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Canine Hip Dysplasia

We are fortunate to have the guidance of Dr. Kerstin Lindblad-Toh and Dr. Andrew Lundquist who are behind the Airedale DNA Bank - they guide us to key researchers and studies when owners bring Airedale health issues to our attention.  This allows us to post the following types of information for education purposes and information on improving health of our dogs.
 
 
Research Findings in CHD Studies:
 
CHD is a common polygenic trait characterized by hip malformation that results in osteoarthritis (OA). The condition in dogs is very similar to developmental dysplasia of the human hip which also leads to OA. Hip dysplasia was first described in 1937 by Dr. Gerry B. Schnelle in a paper entitled "Bilateral Congenital Subluxation of the Coxofemoral Joints of a Dog".  The term "hip dysplasia" is defined as the abnormal or faulty development of the hip. Abnormal development of the hip causes excessive wear of the joint cartilage during weight bearing, eventually leading to the development of arthritis, often called degenerative joint disease (DJD) or osteoarthritis. The terms DJD, arthritis and osteoarthritis are used interchangeably.

The traditional phenotypic evaluation for CHD is based on a hip joint-extended, ventrodorsal radiographic projection of the pelvis. Other methods to assess hip joint conformation associated with CHD include distraction index (DI), age at detection of femoral capital ossification, and dorsolateral subluxation (DLS) hip joint score.  Unfortunately, because CHD is a quantitative trait, none of these methods have 100% sensitivity and specificity for diagnosis in young dogs, and CHD remains the most prevalent orthopedic disease in dogs.  (*See the list of references below for references to the above.)
     The following is an excerpt taken from a recent (2009) research review on CHD, "The long (and winding) road to gene discovery for canine hip dysplasia" (Lan Zhu et. al. The Veterinary Journal 181 (2009) 97-110.) This paper reviews recent developments in CHD genetic locus mapping and assesses how phenotypic and genotypic information can be used to reduce the incidence of this condition. 
     "The concept (behind the genetic studies in CHD is to find the genes that contribute to hip dysplasia and to use molecular markers near these contributing genes or the genetic mutations themselves to identify susceptible or resistant dogs. This information is then used in conjunction with radiographic hip screening on a pedigree to derive BVs that could be applied in breeding programs or registries to reduce the incidence of the trait. These BVs and genetic marker information could be used by purchasers of purebred puppies to assess the potential orthopedic health of the animal. Genetic marker information would be particularly helpful in this context as the purchaser
would have no information on the offspring of that individual." 
 
   Genetic mapping for the polygenic traits (meaning more than one gene is involved in producing the condition of CHD and OA) is the process of locating a region on a chromosome that harbours a genetic locus that contributes to, or causes, an inherited trait. Subsequent studies aim to discover the contributing mutations within those chromosomal regions.
     The following is from "Canine Genomics and Genetics: Running with the Pack" by Heidi G. Parker, Elaine A. Ostrander,(PLoS Genetics, November 2005 | Volume 1 | Issue 5 | e58) Hip dysplasia affects up to 50% of the large breeds. The disease is recognized radiographically as subluxation of the femoral head from the acetabulum of the hip joint, and is likely caused by a mixture of genetic [41-45] and environmental factors. Two approaches have been used to try to identify causative genes. Investigators at the University of Utah have looked for a genetic association in a population of well-characterized and densely genotyped Portuguese water dogs (PWD) using the Norberg angle, a highly heritable and quantitative radiographic measure of joint laxity. They report the presence of two unlinked quantitative trait loci (QTLs) on CFA1, located more than100 megabases apart, which demonstrated statistically significant associations. A third locus on a different chromosome was found to be associated with osteoarthritis.
     By comparison, Todhunter and colleagues have developed a large outcrossed pedigree of affected Labrador retrievers crossed with unaffected greyhounds. A variety of measures, including age at detection of femoral capital epiphyseal ossification, distraction index, hip joint dorsolateral subluxation score, and hip joint osteoarthritis, are being used in a genome-wide scan for classical linkage. While no gene has yet been found, pedigree analysis suggests that loci controlling these traits act additively, and that the distraction index may be controlled by a single major locus. 
     These studies represent two distinct methods for approaching a complex problem. Both highlight different advantages of using the canine system for genetic analysis. The first makes use of the availability of large controlled populations with limited genetic diversity. The second demonstrates the ability to cross populations showing extremes of phenotype in order to map genes. Each has the potential for success, and comparison of the two methods will improve the design of future studies. 
 
Current methods of examining dogs for CHD:   (the following is another excerpt for the preceding reference by Lan Zhu et.al. (2009)
 
Canine hip dysplasia phenotype
     Radiology has commonly been used to diagnose CHD.The technique has been standardized worldwide, although there is some variation in radiograph evaluation (Flu¨ ckiger,2007). There are three (somewhat different) international
scoring methods:  the Federation Cynologique Internationale (FCI), the OFA, and the British Veterinary Association/Kennel Club (BVA/KC) methods.
      The FCI scoring method is used in most mainland European countries, Russia, South America, and Asia. The OFA approach is used exclusively in the USA and Canada; and the BVA/KC method is used in Britain, Ireland,
Australia and New Zealand.     Details of each scoring method are described by Fluckiger, M., 2007. (Scoring radiographs for canine hip dysplasia - the big three organizations in the world. European Journal of Companion Animal Practice 17, 135-140.)
     The North American method of assessing hip conformation is the extended-hip radiographic score of ‘excellent', ‘good', and ‘fair' with ‘borderline', ‘mild', ‘moderate' and ‘severe' hip dysplasia as developed by the OFA and is one of the methods used in the studies (Fig. 1) of this review.
 
 Additional Review and Article References:
 
"Genetic structure of susceptibility traits for hip dysplasia and microsatellite informativeness of an outcrossed canine pedigree"
Todhunter RJ, Bliss SP, Casella G, Wu R, Lust G, et al.  
J Hered. 2003;94:39-48. [PubMed] 
 
"Genetics of canine hip dysplasia."  Journal of the American Veterinary Medical Association (JAVMA), 1997 May 1; 21 (1.0). pp. 1474-9 Author: Leighton, EA.
 
"Evaluation of risk factors for degenerative joint disease associated with hip dysplasia in German Shepherd Dogs, Golden Retrievers, Labrador Retrievers, and Rottweilers."  JAVMA, Vol 219, No. 12, December 15, 2001. pp. 1719-1724.  Gail K. Smith, VMD, PhD; Philipp D. Mayhew, BVM&S; Amy S. Kapatkin, DVM, DACVS; Pamela J. McKelvie, VMD; Frances S. Shofer, PhD; Thomas P. Gregor, BS.

"Differential genetic regulation of canine hip dysplasia and osteoarthritis."  PLoS One. 2010 Oct 11;5(10):e13219.  Authors: Zhou Z, Sheng X, Zhang Z, Zhao K, Zhu L, Guo G, Friedenberg SG, Hunter LS, Vandenberg-Foels WS, Hornbuckle WE, Krotscheck U, Corey E, Moise NS, Dykes NL, Li J, Xu S, Du L, Wang Y, Sandler J, Acland GM, Lust G, Todhunter RJ.  CONCLUSION/SIGNIFICANCE:  The identified SNPs included those near known genes (PTPRD, PARD3B, and COL15A1) reported to be associated with, or expressed in, OA in humans. This suggested that the canine model could provide a unique opportunity to identify genes underlying natural HD and hip OA, which are common and debilitating conditions in both dogs and humans.

REFERENCES

1. Leighton EA. Genetics of canine hip dysplasia. J Am Vet Med Assoc 1997;210:1474-1479.
2. Cardinet GH III, Guffy MH, Wallace LJ, et al. Canine hip dysplasia in German Shepherd Dog-Greyhound crossbreeds. J Am Vet
Med Assoc 1983;182:393-395.
3. Corley EA. Role of Orthopedic Foundation for Animals in the control of canine hip dysplasia. Vet Clin North Am Small Anim
Pract 1992;22:579-593.
4. Leighton EA, Linn JM, Willham RL, et al. A genetic study of canine hip dysplasia. Am J Vet Res 1977;38:241-244.
5. Lust G. An overview of the pathogenesis of canine hip dysplasia. J Am Vet Med Assoc 1997;210:1443-1445.
6. Willis MB. Hip dysplasia. In: Genetics of the dog. New York: Howell Book House, 1989;144-179.
7. Kaneene JB, Mostosky UV, Padget GA. Retrospective cohort study of changes in hip joint phenotype of dogs in the United States. J Am Vet Med Assoc 1997;211:1542-1544.
8. Henry GA. Radiographic development of canine hip dysplasia. Vet Clin North Am Small Anim Pract 1992;22:559-578.
9. Kealy RD, Olsson SE, Monti KL, et al. Effects of limited food consumption on the incidence of hip dysplasia in growing dogs. J Am Vet Med Assoc 1992;201:857-863.
10. Kealy RD, Lawler DF, Ballam JM, et al. Five-year longitudinal study on limited food consumption and development of osteoarthritis in coxofemoral joint of dogs. J Am Vet Med Assoc 1997;210:222-225.
11. Kealy RD, Lawler DF, Ballam JM, et al. Evaluation of the effect of limited food consumption on radiographic evidence of osteoarthritis in dogs. J Am Vet Med Assoc 2000;217:1678-1680.
12. Smith GK, Gregor TP, Rhodes H, et al. Coxofemoral joint laxity from distraction radiography and its contemporaneous and prospective correlation with laxity, subjective score, and evidence of degenerative joint disease from conventional hip-extended radiography in dogs. Am J Vet Res 1993;54:1021-1042.
13. Smith GK. Advances in diagnosing canine hip dysplasia. J Am Vet Med Assoc 1997;210:1451-1457.
14. Madsen JS, Reiman NI, Svalastoga E, et al. Delayed ossification of the femoral head in dogs with hip dysplasia. J Small Anim Pract 1991;32:351-354.

15.  "Power of a Labrador Retriever-Greyhoun pedigree for linkage analysis of hip dysplasia and osteoarthritis."  Rory J. Todhunter, BVSc, PhD; George Casella, PhD; Stuart P. Bliss, DVM; George Lust, PhD; Alma Jo Williams, MS; Samuel Hamilton, BVSc; Nathan L. Dykes, DVM; Amy E. Yeager, DVM; Robert O. Gilbert, BVSc, MMedVet; Nancy I. Burton-Wurster, PhD; Cathryn C. Mellersh, PhD; Gregory M. Acland, BVSc. AJVR, Vol 64, No. 4, April 2003. pp. 418-
 

For Further Study - Researchers involved in the study of CHD:

Rory J. Todhunter - College of Vet. Med., Cornell University. 

Research/Clinical Interests
Osteoarthritis and Hip Dysplasia: Over the last 5 years, my research investigations have focused on the problem of hip dysplasia and osteoarthritis in dogs. I am bringing contemporary methods to bear on this major canine problem. My focus has been (1) to reduce the false positive and negative diagnoses that arise with the current radiographic methods to diagnose hip dysplasia with an imaging method called the dorsolateral subluxation test; and (2) to find genetic markers for the traits underlying hip dysplasia in dogs and, in the long term, the mutations that predispose to these traits. We have an ongoing study headed by surgery resident Dr. Dan Ogden, to compare the DLS test across breeds. We are in need of 8-12 month old dogs for this study.   We have identified chromosomal regions harboring the genes that confer susceptibility to, and protect against, canine hip dysplasia. We have discovered several markers (single nucleotide polymorphisms) that predict a dog's breeding value or genetic potential for hip conformation. We are validating these markers.

 

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