UC Davis School of Veterinary Medicine Veterinary Genetics Laboratory

Nova Scotia Duck Tolling Retriever (NSDTR) Tests

NSDTR-specific information:
CDDY | CLPS | CP1 | JADD

Other tests of interest:
DM | Dilute (Buff)

Chondrodystrophy (CDDY and IVDD Risk)

Chondrodysdrophy (CDDY) is a trait that defines many dog breeds and is characterized by reduction of long bone length (shorter legs) as a consequence of early changes in the structure of growth plates. CDDY can also impact health of animals through an abnormal process that causes premature degeneration of the intervertebral discs.

The Chondrodysdrophy (CDDY) mutation was recently discovered by researchers in the Bannasch Laboratory at the University of California, Davis (Brown et al. 2017) as a second FGF4-retrogene insertion in dog chromosome 12.  CDDY includes a short-legged phenotype and abnormal premature degeneration of intervertebral discs leading to susceptibility to Hansen’s type I Intervertebral Disc Disease (IVDD). The intervertebral disc, which sits between vertebrae, is composed of an outer fibrous basket (annulus fibrosus) made of 70% collagen and an inner gel-like layer called the nucleus pulposus. These structures allow for flexibility of the vertebral column. In Chondrodystrophic breeds, premature calcification of the nucleus pulposus at early age (from birth to 1 year of age) results in degeneration of all discs in young dogs. These abnormal discs are predisposed to herniation into the spinal canal where the inflammation, and hemorrhage can cause severe pain and neurological dysfunction (myelopathy) termed IVDD. IVDD has high mortality rate and high cost of surgical and medical veterinary care.

 CDDY is inherited as a semi-dominant trait for height, meaning that dogs with 2 copies of the mutation are smaller than dogs with only 1 copy. With respect to IVDD, the inheritance follows a dominant mode, meaning that 1 copy of the FGF4-12 mutation is sufficient to predispose dogs to IVDD. Dogs that have both FGF4-12 and FGF4-18 show a more drastic reduction of leg length.  One area of current investigation is how CDDY and CDPA might work in concert to increase the risk of IVDD.

The Veterinary Genetics Laboratory offers the CDDY test for Nova Scotia Duck Tolling Retrievers (NSDTR or Tollers). Testing for this mutation can help breeders determine if CDDY is present among breeding stock and to identify dogs at risk for IVDD. Breeders can benefit from the test result to implement breeding strategies to reduce incidence of CDDY.

ORDER TEST KITS | PRICE LIST
Allow 5-10 business days for results.

Results reported as:

Chondrodystrophy

N/N

No copies of CDDY mutation.

N/CDDY

1 copy of CDDY mutation. Dog is short-legged and at risk for IVDD. When bred to an N/N dog will produce 50% of normal sized puppies and 50% short-legged puppies at risk for IVDD.

CDDY/CDDY

2 copies of CDDY. Dog is short-legged and at risk for IVDD. Will produce 100% short-legged puppies at risk for IVDD.

References:

Emily A. Brown, Peter J. Dickinson, Tamer Mansour, Beverly K. Sturges, Miriam Aguilar, Amy E. Young, Courtney Korff, Jenna Lind, Cassandra L. Ettinger, Samuel Varon, Rachel Pollard, C. Titus Brown, Terje Raudsepp, Danika L. Bannasch. 2017. FGF4 retrogene on CFA12 is responsible for chondrodystrophy and intervertebral disc disease in dogs. http://m.pnas.org/content/early/2017/10/09/1709082114.

 

Cleft Lip/Palate and Syndactyly (CLPS)

Cleft palate is a hole (cleft) in the roof of the mouth (palate) that occurs during development of the puppy. Puppies are born with cleft palate. Cleft Lip is a split in the lip and can occur on one or both sides of the mouth. Syndactyly is the fusion of the middle two digits of the feet. The NSDTR, or Toller, breed has multiple genetic causes of cleft palate. A mutation test is already available for CP1 in the NSDTR which causes cleft palate. The mutation that causes a second form of cleft lip and cleft palate called CLPS has been recently identified by scientists from the Bannasch Laboratory at the University of California, Davis and the Wade Laboratory from the University of Sydney. This CPLS test is BREED specific and does not apply to any breed except the NSDTR.
CLPS is inherited as an autosomal recessive disease. Affected puppies inherit two mutant copies of this defective gene, one from each of their parents. The phenotype of puppies with two copies of CLPS can vary from cleft palate only to cleft lip and cleft palate and in both cases puppies can have syndactyly but don’t always. Dogs that have 1 copy of the CLPS mutation (carriers) are completely normal and can be safely bred to N/N dogs in order to maintain diversity within the breed and select for other positive attributes in carrier dogs.
The Veterinary Genetics Laboratory offers a test for CPLS in Tollers. Breeders can use results from the test as a tool to select mating pairs to avoid producing affected dogs. About 2% of Tollers carry the CPLS mutation. This mutation accounts for 39% of cleft puppies from North America.

ORDER TEST KITS | PRICE LIST
Allow 5-10 business days for results.

Results reported as:

N/N Normal – no copies of the CLPS mutation are present.
N/A Carrier – 1 copy of the CLPS mutation is present. If carriers are bred together, 25% of offspring are expected to be affected.
A/A Affected – 2 copies of the CLPS mutation.

Reference:

Wolf ZT, Leslie EJ, Arzi B, Jayashankar K, Karmi N, Jia Z, Rowland DJ, Young A, Safra N, Sliskovic S, Murray JC, Wade CM, Bannasch DL. A LINE-1 insertion in DLX6 is responsible for cleft palate and mandibular abnormalities in a canine model of Pierre Robin sequence. PLoS Genet. 2014 Apr 3; 10(4):e1004257. doi: 10.1371/journal.pgen.1004257

Cleft Palate (CP1)

A cleft palate is a birth defect whereby a hole (cleft) in the roof of the mouth (palate) develops in a puppy during gestation. Puppies born with cleft palate can experience difficulty nursing which will greatly increase their risk of developing aspiration pneumonia - a serious life threatening condition. There are multiple genetic causes of cleft palate within the NSDTR breed; however, the most common form has been identified as CP1.

Researchers from the Bannasch Laboratory at the University of California, Davis discovered the genetic cause of CP1 cleft palate in the Nova Scotia Duck Tolling Retriever. Dogs with this form of cleft palate have a large insertion into a gene known to affect the proper development of the palate. This mutation is not present in any other breed based on testing conducted on over 300 individual animals of over 80 different dog breeds.

Cleft palate caused by CP1 is inherited as an autosomal recessive disease. Affected puppies inherit two mutant copies of this defective gene, one from each of their parents. Dogs that have 1 copy of the CP1 mutation (carriers) are completely normal and can be safely bred to N/N dogs in order to maintain diversity within the breed and select for other positive attributes in carrier dogs.

The Veterinary Genetics Laboratory offers a DNA test for CP1 in Tollers. This TEST does not apply to any breed other than the NSDTR. Breeders can use results from the test as a tool to select mating pairs to avoid producing affected dogs. At the time that this test was released, approximately 15% of Tollers were carriers of CP1 (N/A). This mutation accounted for 62% of cleft puppies from North America. These numbers can change with each generation.

ORDER TEST KITS | PRICE LIST
Allow 5-10 business days for results.

Results reported as:

N/N

Normal – no copies of the CP1 mutation are present

N/A

Carrier – 1 copy of the CP1 mutation is present. If carriers are bred together, 25% of offspring are expected to be affected.

A/A

Affected – 2 copies of the CP1 mutation

Reference:

Wolf ZT, Brand HA, Shaffer JR, Leslie EJ, Arzi B, Willet CE, Cox TC, McHenry T, Narayan N, Feingold E, Wang X, Sliskovic S, Karmi N, Safra N, Sanchez C, Deleyiannis FW, Murray JC, Wade CM, Marazita ML, Bannasch DL. Genome-wide association studies in dogs and humans identify ADAMTS20 as a risk variant for cleft lip and palate. PLoS Genet. 2015 Mar 23;11(3):e1005059. doi: 10.1371/journal.pgen.1005059.

 

Juvenile Addison's Disease (JADD)

Addison’s disease (hypoadrenocorticism) occurs when the adrenal glands stop secreting the natural steroid hormones necessary for the regulation of glucose metabolism, immune function (glucocorticoids), sodium and potassium levels in the blood (mineralocorticoids). Addison’s disease can occur in any breed of dog and it has an average age of onset of 4 years. Addison’s disease is diagnosed by a veterinarian using a blood test called ACTH stimulation test. The clinical signs of Addison’s disease can include lethargy, lack of appetite, vomiting and diarrhea.

In the NSDTR, or Toller, breed a genetic form of this disease, called JADD, occurs in much younger animals. The average age of puppies affected with JADD is 5 months; however, puppies as young as 8 weeks and as old as 12 months of age have been identified. Treatment of puppies affected with JADD requires both mineralocorticoid and glucocorticoid replacement therapy. Puppies can have other concurrent diseases including eye problems (corneal edema, conjunctivitis or uveitis) that may require specialized treatment.

Scientists from the Bannasch Laboratory at the University of California, Davis have developed a DNA test to identify carriers of JADD in Toller breed. The juvenile form of Addison’s disease is genetically distinguishable from the adult onset form in that all dogs that develop the juvenile form have two identical copies of a specific region within their genome and a specific mutation within a novel gene. The mutation responsible for JADD causes a change the amino acid sequence in a highly conserved region of this protein. This mutation is not present in any other breeds of dogs based on testing of over 250 individual animals in 80 different breeds.

JADD in Tollers is inherited as an autosomal recessive disease. Affected puppies inherit two copies of the defective gene, one from each of their parents. In addition, JADD is not completely penetrant meaning that not all puppies with two copies of the mutation will go on to develop the disease. According to researchers, approximately 75% of puppies with two copies of the mutation will develop Addison’s disease. Dogs that are carriers (N/A) are normal themselves and can be safely bred to N/N dogs in order to maintain diversity within the breed and select for other positive attributes in carrier dogs.

The Veterinary Genetics Laboratory offers a DNA test for JADD in Tollers. Breeders can use results from the test as a tool to select mating pairs to avoid producing affected dogs. At the time that the mutation was discovered, about 20% of Tollers were carriers (N/A) of JADD. 

ORDER TEST KITS | PRICE LIST
Allow 5-10 business days for results.

Results reported as:

N/N

Normal – no copies of the JADD mutation are present

N/A

Carrier – 1 copy of the JADD mutation is present. If carriers are bred together or to an affected mate, affected offspring can be produced.

A/A

Affected – 2 copies of the JADD mutation. Dog has 75% chance of developing Addison’s disease by 1 year of age.

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