UC Davis School of Veterinary Medicine Veterinary Genetics Laboratory

Irish Setter, Irish Red & White Setter Health Panel

Tests Offered:

Canine Leukocyte Adhesion Deficiency (CLAD/LAD)

Canine leukocyte adhesion deficiency (CLAD) is an inherited blood disorder affecting Irish Setters and German Shepherd Dogs. The disease results from breed-specific mutations in genes that are integral to platelet and blood cell activity. Affected dogs have abnormal blood clotting and immune system functions. Affected German Shepherd Dogs and Irish Setters may present with lameness, recurrent skin infections including pyoderma (pus filled skin infections), furunculosis (boils) and ulceration, osteomyelitis (bone infections) and gingivitis. Additionally, Irish Setter pups may exhibit omphalophlebitis (umbilical vein infection), generalized lymphadenopathy (swollen or inflamed lymph nodes), and a failure to gain weight. Although some dogs can live for years with this condition, most affected dogs die early from severe infection or bleeding from an accidental injury, or during a surgical procedure. Veterinarians should be informed of affected dogs prior to any surgical procedures.

CLAD-Type I (reported as CLADis) in Irish Setters results from a single nucleotide change (c.107G>C) in the beta-2 integrin gene (ITGB2). CLAD-Type III (reported as CLADgs) in German Shepherd Dogs results from a 12bp insertion (c.1358_1359insAAGACGGCTGCC) in fermitin family member 3 gene (FERMT3).  In both cases, the disease is inherited in an autosomal recessive fashion, which means that males and females are equally affected and that two copies of the defective gene are needed to cause CLAD. Dogs with one normal and one affected gene (carriers) are normal and show no signs of disease.
The Veterinary Genetics Laboratory offers genetic tests for CLAD. Test results assist veterinarians with diagnosis of CLAD and help breeders identify carriers among breeding stock to avoid producing affected dogs. Matings between carriers are expected to produce 25% of affected puppies.

Allow 5-10 business days for results.

Results reported as:


Normal - no copies of the CLADmutation


Carrier - 1 copy of the CLAD mutation


Affected - 2 copies of the CLADmutation

* Report will specify CLADis or CLADgs, according to breed


Boudreaux MK, Wardrop KJ, Kiklevich V, Felsburg P, Snekvik K. (2010) A mutation in the canine Kindlin-3 gene associated with increased bleeding risk and susceptibility to infections. Thromb Haemost. 103(2):475-477.

Kijas JM, Bauer TR Jr, Gäfvert S, Marklund S, Trowald-Wigh G, Johannisson A, Hedhammar A, Binns M, Juneja RK, Hickstein DD, Andersson L. (1999) A missense mutation in the beta-2 integrin gene (ITGB2) causes canine leukocyte adhesion deficiency. Genomics 61, 101–110.

Degenerative Myelopathy

Degenerative myelopathy (DM) is an inherited neurologic disorder of dogs similar to Lou Gehrig’s disease in humans and results from a mutation (c.118G>A) in the SOD1 gene. Affected dogs usually present clinical signs of disease in adulthood (at least 8 years of age) with gradual muscle wasting and loss of coordination that typically begins in the hind limbs because of nerve degeneration. Disease progression continues until the dog is unable to walk. Small breed dogs tend to progress more slowly. In late stages of the disease, dogs may become incontinent and the forelimbs may be affected. Affected dogs may fully lose the ability to walk 6 months to 2 years after the onset of signs. The disease is inherited in an autosomal recessive fashion with incomplete penetrance. Thus, two copies of the SOD1 mutation (DM/DM) confer increased risk for DM but not all DM/DM dogs across breeds will develop the disease. The variable presentation between breeds suggests that other genetic and environmental factors play a role in disease expression. There is ongoing research to identify other genetic factors that modify risk for DM in different breeds. In addition, similar disease presentation is observed in some animals lacking the SOD1 mutation. Breeding two carriers of the SOD1 mutation together is predicted to produce 25% of pups that may develop DM.

The VGL offers a genetic test for the SOD1 c.118G>A mutation, reported here as DM. Genetic screening helps breeders establish the genetic status of breeding stock and select mating pairs appropriately to reduce the risk of producing DM-affected offspring

Testing is appropriate for: many breeds

The Degenerative Myelopathy (DM) test is a patented test. The Veterinary Genetics Laboratory is authorized to offer the DM test to residents of the United States, Canada and Australia.

Allow 5-10 business days for results.

Results reported as:


Normal - no copies of the CLADmutation


1 copy of the DM mutaion


2 copies of the DM mutation; dog may develop DM disease


Awano T, Johnson GS, Wade CM, Katz ML, Johnson GC, Taylor JF, Perloski M, Biagi T, Baranowska I, Long S, March PA, Olby NJ, Shelton GD, Khan S, O'Brien DP, Lindblad-Toh K, Coates JR. 2009. Genome-wide association analysis reveals a SOD1 mutation in canine degenerative myelopathy that resembles amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A. 106(8):2794-2799. [PubMed: 19188595]

Coates JR, March PA, Oglesbee M, Ruaux CG, Olby NJ, Berghaus RD, O'Brien DP, Keating JH, Johnson GS, Williams DA. 2007. Clinical characterization of a familial degenerative myelopathy in Pembroke Welsh Corgi dogs. J Vet Intern Med. 21(6):1323-1331. [PubMed: 18196743]

Shelton GD, Johnson GC, O’Brien DP, Katz ML, Pesayco JP, Chang BJ, Mizisin AP, Coates JR. 2012. Degenerative myelopathy associated with a missense mutation in the superoxide dismutase 1 (SOD1) gene progresses to peripheral neuropathy in Pembroke Welsh Corgis and Boxers. J Neurol Sci 318(1-2):55-64. [PubMed: 22542607]

Zeng R, Coates JR, Johnson GC, Hansen L, Awano T, Kolicheski A, Ivansson E, Perloski M, Lindblad-Toh K, O'Brien DP, Guo J, Katz ML, Johnson GS. 2014. Breed Distribution of SOD1 Alleles Previously Associated with Canine Degenerative Myelopathy. J Vet Intern Med 28(2):515-521. [PubMed: 24524809]


Progressive Retinal Atrophy (PRA)

Progressive Retinal Atrophy (PRA) in the Irish Setter and Irish Red and White Setter is an early onset inherited rod-cone dysplasia (type 1-rcd1) resulting from a mutation in phosphodiesterase 6B (PDE6B) enzyme. Dogs with this disease are typically completely blind before two years of age with signs often evident by 6 weeks. The disease is inherited in an autosomal recessive fashion thus two copies are required for an animal to be affected with both sexes being equally affected. Carrier dogs with one normal and one mutated PDE6B gene are unaffected but breeding two carriers together is expected to produce 25% affected offspring and 50% carriers.

The VGL offers a test for Irish and Irish Red and White Setter rcd1-PRA to assist owners and breeders in identifying affected and carrier dogs. The test uses DNA collected from buccal (cheek) swabs, thus avoiding blood sample collection. Breeders can use results from the test as a tool for selection of mating pairs to avoid producing affected dogs.

Allow 5-10 business days for results.

Results reported as:

N/N No copies of the rcd1-PRA mutation; dog is normal
N/PRA 1 copy of the rcd1-PRA mutation; dog is a carrier
PRA/PRA Affected 2 copies of the rcd1-PRA mutation; dog is affected.


M L Suber, S J Pittler, N Qin, G C Wright, V Holcombe, R H Lee, C M Craft, R N Lolley, W Baehr, and R L Hurwitz. (1993) Irish setter dogs affected with rod/cone dysplasia contain a nonsense mutation in the rod cGMP phosphodiesterase beta-subunit gene. Proc Natl Acad Sci USA. 90(9): 3968–3972.


Von Willebrand Disease Type 1 (vWD Type 1)

Von Willebrand disease (vWD) is an inherited bleeding disorder resulting from a lack or reduced level of a normal blood clotting protein called von Willebrand factor (vWF). Disease presentation varies from asymptomatic to spontaneous hemorrhaging and prolonged bleeding after injury, surgery or giving birth. Furthermore, age of onset varies with some dogs only becoming obvious “bleeders” later in life. Without medical intervention, uncontrolled bleeding can result in death. Several genetic mutations that prevent normal functioning of vWF have been identified. These mutations are associated with different clinical bleeding disorders known as vWD Type 1, Type 2 and Type 3. 

vWD Type 1 is the most common bleeding disorder among dogs and is present in several breeds. The disorder is characterized by a low concentration of vWF in blood. While vWD Type 1 can cause serious bleeding problems, it is generally less severe than the other two types of vWD and can be alleviated by treatment. A mutation in vWF (c.7437G>A) is associated with vWD Type 1. This disorder is inherited as a dominant trait with incomplete penetrance, which means that not all dogs that have the vWF mutation will present clinical signs of the disease.

Allow 5-10 business days for results.

Results reported as:


Normal - No copies of vWF mutation associated with vWD Type 1.


1 copy of vWF mutation. Dog may be affected and may develop vWD Type 1.


2 copies of vWF mutation. Dog may be affected and may develop vWD Type 1.


Brooks MB, Erb HN, Foureman PA, Ray K. (2001) von Willebrand disease phenotype and von Willebrand factor marker genotype in Doberman Pinschers. Am J Vet Res 62(3):364-369.

Crespi JA, LS Barrientos, G Giovambattista. (2018) von Willebrand disease type 1 in Doberman Pinscher dogs: genotyping and prevalence of the mutation in the Buenos Aires region, Argentina. J Vet Diagn Investg 30(2):310-314.

Donner J, Kaukonen M, Anderson H, Moller F, Kyostila K, Sankari S, Hytonen M, Giger U, Lohi H. (2016) Genetic Panel Screening of Nearly 100 Mutations Reveals New Insights into the Breed Distribution of Risk Variants for Canine Hereditary Disorders. PLoS One 11(8). DOI:10.1371/journal.pone.0161005

Vos-Loohuis M, van Oost BA, Dangel C, Langbein-Detsch I, Leegwater PA. (2017) A novel VWF variant associated with type 2 von Willebrand disease in German Wirehaired Pointers and German Shorthaired Pointers. Anim Genet 48:493–496.

Rieger M, Schwarz HP, Turecek PL, Dorner F, van Mourik JA, Mannhalter C. (1998) Identification of mutations in the canine von Willebrand factor gene associated with type III von Willebrand disease. Thromb Haemost 80(2):332-337.

Venta PJ, Li J, Yuzbasiyan-Gurkan V, Brewer GJ, Schall WD. (2000) Mutation causing von Willebrand’s Disease in Scottish Terriers. J Vet Intern Med 14(1):10-19.



Veterinary Genetics Laboratory, Tel 530-752-2211, Email VGL