Breeding Resistance to Scrapie in Goats

A New DNA Test to Enhance Goat Health and Your Business

scrapie-in-goats

Scrapie in goats is a deadly infectious disease that can shut down an entire operation with a single diagnosis. But scientists have concluded that two naturally occurring goat alleles in the prion gene each confer resistance to classical scrapie. You may already have these genetics in your herd.

“Breeding Scrapie Resistant Goats” by Stephen N. White PhD, David A. Schneider DVM, PhD, DACVIM(LAIM) 

Key Points:

  • Classical scrapie is a deadly infectious disease of goats and sheep that destroys a goat’s (or sheep’s) brain.
  • Common signs of scrapie in goats are lack of coordination and abnormal movement, but the first sign is often a behavioral change.
  • Even one scrapie diagnosis can lead to permanent quarantine or euthanasia of every goat on a farm. Historically, those have been the only options.
  • Recently, however, a panel of experts concluded that two naturally occurring goat alleles in the prion gene (S146 and K222) each confer resistance to classical scrapie.
  • The National Scrapie Eradication Program is successfully helping producers in the fight to eradicate scrapie and is now planning to pilot test genetic-based cleanup for goats that is similar to the early actions taken to utilize genetic scrapie resistance in sheep.
  • Survey data suggest your goats or those of someone you know may already have S146 or K222. New DNA tests are commercially available to determine the genetic status of your goats for these alleles.

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What is Scrapie, and What are the Risks to Your Goats?

Scrapie is a fatal brain disease of goats and sheep that is not infectious to people. There are two forms of scrapie, classical scrapie and Nor98-like scrapie (an atypical form). Nor98-like scrapie has not been shown to be naturally infectious between animals, so we will focus only on classical scrapie for this article. Classical scrapie results in progressive accumulation of abnormal, difficult-to-degrade prion protein that kills brain cells. The loss of brain cells can lead to abnormal behavior, lack of coordination, unusual gait, reduced mobility and body condition – and is always fatal in the end. Under the microscope, the progressive loss of brain cells eventually causes the brain to develop small holes that make it look like a sponge.

Classical scrapie has led to trade restrictions worldwide, and several counties including the U.S. and Canada have developed scrapie eradication programs. Such programs simply must be a joint effort in goats and sheep because these species can share scrapie with each other, particularly through exposure to birth products from scrapie-infected animals. For example, goat milk from an infected doe can give scrapie to foster lambs. Sheep also can spread scrapie to goats through the shed placenta, which means goats can be exposed if they are cohoused with sheep during lambing.  Just one case of classical scrapie can be devastating for large producers and small family operations alike, since eradication has historically required either permanent quarantine or euthanasia of all scrapie-exposed goats and genetically susceptible sheep.

Sheep genetic resistance to classical scrapie has been an important component in scrapie eradication. Some sheep have an amino acid (R171, which means arginine at position 171) in the prion protein that confers strong resistance to classical scrapie. The variation in the prion gene that codes for this scrapie-resistant form of the protein is referred to as the R171 allele. The genetic story in sheep is complicated a little bit by the potential to inherit a separate susceptibility allele (V136, which means valine at position 136). But sheep that have at least one R171 allele and no V136 allele are known to have strong resistance to classical scrapie.

Improving genetic resistance to classical scrapie in sheep reduces overall risk of contracting scrapie on a farm. Keeping only genetically resistant sheep (those with at least one copy of R171 and no V136) eliminates the need to quarantine permanently or euthanize sheep if classical scrapie is diagnosed in a susceptible animal, such as one sold from a farm. Thus, using genetically resistant animals means the operation is not at risk of being shut down due to scrapie. Large scrapie eradication programs have also benefitted from the growing use of sheep genetic resistance. Near the start of the accelerated National Scrapie Eradication Program in 2005, 180 flocks and herds with scrapie were identified in the U.S. While the program has been very successful in lowering this number to a few flocks/herds per year with none in 2017, the U.S. still has not achieved scrapie-free status.

scrapie-in-goats

Figure 1. The hair loss seen over the shoulder of this goat is characteristic of many goats with scrapie disease.

Developing International Recognition for Goat Genetic Scrapie Resistance

Promising research has identified genetic scrapie resistance in goats. While in sheep only one resistance allele is known, two alleles have shown exceptional promise in goats. One is S146, which means serine at position 146. The other is K222, which means lysine at position 222. The initial evidence that these alleles might confer resistance to classical scrapie comes from the observation that in many herds with scrapie, goats bearing either one of these alleles were not themselves infected. Research has since demonstrated that goats bearing either S146 or K222 are very difficult or impossible to infect, even if the goats had only one copy of the resistance allele and were directly challenged with large doses of scrapie. Also promising is the fact that a susceptibility allele that could weaken resistance to scrapie (like the V136 allele found in sheep) has not been found to occur in goats.

Goat scrapie has been a severe problem in some member states of the European Union, collectively reporting more than 10,500 cases in the last 15 years (2002-2017). Thus, the European Commission requested that the European Food Safety Authority (EFSA) evaluate the evidence for goat genetic scrapie resistance and how to use it to reduce goat scrapie. The EFSA responded by organizing a panel of scrapie experts who recently published a comprehensive report that has important implications for the goat industry.

Based on a thorough evaluation of all the scientific evidence, the expert panel concluded that the goat prion alleles, S146 and K222, each provide genetic resistance to classical scrapie and, importantly, that the strength of evidence for each of these goat alleles is presently greater than was the evidence for the sheep resistance allele R171 when it was originally recognized. Given the strength of evidence, the EFSA-commissioned report recommended the use of goat genetic scrapie resistance from S146 and K222 to assist with scrapie eradication. The adoption and implementation of the EFSA panel’s recommendations were left up to each European Union member state but no rules have been finalized at the time of this writing. In the U.S., the National Scrapie Eradication Program plans to conduct a pilot project of genetic-based goat herd cleanup similar to that used when genetic resistance was first identified in sheep.

scrapie-in-goats

Figure 2. The left microscopic image shows a goat brain with scrapie infection where accumulation of abnormal prion protein (stained red) damages brain cells leaving holes that give a sponge-like appearance. The right microscopic image shows the brain of a healthy goat comparison.

Advantages of Breeding for Goat Scrapie Resistance

Breeding your goats to increase the number of S146 and/or K222 alleles will improve your herd’s scrapie resistance. This can help your farm in some key ways. First, improved scrapie resistance in your herd will minimize the chance of scrapie infection occurring on your farm. This not only helps protect your goats health, but also improves the sustainability of your operation should your farm become exposed to scrapie. Second, the first producers to adopt new technologies like this often have advantages in their markets. For example, becoming one of the first sources of known scrapie-resistant goats could improve your visibility and sales. Finally, export market opportunities are likely to emerge for scrapie resistant animals, semen, and embryos.

You May Already Have Scrapie Resistant Goats – How to Find Out

Some of your goats (or those of someone you know) may already have S146 or K222. The S146 allele is common in the U.S., and an initial survey of U.S. goats identified S146 in 7 out of 10 goat breeds tested. Those breeds included Boer, Nubian, LaMancha, Alpine, Saanen, Tennessee fainting goats (myotonic), and Pygmy goats. Further, the S146 version is probably present in even more breeds and will be found once additional goats from those breeds are tested.

The K222 allele is present in many goat breeds, too, and especially in dairy breeds. An initial U.S. study identified K222 in both Toggenburg and LaMancha goats. Other studies have identified K222 in many European breeds, including Saanen, Alpine, and Anglo-Nubian. As with S146, the K222 allele is probably present in even more breeds and will be found once additional goats from those breeds are tested.

Genetic testing services are available at the Veterinary Genetics Laboratory of UC-Davis for $30. (Discount pricing is available for members of some registries and breed associations.) Details about testing are available at this website: https://www.vgl.ucdavis.edu/services/GoatScrapie.php

Additional testing services are in development at NeoGen Genomics, Inc. (GeneSeek). Once finalized, details will be available at this website: http://genomics.neogen.com/en/research-and-development-genomic-discovery#sheep-and-goat

Resistance to Scrapie in Goats

How to Breed Better Goats by Incorporating Scrapie Resistance

Scrapie resistance from S146 and/or K222 can enhance your breeding program and the health of your herd, and best practices will maximize value for your operation. In particular, selecting goats superior for many traits (as opposed to scrapie resistance alone) will help maintain balanced health and productivity in your herd. Also, selective breeding of goats from diverse family backgrounds will help minimize inbreeding. Taken together, the breeding objective is to enhance or add scrapie resistance without diminishing other valuable traits and characteristics in your herd. By doing this, you will improve your herd’s health, sustainability and profitability.

 

Stephen White has 15 years of experience as a geneticist with the USDA Agricultural Research Service. Dr. White studies genetics of small ruminant susceptibility to infectious disease.

David Schneider has 11 years of experience as a veterinary scientist with the USDA Agricultural Service. Dr. Schneider studies the prion diseases of small ruminant and cervid species.

Mention of trade names or commercial products in this publication is solely for the purpose of providing specific information and does not imply recommendation or endorsement by the USDA to the exclusion of others that may also be suitable. USDA is an equal opportunity provider and employer.

References:

Ricci, A., Allende, A., Bolton, D., Chemaly, M., Davies, R., Fernández Escámez, P. S., Gironés, R., Herman, L., Koutsoumanis, K., Lindqvist, R., Nørrung, B., Robertson, L., Ru, G., Sanaa, M., Skandamis, P., Speybroeck, N., Simmons, M., Kuile, B.T., Threlfall, J., Wahlström, H., Acutis, P.L., Andreoletti, O., Goldmann, W., Langeveld, J., Windig, J.J., Ortiz-Pelaez, A.,  and Snary, E. (2017). Genetic resistance to transmissible spongiform encephalopathies (TSE) in goats. EFSA Journal, 15(8).

http://onlinelibrary.wiley.com/doi/10.2903/j.efsa.2017.4962/epdf

***The original European Food Safety Authority (EFSA) review and recommendation document is available for free at the internet address above.

White, S., Herrmann-Hoesing, L., O’Rourke, K., Waldron, D., Rowe, J., & Alverson, J. (2008). Prion gene (PRNP) haplotype variation in United States goat breeds (Open Access publication). Genetics Selection Evolution, 40(5), 553.

https://gsejournal.biomedcentral.com/track/pdf/10.1186/1297-9686-40-5-553?site=gsejournal.biomedcentral.com

*An initial U.S. survey of prion gene alleles in 10 U.S. goat breeds. The article is available for free at the internet address above.

White, S. N., Reynolds, J. O., Waldron, D. F., Schneider, D. A., & O’Rourke, K. I. (2012). Extended scrapie incubation time in goats singly heterozygous for PRNP S146 or K222. Gene, 501(1), 49-51.

http://www.sciencedirect.com/science/article/pii/S0378111912003812

*Some evidence that the S146 and K222 alleles provide resistance against U.S. scrapie. The article is available for free at the internet address above.

Cinar, M.U., Schneider, D.A., Waldron, D.F., O’Rourke, K.I., White, S.N. (2018). Goats singly heterozygous for PRNP S146 or K222 orally inoculated with classical scrapie at birth show no disease at ages well beyond six years. The Veterinary Journal, 233:19-24.

https://www.sciencedirect.com/science/article/pii/S1090023317302629?via%3Dihub

**This article shows that even a rigorous challenge with U.S. scrapie did not produce clinical scrapie disease in goats with one copy of either S146 or K222 even during examination periods extending beyond the commercial lifetimes of many goats. The article is available for free at the internet address above.

Originally published in the July/August 2018 issue of Goat Journal.

Have you dealt with scrapie in goats and sheep? Let us know in the comments below!

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