1d. Breeding a scrapie resistant international sheep flock
Submitting Institutions
University of Edinburgh,
SRUCUnit of Assessment
Agriculture, Veterinary and Food ScienceSummary Impact Type
TechnologicalResearch 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.
    Underpinning research
    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
      Goldmann [3.6].
    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
      disease control.
    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
      Britain
      http://tinyurl.com/ovrsjob
    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)