UC Davis School of Veterinary Medicine Veterinary Genetics Laboratory

Havanese Health Panel

Tests Offered:
CDDY+CDPA | CMR1 | vWF1

Chondrodystrophy (CDDY and IVDD Risk) and Chondrodysplasia (CDPA)

Introduction

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. Two retrogene insertions of functional fibroblast growth factor 4 (FGF4) explain short-legged phenotypes of dogs. FGF4 gene is involved in many biological processes including bone development.

The first insertion discovered (Parker et al 2009) is an FGF4-retrogene insertion in dog chromosome 18 (FGF4-18). This FGF4-18 insertion explains a short-legged phenotype known as chondrodysplasia (CDPA) in breeds such as Basset Hound, Pembroke Welsh Corgi, Dachshunds, West Highland White Terriers and Scottish Terriers. CDPA inheritance is considered to follow am autosomal dominant mode.

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 Intervertebral Disc Disease or 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 a combined test for CDDY and CDPA for breeds that have long and short leg phenotypes. CDDY and CDPA occur in many breeds. Testing for these mutations can help breeders determine if CDDY is present among breeding stock and to identify dogs at risk for IVDD. In breeds where both mutations are present, breeders can benefit from test results to implement breeding strategies to reduce incidence of CDDY, while retaining the short-legged phenotype conferred by CDPA.

CDDY variant has been found in breeds such as: Basset Hound, Beagle, Bichon Frise, Cardigan Welsh Corgi, Cavalier King Charles Spaniel, Chesapeake Bay Retriever, Chihuahua, American Cocker Spaniel, Coton de Tulear, Dachshund, Dandie Dinmont Terrier, English Springer Spaniel, French Bulldog, Havanese, Jack Russell Terrier, Nova Scotia Duck Tolling Retriever, Pekingese, Pembroke Welsh Corgi, Poodle (Miniature and Toy), Portuguese Water Dog, Scottish Terrier, Shih Tzu. This is not a complete list of breeds. Research on the distribution of this mutation across breeds is ongoing.

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

Results reported as:

Chondrodystophy (CDDY and IVDD Risk)

N/N No copies of CDDY mutation.
N/CDDY 1 copy of CDDY mutation. Dog is short-legged and at risk for IVDD.
CDDY/CDDY 2 copies of CDDY. Dog is short-legged and at risk for IVDD.

Chondrodysplasia

N/N No copies of CDPA mutation.
N/CDPA 1 copy of CDPA. Dog is short-legged.
CDPA/CDPA 2 copies of CDPA. Dog is short-legged.

References:

Parker HG, VonHoldt BM, Quignon P, Margulies EH, Shao S, Mosher DS, Spady TC, Elkahloun A, Cargill M, Jones PG, Maslen CL, Acland GM, Sutter NB, Kuroki K, Bustamante CD, Wayne RK, Ostrander EA. 2009. An expressed fgf4 retrogene is associated with breed-defining chondrodysplasia in domestic dogs. Science 325(5943):995-8. doi: 10.1126/science.1173275.

Brown EA, Dickinson PJ, Mansour T, Sturges BK, Aguilar M, Young AE, Korff C, Lind J, Ettinger CL, Varon S, Pollard R, Brown CT, Raudsepp T, & Bannasch DL. (2017) FGF4 retrogene on CFA12 is responsible for chondrodystrophy and intervertebral disc disease in dogs.
PNAS 114 (43) 11476-11481.
http://m.pnas.org/content/early/2017/10/09/1709082114.

Canine Multifocal Retinopathy 1

Introduction

Canine Multifocal Retinopathy 1 (CMR1) is an inherited eye disease caused by a mutation (c.73C>T) in the Bestrophin 1 gene that results in a shortened, dysfunctional protein. Affected dogs typically present with multiple, discrete circular areas of retinal detachment between 11 and 16 weeks of age. Fluid accumulates under the detached retina resulting in gray, tan, orange or pink “blisters” in the eye. Progression of retinal changes is slow, ceases by 1 year and does not lead to blindness. In some cases, the blisters appear to heal as the dog ages but vision loss has been reported. The disease is inherited in an autosomal recessive fashion thus two copies of the CMR1 mutation must be present to produce the disease. Breeding two carriers is predicted to produce 25% affected pups

The VGL offers a genetic test for the CMR1 mutation. Genetic screening helps breeders establish the genetic status of breeding stock and select mating pairs appropriately in order to reduce the risk of producing CMR1-affected offspring.

Testing is recommended for: American Bulldog, American Bully, Aussiedoodle, Australian Koolie, Australian Shepherd, Brazilian Terrier, Bulldog, Bullmastiff, Cane Corso, Dogue de Bordeaux, French Bulldog, Great Pyrenees, Havanese, Koolie, Mastiff, Miniature American Shepherd, Miniature Australian Shepherd, Perro de Presa Canario, Shorty Bull, South African Boerboel, Toy Australian Shepherd

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

Results reported as:

N/N Normal - no copies of the CMR1 mutation
N/CMR1 Carrier - 1 copy of the CMR1 mutation; dog is normal
CMR1/CMR1 Affected - 2 copies of the CMR1 mutation; dog will develop multifocal retinopathy

Reference:

Gornik KR, Pirie CG, Duker JS, Boudrieau RJ. Canine multifocal retinopathy caused by a BEST1 mutation in a Boerboel. Vet Ophthalmol. 2013 Sep 3. [PubMed: 23998685]

Donner J, Kaukonen M, Anderson H, Moller F, Kyostila K, Sankari S, Hytonen M, Giger U, Lohi H. Genetic Panel Screening of Nearly 100 Mutations Reveals New Insights into the Breed Distribution of Risk Variants for Canine Hereditary Disorders. PLoS One. 2016 Aug 15;11(8). [PubMed: 27525650]

Von Willebrand's Disease Type 1
Introduction

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.

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.

The genetic tests for vWD Type 1 is offered by the VGL. Results from the test help breeders determine the genetic status of breeding stock and risk for bleeding disorder. Veterinarians can use test results to confirm clinical findings and inform appropriate courses of treatment or management.

Testing is recommended for:

vWD Type 1: Australian Cobberdog, Barbet, Bernese Mountain Dog, Brazilian Terrier, Cardigan Welsh Corgi, Coton de Tulear, Doberman Pinscher, Drentsche Patrijshond, Dutch Partridge Dog, Dutch Shepherd, French Water Dog, German Pinscher, Havanese, Irish Red and White Setter, Irish Setter, Kerry Blue Terrier, Kromfohrländer, Manchester Terrier, Papillon, Pembroke Welsh Corgi, Phalene, Poodles, Doodle and Poo breeds, Stabyhoun, Toy Manchester Terrier, West Highland White Terrier

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

Results for vWD Type 1 reported as:

N/N Normal - No copies of vWF mutation associated with vWD Type 1
N/vWF 1 copy of vWF mutation. Dog may be affected and may develop vWD Type 1.
vWF/vWF 2 copies of vWF mutation. Dog may be affected and may develop vWD Type 1.

References:

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.

 
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