Dermatomyositis Learning Exercies

Answers to the exercises can be found HERE, but links are provided where one can try to find the answers before viewing the answer document. Summary bullet points are at the bottom.

Exercise #1:

You have a bitch with the following genotype, DLA-DRB1 002:01/002:01 aabb. You don’t have to worry about knowing the genotype of any stud you might consider for her because all of her pups will have low risk genotypes no matter the genotype of the stud. TRUE or FALSE?

Go to the following webpage, https://americanshetlandsheepdogassociation.org/dermatomyositis/ , to find the answer either by using the “Genotype Calculator” or by clicking on the Punnett square link.

 

Exercise # 2:

You have a beautiful bitch with the following genotype, 002:01/023:01 AaBb. Which of the following statement(s) is/are true? You can find answers by going to: https://americanshetlandsheepdogassociation.org/dermatomyositis/ .

  1. DLA-DRB1*002:01, A, and B are risk alleles for DMS.
  2. Since this is a moderate risk genotype, you should not breed her!
  3. This is a low risk genotype and you can breed her to any stud with a low risk genotype and not be concerned about producing pups with dermatomyositis.
  4. She has the DLA-DRB1*023:01 allele which is desirable!

Exercise # 3:

You have a bitch with 002:01/002:01 Aabb genotype (low risk) and would like to breed her to a male with 002:01/023:01 AaBb (also low risk). What are the possible genotypes of the offspring and associated risk assessments?

Go to https://americanshetlandsheepdogassociation.org/dermatomyositis/ , to find the answer either by using the “Genotype Calculator” or by clicking on the Punnett square link.

Exercise #4:

You have a bitch that has had several previous litters with no DMS affected pups. Unfortunately, in her most recent litter of 4, 2 of the pups were affected with DMS. Which of the following are TRUE?

  1. a) Obviously, this is the fault of the stud. Never touch him or any of his offspring again!
  2. b) Not only should the DMS affected pups be spayed/castrated, the normal appearing littermates should be sterilized also.
  3. c) Your bitch, like most Shelties, has some risk alleles for DMS. It is likely that the studs used in the earlier breedings had genotypes that when combined with that of your bitch resulted in each pup inheriting a low risk genotype.
  4. d) You should have your bitch tested and urge the stud dog owner to do the same. Both the sire and dam had risk alleles and crossing those two genotypes resulted in each pup having the chance of inheriting low, moderate, or high risk genotypes.

DMS Exercise # 5:

This exercise may not be as much “fun” as the others, but it is intended to encourage you to try to understand how risk assessments were developed. Below is a portion of Table 3 from the scientific article by the Evans et.al. [1] You can access a larger version at: https://americanshetlandsheepdogassociation.org/dermatomyositis/ . DO NOT BE INTIMIDATED!

In the table, C = DLA-DRB1*002:01, lower-case letter “c” represents any alternate allele of DLA-DRB1 such as DRB1*023:01 or DRB1*015:01. Cases = dogs with confirmed dermatomyositis. Controls = normal dogs. Penetrance = % of dogs with a particular genotype that were affected.

Using the Table below:

  1. How many Shelties had the genotype aabbCC (which is seen on individual dog reports as 002:01/002:01 aabb) and how many of those developed DMS?
  2. For Shelties, which was the most common genotype in which NO cases of DMS were reported?
  3. What percent of Shelties with AABBCC or AABBCc genotypes developed DMS?
  4. What was the risk assessment for dogs with the aabbcc genotype?

Remember, cc = 023:01/023:01, 015:01/015:01, or 015:01/023:01.

I’ll admit that my eyes glazed over the 1st time I looked at this table and had to “whip” my brain into submission. J

The results for Collies and Shelties were pooled together to develop risk assessments.


 

DMS Exercise # 6:

You have a gorgeous stud dog with the following genotype: DLA-DRB1 002:01/015:01 aaBB. He was bred several times before you knew his genotype. So far, no puppies have shown any signs of DMS, and several have championship points! Now, how do you handle future requests for stud service?

  1. Inform bitch owners of your dog’s genotype and let them decide whether or not to use your dog. After all, his genotype is low risk.
  2. Inform the bitch owners of your dog’s genotype and point out that the DLA-DRB1 015:01* is quite uncommon in the breed, and it is important to maintain that allele and increase its frequency within the breed.
  3. Insist that all bitches bred to your stud be genotyped for DMS and that only bitches with low risk genotypes be bred to him.
  4. To ensure that only puppies with low risk genotypes be sired by your dog, you will insist that only bitches with the following genotypes be bred to him: aabb, Aabb, AAbb. (Hint: check the Punnett squares for aaBB genotype at: https://americanshetlandsheepdogassociation.org/dermatomyositis-dna-test/ .

* The DLA-DRB1 015:01* allele was found primarily in Shelties from Europe, not the USA.

 

DMS Exercise # 7: This is a series of questions.

  1. I have always used the acronym DM when talking about dermatomyositis, but I now see DMS being used. What’s the difference?
  2. My dog’s certificate from Clemson for dermatomyositis lists the DLA as 003:01/009:01; however, these numbers are not mentioned in previous test questions nor in the ASSA website. Why?
  3. I submitted dermatomyositis test results to OFA, but they were not accepted. Why?
  4. In the “risk interpretation” section of the DMS section of the ASSA website, what is meant by homozygous or heterozygous DLA-DRB1*002:01?

DMS Exercise # 8:

Why do some DMS-affected dogs develop lesions as young dogs while others may not develop lesions until later? (Hint: The likely answer can be found in the Summary document at https://americanshetlandsheepdogassociation.org/wp-content/uploads/2016/07/DMS-article-summary.pdf ).

DMS Exercise #9:

You have a beautiful, young dog with the following genotype: DLA-DRB1*002:01/002:01 AaBB. This dog is exactly what you have been trying to get for years. He has won multiple specialties and finished quickly. Quite simply, he is exceptional. He had a bit of hair loss below one eye that you thought was the result of a scuffle with a kennel mate, but the hair has grown back. What is his risk for developing DMS?   How can this dog be used in a breeding program?

DMS Exercise #10:

How many Shetland Sheepdog DMS test results have been entered into the OFA database?

This exercise is for those who have never used the search functions of the OFA website.   Go to the OFA homepage: http://www.ofa.org/. In the upper left corner is a blue box as shown in Figure 1. Click on the “Advanced Search” button. On the next page that appears, select “Shetland Sheepdog” from the breed list (Figure 2) then scroll down to the “Report Type” section (Figure 3) and scroll down until you find “Dermatomyositis” and highlight that. Lastly, hit the “Begin Search” button at the bottom of the page.

      

  


There are several ways to use the search functions of the OFA database. If you know the registered name or number of a particular dog you are interested in, just enter that information in the blue box on the home page and click the blue arrowhead. If you want to find Shelties that have had certain tests done, you can go to the “Advanced Search” page and enter the breed, sex (if you only want to see males or females) and select the desired tests. If you want to view tests done on dogs with a certain kennel name, you can enter the kennel name in the “Part of Name” section toward the top of the page.

As DMS testing becomes more commonplace and results are reported to OFA, a person looking for a stud with a particular genotype could find a list of such dogs there. For instance, if you have a bitch with AaBb genotype and want to breed her to a male with aabb, so all pups would have low risk genotypes, you could find males with that genotype by using the search function. Once you get the list of males with DMS test results, you would then click on the name of each dog to go to the OFA page for that dog and view the genotype posted there.

DMS Exercise #11:

You have a dog with the following genotype, DLA-DRB1* 002:01/002:01 AaBB. Neither the sire nor dam of this dog have been DNA tested for DMS.  What, if anything, can you surmise about the genotype of the parents?

DMS Exercise #12:

You test your new puppy that you hope to use as a stud. His genotype is 002:01/023:01 AAbb, a moderate risk genotype. (42% of the dogs in the study with this genotype developed DMS.) Which of the following is/are true?

  1. This result tells you little about his likelihood for developing DMS. He may, or may not, develop DMS.
  2. You should find a pet home for this puppy and not use it in your breeding program.
  3. You now know that you should select mates that do not carry A in their genotype.

 

DMS Exercise #13:

Which of the following have been reported as preceding the initial outbreak of DMS and so are likely “triggers” for disease development?

  1. Parvovirus infection.
  2. Being returned to the breeder by the adoptive family after several years.
  3. Rattlesnake vaccinations.
  4. Cross-country road trip to a dog show.
  5. Severe owner neglect (i.e., long hours in a crate; unsanitary conditions).
  6. Bee stings.

Summary Bullet Points for Dermatomyositis:

  • A dog inherits genes from each parent. In the case of the test for dermatomyositis a dog with the genotype of DLA-DRB1 002:01/002:01 Aabb means that one parent contributed 002:01 A b and the other 002:01 a b.
  • 3 genes (DLA, Locus A and Locus B) act together to contribute toward the development of dermatomyositis (DMS) in Shelties and Collies.
  • DLA-DRB1* 002:01, “A” and “B” are risk alleles (allele = version of a gene)
    • 015:01 and 023:01 are 2 of the known alternate (good) alleles of DLA-DRB1.
    • Lower case letters, “a” and “b” represent normal alleles of the A and B genes.
  • Concerning the DLA – 2 different numbers such as 002:01/023:01 (heterozygous) is better than having 2 copies of 002:01 i.e., 002:01/002:01 (homozygous).
  • Concerning the DLA – An owner should NOT be upset if his/her dog has 2 copies of 002:01 (ex. 002:01/002:01). About 60% of Shelties tested in the research study were homozygous for 002:01 and 78% had at least one copy. It will take years of breeding to increase the number of dogs with alternate alleles, for example, 015:01 and 023:01. Since 023:01 is essentially the only alternate allele to 002:01 in the USA, US breeders should consider importing dogs with alternate alleles to increase the diversity of the DLA in American Shelties.
  • Concerning the “A, B” genes, the goal is to gradually work toward dogs with aabb genotype.
  • A dog with the aabb genotype, regardless of the DLA, can be bred to any dog to produce litters in which all pups have low risk genotypes.
  • Depending on the genotypes, breeding 2 dogs with low risk genotypes can produce pups with high risk genotypes.
    • Except for the aabb genotype noted above, one must know the genotypes of a mating pair and use the Punnett squares (available on the ASSA website) to know the possible genotypes each pup could inherit.
    • There is NO dog that cannot be used in a breeding program to produce pups with low risk genotype!
  • On DMS test certificates, the “Risk” interpretation refers to the risk of the dog tested to develop clinical signs of DMS, NOT necessarily the ability of that dog to produce pups with high risk genotypes.
  • DMS test results, when posted on the OFA website, can be used as one of the electives for a CHIC number. Only the genotype, not the risk interpretation is posted on the website.

[1] Evans JM, Noorai RE, Tsai KL, Starr-Moss AN, Hill CM, Anderson KJ, et al. (2017) Beyond the MHC: A canine model of dermatomyositis shows a complex pattern of genetic risk involving novel loci. PLoS Genet 13(2): e1006604. doi:10.1371/journal.pgen.1006604. http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1006604#abstract1