Sheep Genetics and Scrapie

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The genetic makeup of sheep has been determined to be a significant factor in their susceptibility to infection with classical scrapie. As a result, sheep genotyping is a disease control measure used in Canada's National Scrapie Eradication Program. Testing for scrapie susceptibility in sheep is performed routinely at the Canadian Food Inspection Agency's (CFIA) National and World Organization for Animal Health (OIE) Reference Laboratory for Scrapie and CWD and at other animal health laboratories in Canada and the United States.

At the present time, studies on goat genetics and scrapie susceptibility are more limited and less clear. As a result, genotyping goats for susceptibility to scrapie infection is not currently implemented as a disease control measure internationally nor a tool used in Canada's National Scrapie Eradication Program.

Scrapie Genotyping in Sheep

A genotype is an individual's collection of genes. Like all animals, sheep receive one allele for each gene from their dam (ewe) and one allele from their sire (ram). Alleles are the different versions of a gene. Scrapie genotyping refers to testing that reveals the specific alleles inherited for the animals' prion gene that makes an animal more or less susceptible to scrapie.

The different alleles inherited for a sheep's prion gene determine which particular amino acids will be included at particular locations of the sheep's prion protein. Current scientific literature indicates that the presence of certain combinations of amino acids at three specific locations (known as codons) on the sheep's prion gene influence a sheep's relative susceptibility to scrapie. In North America codons at positions 136 and 171 are of primary importance in association with classical scrapie. Codon 136 codes for either the amino acid valine (V) or alanine (A). Codon 171 codes for the amino acid glutamine (Q) or arginine (R). One common way to write genotypes for sheep is by the codon number followed by the corresponding amino acid: @136 V for valine or A for alanine, @ 171 R for arginine and Q for glutamine. The possible amino acid combinations at these two locations on the sheep prion gene and their impact on susceptibility to scrapie are listed below:

Susceptibility to classical scrapie based on genotype

Sheep's Genotype (136, 171) Susceptibility to classical scrapie
136AA 171RR Negligible
136AA 171QR Very low
136AV 171QR Intermediate
136AA 171QQ
136AV 171QQ
136VV 171QQ
High

It is important to understand that scrapie genotyping is not disease testing. A 171QQ sheep does not automatically have scrapie, just as it is not an absolute guarantee that a 171RR sheep cannot get scrapie.

  • Scrapie genotyping is a tool used by the CFIA during disease control actions. All mature exposed sheep in a scrapie infected flock are subject to a blood test to determine their susceptibility to scrapie infection. Typically, only the intermediate and highly susceptible sheep are ordered destroyed and this minimizes the number of sheep ordered destroyed on the scrapie infected premises.
  • Scrapie genotyping is a tool that can be used by a producer in an overall plan to manage the risk of scrapie on their farm. Whether or not a particular producer should use scrapie genotyping is a decision based on individual factors.

Who might consider selective breeding for genetic resistance to scrapie?

  • A producer who provides a large number of breeding ewes to other producers.
  • A producer who purchases breeding ewes from multiple sources of unknown scrapie status.
  • A producer who has a significant number of 171 RR breeding animals in their flock, thus breeding for resistance would be easy, achieved relatively quick and would not have a significant impact on breeding for other production traits.

Consider

A very effective way to breed for genetic resistance for scrapie is to select only rams that are 171RR genotype. All lambs from 171RR rams will inherit at least one R and will be more resistant to scrapie.

As well, recent studies related to the transmission of scrapie have shown that the genotype of the fetus influences the accumulation of the scrapie prion in the placenta of a scrapie infected ewe. A 171QQ scrapie infected ewe, carrying a 171 QQ fetus (high susceptibility), results in the accumulation of large quantities of scrapie prion in the placenta, which is subsequently shed during birth. However, when a scrapie infected ewe carries a 171 QR fetus (very low susceptibility), the scrapie prion does not cross the placenta and the shedding of scrapie prion is prevented at lambing. The use of a 171 RR ram for breeding, therefore, can prevent the spreading of infectious scrapie prion during lambing from infected ewes.

Who might not consider selective breeding for genetic resistance to scrapie?

  • A producer with a flock that has been closed for a long time and has no evidence of scrapie.
  • A producer that has a breed of sheep or a flock with few or no animals with a 171QR or 171RR genotypes.
  • A producer that does not want to deviate from their breeding plan for selection of other production traits.

It is highly recommended that producers that chose not to selectively breed for scrapie resistance either close their ewe flock or purchase ewes from flocks in a scrapie flock certification program and commence scrapie testing in mature deadstock.

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