(Legg-Calve Perthes, Patellar Luxation, Elbow Dysplasia, and Hypothyroidism)

You can’t create the future by focusing on the past

Introduction

In Part I our discussion focused on strategies known to reduce the incidence of complex (polygenic) diseases. Recommendations were offered that are useful in the control and elimination of these disorders whether genetic tests are or are not available. This paper will discuss four genetic diseases and the recommendations that are useful in reducing their risk, while controlling and eliminating them. The focus of this paper will be on the strategies useful in the control of the problems associated with Legg-Calve Perthes, Patellar Luxation, Elbow Dysplasia, and Hypothyroidism. The recommendations offered vary depending on whether the disorder is a simple or complex disease and whether there are genetic tests available. A brief review of the recommendations and strategies offered in Part I are repeated in this paper. Selective breeding using pedigree analysis is known to reduce risk, control and eliminate unwanted diseases and is recommended to those who rely on records.

Simple and Complex Diseases

Genetic health problems can be divided into two categories. They are called simple or complex. The more troublesome disorders are usually complex and are often called polygenic disorders because they are caused by more than one pair of genes. Most polygenic disorders do not have a genetic test for carriers, but they do have phenotypic tests that can identify affected individuals. Controlling inherited problems involves: 1) Identify traits that closely represent the genes being selected against, 2.) Standardize nuisance factors (such as the environment) that can limit selective pressures against genes and, 3) Make selections based on the breadth and depth of a pedigree. Complex polygenetic disorders can be grouped into several categories. One category that is most troubling is called the dreaded diseases. They are defined as disorders that are known to cripple, kill, and cause early death or blindness. Because of their consequences, these disorders must be given a high priority.

The breeding recommendations offered in Part I focused on a breed and replace strategy using the Symbols pedigree. This pedigree is recommended because it is a powerful tool that collects information vertically and horizontally about ancestors and their littermates (breadth and depth). The Symbols pedigree is drawn with two symbols. Males are represented as a square and females as a circle. As information is collected about each individual their symbol is coded using designated colors that represent a specific trait or disease. Because breeders are interested in many traits and diseases they will use several colors to code their pedigrees. The color of the dot indicates a specific trait or disorder. The repetition of a color usually signals the presence of a genetic trend. Dots are used to indicate a carrier. For more information about how to code this pedigree for traits and disorders see "Breeding Dogs to Win".

Figure 1 Traditional Pedigree

Notice in Figure 1 the number of carriers (dots) and affected individuals (solid colors). With this kind of information, risk for certain traits and disorders can easily be seen and appreciated.

Strategies for Managing Disease

The goal of each breeder is to make improvements in their breed while managing the spread of unwanted disorders. The management of problems is something every breeder will face and there is no single recommendation that will fit every breeding situation while preserving blood lines and maintaining genetic diversity. This means that some goals will be achieved with the use of genetic tests but others will be achieved when tests are not available. Both situations require the use of the Symbols pedigree because information that has been collected about each ancestor provides key information about risk and the likelihood of control and elimination.

Diseases for which there are no genetic tests

Many diseases have no genetic tests, which means that breeding decisions will be more difficult. What complicates these situations is that in every breed there are quality dogs that will be carriers and unfortunately most of them will not be known until they produce a disorder. This is because a large number of diseases have a late onset. In order to better understand this subject, two terms, phenotype and genotype will be used. Phenotype refers to the characteristics that can be seen, meaning their external appearance. For example, a dog that is healthy that also has a black coat may not produce healthy pups that are black. It could produce pups with other colors that have polygenic disorders such as Leggs-Calve Perthes or hip dysplasia. Such a dog could have a genetic make-up (genotype) that includes unwanted genes. Without genetic tests, the genotype cannot be seen directly. In these cases, indirect methods must be used to learn about the unwanted traits. Indirect methods are not estimates or guessing games. Instead, they require the collection of detailed information which includes protocols such as radiographs, laboratory tests etc. When information about several ancestors including their littermates has been collected for three generations, the risk for a problem is better known. This means the selection of sires and dams will not be based just on the appearance of a sire or dam but on the information gathered about their relatives. Coding this information on a Symbols pedigree provides the breeder with a visual picture of the disease (Figure 1) which is superior to the Traditional pedigree which places emphasis on learning the names and titles of ancestors.

The strategy recommended when no tests are available is to retire the dogs that produce a disease from breeding and replace them with a quality offspring. This will reduce the carrier risk by half (50%). Replacing carriers with quality offspring means that the replacements should exceed or be equal to the quality of the carrier parent. This strategy is called a breed, evaluate and replace. This approach is intended to replace carrier animals with normal’s, which over time, will reduce and diminish the problem.

Diseases when genetic tests are available

Testing breeding stock before a breeding decision is made tells the breeder whether the animal is normal, a carrier or affected for a disease. In most cases, breeders will breed a normal tested animal to a normal testing animal with the goal of producing normal offspring that will not carry the disease. There are times when animals of exceptional quality will be tested and found to be carriers or affected.

In these cases the recommendation is to breed the carriers only if they meet two conditions. First, they are of exceptional quality and second, they are bred to normal testing partners. This decision should be based on the quality of the carrier for other needed traits that cannot be found in other normal testing animals. In breedings that involve a tested carrier and a normal partner, the offspring should be tested, and if there is an exceptional pup that tests normal it, should replace the parent. This approach manages and controls risk while reducing the extent of the problem. This strategy is called breed, test and replace. The ideal breeding tool for this purpose is the Symbols pedigree which was previously discussed.

Legg-Calve-Perthes Disease (LCP)

LCP is a complex (polygenic) dreaded disease of small and toy breeds. It occurs when the blood supply to the hip collapses, causing degeneration and arthritis. Radiographs can be used to identify affected dogs between 4 months and 1 year of age. For breeds that have both LCP and hip dysplasia, a radiograph at 2 years of age can be used to identify affected dogs (Bell 2b). The recommended breeding tool for this disorder is the Symbols pedigree (discussed earlier) because it includes the ancestors and their littermates (breadth and depth). The frequency of occurrences among the ancestors and their littermates are good indicators of risk, especially when the disorder is complex or polygenic.

Legg-Calve-Perthes Disease

Table 1 Breeds at Risk for Legg-Calve-Perth

Affenpinscher	Fox Terrier	Pug
Australian Terrier	Jack Russell Terrier	Schipperke
Bichon Frise	Lakeland Terrier	Scottish Terrier
Border Terrier	Manchester Terrier	Shetland Sheepdog
Boston Terrier	Miniature Schnauzer	Silky Terrier
Cairn Terrier	Miniature Pinscher	Welsh Terrier
Chihuahua	Pomeranian	West Highland White
Cocker Spaniel	Pekingese	Terrier
Dachshund	Poodle	Yorkshire Terrier

Elbow Dysplasia

This is another dreaded disease that is found in many breeds. It is complexly inherited (polygenetic) and involves the uncoordinated growth between the radius and ulna - the two bones of the lower forearm. When their growth is not coordinated, the radius bumps into the humerus and causes abnormalities of the elbow joint. Disorders of the elbow include: the ununited anconeal process (UAP), the fractured coronoid process (FCP), or osteochondritrs dessican (OCD) of the elbow joint. Of all dogs with radiographs submitted to the OFA, about 15% are rated with elbow dysplasia (Keller). Over 70% of these dogs have Grade I elbow dysplasia, which is a radiographic diagnosis that will not cause clinical disease (Bell 2b). Whenever a dog with Grade I or Grade II elbow dysplasia is identified they usually have several close relatives with Grade I, elbow dysplasia (Bell 2b). Therefore, screening for elbow dysplasia and recording the results on the Symbols pedigree provides a record of the frequency of occurrences which is an essential step in evaluating breeding stock. The OFA certifies elbows at two years of age, and a discount is offered when elbow and hip radiographs are submitted together on the same dog.

Elbow Dysplasia

Table 2 Breeds with the highest incidence of elbow dysplasia

Breed	Percentage %
Pug	50.0
Chow Chow	48.5
Rottweiler	39.7
Bulldog	36.5
Black Russian Terrier	29.6
Bernese Mountain Dog	28.3
Chinese Shar-Pei	24.3
Newfoundland	23.6
Fila Brasileiro	21.8
American Bulldog	20.1
Dogue De Bordeaux	20.0
German Shepherd Dog	19.1
Irish Water Spaniel	18.2
Am, Staffordshire Terrier	16.9
Staffordshire Bull Terrier	16.0
St. Bernard	15.8
American Bull Terrier	15.5
English Setter	15.5
Bloodhound	15.1
Mastiff	14.6
Tibetan Mastiff	14.1
Bullmastiff	14.0
English Springer Spaniel	13.7
Irish wolfhound	13.2
Gordon Setter	13.0
Cane Corso	11.0
Golden Retriever	11.0
Greater Swiss Mountain Dog	11.0

Patellar luxation

Patellar luxation is another one of the dreaded disorders. It is complex (polygenic) and results in a structural problem of the rear legs. It involves the patella or kneecap which is part of the stifle (knee) joint on the hind leg. Patellar luxation is a complexly inherited disorder that causes the kneecap to pop out of its groove in the medially (toward the center of the body), or laterally (toward the outside of the body). This causes pain and instability of the joint. Some dogs that are affected will have no clinical signs and for others it will be painful and require surgery. Most affected dogs will develop arthritis of the stifle joint as they grow older (Bell 2b). Patella luxation is more common in the small breeds: however several large breeds also have a high incidence of the disorder. An OFA patellae evaluation at 1 year of age is recommended (Bell 2b).

Grade l - Can be located manually at full extension of the stifle joint, which returns to the trochlear groove when released.

Grade 2 - Evaluation shows that the patella naturally returns to the trochlea.

Grade 3 - The patella remains in a located position though it can be manually returned to the trochlea.

Grade 4- The patella is permanently luxated and cannot be returned to the trochiea.

Because of its complex mode of inheritance information about the parents, ancestors and their littermates (breadth and depth) must be included when their pedigrees are studied.  The recommended tool for understanding the risk of patella luxation is the Symbols pedigree (Battaglia).

Table 3 Breeds with the highest incidence of Patellar luxation

Breed	Percentage %
Pomeranian	41.1
Yorkshire Terrier	24.3
Boykins Paniel	18.9
Cocker Spaniel	15.8
Australian Terrier	12.6
Japanese Chin	11.8
Tibetan Spaniel	11.8
Chow Chow	10.2
Bedlingtotn Terrier	9.1
Shetland Sheepdog	9.0
Lhasa Apso	8.5
Chinese Shar-Pei	8.3
Labrador Retriever	6.8
Scottish Terrier	6.5
Tibetant Terrier	6.5
Shiba Inu	6.4
Pug	6.3
American Eskimo	5.7
Boston Terrier	5.6
Norfoltk Terrier	5.6
Petit Basset Griffons Ven Deen	5.6
Chihuahua	5.5
Brussel Griffon	5.3
Dachshund	5.3
French Bulldog	5.1

Hypothyroidism

This is another dreaded disease caused by autoimmune thyroiditis (Bell 2a). This is an inherited autoimmune disorder where the thyroid gland is destroyed by autoantibodies. In order to diagnose this disease a thyroid test is used to identify affected dogs, usually between 1 and 4 years of age. Most affected dogs have clinical signs between 2 and 6 years of age. A thyroid profile, including autoantibodies, will identify most affected dogs. Based on a study of all dogs that were thyroid tested by the Michigan State University endocrinology laboratory, 7.5% tested positive for thyroglobulin autoantibodies. Higher rates were found among mixed breeds that tested positive 10.7% of the time for thyroid autoantibodies (Bell 2b). The recommended breeder’s tool for understanding the risk for hypothyroidism is the Symbols pedigree because it collects information about the ancestors and their littermates (breadth and depth).

Table 4 Breeds with the highest incidence Hypothyroidism

Breed	Percentage %
English Setter	31.4
Havanese	22.6
Old English Sheepdog	21.9
German Wirehaired Pointer	18.6
American Pitbull Terrier	18.2
Boxer	18
Tibetan Terrier	17.7
Nova Scotia Duck  Tolling Ret.	17.7
Maltese	16.5
Beagle	16.5
Dalmatian	16.3
Pointer	15.9
Cocker Spaniel	15.7
Giant Schnauzer	15.5
Rhodesian Ridgeback	15.4
Kuvasz	15.1
American Staffordshire Terrier	14.6
Welsh Springer Spaniel	13.9
Golden Retriever	13.2

Conclusion

Regardless of the disease or disorder, the selection of breeding partners is the responsibility of the breeder. The achievement of specific goals always depends upon the ability of the breeder to evaluate the predictive breeding value of each sire and dam. To this end, information is a key component to making quality decisions and notable improvements. To aid in this process there are genetic tests for more than 60 disorders. Unfortunately, few if any tests are available for disorders that are polygenic. However, with or without genetic tests, most diseases and other unwanted traits can be reduced or eliminated using one of the two recommended breeding strategies. In both instances pedigree analysis is recommended. Finally, in order to achieve specific breeding goals breeders must fine tune their breeding skills and understand each animal’s predictive breeding value. To this end, a key component to solving and making notable improvements will require pedigree analysis and quality information.

References

1. Battaglia, Carmen, 2009. Breeding Dogs to Win, BEI publications, Atlanta, Georgia, pg. 113- 168.
2. Keller, Greg, 2006. The use of health databases and selective breeding, Orthopedic Foundation for Animals, Inc., Columbia MO. Sept. 28, 2012, Pg. 9-11.
3. Bell, Jerold, Cavanagh, K, Tilley, L, Smith, F., 2012. Veterinary Medial Guide to Dog and Cat Breeds, Teton New Media, Jackson, WY.
4. Bell, Jerold, 2012. What you need to know about Genetic Disorders of Dogs. BEC, Goodman, MO.