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DMS-Dermatomyositis        DMS Test          Code 260

Test Pricing

For breeds: Collie, Rough Collie, Shetland Sheepdog, Smooth Collie

Clinical signs/Disease description:
Dermatomyositis (DMS) is an autoimmune disease of the skin and muscle that is routinely diagnosed in Shetland Sheepdogs and Collies. Skin lesions consist of hair loss and crusts on areas with minimal muscle overlying the bone such as the face, ear tips, legs and feet, and the tip of the tail. Onset of lesions is variable and may occur as early as 12 weeks of age or in mature dogs. In some affected puppies, lesions may diminish with age and may or may not return at an older age. Definitive diagnosis can only be made with a skin biopsy.

In affected Collies, muscle wasting manifests as atrophy of the head musculature, difficulty eating, drinking, and swallowing and an atypical, high-stepping gait. Muscle involvement is uncommon in Shelties.

The causes of the disease are multifactorial. In Collies and Shelties DMS is determined by a combination of genetic and environmental factors. Being an immune-mediated disease, DMS typically develops following a trigger, such as a vaccination or viral infection, and is worsened by subsequent immunizations and other stress-related factors, such as UV exposure, owner surrender, and mistreatment.

DMS test
Researchers from Clemson University have identified three genetic variants located on three different chromosomes that, in combination, contribute to the development of DMS in Shelties and Collies (1). Only certain combinations of risk alleles at these three loci are associated with an increased risk for development of DMS, while other combinations are rarely observed in affected dogs.

Locus A=PAN2 gene on chr 10
Locus B=MAP3K7CL gene on chr 31
Locus C=DLA-DRB1 (Dog Leukocyte Antigen) on chr 12

The table below lists all 27 possible three-locus genotypes with corresponding risk interpretations. Please refer to Table 1 in the research article by Evans et al., 2017 for detailed information on distribution of three-locus genotypes in the test study of 132 cases and 390 control samples in these breeds of dogs.

Normal (wild type) alleles of loci A and B are represented by lower case letters, a and b, while the risk alleles are represented by upper case letters A and B. The risk allele at Dog Leukocyte Antigen (DLA) complex (DLA-DRB1*002:01) is referred to as C, and the lower case letter c represents any alternate allele for DLA-DRB1.

Genotype

Penetrance (%)

Risk*

aabbcc

-

-

aabbCc

-

low

aabbCC

-

low

Aabbcc

-

-

AabbCc

-

low

AabbCC

-

low

aaBbcc

-

low

aaBbCc

-

low

aaBbCC

-

low

AaBbcc

-

-

AaBbCc

-

low

AaBbCC

-

low

AAbbcc

-

-

AAbbCc

42

moderate

AAbbCC

39

moderate

aaBBcc

-

-

aaBBCc

-

low

aaBBCC

46

moderate

AaBBcc

-

-

AaBBCc

50

moderate

AaBBCC

90

high

AABbcc

-

-

AABbCc

33

moderate

AABbCC

92

high

AABBcc

-

-

AABBCc

100

high

AABBCC

100

high

*Out of 27 possible combinations, 9 genotypes with cc are rarely seen in these breeds. Consequently, the risk could not be estimated for these genotypes.

Assessment of Risk:
Genotypes of DLA-DRB1, Locus A, and Locus B are considered together. For each possible genotype, the percentage of affected dogs (penetrance) in that group was determined. Based on the genotype, the likelihood of an individual dog developing DMS is classified as low (0%-5%), moderate (33%-50%), or high (90%-100%).

Genotypes and risk interpretations:


LOW RISK GENOTYPES - In the research group, these genotypes were rarely found in affected dogs.

aabb (homozygous or heterozygous DLA-DRB1*002:01)

Aabb (homozygous or heterozygous DLA-DRB1*002:01)

aaBb (homozygous or heterozygous DLA-DRB1*002:01)

AaBb (homozygous or heterozygous DLA-DRB1*002:01)

aaBB (homozygous or heterozygous DLA-DRB1*002:01)

MODERATE RISK GENOTYPES - In the research group, up to half of dogs with these genotypes developed DMS.

AAbb (homozygous or heterozygous DLA-DRB1*002:01)

aaBB ((homozygous DLA-DRB1*002:01) 

AaBB (heterozygous DLA-DRB1*002:01)

AABb (heterozygous DLA-DRB1*002:01) 

HIGH RISK GENOTYPES - In the research group, over 90% of dogs with these genotypes developed DMS.

AABb (homozygous DLA-DRB1*002:01)

AaBB (homozygous DLA-DRB1*002:01) 

AABB (homozygous or heterozygous DLA-DRB1*002:01)

Notice that homozygosity for DLA-DRB1*002:01 increases the risk of DMS from low to moderate for dogs with an aaBB genotype, and moderate to high (AABb and AaBB). Also, 100% of dogs having AABB were affected with DMS.

Using the DMS test in a breeding program:

It is recommended that breeding pairs be selected based on their genotypes at locus A and B.  Ideally, matings that could produce puppies with high risk genotypes (AABB, AABb, and AaBB) should be avoided.  For example, if a bitch's genotype is AAbb, it is recommended that she be bred to a dog with one of the following genotypes: aaBB, aaBb or aabb.  This mating will not produce puppies that are homozygous for A or B.  Any aa-- genotype can be crossed with any --bb genotype without producing moderate or high risk genotypes, and aabb genotypes can likewise be crossed with any genotype.  In general, a dog with a genotype of aabb can be bred to any other genotype to produce low risk puppies.  For more information on how to select mating pairs based on test results, please refer to the Genotype Calculator on the ASSA site (scroll down the page and click on DMS Genotype Calculator the Excel file DMS_Genotype_Calculator_for_release.xlsx where you can open or save the file).

References:

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

 

 

   

 

 

 

 

 


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