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Sheep genetics and scrapie

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The genetic makeup of sheep is 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 (NSEP). Testing for scrapie susceptibility in sheep is performed routinely at the Canadian Food Inspection Agency's (CFIA) National and World Organisation for Animal Health (WOAH; founded as Office International des Épizooties (OIE)) reference laboratory for scrapie and chronic wasting disease (CWD) and at other animal health laboratories in Canada and the United States.

Recently, enough scientific information has become available on goat genetics and scrapie susceptibility both internationally and in Canada, to allow the goat industry to consider using genetics as a risk management tool for scrapie. As a result, the CFIA will pilot genotyping goats for susceptibility to scrapie infection as a disease control measure in conjunction with the other tools currently available in Canada's NSEP.

Scrapie genotyping in sheep

A genotype is an individual's collection of genes. Like all mammals, sheep receive 1 allele for each gene from their dam (ewe) and 1 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 3 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.

1 common way to write genotypes for sheep is by the codon number followed by the corresponding amino acid: at 136 V for valine or A for alanine, at 171 R for arginine and Q for glutamine. The possible amino acid combinations at these 2 locations on the sheep prion gene and their impact on susceptibility to scrapie are listed below:

Susceptibility to classical scrapie based on genotype

Table 1: Genotype and scrapie susceptibility in sheep.
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.

Who might consider selective breeding for genetic resistance to scrapie

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

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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