinyurl.com/qexvthf
5.6 The USDA Scrapie information website: http://tinyurl.com/oudeuab
5.7 Many sheep breeders' web sites list scrapie resistance genotypes
routinely as sought-after features for rams in sales documents. Below are
some examples of sources of corroboration.
National Sheep Association (www.nationalsheep.org.uk)
Swaledale Sheep Association (http://www.swaledale-sheep.com)
Suffolk Sheep Association (http://suffolksheep.org)
Shetland Sheep Society (http://Shetland-sheep.org.uk)
Shetland sheep breeders in France (http://Shetlandsheepinfrance.com)
Shropshire Sheep Association (http://www.shropshire-sheep.co.uk)
Hampshire Down Sheep Breeders Association (http://hampshiredown.org.uk)