Assessment of Inherited Disorders and Disorders Related to Breed Standards in Pedigree Dogs and Cats

Assessment of inherited disorders and disorders related to breed standards in pedigree dogs and cats

Bernese Mountain Dog Dutch Shepherd Dog Cavalier King Charles Spaniel & Maine Coon Cat

P.M. Douma (9545131)

Utrecht University, Faculty of Veterinary Medicine. Yalelaan 1, 3584 CL Utrecht, the Netherlands

Supervisors: Drs. L.E. Meijndert and Prof. Dr. J. Rothuizen.

Abstract

Concerns about dog breeding within closed populations and thus inevitable inbreeding leading to health issues aren’t new but have taken a flight in the last decade. The Dutch media eagerly pays attention and adds to the growing awareness by means of television and the Internet. Especially unhealthy breed characteristics are getting more and more attention. For the Dutch purebred population valid scientific data are to date not available. In order of the Ministry of Economics a large study has been started that basically wants to answer the pressing questions: Are purebreds really less healthy than crossbreeds? Is there a difference even between a purebred with pedigree and its look-alike without? And, consequently, what can be done if so.

Our study is a pilot part of that larger scale study and four breeds (three canine, one feline) have been selected to research the main question: To what extend occur harmful breed characteristics and heritable disorders in The Bernese Mountain Dog, The Dutch Shepherd Dog, the Cavalier King Charles Spaniel and the Maine Coon Cat in the Netherlands.

To answer this question we first extensively studied literature to get quantitative information and form an initial idea of the problems occurring within these breeds. We categorised those in three lists. Secondly, we analysed information collected from the clinical database of the University Clinic for Companion Animals (UKG) in Utrecht, the Netherlands which provide us with qualitative information.

In result we combined the two to form a final A-list: a list with most the most important disorders for this breed in the Netherlands.

For the Bernese Mountain Dog we found: Malignant Histiocytosis, Mastocytoma, Hip dysplasia and Elbow dysplasia.

For the Dutch Shepherd Dog we found no disorder of enough importance (in terms of incidence to form a final A-list.

For the Cavalier King Charles Spaniel we found: Mitral valve disease, Primary Secretory Otitis Media (SPOM), Chiari-like malformation (CM) and Syringomyelia (SM).

For the Maine Coon Cat we found: Hypertrophic Cardiomyopathy, Feline Gingivitis-Stomatitis- Pharyngitis Complex and Polyps.

Index

1. Introduction 4 1.1 Important definitions 5 1.2 Aim of this study 5 2. Background 6 2.1 Inherited disorders 6 2.2 Disorders related to breed standard 6 2.3 Dogs and cats in the Netherlands 6 2.4 The Selected breeds 7 2.4.1 Bernese Mountain Dog 7 2.4.2 Dutch Shepherd Dog 8 2.4.3 Cavalier King Charles Spaniel 8 2.4.4 Maine Coon Cat 9 3. Material and Methods 11 3.1 Literature study 11 3.2 UKG Clinical Database Analysis 12 3.2.1 Data collected 12 3.2.2 Data analysis and statistics 12 3.3 Combined results 13 4. Results 14 4.1 Control groups 14 4.2 Bernese Mountain Dog 14 4.2.1 Literature Study 14 4.2.2 UKG clinical database analysis 14 4.3 Dutch Shepherd Dog 15 4.3.1 Literature study 15 4.3.2 UKG clinical database analysis 16 4.4 Cavalier King Charles Spaniel 17 4.4.1 Literature Study 17 4.4.2 UKG clinical database analysis 17 4.5 Maine Coon Cat 18 4.5.1 Literature study 18 4.5.2 UKG clinical database analysis 18 5. Discussion 20 5.1 General considerations 20 5.2 Literature study 21 5.3 UKG clinical database analysis 21 5.3.1 Bernese Mountain Dog 22 5.3.2 Dutch Shepherd Dog 22 5.3.3 Cavalier King Charles Spaniel 22 5.3.4 Maine Coon 23 6. Conclusion 24 6.1. Bernese Mountain Dog 24 6.2. Dutch Shepherd Dog 24 6.3. Cavalier King Charles Spaniel 24 6.4 Maine Coon Cat 25 7. References 26 8. Appendices 27 8.1 Appendix 1: FCI breed standard Bernese Mountain Dog 27 8.2 Appendix 2: FCI breed standard Dutch Shepherd Dog 31 8.3 Appendix 3: FCI breed standard Cavalier King Charles Spaniel 34 8.4 Appendix 4: TICA breed standard Maine Coon Cat 37 8.5 Appendix 5: A-, B- and C-List Bernese Mountain Dog and references 40 8.6 Appendix 6: A-, B- and C-List Dutch Shepherd Dog and references 45 8.7 Appendix 7: A-, B- and C-List Cavalier King Charles Spaniel and references 47 8.8 Appendix 8: A-, B- and C-List Maine Coon Cat and references 53

1. Introduction

Concerns about dog breeding within closed populations and thus inevitable inbreeding leading to health issues aren’t new but have taken a flight in the last decade. The media eagerly pays attention and adds to the growing awareness by means of television 1, 2, 3 and the Internet 4. These concerns aren’t limited to the Dutch population and are spread well and beyond Europe 5, but the scope of this research is confined to pet populations in the Netherlands.

Two major groups of breed-related health issues can be depicted 6,7:

1. Inheritable disorders

2. Disorders related to breed standard.

Breeding within closed populations is inherent to the breeding of purebred animals.

Although simple common sense might prompt to conclusions that breeding within limited gene pools, which per definition leads to increasing homozygosity, renders dog and cat breeds prone to enhanced risk on inheritable diseases, no real valid (scientific) data exist on this subject in the Netherlands.

Rigorous selection such as the use of popular sires (matador-effect), line- or inbreeding and breeding animals with extreme breed characteristics not only further enhances homozygosity, but can also lead to disorders directly related to those extreme characteristics. Add to that the tendency of breeders to wear blinkers concerning their own animals and the downward spiral in breed health seems inevitable.

Are purebreds really less healthy than crossbreeds? Is there a difference even between a purebred with pedigree and its look-alike without?

Three dog breeds and one cat breed have been selected for this survey: The Cavalier King Charles Spaniel, Bernese Mountain Dog, Dutch Shepherd Dog and the Main Coon Cat. The cat breed was included to emphasize that problems due to breeding within closed populations of purebreds are not limited to dogs but also occur in other species.

For selection of he breeds the following criteria were taken into account:

• Population size

• Makeability (selection in favor of desired traits)

• Inherited disorders due to inbreeding

• Percentage of look-alike animals within the breed population

• Degree of organization by the parties involved (breedclubs , breeders etcetera)

• Knowledge/know how/infrastructure available for research

• Willingness to cooperate of the parties involved

• Social support

Both the Cavalier King Charles Spaniel and Bernese Mountain Dog are popular breeds well known for their extended health problems and hardly need further introduction to the public. The Dutch Shepherd Dog is a rather small breed, implicating limitations on gene pool variety. The Main Coon cat is also known for popularity and several breed-linked diseases. The four breeds will be shortly introduced in the next chapter.

1.1 Important definitions

Breed: a stock of animals or plants within a species having a distinctive appearance and typically having been developed by deliberate selection (Oxford Dictionary).

Purebred: An animal bred from parents of the same breed or variety (Oxford Dictionary). A purebred is always accompanied by a pedigree.

Look-alike: An animal that resembles a certain breed in both appearance and behaviour according to the breed standard of that certain breed, but has no pedigree.

1.2 Aim of this Study

The aim of this survey is to assess the described inherited disorders and the disorders related to breed standard due to (in)-breeding of four selected pet breeds and which of those disorders are relevant for the Dutch population of these breeds. This survey follows a previous pilot study on four other breeds.8

This assessment is followed by a study of quantitative data from first line veterinary practices on the relevant disorders and is part of a bigger scale project, which is aimed upon the implementation of a to be widely used veterinary practice patient chart system. This system will eventually give rise to a large database of information that enables collection of both quantitative and qualitative data on pet health in the future.

The main research question:

To what extend occur harmful breed characteristics and heritable disorders in The Bernese Mountain Dog, The Dutch Shepherd Dog, the Cavalier King Charles Spaniel and the Maine Coon Cat.

Sub questions were formulated to gain the information needed:

1. Which disorders are described for the Bernese Mountain Dog, the Dutch Shepherd Dog, the Cavalier King Charles Spaniel and the Maine Coon Cat? 2. Which of these disorders are overrepresented in these breeds in comparison to crossbreed dogs and cats? 3. Are these disorders a direct consequence of harmful breed characteristics? Or do they possibly have an hereditary background? 4. Which organs systems (disciplines) are affected by these disorders 5. Are the four breeds overrepresented in those affected organ systems as compared to crossbreeds? 6. Which of the diseases (of overrepresentation) are most frequently diagnosed in the four breeds; to which diseases the breeds are predisposed?

These sub questions will eventually lead to the formation of an A-list of diseases to which the breed is not only predisposed but whom are most frequently diagnosed within the breed.

2. Background

2.1 Inherited disorders

Not all disorders are genetic. Not all genetic disorders are inherited. Non-hereditary genetic disorders are caused by new mutations or damage to DNA.

Inherited disorders however, are the result of unfortunate combination of genes carried by the parents.

To distinguish between non-hereditary and hereditary, or even genetic and non-genetic is not always easy. Cancer, for example, can be hereditary, caused by new mutations or have environmental causes.

In an open population incidence of defect genes is rather low and chances that two (or more in polygenic hereditary disorders) genes carrying harmful mutations combine are rare. However, within a closed population of purebreds inherent inbreeding is inevitable leading to diminished gene-variety and increased homozygocity thus increasing chances genes that carry defects combine in any given combination. Rigorous selection of parent animals (e.g. popular sire effect, using only 5 % of the population, selecting for exterior) further enhances these effects.9

2.2 Disorders related to breed standard

Breed standards depict the ideal version of the breed, thus providing an aim for breeders to reach.

Unfortunately, most standards are open to subject interpretation. Fact is, some breed standards contain morphological features that are, when taken to extremes, detrimental to health. Examples are endless: brachycephalic features, excessive skin, chondrodysplasia, giant size, Dalmatian spots on white (gene linked with deafness).

It is quite possible this was not at all intentional at first but that interpretation to extremes developed through the decades. “The nose should be rather short” might have meant “rather short in comparison to long nosed breeds” but when reference is left out as how to interpret “short nose” exactly it is no wonder that interpretations shifted over the years. For if one starts comparing within the breed, there would always be a “shortest nose” leading to unaware selection of shorter and shorter noses. An equivalent development could be imagined about excessive skin, shade of colour or any other feature described within the breed standard. As a result, dogs and cats are bred to extremes.9

2.3 Dogs and cats in the Netherlands

In the Netherland over 29 million companion animals are held. Dogs number about 1,5 million animals, of which is an estimated 0.5 million of pedigree purebreds. The cat population is almost double in size with approximately 2,9 million animals. The remainder is comprised of look- alikes/purebreds without pedigree and crossbreeds.10

The international kennel club, Fédération Cynologique International (FCI), recognises 356 dog breeds; in the Netherlands about 350 breeds make up the Dutch pedigree dog population.8

The Dutch Studbook is called the “Nederlands Hondenstamboek “(NHSB). Pedigrees are FCI- registered and provided by the Dutch Kennel Club, the Raad van Beheer op Kynologisch Gebied (RvB).11 Internationally some countries have their own studbooks, like the United Kingdom and the United States.

It is unclear how many pedigree purebred cats there are in the Netherlands. This is mostly due to the fact that in contrast to the situation for dogs, not one coordinating kennel club (Raad van Beheer op Kynologisch Gebied for dogs, RvB) but several different organisations provide pedigrees for cats.

The Féderation Internationale Féline (FiFé) recognises 48 cat breeds but, as said, is not the equivalent of the FCI. Two of the Dutch pedigree-providing clubs are members of FiFé, ten other organisations aren’t. Those ten are connected in yet another organisation called Federatie Nederlandse kattenverenigingen (Federation of Dutch Cat Clubs). Therefore reliable numbers of known pedigreed cats are unavailable. It is estimated that around 90.000 cats have pedigrees.10 Purebred cats without pedigree are rare meaning that the vast majority of cats in the Netherlands are crossbreed.12

2.4 The selected breeds

Researched dog breeds in this study were the Bernese Mountain Dog, Dutch Shepherd Dog (shorthaired, rough coated and longhaired) and Cavalier King Charles Spaniel. The one cat breed in our study was the Maine Coon Cat.

2.4.1. Bernese Mountain Dog

Fig.1 Bernese Mountain Dog. Devael Just Call Me Earl.

Originally named “Dürrbachler” after the place where they were once most numerous, the Bernese Mountain Dog’s origin lies in Switzerland. These longhaired tricoloured farm-dogs were historically used as guard- draught- and cattle dogs on farms in the Canton Bern. Nowadays the breed is a popular all over the world well appreciated family dog and versatile worker. As early as 1907 a group of motivated breeders promoted pure breeding of the dog and founded the “Schweizerischer Dürrbach-Klub” after which they fixed the characteristic traits of the breed in a standard.

Soon after, the name was changed into Bernese Mountain Dog (Berner Sennenhund) following the example of the three other Swiss Mountain Dogs, the Great Swiss Mountain Dog, The Appenzeller Mountain Dog, and the Entlebucher Mountain dog.

Its general appearance is that of a strong, compact, sturdy yet agile built working dog, of above medium size and harmoniously balanced. The long, straight or slightly wavy coat is always tricoloured. The full FCI breed standard for the Bernese Mountain Dog can be found in Appendix 1.

2.4.2 Dutch Shepherd Dog

Fig.2 Dutch Shepherd Longhair. www.vtbikseland.nl

The Dutch Shepherd Dog is, as its name suggests originated in the Netherlands. From early times it worked alongside farmers and shepherds. Some of its tasks were to keep the flock of sheep from damaging crops and to accompany them on the road when they were on the move, patrolling the borders of road and fields. On farm grounds they not only alerted the farmers on strangers, but also collected cows to be milked, pulled the milk carts and kept hens from the kitchen. As early as 1898 the first breed standard was written. After disappearance of the great sheep flocks, depriving them of herding work, their versatile skills did not go unnoticed and they became rapidly popular in diverse dog training such as police work, search- and tracking, or guidance of the blind. To this day however its herding talent is still present.

Its general appearance is that of a medium size, middle weighted, well-muscled dog of powerful and well-balanced structure (see FCI standard, Appendix 2). It has a lively temperament and an intelligent expression. There are three varieties, distinguished by their coat: short haired, longhaired and rough coated (wire haired).

2.4.3 Cavalier King Charles Spaniel

The Cavalier King Charles Spaniel, not to be confused with its older relative the King Charles Spaniel, is a highly popular Companion dog, due to its small size and gay and friendly appearance with a shiny silky long coat. Its origin lies in Great Britain.

It was created in the early 20s in response to criticism about the short-muzzled Toy Spaniels (e.g. King Charles Spaniel) to regain the appearance of earlier spaniels with longer muzzles. Several breeds were used to create the then long-muzzled Cavalier King Charles Spaniel which was recognised as a breed by the UK Kennel Club in 1945.

Fig.3 Cavalier King Charles Spaniel, Blenheim. Wikipedia.

The breed standard has changed since 1904, mostly concerning the skull that used to be long and flat but nowadays ideally is short and high.13

The FCI standard for this breed is actually rather short (Appendix 3). The general appearance of a Cavalier King Charles Spaniel according to the standard is: active, graceful and well balanced, with gentle expression. The skull of the dog is desirably almost flat between the ears, and the stop should be shallow. The length of the nose is specifically noted and should from base of the stop to the tip of the nose be around 1,5 inch (3,8 cm) long. The complete FCI breed standard for the Cavalier King Charles Spaniel can be found in Appendix 3.

2.4.4. Maine Coon Cat

The Maine Coon Cat is currently the most popular cat breed.12 It is “a large breed, with big ears, broad chest, substantial boning, a long, hard muscled rectangular body and a long flowing tail, and large feet with tuffs” (Appendix 4, TICA Maine Coon Breed standard). An additional variety is one with polydactyly.

Fig. 4 Ranchcats Sun King

The Maine Coon was developed as a “working cat” meaning as much as that it should be at all times be able to fend for itself in diverse terrains and under extreme climate conditions (Appendix 4)..

Several breed standard have been written and differ on parts. For instance according to TICA (The International Cat Association), all colours are accepted, while according to WCF (World Cat Federation) pointed patterns are prohibited, as are chocolates and cinnamon. The Main Coon Breeders and Fanciers Association (MCBFA) has collected links to the different breed standards on its website.14

3. Material and Methods

This study was comprised of three parts. First, a literature study and analysis was performed to investigate prevalence of (possibly inherited or breed related) disorders in the selected breeds. Secondly, data collected from the database of the University Clinic for Companion Animals (UKG) in Utrecht, the Netherlands were statistically analysed. Lastly, results from both were combined to form a final conclusion.

3.1. Literature study

A broad literature study was performed to first determine which disease are described in literature or otherwise (reliable) recorded. Health assessment and selecting qualitative data of the aforementioned breeds in literature to answer the prime question:

Which (inheritable) diseases are found in the Cavalier King Charles Spaniel, Bernese Mountain Dog, Dutch Shepherd and Main Coon cat?

Literature sources:

• Scientific articles (Pubmed)

• Veterinary Books

• Survey/Research Rapports of Breed Clubs

• Online databases

• Websites of laboratories

This resulted in a list of disorders that were organised in the following disciplines: Cardiology/Pulmonology, Behaviour, Dermatology, Endocrinology, Gastroenterology, Haematology, Otolaryngology, Nephrology, Neurology, Oncology, Ophthalmology, Orthopaedics/Neurosurgery, Urology and Reproduction. Disciplines were chosen in order to correspond with clinical division disciplines within the UKG.

Next, disorders were categorised in three lists according to the following criteria:

A-list:

The top of described diseases for the given breed, mentioned most often and/or in most reliable sources (peer-reviewed journals, official databases), by several different authors.

- Diseases with most published articles about that disorder or disease - Most published diseases in reviews, preferably with data or prevalence information - Proven or suggested predisposition for a disease (in addition to importance) - When available: noted important in reliable publications concerning Dutch or European population

B-List:

Mentioned several times in reliable sources.

- A couple of to several articles about the disease - Review articles - Multiple case reports

C-List:

Mentioned only once and/or in less reliable sources.

- Only one publication of any kind (article, review or case report) - Articles with dubious sources/references - Exclusively published in books with no or just one proper reference - Kennel Club information - Websites with gathered health information (with references)

3.2. UKG Clinical Database Analysis

Using the databank of the University Clinic of Companion Animals (UKG), a referral clinic from the faculty of Veterinary Medicine to assess in which disciplines (divided by organ systems) the four breeds are over-represented in comparison with a control group.

The dog and cat control groups, consisting respectively of dogs listed in the database as crossbreed and cats listed as crossbreed, European shorthair or “house cat”, were chosen to represent/mimic the genetic diversity in an open population, in contrast to the limited diversity within the closed populations of breeds. (Note: The common Dutch term European shorthair to describe any non breed cat should not be confused with the existing European Shorthair breed in other countries).

For each breed and control group a number of data was collected within the patient database of the UKG clinic. In order to obtain both adequate numbers to enable statistic analysis of the data and to collect as recent of information as possible, we selected a timeframe of 5 recent years (01-01-2009 to 31-12-2013). For the Dutch Shepherd Dog a five-year period generated insufficient numbers to perform statistical reliable analysis, therefore in that particular case we used data from a decade (01- 01-2004 to 31-12-2013). Even though we did perform 10-period analysis for all four breeds, we chose not to present those in order to maintain as recent information as possible since the aim of our study was to investigate current breed-related problems.

Data were collected from the following disciplines: General Surgery, Cardiology and pulmonology, Dermatology, Endocrinology, Gastroenterology, Haematology, Hepatology, Internal Medicine, Otolaryngology, Nephrology, Neurology, Oncology, Ophthalmology, Orthopaedics and Neurosurgery, Dentistry, Urology and Reproduction.

3.2.1 Data collected

For each of the four breeds and their control groups we first collected, within the given timeframe, the total number of unique cases at the UKG. Subsequently the total number of unique patients per discipline was counted.

For each individual patient per discipline we collected the following information:

• Patient number • Case number • Date of first consult • Animal species • Breed • Date of Birth • Sex • Discipline visited • Diagnosis (confirmed or probable/likely)

3.2.2. Data analysis and statistics

The collected data were statically analysed using the statistical program SPSS. In order to investigate possible overrepresentation within a given discipline the Odds Ratio (OR) was used to compare visits of the breed to those of the control group. An OR >1 means the chances of the investigated breed to visit a certain discipline are higher than the control group, thus being overrepresented. Significant overrepresentation was determined with p-value <0.05 and confidence interval of 95%.

The following factors were further investigated in the overrepresented disciplines:

• Total number of patients (breed and control group) • Mean age of patients when first presented in given discipline • Most frequently diagnoses disorders

3.3. Combined results

In order to produce a final A-list results from the literature study and UKG Clinical Database Analysis were combined. The final A-list is thus comprised of diseases that are most important within the breed and for which the breed is predisposed.

4. Results

4.1. Control Groups

The collected data obtained from the UKG database were analysed and compared to a control group comprised of those registered as cross breed (table 1). Due to insufficient numbers over the desired five-year period (2009-2013), we chose a ten year period for collecting Dutch Shepherd dog data (2004-2013) and therefore its control group data were collected over the same ten year time span.

Control group Period Numbers Crossbreed dogs 5 years (2009-2013) 2199 Crossbreed dogs 10 years (2004-2013) 4271 Crossbreed cats 5 years (2009-2013) 3131 Table 1. The total number of cross breed dogs and cats visiting the UKG during the given time frame.

4.2. Results Bernese Mountain Dog

4.2.1. Literature study

Literature study revealed 60 disorders in Bernese Mountain Dogs in the following disciplines: Cardiology, Dermatology, Endocrinology, Gastroenterology, Haematology, Otolaryngology, Nephrology, Neurology, Oncology, Ophthalmology, Orthopaedics/Neurosurgery, Urology and Reproduction. The most important diseases according to this literature study, in disciplines Oncology and Orthopaedics, are presented in the A-list (table 2.) . Complete results in A-, B- and C-lists are to be found in Appendix 5.

Discipline Condition Oncology Malignant histiocytosis (histiocytair sarcoom) 2, 3, 5, 7, 8, 9, 21, 22, 23, 24, 25, 26, 52

Orthopaedics Hip dysplasia 2, 3, 4, 5, 7, 8, 13, 20, 30, 51 Elbow dysplasia 2, 3, 4, 5, 7, 8, 10, 20, 30, 31, 32, 40, 45, 51 Table 2. A-list: Most important disorders in Bernese Mountain Dogs according to literature

4.2.2. UKG Clinical database analysis

423 Bernese Mountain Dogs visited the University Clinic for Companion animals (UKG) in the 5 year period of 2009-2013. Data analyses showed that during that period Bernese Mountain Dogs were significantly overrepresented in two disciplines: Oncology and Internal Medicine. Results of data analysis per discipline are shown in table 3 in which Odds Ratio (OR), confidence interval (CI) and p- value (Fishers Exact) are given. Disciplines are ranked by Odds Ratio value (high to low).

Analysis of the ages when first presented in the clinic at the given disciplines: when compared to crossbreeds, we found a significant difference in the discipline Oncology (Table 4).

Discipline and breed Mean Median Minimum Maximum p-value Internal Medicine BMD 5.1 5.2 0.2 10.6 0.068 Internal Medicine Crossbreed 7.0 7.3 0.2 15.1 Oncology BMD 7.1 7.0 3.7 12.0 <0.001* Oncology BMD 8.9 9.4 2.6 15.9 Table 4. Comparison of age when presented in given Disciplines for the Bernese Mountain Dog as compared to crossbreeds

Discipline OR [CI 95%] p-value (FE) Nephrology 2.246 [0.858 – 5.877] 0.118 Oncology* 2.019 [1.388 – 2.936] 0.000 Gastroenterology 1.977 [1.010 – 3.871] 0.590 Urology 1.749 [0.816 – 3.746] 0.167 Internal Medicine * 1.526 [1.042 – 2.233] 0.038 Reproduction 1.227 [0.564 – 2.671] 0.532 Orthopaedics/Neurosurgery 1.134 [0.851 – 1.579] 0.485 Neurology 1.070 [0.681 – 1.682] 0.725 Hepatology 0.990 [0.529 – 1.852] 1.000 General Surgery 0.823 [0.589 – 1.148] 0.293 Otolaryngology 0.633 [0.335 – 1.195] 0.168 Dentistry 0.493 [0.115 – 2.109] 0.566 Cardiology/Pulmonolgy 0.429 [0.216 – 0.855] 0.013 Haematologie 0.376 [0.116 – 1.220] 0.100 Dermatology 0.326 [0.151 – 0.705] 0.002 Ophthalmology 0.264 [0.149 – 0.466] 0.000 Endocrinology 0.259 [0.081 – 0.830] 0.013 Table 3: Odds Ratio per discipline for Bernese Mountain Dogs visiting the UKG in 2009-2013 in comparison to crossbreeds. * Significant overrepresentation.

After determining Oncology and Internal Medicine as the relevant disciplines in which Bernese Mountain Dogs were overrepresented in contrast to cross breeds individual diagnoses were investigated to determine their importance (table 5). Single diagnoses were left out. Some diagnoses weren’t confirmed though highly probable and are thus listed Probability Diagnosis (PD).

Discipline (number of animals) Condition (number of animals) Internal Medicine (37) Maligne Histiocytose (7, of which 2 PD) Cystitis (3) Pyelonefritis (2) Maligne Lymfoom (2)

Oncology (41) Maligne Histiocytose (15, of which 4 PD) Mastocytoom (11) Maligne Lymfoom (5) Hemangiosarcoom (2) Table 5. Most diagnosed disorders in Bernese Mountain Dogs in the disciplines in which they were overrepresented. PD = Probability Diagnose.

4.3. Dutch Shepherd

4.3.1. Literature Study

Literature study revealed 25 disorders in the Dutch Shepherd Dog in the following disciplines: Cardiology, Behaviour, Dermatology, Endocrinology, Gastroenterology, Haematology, Neurology, Oncology, Ophthalmology, Orthopaedics/Neurosurgery and Reproduction. Literature about Dutch Shepherd was very limited and hard to find. None of the found disorders met the selective criteria to be listed in an A-list. Only one disorder, hip dysplasia, was considered important enough to make the C-list. Complete results in B- and C-lists are to be found in Appendix 6.

4.3.2 UKG Clinical database analysis

In a ten-year period of 2004-2013, 107 Dutch Shepherd Dogs visited the University Clinic for Companion Animals (UKG) of which 60 shorthaired, 29 longhaired and 18 rough coated dogs. Data analyses showed that during that period Dutch Shepherds were significantly overrepresented in Reproduction. Results of data analysis per discipline are shown in table 5 in which Odds Ratio (OR) , confidence interval (CI) and p-value (Fishers Exact) are given.

A closer look at the diagnoses in Reproduction shows only 8 visits in ten years:

- 2 short haired, 3 rough coated, 3 longhaired - 2 dogs, 6 bitches

An attempt to analyse possible predisposition differences between varieties (coat) could not be made due to extremely limited numbers.

We did not analyse median age for the Dutch Shepherd Dog.

Discipline OR [CI 95%] P-value (FE) Reproduction* 5.312 [2.480 – 11.376] 0.000 Dentistry 1.838 [0.569 - 5.941] 0.237 Orthopaedics/ Neurosurgery 1.634 [0.951- 2.806] 0.097 Gastroenterology 1.531 [0.475 – 4.928] 0.453 Neurology 1.297 [0.562 – 2.995] 0.474 Urology 1.195 [0.289 – 4.943] 0.686 Dermatology 1.025 [0.445 – 2.360] 0.831 General Surgery 0.788 [0.420 – 1.481] 0.556 Otolaryngology 0.762 [0.278 – 2.090] 0.819 Endocrinology 0.761 [0.239 – 2.425] 1.000 Oncology 0.722 [0.227 – 2.301] 0.799 Cardiology/Pulmonology 0.663 [0.208 – 2.111] 0.628 Internal Medicine 0.527 [0.193 – 1.442] 0.249 Ophthalmology 0.458 [0.200 – 1.050] 0.063 Hepatology 0.301 [0.042 – 2.170] 0.379 Haematology - 0.413 Nephrology - 0.626 Table 6: Odds Ratio per discipline for Dutch Shepherd Dogs visiting the UKG in 2004-2013 in comparison to crossbreeds. * Significant overrepresentation.

After excluding three bitches that visited the clinic for fertility counselling (determining ovulation to optimise breeding) and two bitches with vague complaints that didn’t lead to a diagnosis of any kind, overrepresentation was lost. The three remaining case were single diagnoses.

Discipline (number of animals) Diagnose (number of animals) Reproduction(8) cryptorchidy (1) sterile (1) vaginal fold prolapse (1)

on closer inspection no diagnose (2) fertility counselling (3) Table 7. Most diagnosed disorders in Dutch Shepherd Dogs in the discipline in which they are overrepresented.

4.4. Cavalier King Charles Spaniel

4.4.1 Literature study

Literature study revealed 78 disorders in Cavalier King Charles Spaniels in the following disciplines: Cardiology/Pulmonology, Dermatology, Endocrinology, Gastroenterology, Haematology, Otolaryngology, Nephrology, Neurology, Oncology, Ophthalmology, Orthopaedics/Neurosurgery and Urology. The most important diseases according to this literature study, in disciplines Cardiology and Neurology, are presented in the A-list (table 8). Complete results in A-, B- and C-lists are to be found in Appendix 7.

Discipline Condition Cardiology Mitral valve disease 2, 3, 4, 5, 12, 13, 14, 37, 58, 61, 62

Neurology Chiari-like malformation (CM) # 2, 3, 14, 15, 23, 34, 36, 45, 49, 65, 66 Syringomyelia (SM) 2, 13, 14, 15, 23, 30, 31, 34, 42, 44, 45, 46, 54, 59, 66 Table 8. A-List: Most important disorders in Cavalier King Charles Spaniels according to literature.

4.4.2 UKG Clinical database analysis

248 Cavalier King Charles Spaniels visited the University Clinic for Companion animals (UKG) in the 5 year period of 2009-2013. Data analyses showed that during that period Cavalier King Charles Spaniels were significantly overrepresented in two disciplines: Cardiology/Pulmonology and neurology. Results of data analysis per discipline are shown in table 8 in which Odds Ratio (OR) , confidence interval (CI) and p-value (Fishers Exact) are given. Disciplines are ranked to Odds Ratio (high to low).

Discipline OR [CI 95%] p-value (FE) Cardiology/Pulmonology* 4.026 [2.739 – 5.916] 0.000 Neurology* 3.733 [2.558 – 5.446] 0.000 Otolaryngology* 2.423 [1.502 – 3.911] 0.001 Internal Medicine 1.627 [1.023 – 2.588] 0.051 Gastroenterology 1.110 [0.389 – 3.165] 0.780 Ophthalmology 0.850 [0.542 – 1.333] 0.586 Dentistry 0.843 [0.197 – 3.618] 1.000 Reproduction 0.780 [0.238 – 2.557] 1.000 Dermatology 0.729 [0.365 – 1.458] 0.435 Nephrology 0.632 [0.083 – 4.826] 1.000 Endocrinology 0.595 [0214 – 1.651] 0.400 Hepatology 0.556 [0.201 – 1.540] 0.309 General Surgery 0.509 [0.306 – 0.845] 0.007 Orthopaedics/Neurosurgery 0.295 [0.144 – 0.606] 0.000 Oncology 0.076 [0.011 – 0.548] 0.000 Haematologie - 0.018 Urology - 0.104 Table 9. Odds Ratio per discipline for Cavalier King Charles Spaniels visiting the UKG in 2009-2013 in comparison to crossbreeds. * Significant overrepresentation.

For the Cavalier King Charles Spaniel we found a significant difference in age when first presented at the clinic in the discipline Otolaryngology. They are first presented with problems over 2 years earlier than the average crossbreed (table 10).

Discipline and breed Mean Median Minimum Maximum p-value Cardiology CKCS 6.3 7.0 0.2 12.0 0.767 Cardiology Crossbreed 6.6 7.0 0.3 14.2 Otolaryngology CKCS 5.4 5.4 1.3 8.6 0.003* Otolaryngology Crossbreed 7.6 7.9 0.2 15.0 Neurology CKCS 4.6 4.7 0.2 9.4 0.314 Neurology Crossbreed 5.7 5.7 0.3 12.3 Table 10. Comparison of age when presented in given Disciplines for the Cavalier King Charles Spaniel as compared to crossbreeds

After determining Cardiology/Pulmonology and Neurology as the relevant disciplines in which Cavalier King Charles Spaniels were overrepresented in contrast to crossbreeds all individual diagnoses were investigated. Single diagnoses were excluded. Probability Diagnoses (PD) are listed as such. The most diagnosed disorders in both disciplines are show in table 11.

Discipline (number of animals) Condition (number of animals) Cardiologie/Pulmonologie (42) Myxomateuze mitralisklepdegeneratie (29) Pulmonale hypertensive (3)

KNO (23) PSOM: Primary Secretory Otitis Media (11, of which 3 PD) Otitis Media (5)

Neurologie (43) Chiari-Malformatie (17) Syringomyelie (15 of which 3 PD) Fascialis paralyse (4) Table 11. Most diagnoses disorders in Cavalier King Charles Spaniels in the disciplines in which they were overrepresented. PD = Probability Diagnosis.

4.5. Maine Coon Cat

4.5.1. Literature study

For the Maine Coon cat we found 22 diseases and/or conditions described in the breed in our literature study. Those can be divided into the following disciplines: Cardiology/Pulmonology, Dermatology, Haematology, Otolaryngology, Nephrology, Neurology, Orthopaedics/Neurosurgery, Oncology, Reproduction and Urology. By applying the previous listed criteria we organised the diseases in an A-, B- and C-list (see Appendix 8). The most important condition concerning the breed according to literature is displayed in table 12, the A-list.

Discipline Condition Cardiology Hypertrophic Cardiomyopathy (HCM) 12, 60, 65 Table 12. A-list. Most important disorder in the Main Coon cat according to literature

4.5.2. UKG database analysis

242 Main coon cats visited the University Clinic for Companion Animals (UKG) in the 5-year period of 2009-2013 as compared to 3131 control group cats. Analysis of collected data revealed three UKG- disciplines in which the Main Coon cats were significantly overrepresented as compared to the control group: Cardiology/Pulmonology, Otolaryngology and Dentistry. Results of the analysis are

shown in table 13, in which Odds Ratio, p-value (p < 0.05, 95% confidence level) and 95% confidence interval (CI 95%) are given for each discipline.

Discipline OR [CI 95%] p-value (FE) Dentistry* 2.537 [1.411 - 4.562] 0.005 Reproduction 2.425 [0.926 - 6.356] 0.075 Otolaryngology* 2.393 [1.687 - 3.396] 0.000 Nephrology 2.043 [0.789 - 5.292] 0.184 Cardiology/Pulmonology* 1.882 [1.202 – 2.948] 0.010 Orthopaedics/Neurosurgery 1.475 [0.800 – 2.718] 0.205 Haematology 1.441 [0.332 – 6.248] 0.651 Urology 1.327 [0.524 – 3.362] 0.589 Hepatology 1.179 [0.420 – 3.310] 0.775 Dermatology 0.858 [0.414 – 1.776] 0.861 Oncology 0.652 [0.316 – 1.343] 0.280 General Surgery 0.633 [0.429 – 0.932] 0.020 Ophthalmology 0.574 [0.309 – 1.065] 0.076 Neurology 0.558 [0.226 – 1.380] 0.275 Internal Medicine 0.536 [0.281 – 1.024] 0.053 Endocrinology 0.480 [0.175 – 1.313] 0.186 Gastroenterology 0.128 [0.018 – 0.925] 0.009 Table 13. Odds Ratio per discipline for Maine Coon cats visiting the UKG in 2009-2013 in comparison to crossbreeds. * Significant overrepresentation

Subsequently, individual diagnoses in the thus selected disciplines were studied to investigate importance. Single diagnoses were left out. Several forms of Polyps were diagnosed: 22 times of which polypus otitis media (12) polypus otitis externa (6) and polypus nasopharyngealis (4). We have collected all of those together as one disorder (Polypus).

Discipline (number of animals) Condition (number of animals) Cardiology (24) Hypertrofische Cardiomyopathie (7) Myocard Hypertrofie Linker ventrikel (2)

Otolaryngology (44) Polypus (22) Rhinitis (7)

Dentistry (14) Feline Gingivitis-stomatitis-Pharyngitis-Complex (9) Parodontitis (2) Table 14. Most diagnosed disorders in Maine Coon cats in the disciplines in which they were overrepresented a 5-year period (2009-2013).

5. Discussion

5.1. General considerations

Finding proof of a disease existing in a breed does not mean it is actually an issue within the breed. The condition might be extremely rare, due to genetic mutation or to environmental factors. Very rare hereditary condition should of course not make it to our A of even B-lists, even if hereditary. Likewise, finding many different disorders for a breed does not mean the breed is an unhealthy breed. The health status of a breed depends to a greater extend on the incidence, prevalence, severity and type of disorders. And again, a very severe disease with extreme low prevalence does not make the breed an unhealthy breed. It is therefore not always easy to weigh results and categorise them to effect.

Asher and colleagues developed a method to measure the degree of well being of a breed, the Generic Illness Severity Index for Dogs. It is built upon several factors: prognosis, treatment type, chance of complications, and behavioural changes all of which are scored in severity from 0-4. The maximum score 16 (fig.1)

Fig.5 GISID score schedule, from Asher et al (2009). Vet. J.

When you score the diagnosed/found disorders for a breed it might give you additional information on the importance of the disorder and of the health status of the breed. As mentioned above, incidence and/or prevalence to also be taken into account.

5.2. Literature Study

Even though this was a literature study to find and categorise described disorders in the four selected breeds, it wasn’t as straightforward to interpret as that sounds. One has to take into account several considerations.

• Many publications doesn’t necessarily mean high incidence (especially if written by one or just two research groups) • Older literature might not reflect current importance of disorders • Case reports are rarely truly evaluated on their value. • Information that would be valuable, like experiences of breed owners, or breed clubs are not very reliable, scientifically spoken. • Surveys with (subjective) opinions are neither scientifically reliable. • It’ s impossible to find everything that is ever written • Some articles are in foreign languages that could be translated (in the time given) • Most information found was not specific for the population in the Netherlands

A peculiarity is the name of the cat breed. Written by some as Maine Coon and other as Main Coon it was necessary to use both spellings in search for relevant literature in our study.

5.3. UKG Database Analysis

Using the database of a specialised clinic such as the UKG has advantages but also it limitations. There could be a referring bias due to many factors like money, economic status, distance to the clinic, opinion of the own veterinarian, prognosis, reputation of the clinic, emotional value of the animal (or lack of) etcetera. In addition, many disorders can be readily diagnoses in a first line clinic. The patient s in the UKG clinics would thus never be a true reflection of the Dutch breed population. Quantitative information is therefore not to be found in the UKG database.

However, since the problems for which patients are referred to specialised clinics are usually more severe, more complicated or need expert opinion is does provide qualitative information.

Another advantage is that in a specialised clinic more often final diagnoses are made, whereas in first line clinics many or even most diagnoses are made upon probability.

The previous pilot study already revealed some additional limitations. Incomplete files. These limitations are even more relevant in first line clinic patient files, but also in the UKG database sometimes information was missing. We had to look manually into the patient files to find definitive diagnoses, since they were not correctly listed. Some were probability diagnoses.

5.3.1 Bernese Mountain Dog

Orthopaedics did not come up in our analysis over the most recent 5-year period, even though its importance according to literature was as such that we added it to our original A-list. Although we did find a significant overrepresentation when we run our analysis over 10 years (not presented) we chose not to use the ten-year data, because 1. Five years yielded sought after recent information with 2. Enough patients to be able to generate statistically reliable results.

The fact that over a ten-year time spam indeed Orthopaedics was selected, could mean that problems in that department are actually improving. That could be an interesting prospect to be further investigated. Another possibility is that (some) patients did not get referred to the UKG clinic and were treated, if treated, elsewhere. Referring habits might well have changed over a decade.

When we looked at the individual diagnoses in Internal Medicine, most of those were actually cancer (Malignant Histiocytosis, 7 cases). Would these patients have been categorised under Oncology we would not have found significant overrepresentation of Bernese Mountain Dogs in Internal Medicine. Therefore in our final A-list we excluded Internal Medicine as relevant discipline.

By calculating the mean and median age of which the dogs were first presented we did find a significant difference in the Oncology department. De median age for Bernese Mountain Dogs first presented is over 2 years younger than in crossbreeds. This might indicate a heritable ground for the cancers found in the Bernese Mountain Dog. When a disorder is already present at birth (or a sensitivity to develop a disease) problems are likely to arise in earlier age than when caused by external factors. This result endorses what can be found in literature about Malignant Histiocytosis in Bernese Mountain Dogs.

5.3.2. Dutch Shepherd Dog

Numbers of Dutch Shepherd Dogs that visited the UKG were extremely limited even over a ten-year time span. This could possibly mean it is a relatively healthy breed or other factors played a role as to why they are so rarely presented at the UKG. Hopefully, in the near future, the information generated by the implemented database for first-line clinics will give more accurate information.

In a Finnish survey disciplines most affected in Dutch Shepherd Dogs were Gastroenterology, Dermatology and Neurology (Spine). This is not the same as the breed being overrepresented in a certain discipline as compared to others (in our research: crossbreed). It should therefore not be interpreted as such.

Inflammation of the eyes and lameness in fore- and hind limbs were also seen more often than other diseases. In addition they compared the results of the three coat varieties after which they found that incidence of inflammation of the eye was significantly higher ( p<0.05) in long haired dogs as compared to the two other varieties. Significant gender differences were not found. The overall conclusion of the survey is that Dutch Shepherd Dogs are a fairly healthy breed in Finland. That said, it was also stressed that the population is relatively small so that attention should be directed to the incidence of hereditary diseases in the breed.15

These Finnish findings might subscribe the fact that we did not find much evidence of breed related problems.

5.3.3. Cavalier King Charles Spaniel

Both Neurological conditions found frequently in Cavalier King Charles Spaniels are directly related to breed characteristics, even though the breed standard is not very direct on skull size and form. The skull form Cavalier King Charles Spaniels has developed from a skull with a rather long nose to one with a very short nose (ideally 3,8 cm) and very shallow stop. Even though the breed standard describes a flat skull, the skull had developed into a high, rounded short skull.

Fig.6 Picture from Dier& Recht. Cavalier King Charles Spaniel. Inventarisatie van de erfelijke aandoeningen. Oktober 2010.

Chiari-like Malformation (CM) is a condition in which the volume of the fossa caudalis (the back of the skull) is not in proportion with the volume of its contend, the cerebellum and the brain stem. Part of the central nervous system might protrude the foramen magnum what can lead to blockade of the cerebrospinal fluid. Subsequently Syringomyelia (SM) can develop.16 Not all dogs with Chiari-like malformation will develop SM.

Syringomyelia is as said, secondary to CM and is characterised by the accumulation of fluids in the spine. The most important symptom of the combination CM/SM is pain. Pain is expressed in many ways; one that is often encountered is scratching, or screaming.

It is obvious that these conditions are not easily prevented or even reversed by selective breeding. It is estimated that up to 95% of all cavalier king Charles spaniels have CM and up to 50% suffers from CM/SM13. It is of utmost importance that selection must be made (if still possible) to reverse the dwarfism of the skull. Selection of puppies with the longest noses and the biggest skull might be a start. In the Netherlands Cavaliers for reproduction are screened for CM/SM. Education of both breeders and buyers is another important step. In addition exterior judges should be trained not to prise dogs with extreme features.

Calculations of the mean age tells us that Cavalier King Charles Spaniels are presented about 2,5 years earlier in Otolaryngology than crossbreeds were. This would indicate possible hereditary factors in the disorders for which they came. Primary Secretory Otitis Media (PSOM) is a condition solely described for the Cavalier King Charles Spaniel, yet another strong indication this is indeed inheritable or breed characteristic related.

5.3.4. Maine Coon Cat

Results for the Maine Coon Cat in Cardiology were straightforward. In Otolaryngology is was a little less obvious since several forms of Polypus Otitis were diagnosed and distinguishing between different types wasn’t always easy. Therefore we chose to denote them all together as “Polyps” which they indeed all were.

6. Conclusion

Combined results of both literature study and UKG Database analysis lead to the formation of a final A-list of most diagnosed diseases in disciplines in which the given breed was overrepresented.

6.1. Bernese Mountain Dog

The original A-list resulting from the literature study comprised of three main disorders, in two disciplines: Oncology and Orthopaedics. Data analysis of the UKG clinical database confirmed overrepresentation of Bernese Mountain Dogs in Oncology but also revealed another discipline in which they were: Internal Medicine.

Together with 7 casus of Malignant Histiocytoses in Internal Medicine our main A-list disease in the discipline Oncology (15 cases) has been confirmed. Additionally, we found 11 cases of Mastocytoma, which prompted us to move that disorder from our original C-list to our final A-list (table 13).

Discipline Condition Oncology Malignant Hystiocytosis Mastocytoma

Orthopaedics Hip Dysplasia Elbow Dysplasia Table 13. Final A-list Bernese Mountain Dog.

6.2. Dutch Shepherd Dog

Combined results for out literature study and the analysis of the UKG database did not yield additional information.

In conclusion: we did not formulate a final A-list for the Dutch Shepherd Dog.

6.3. Cavalier King Charles Spaniel

The original A-list resulting form the literature study comprised of three main disorders, in two disciplines: Cardiology/Pulmonology and Neurology. Data analysis of the UKG clinical database confirmed overrepresentation of Cavalier King Charles Spaniels in both Cardiology/Pulmonology and Neurology but also revealed another discipline in which they were overrepresented: Otolaryngology.

A closer look at the individual diagnoses in those disciplines strongly confirmed our three main disorders found in literature and revealed two others: Primary Secretory Otitis Media (PSOM) and Otitis Media (which might possible be the same yet differently categorised). The amount of cases in combination with the significant overrepresentation within the discipline made us move PSOM from the B-list to our final A-list.

Discipline Condition Cardiology/Pulmonology Mitral valve disease

Otolaryngology Primary Secretory Otitis Media^

Neurology Chiari-like Malformation (CM)* Syringomyelia (SM) *

Table 14. Final A-list for the Cavalier King Charles Spaniel *related to breed characteristics. ^ in Cavalier King Charles Spaniels only

6.4. Maine Coon Cat

The original A-list resulted from the literature study contained one disorder, Hypertrophic Cardiomyopathy (HCM) in the discipline Cardiology/Pulmonology. Database analysis yielded three disciplines in which the Maine Coon Cat was overrepresented in comparison to crossbreeds. Cardiology/Pulmonology was confirmed and the others were Otolaryngology and Dentistry.

Evaluating individual diagnoses Polyps and Feline Gingivitis-Stomatitis-Pharyngitis-Complex were considered important enough to be included in our final A list.

Discipline Condition Cardiology/Pulmonology Hypertrophic Cardiomyopathy

Otolaryngology Polyps

Dentistry Feline Gingivitis-Stomatitis-Pharyngitis-Complex Table 15. Final A-list for the Maine Coon Cat.

7. References

1. TV uitzending. Einde van de rashond. Zembla (2010)

2. TV uitzending. Rashonden. Tros Radar (2011)

3. TV uitzending. Rashond vaak te ver doorgefokt. RTL Nieuws (2012)

4. www.rashondenwijzer.nl (Dier en Recht, advocaat van de dieren)

5. Higgins, A. & Nicholas, F.W. The breeding of pedigree dogs: time for strong leadership. Vet. J. 178, 157-158 (2008).

6. Asher, L., Diesel, G., Summers, J. F., McGreevy, P.D., & Collins, L.M. Inherited defects in pedigree dogs. Part 1. Disorders related to breed standards. Vet. J. 182, 402-411 (2009).

7. Asher, L., Diesel, G., Summers, J. F., McGreevy, P.D., & Collins, L.M. Inherited defects in pedigree dogs. Part 2. Disorders that are not related to breed standards. Vet.J. 183, 39-45 (2010).

8. Incidentie van schadelijke raskenmerken en erfelijke gebreken bij populaties van gezelschapsdieren. Expertisecentrum Genetica Gezelschapsdieren, Faculteit Diergeneeskunde. Utrecht. April 2014

9. Frankling, E. Abnormalities and defects in pedigree dogs. VI. The breeders' point of view. 1963, Journal of Small Animal Practice, Vol. 4, pp. 475-478.

10. Rapport. Feiten en Cijfers – Gezelschapsdierensector 2011. HAS Kennistransfer i.o.v Ministerie van Economische Zaken (2011).

11. www.raadvanbeheer.nl

12. Kurushima, JD, et al. variation of cats under domestication: genetic assignment of domestic cats to breeds and worldwide random-bred populations Anim. Genet. 44, 311-324 (2014)

13. Cavalier King Charles Spaniel. Inventarisatie van de erfelijke aandoeningen. Dier & Recht. Oktober 2010.

14. http://www.mcbfa.org/breedinfo.html

15. Mia Mäkinen and Outi Laitinen, Health survey of Dutch Shepherd dogs in Finland. Suomen Eläinlääkärilehti – Finsk Veterinärtidskrift (2004) 110 (5) 239-247

16. Rushbridge, C., Knowler, S.P. Inheritance of occipital bone hypoplasia (Chiari type I malformation) in Cavalier King Charles Spaniels. J Vet Intern Med (2004) Sep-Oct; 18(5):673-8.

8. Appendices

Appendix 1: FCI breed standard – Bernese Mountain Dog

Berner Sennenhund, Dürrbächler FCI-St. N° 45 / 05.05.2003

Fig. from FCI-St. N° 45 / 05.05.2003

TRANSLATION: Mrs. Peggy Davis, revised by Elke Pepper.

ORIGIN : Switzerland.

DATE OF PUBLICATION OF THE OFFICIAL VALID STANDARD : 25.03.2003.

UTILIZATION : Originally used as a guard-, draught-and cattle dog on farms in the Canton Bern, today also family dog and versatile working dog.

FCI-CLASSIFICATION : Group 2 Pinscher and Schnauzer type-Molossoid breeds- Swiss Mountain and Cattle- Dogs. Section 3 Swiss Cattle Dogs. Without working trial.

BRIEF HISTORICAL SUMMARY : The Bernese Mountain Dog is a farm dog of ancestral origin which was used as a guard and draught dog and for driving cattle in the prealpine regions and in the midland areas around Bern. Originally he was named “Dürrbächler” according to the name of the hamlet and of the inn of Dürrbach, near Riggisberg in the Canton Bern where these long-haired tricoloured farm dogs were especially numerous. In 1902, 1904 and 1907 specimen of this breed had already been exhibited at dog shows, and in 1907 some breeders of the region of Burgdorf decided to promote the pure breeding of these dogs by founding the “Schweizerischer Dürrbach-Klub”, and fixing the characteristic traits of the breed. In 1910, at a show in Burgdorf where many farmers of that region brought their Dürrbächler dogs to, already 107 specimen were shown. From that day onward this dog, renamed “Bernese Mountain Dog” following the example of the other breeds of Swiss Mountain Dogs, became rapidly appreciated all over Switzerland and in the neighbouring parts of Germany. Today the Bernese Mountain Dog is well known and appreciated all over the world as a family dog thanks to its striking tricoloured coat and its great adaptability.

GENERAL APPEARANCE : Longhaired, tricoloured, strong and agile working dog, of above medium size, with sturdily built limbs; harmonious and well balanced.

IMPORTANT PROPORTIONS :

• Height at withers : length of body (measured from the point of the shoulder to the point of the buttock) = 9 : 10, rather compact than elongated. • Ideal relation of height at withers : depth of chest = 2 : 1.

BEHAVIOUR / TEMPERAMENT : Self-confident, attentive, vigilant, fearless in every day situations; good- natured and devoted to his own people, self-assured and placid towards strangers ; of medium temperament, docile.

HEAD : Strong. In size balanced to general appearance, not too massive.

CRANIAL REGION :

Skull : Viewed from the front and in profile little rounded. Frontal furrow hardly marked.

Stop : Well defined, but without being too pronounced.

FACIAL REGION :

Nose : Black.

Muzzle : Strong, of medium length; nasal bridge straight.

Lips : Close fitting; black.

Jaws/Teeth : Strong, complete scissor bite (molars 3 (M3) are not taken into consideration). Pincer bite accepted.

Eyes : Dark brown, almond-shaped, with close fitting eyelids. Neither too deep-set nor prominent. Loose eyelids are faulty.

Ears : Medium-sized, set high, triangular in shape, slightly rounded at the tips, in repose hanging flat and close to the head. When alert, the rear part of the set-on is raised while the front edge of the ear remains close to the head.

NECK : Strong, muscular, of medium length.

BODY :

Topline : From the neck running slightly downwards to the withers in a harmonious line, then running on straight and level.

Back : Firm, straight and level.

Loins : Broad and strong; seen from above slightly less broad than the chest.

Croup : Smoothly rounded.

Chest : Broad and deep, reaching to the elbows; forechest distinctly developed; ribcage of wide-oval section extending as well back as possible.

Underline/belly : Slightly rising from chest to hindquarters.

TAIL : Bushy, reaching at least to the hocks; hanging straight down when at rest; carried level with back or slightly above when moving.

LIMBS : Strong bones.

FOREQUARTERS :

General appearance : Forelegs seen from the front straight and parallel, standing rather wide apart.

Shoulders : Shoulder blade long, strong and well laid back, forming a not too obtuse angle with the upper arm, well attached to the chest, well muscled.

Upper arm : Long, set oblique.

Elbows : Close fitting; neither turned in nor out.

Forearm : Strong, straight.

Pastern : Seen from the side almost upright, firm; seen from the front in straight line with the forearm.

Forefeet : Short, roundish; with well-knit, well-arched toes. Turned neither in nor out.

HINDQUARTERS :

General appearance : Seen from the rear straight and parallel, not too close.

Upper thigh : Long, broad, strong and well muscled.

Stifle : Distinctly well bent.

Lower thigh : Long and oblique.

Hock joint : Strong, well angulated.

Metatarsus : Set almost vertically. Dewclaws to be removed (except in those countries where it is prohibited by law).

Hind feet : Slightly less arched than forefeet, turned neither in nor out.

GAIT / MOVEMENT : Sound and balanced movement in all gaits covering a lot of ground; free stride reaching well out in front, with good drive from behind; at the trot, coming and going, legs moving forward in a straight line.

COAT HAIR : Long, shining, straight or slightly wavy.

COLOUR : Jet black main colour with rich tan markings on the cheeks, above the eyes, on all four legs and on the chest, and with white markings as follows :

• Clean white symmetrical markings on the head : blaze extending towards the nose on both sides to a muzzle band; the blaze should not reach the tan markings above the eyes, and the white muzzle band should not extend beyond the corners of the mouth. • Moderately broad, unbroken white marking on throat and chest. • Desirable : white feet, white tip of tail. • Tolerated : small white patch on nape of neck, small white anal patch.

SIZE :

Height at withers : for dogs : 64 -70 cm, ideal size : 66-68 cm.

for bitches : 58-66 cm, ideal size : 60-63 cm.

FAULTS : Any departure from the foregoing points should be considered a fault and the seriousness with which the fault should be regarded should be in exact proportion to its degree and its effect upon the health and welfare of the dog.

• Unsure behaviour. • Fine bones. • Irregular set of the incisors provided that the bite remains correct. • Absence of any other teeth than 2 PM1 (premolars 1); the M3 (molars 3) are not taken into consideration.

• Coat: - Distinctly curly coat. - Faults of colour and markings: - Absence of white on head. - Blaze too large and/or muzzle band reaching noticeably beyond the corners of the mouth. - White collar. - Large white patch on nape of neck (maximum diameter more than 6 cm). - White anal patch (maximum size 6 cm). - White markings on forelegs reaching distinctly beyond half-way of pasterns (“boots”). - Disturbingly asymmetrical white markings on head and/or chest. - Black ticks and stripes within the white on the chest. -“Dirty” white (strong spots of pigmentation). - Black coat with a touch of brown or red.

DISQUALIFYING FAULTS:

• Aggressive, anxious or distinctly shy. • Any dog clearly showing physical or behavioural abnormalities shall be disqualified. • Split nose. • Undershot or overshot mouth, wry mouth. • One or two blue eyes (wall eye). • Entropion, ectropion. • Kinky tail, ring tail. • Short coat, double coat (Stockhaar). • Other than tricoloured coat. • Other main colour than black. N.B.: • Male animals should have two apparently normal testicles fully descended into the scrotum. • Only functionally and clinically healthy dogs, with breed typical conformation should be used

Appendix 2: FCI breed standard – Dutch Shepherd Dog

FCI-Standard N° 223

Dutch Shepherd Dog (Hollandse Herdershond)

Fig. from FCI- St N°223/21.10.2009

TRANSLATION: N.H.C. (Nederlandse Herdershonden Club, 08.07.2008)

ORIGIN: The Netherlands.

DATE OF PUBLICATION OF VALID OFFICIAL STANDARD : 28.07.2009.

UTILIZATION: Companion dog and Sheepdog.

CLASSIFICATION F.C.I. : Group 1 Sheepdogs and Cattle Dogs. Section 1 Sheepdogs. Without working trial.

BRIEF HISTORICAL SUMMARY: Originally the main function of the Dutch Shepherd Dog was that of a shepherd’s dog in the countryside. From early times, the Dutch had an arable culture that was – among other things – maintained by flocks of sheep. The dogs had to keep the flock away from the crops, which they did by patrolling the borders of the road and the fields. They also accompanied the flocks on their way to the common meadows, markets and ports. At the farm, they kept the hens away from the kitchen garden, they herded the cows together for milking and pulled the milk carts. They also alerted the farmers if strangers entered the farmyard. Around 1900, sheep flocks had for the greater part disappeared in the Netherlands. The versatile skills of the Dutch Shepherd Dog made him suitable for dog training, which was then starting to become popular. Thus he started on a new career as a police dog, as a search- and tracking dog and as a guide dog for the blind. He is, however, still capable of herding sheep. The breed’s first standard dates from 12 June 1898.

GENERAL APPEARANCE : A medium-sized, middle-weighted, well-muscled dog of powerful and well-balanced structure. A dog with lots of endurance, a lively temperament and an intelligent expression. Depending on the coat the breed is distinguished in the following varieties: short-, long- and wire haired.

IMPORTANT PROPORTIONS: The length of the body (from point of shoulder to point of buttock) exceeds the height at the withers, approximately at a ratio of 10:9, as suits a trotting dog. The proportion of the length of the skull to the muzzle is 1:1.

BEHAVIOUR/TEMPERAMENT : Very loyal and reliable, always alert, watchful, active, independent, with persistence, intelligence, prepared to be obedient and gifted with the true shepherding temperament. The Dutch Shepherd Dog works willingly together with its owner and he deals independently with any task which is assigned to him. When herding larger flocks he must have the capacity to work together with several other dogs

HEAD : In good proportion to the body. Seen from above and in profile it is wedge-shaped. Its shape is rather elongated , without wrinkles; dry, with flat cheeks and no pronounced cheekbones. Because of the coat, the head of the wire-haired variety appears to look more square, but this is an illusion.

CRANIAL REGION : Skull : Flat Stop : Slight, though clearly present.

FACIAL REGION : Muzzle : Slightly longer than the flat forehead. Bridge of the muzzle straight and parallel to the top line of the cranial region. Nose : Black. Lips : Tight and well pigmented. Jaws/Teeth : Scissors bite, strong, regular and complete. Eyes : Dark coloured and medium sized. The eyes are almond shaped and slightly oblique. The eyes should not be set too wide and should not protrude. Ears : Medium sized. When the dog is alert, the ears are carried high and erect.

NECK : Not too short, dry, without folds and gradually flowing into the body.

BODY : Firm, but not coarse. Top line : There is a smooth, gentle transition from the neck to the topline of the body, in which head and neck are carried in a natural pose. Back : Straight and firm. Loin : Firm, neither long nor narrow. Croup : Slightly sloping, not short. Underline and belly : Slight tuck up. Chest : Deep and long enough, not narrow, ribs slightly sprung. Fore chest : Fairly well developed.

TAIL : At rest, hanging straight down or with a slight curve. Reaches to the hock. In action, carried gracefully upwards, never curled or carried sideways.

LIMBS :

FOREQUARTERS : The forelegs are powerful, of good length, well muscled. The bone is solid but not heavy. Always generally showing a straight line, but with sufficient suppleness of pastern.

Shoulder : Shoulder-blades well joined to the body and well sloping. Upper arm : Approximately equal length to the shoulder-blades and well angulated with the connecting bones. Elbow : Well attached. Forefeet : Oval. Well knit, toes arched. Black nails and elastic dark pads.

HINDQUARTERS : The hind-legs are powerful and well muscled. The bone is solid but never heavy. Not excessively angulated.

Thigh and lower thigh : Of approximately equal length. Hock : Perpendicular below the point of buttock.

Dewclaws : None present Hind feet : Oval. Well knit, toes arched. Black nails and elastic dark pads.

GAIT/MOVEMENT : The Dutch Shepherd Dog is a trotter with free, smooth and supple movement, without exaggerated drive or stride.

COAT Hair : Short hair : All over the body, quite hard, close-fitting, not too short coat with woolly undercoat. Ruff, breeches and tail plume are clearly visible. Long hair : All over the body, long, straight, well fitting, harsh to the touch, without curls or waves and with a woolly undercoat. Distinct ruff and breeches. Tail abundantly coated. Head, ears and feet and also the hind legs below the hocks are short and densely coated. The backsides of the forelegs show a strongly developed coat, shortening in length towards the feet, the so called feathering. No fringes at the ears. Wire hair : Dense, harsh tousled coat and a woolly, dense undercoat all over the body except for the head. The coat should be close. Upper- and lower lip should be well-covered with hair, the whiskers and beard, and two well defined, coarse rough eyebrows that are distinct but not exaggerated. Furnishings are not soft. The hair on the skull and on the cheeks is less strongly developed. In profile it seems as if the head has a more square appearance. Strongly developed breeches are desirable. Tail is covered all round with hair. The brindle colour may be less pronounced because of the tousled coat. The wire hair coat should be hand-plucked on average twice a year.

COLOUR : Brindle. The basic colour is golden or silver. Golden can vary from light sand- coloured to chestnut red. The brindle is clearly present all over the body, in the ruff, breeches and tail. Too much black is undesirable. A black mask is preferable. Heavy white markings on chest or feet is not desirable.

SIZE AND WEIGHT : Height at the withers: Males : 57 - 62 cm. Females : 55- 60 cm.

DISQUALIFYING FAULTS : • Aggressive or overly shy. • Any dog clearly showing physical or behavioural abnormalities shall be disqualified. • Lack of breed-type.

N.B: • Male animals should have two apparently normal testicles full descended into the scrotum. • Only functionally and clinically healthy dogs, with breed typical conformation, should be used for breeding.

Appendix 3: FCI breed standard – Cavalier King Charles Spaniel

FCI-Standard N° 136

Cavalier King Charles Spaniel

ORIGIN: Great Britain.

DATE OF PUBLICATION OF THE OFFICIAL VALID STANDARD: 04.11.2008.

UTILIZATION: Companion and Toy.

FCI-CLASSIFICATION: Group 9 Companion and Toy Dogs. Section 7 English Toy Spaniels. Without working trial.

GENERAL APPEARANCE: Active, graceful and well balanced, with gentle expression.

BEHAVIOUR / TEMPERAMENT: Sporting, affectionate, absolutely fearless. Gay, friendly, non-aggressive; no tendency towards nervousness.

HEAD

CRANIAL REGION:

Skull: Almost flat between ears.

Stop: Shallow.

FACIAL REGION:

Nose: Nostrils black and well developed without flesh marks.

Muzzle: Length from base of stop to tip of nose about 1 1/2 ins. (3,8 cm). Well tapered. Face well filled below eyes. Any tendency to snipiness undesirable.

Lips: Well developed and not pendulous.

Jaws/Teeth: Jaws strong, with a perfect, regular and complete scissor bite, i.e. the upper teeth closely overlapping the lower teeth and set square to the jaws.

Eyes: Large, dark, round but not prominent; spaced well apart.

Ears: Long, set high, with plenty of feather.

NECK: Moderate length, slightly arched.

BODY :

Back : Level.

Loin : Short-coupled.

Chest : Moderate; good spring of ribs.

TAIL: Length of tail in balance with body, well set on, carried happily but never much above the level of the back. Docking previously optional when no more than one-third was to be removed.

LIMBS

FOREQUARTERS:

General appearance: Legs moderately boned, straight.

Shoulders: Well laid back.

HINDQUARTERS:

General appearance: Legs with moderate bone.

Stifle: Well turned.

Hocks: No tendency to cow- or sickle-hocks.

FEET: Compact, cushioned and well feathered.

GAIT / MOVEMENT: Free-moving and elegant in action, plenty of drive from behind. Fore-and hindlegs move parallel when viewed from in front and behind.

COAT

HAIR: Long, silky, free from curl. Slight wave permissible. Plenty of feathering. Totally free from trimming.

COLOUR: Recognized colours are :

• Black and Tan: Raven black with tan markings above the eyes, on cheeks, inside ears, on chest and legs and underside of tail. Tan should be bright. White marks undesirable. • Ruby: Whole coloured rich red. White markings undesirable. • Blenheim: Rich chestnut markings well broken up, on pearly white ground. Markings evenly divided on head, leaving room between ears for much valued lozenge mark or spot (a unique characteristic of the breed). • Tricolour: Black and white well spaced, broken up, with tan markings over eyes, cheeks, inside ears, inside legs, and on underside of tail.

Any other colour or combination of colours highly undesirable.

WEIGHT: 5,4 - 8 kg (12 - 18 lbs). A small, well-balanced dog well within these weights desirable.

FAULTS: Any departure from the foregoing points should be considered a fault and the seriousness with which the fault should be regarded should be in exact proportion to its degree and its effect upon the health and welfare of the dog.

DISQUALIFYING FAULTS:

• Aggressive or overly shy dogs. • Any dog clearly showing physical of behavioural abnormalities shall be disqualified.

N.B.:

• Male animals should have two apparently normal testicles fully descended into the scrotum. • Only functionally and clinically healthy dogs, with breed typical conformation should be used for breeding.

Appendix 4: TICA breed standard – Maine Coon Cat

MAINE COON BREED GROUP (MC/MCP) This Breed Group is comprised of the Maine Coon (MC) and the Maine Coon Polydactyl (MCP).

HEAD ...... 40 points Shape 8 Eyes 5 Ears 10 Muzzle and Chin 10 Profile 7

BODY ...... 35 points Torso 10 Legs and Feet 3 Tail 5 Boning 7 Musculature 10

COAT/COLOR/PATTERN . . . 25 points Length 10 Texture 5 Color 5 Pattern 5

CATEGORY: Traditional.

DIVISION: All.

COLOR: All.

PERMISSIBLE OUTCROSSES: None.

Overall balance and proportion are essential to the Maine Coon and no one feature should dominate the eye’s attention over any other.

HEAD: Shape: Broad, modified wedge. Size in proportion to body. Slightly longer than wide. Distinct muzzle break can be seen under high prominent cheekbones. Eyes: Large, slightly oval, appear round when wide open. Outer corner of eye points toward outer base of ear. Wide-set. Color: Any shade of green and/or gold. No relation to coat color. Blue and odd-eyes accepted in whites and particolors. Ears: Large, wide at base with outer base set just slightly farther back than inner base. Outer base just above the level of the top of the eye. Outside edges have a very slight outward tilt that is not past eleven and one o'clock. Set fairly high on head with inner edge of bases no more than one ear's width apart. Taller than the width at base but still in balance with head length. Moderately pointed ears appear taller due to lynx tips. Furnishings extend beyond outer edge of ear. Chin: Wide and deep enough to complete square look of muzzle. Firm, in line with upper lip. Muzzle: Square. Profile: Gently curving forehead. Gentle concave curve at bridge of nose flowing into a smooth nose line. Slight nose bump allowed in kittens.

BODY: Torso: Large, long, substantial, rectangular, equal in breadth from shoulders to hips. Broad chest. Level back. Females may be noticeably smaller than males. Boning: Substantial. Musculature: Substantial, powerful. Legs: Medium length to form a rectangle with the body. Feet: MC: Large, round and well-tufted. MCP: Large, well-tufted. Additional toes allowed on either fore or hind paws or both. Paws may be mitten or patty foot. Symmetrical expression preferred. Maximum of 7 toes on any one foot. Tail: At least as long as the body. Wide at base and tapering to tip with full, flowing fur.

COAT/COLOR/PATTERN: Length: Uneven; shorter on shoulders, gradually lengthening down the back and sides. Long, full, shaggy belly fur and britches. Tail fur long, full, flowing. Frontal ruff becomes more developed with age. Texture: All-weather coat. A slight undercoat gives the coat body but coat still falls smoothly. Not cottony. Color: Particolors must have some white on all four feet.

GENERAL DESCRIPTION: The Maine Coon is America's native longhaired cat. The breed, with its essentially amiable disposition, developed through a natural selection process where only the fittest survived. It should always be remembered that the Maine Coon developed basically as a "working cat" able to fend for itself in rough, woody terrain and under extreme climatic conditions. The Maine Coon is a large breed with big ears, broad chest, substantial boning, a long, hard-muscled, rectangular body and a long, flowing tail, and large feet with tufts. ALLOWANCES: Standard favors the male. Allowance MUST be made for a significant size difference between the male and the female. Type should not be sacrificed for size. Breed is slow to mature. Allow for tight ear set in kittens and wider ear set in mature adults. Polydactyly is a trait with variable expression and may produce anything from a single extra dew claw to extra toes on each foot. Any of these expressions are acceptable and there is no preference for more rather than fewer additional toes. Polydactyl mitten paws may appear to toe out.

PENALIZE: Eyes: Slanted, almond-shaped Flat tops on openings. Ears: Very close, set straight up. Narrow bases. Wide-set, flared. Chin: Weak or receding, narrow, lack of depth. Muzzle: Prominent whisker pads. Profile: Straight. Roman nose. Pronounced bump. Torso: Narrow. Tail: Short tail.

Feet: Toes (excluding dewclaws) not touching the table. Coat: Lack of slight undercoat or belly shag . Overall even coat. Color: Obvious lockets.

>-----<

Temperament must be unchallenging; any sign of definite challenge shall disqualify. The cat may exhibit fear, seek to flee, or generally complain aloud but may not threaten to harm. In accordance with Show Rules, ARTICLE SIXTEEN, the following shall be considered mandatory disqualifications: a cat that bites (216.9), a cat showing evidence of intent to deceive (216.10), adult whole male cats not having two descended testicles (216.11), cats with all or part of the tail missing , except as authorized by a board approved standard (216.12.1), cats with more than five toes on each front foot and four toes on each back foot, unless proved the result of an injury or as authorized by a Board approved standard (216.12.2), visible or invisible tail faults if Board approved standard requires disqualification (216.12.4), crossed eyes if Board approved standard requires disqualification (216.12.5), total blindness (216.12.6), markedly smaller size, not in keeping with the breed (216.12.9), and depression of the sternum or unusually small diameter of the rib cage itself (216.12.11.1). See Show Rules, ARTICLE SIXTEEN for more comprehensive rules governing penalties and disqualifications.

8.5 Appendix 5: A-, B- and C-List Bernese Mountain Dog and references

A-List

Discipline Condition Oncology Malignant histiocytosis (histiocytair sarcoom) 2, 3, 5, 7, 8, 9, 21, 22, 23, 24, 25, 26, 52

Orthopaedics Hip dysplasia 2, 3, 4, 5, 7, 8, 13, 20, 30, 51 Elbow dysplasia 2, 3, 4, 5, 7, 8, 10, 20, 30, 31, 32, 40, 45, 51

B-List

Discipline Condition Neurology Epilepsy (idiopathic) 2,3, 34, 46, 52 Degenerative myelopathy 1, 3, 13, 28, 52 (aseptic) Meningitis 2, 7, 20

Ophthalmology Entropion 2, 4, 6, 7, 8, 20, 51

Orthopaedics Cranial Crucial ligament rupture 3, 8, 20, 52

Reproduction (susceptibility to) Pyometra (intact females) 3, 29, 44

C-List

Discipline Condition Cardiology/Pulmonology Subaortic stenosis 2

Dermatology Allergy (general) 20, 51, 52 Aseptic pyogranulomatous sialadenitis 19 Colour dilution alopecia 2, 7 Sebaceous adenitis 14

Endocrinology Hypothyroidism 4, 6, 8

Gastroenterology Gastric volvulus 20 Mesenteric volvulus 16 Portosystemic shunting (intrahepatic) 4, 39, 51, 52 Protein Loosing Enteropathy 4, 7

Hematology Factor I deficiency 3, 5 Von Willebrands Disease (type 5) 1, 3, 5

Otolaryngology Cleft lip 4, 8 Cleft palate 4, 8 Otitis externa 20

Nephrology Congenital renal dysplasia 1, 47 Hereditary glomerulonephritis 2, 3, 5, 7, 8, 35

Neurology Alexander disease-progressive paralysis and dementia 3, 50

Cerebellar cortical (and extrapyramidal) abiotrophy 2, 4, 5, 7 Cerebellar Purkinjecell degeneration 4 # Hepatocerebellar degeneration 3, 4, 5, 8, 49 Hypomyelinating neuropathy (syn. Trembler, “Shaking Pup”) 2, 3, 5, 7, 12 Malignant hyperthermia 1, 7 Necrotising vasculitis in the central nervous system 15, 48 Wobbler 4

Oncology Cutaneous hemangiosarcoma 7, 9 Infiltrative Lipoma 18 Mammary tumours 29 Mast cell tumour 27 Systemic histiocytosis 6, 7, 9, 20

Ophthalmology Cataract 4, 6, 7, 8 Distichiasis 6 Persistent pupilary membrane 6 PRA (general) 2, 4, 6, 7, 8, 42 Retinal Dysplasia 3, 4, 8

Orthopaedics/Neurosurgery Bicipital tenosynovitis 43 Cervical vertebral malformation-malarticulation syndrome 37 Enostosis 20 Hernia nuclei pulposi (HNP) 20 IMPA Immune mediated polyarthritis 15, 36 Lateral torsion and tarsal valgus deformity 7 Osteochondritis dissecans shoulder 3, 4, 7 Patella luxation 6 Polyarthritis 7 Polydactyly 3

Urology Hyperuricosuria 1 Umbilical hernia 4, 8

Reproduction Circumcaval ureter 39 Hypoluteoidism 41 Intersexuality syndrome 33 Reduced fertility (male sterility) 20

# (related to coat colour dilution)

References

1. Laboratory for Clinical Diagnostics: laboklin.co.uk

2. Canine Inherited Disorders Database (CIDD): http://ic.upei.ca/cidd/

3. University of Cambridge- Inherited Diseases in Dogs (IDID): idid.vet.cam.ac.uk

4. LIDA: sydney.eu.au/vetscience/lida

5. Luc J. Peelman. Erfelijke Afwijkingen bij de hond. (Euroscience, Bilthoven, 2009)

6. Orthopedic Foundation for Animals (OFA): offa.org

7. Gough, A. & Thomas, A. Breed predispositions to disease in dogs and cats. (Blackwell Publishing Ltd., 2004

8. Dodds, W.J. Guide to congenital and heritable disorders in dogs. (The Humane Society Veterinary Medical Association, 2011)

9. Jane.M.Dobson. Breed-dispositions to Cancer in Pedigree Dogs. ) ISRN Veterinary Science volume 2013, Article ID 941275

10. Ubbink GJ, Hazewinkel HA, van de Broek J, Rothuizen J. (1999) Familial clustering and risk analysis for fragmented coronoid process and elbow joint incongruity in Bernese Mountain Dogs in The Netherlands. Am J Vet Res. 1999 Sep; 60(9): 1082-7.

11. Bonnett BN, Egenvall A, Hedhammar Å, Olson P

Mortality in over 350,000 Insured Swedish dogs from 1995–2000: I. Breed-, Gender-, Age- and Cause-specific Rates. Acta Vet Scand. 2005; 46(3):105–120. Published online 2005 September 30.

12. Blakemore WF, Wallace ME, Wilkes MK, Herrtage ME, Matic SE. Recognition of 'trembler', a hypomyelinating condition in the Bernese mountain dog. Vet Rec. 1987 Jun 27;120(26):609-12.

13. Bart J. G. Broeckx, Frank Coopman, Geert E. C. Verhoeven, Wim Van Haeringen, Leanne van de Goor, Tim Bosmans, Ingrid Gielen, Jimmy H. Saunders, Sandra S. A. Soetaert, Henri Van Bree, Christophe Van Neste, Filip Van Nieuwerburgh, Bernadette Van Ryssen, Elien Verelst, Katleen Van Steendam, Dieter Deforce. The Prevalence of Nine Genetic Disorders in a Dog Population from Belgium, the Netherlands and Germany. PLoS One. 2013; 8(9): e74811. Published online 2013 September 19.

14. Elisabeth Hernblad Tevell, Kerstin Bergvall, Agneta Egenvall. Sebaceous adenitis in Swedish dogs, a retrospective study of 104 cases. Acta Vet Scand. 2008; 50(1): 11.

15. Meric SM, Child G, Higgins RJ. Necrotizing vasculitis of the spinal pachyleptomeningeal arteries in three Bernese mountain dog littermates. J Anim An Hosp Assoc. 1986;22:459–465.

16. Andrea B. Spevakow, Belle Marie D. Nibblett, Anthony P. Carr, Kathleen A. Linn. Chronic mesenteric volvulus in a dog. Can Vet J. 2010 January; 51(1): 85–88.

17. Diane Frank, Marie C. Bélanger, Véronique Bécuwe-Bonnet, Joane Parent. Prospective medical evaluation of 7 dogs presented with fly biting. Can Vet J. 2012 December; 53(12): 1279–1284.

18. Marc K. Hobert, Christina Brauer, Peter Dziallas, Ingo Gerhauser, Dorothee Algermissen, Andrea Tipold, Veronika M. Stein. Infiltrative lipoma compressing the spinal cord in 2 large-breed dogs. Can Vet J. 2013 January; 54(1): 74–78.

19. Alejandro Pérez-Écija, José Carlos Estepa, Francisco Javier Mendoza. Granulomatous giant cell submandibular sialadenitis in a dog. Can Vet J. 2012 November; 53(11): 1211–1213.

20. Ed. J. Gubbels & Peter Prins.Verslag Gezondheids-inventarisatie bij de Berner Sennenhondenpopulatie. W.K. Hirschfeldstichting. Mei 2000

21. Erich SA, Rutteman GR, Teske E. Causes of death and the impact of histiocytic sarcoma on the life expectancy of the Dutch population of Bernese mountain dogs and Flat-coated retrievers. Vet J. 2013 Dec;198(3):678-83 Epub 2013 Oct 1.

22. van Kuijk L, van Ginkel K, de Vos JP, Brearley MJ, Butinar J, Gielen I, van Garderen E, Chiers K, Verhoeven PS. Peri-articular histiocytic sarcoma and previous joint disease in Bernese Mountain Dogs. J Vet Intern Med. 2013 Mar-Apr;27(2):293-9.. Epub 2013 Mar 4.

23. Abadie J, Hédan B, Cadieu E, De Brito C, Devauchelle P, Bourgain C, Parker HG, Vaysse A, Margaritte-Jeannin P, Galibert F, Ostrander EA, André C. Epidemiology, pathology, and genetics of histiocytic sarcoma in the Bernese mountain dog breed. J Hered. 2009 Jul-Aug;100 Suppl 1:S19-27.. Epub 2009

24. Nielsen L1, Andreasen SN, Andersen SD, Kristensen AT. Malignant histiocytosis and other causes of death in

Bernese mountain dogs in Denmark. Vet Rec. 2010 Feb 13;166(7):199-202.

25. Voegeli E1, Welle M, Hauser B, Dolf G, Flückiger M. Histiocytic sarcoma in the Swiss population of Bernese mountain dogs: a retrospective study of its genetic predisposition. Schweiz Arch Tierheilkd. 2006 Jun;148(6):281-8

26. Padgett GA, Madewell BR, Keller ET, Jodar L, Packard M. Inheritance of histiocytosis in Bernese mountain dogs.J Small Anim Pract. 1995 Mar;36(3):93-8.

27. Leidinger EF1, Freeman K, Kirtz G, Hooijberg EH, Sick K. Breed related odds ratio and anatomic distribution of canine mast cell tumours in Austria. Retrospective study of cases in the years 2000-2010.Tierarztl Prax Ausg K Kleintiere Heimtiere. 2014 Nov 24;42(6):367-373. [Epub ahead of print]

28. Zeng R1, 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. Breed distribution of SOD1 alleles previously associated with canine degenerative myelopathy.J Vet Intern Med. 2014 Mar-Apr;28(2):515-21.. Epub 2014 Feb 13.

29. Jitpean S1, Hagman R, Ström Holst B, Höglund OV, Pettersson A, Egenvall A. Breed variations in the incidence of pyometra and mammary tumours in Swedish dogs. Reprod Domest Anim. 2012 Dec;47 Suppl 6:347-50.

30. Pfahler S1, Distl O. Identification of quantitative trait loci (QTL) for canine hip dysplasia and canine elbow dysplasia in Bernese mountain dogs. PLoS One. 2012;7(11):e49782.. Epub 2012 Nov 26.

31. Hartmann P, Stock KF, Distl O. [Multivariate prediction of breeding values for canine hip and elbow dysplasia as well as humeral osteochondrosis in the Bernese mountain dog].Berl Munch Tierarztl Wochenschr. 2012 Sep-Oct;125(9-10):432-40.

32. Lavrijsen IC1, Heuven HC, Voorhout G, Meij BP, Theyse LF, Leegwater PA, Hazewinkel HA. Phenotypic and genetic evaluation of elbow dysplasia in Dutch Labrador Retrievers, Golden Retrievers, and Bernese Mountain dogs.Vet J. 2012 Aug;193(2):486-92. Epub 2012 Feb 14

33. Switonski M1, Szczerbal I, Nizanski W, Kociucka B, Bartz M, Dzimira S, Mikolajewska N. Robertsonian translocation in a sex reversal dog (XX, SRY negative) may indicate that the causative mutation for this intersexuality syndrome resides on canine chromosome 23 (CFA23). Sex Dev. 2011;5(3):141-6. Epub 2011 Mar 23.

34. Kathmann I1, Jaggy A, Busato A, Bärtschi M, Gaillard C. Clinical and genetic investigations of idiopathic epilepsy in the Bernese mountain dog. J Small Anim Pract. 1999 Jul;40(7):319-25.

35. Minkus G1, Breuer W, Wanke R, Reusch C, Leuterer G, Brem G, Hermanns W. Familial nephropathy in Bernese mountain dogs.Vet Pathol. 1994 Jul;31(4):421-8.

36. van der Wel TJ, Meyer HP. [Discospondylitis and immune-mediated polyarthritis in a Bernese mountain- dog]. Tijdschr Diergeneeskd. 1995 Feb 1;120(3):75-7.

37. Eagleson JS1, Diaz J, Platt SR, Kent M, Levine JM, Sharp NJ, Schatzberg SJ. Cervical vertebral malformation- malarticulation syndrome in the Bernese mountain dog: clinical and magnetic resonance imaging features.J Small Anim Pract. 2009 Apr;50(4):186-93.

38. Boissevain I. [Bernese mountain dog]. Tijdschr Diergeneeskd. 2007 Jun 1;132(11):445.

39. Doust RT1, Clarke SP, Hammond G, Paterson C, King A. Circumcaval ureter associated with an intrahepatic portosystemic shunt in a dog. J Am Vet Med Assoc. 2006 Feb 1;228(3):389-91.

40. Beuing R, Janssen N, Wurster H, Schmied O, Flückiger M. [The significance of elbow dysplasia (ED) for breeding in Bernese Mountain Dogs in Germany]. Schweiz Arch Tierheilkd. 2005 Nov;147(11):491-7.

41. Görlinger S1, Galac S, Kooistra HS, Okkens AC. Hypoluteoidism in a bitch. Theriogenology. 2005 Jul

1;64(1):213-9.

42. Chaudieu G1, Molon-Noblot S. Early retinopathy in the Bernese Mountain Dog in France: preliminary observations.Vet Ophthalmol. 2004 May-Jun;7(3):175-84.

43. Venzin C1, Ohlerth S, Koch D, Spreng D. Extracorporeal shockwave therapy in a dog with chronic bicipital tenosynovitis. Schweiz Arch Tierheilkd. 2004 Mar;146(3):136-41.

44. Egenvall A1, Hagman R, Bonnett BN, Hedhammar A, Olson P, Lagerstedt AS. Breed risk of pyometra in insured dogs in Sweden.J Vet Intern Med. 2001 Nov-Dec;15(6):530-8.

45. Ubbink GJ, Hazewinkel HA, van de Broek J, Rothuizen J. Familial clustering and risk analysis for fragmented coronoid process and elbow joint incongruity in Bernese Mountain Dogs in The Netherlands. Am J Vet Res. 1999 Sep;60(9):1082-7.

46. Kathmann I1, Jaggy A, Busato A, Bärtschi M, Gaillard C. Clinical and genetic investigations of idiopathic epilepsy in the Bernese mountain dog.J Small Anim Pract. 1999 Jul;40(7):319-25.

47. Olenick CL. Congenital renal dysplasia and psychogenic polydipsia in a Bernese mountain dog. Can Vet J. 1999 Jun;40(6):425-6.

48. Gerhardt A1, Risse R, Meyer-Lindenberg A. [Necrotizing vasculitis of the cerebral and spinal leptomeninges in a Bernese mountain dog].Dtsch Tierarztl Wochenschr. 1998 Apr;105(4):139-41.

49. Carmichael KP1, Miller M, Rawlings CA, Fischer A, Oliver JE, Miller BE. Clinical, hematologic, and biochemical features of a syndrome in Bernese mountain dogs characterized by hepatocerebellar degeneration. J Am Vet Med Assoc. 1996 Apr 15;208(8):1277-9.

50. Weissenböck H1, Obermaier G, Dahme E. Alexander's disease in a Bernese mountain dog. Acta Neuropathol. 1996;91(2):200-4.

51. Nederlandse Berner Sennen Vereniging (http://bernersennenhond.nl/wordpress/)

52. Vereniging de Berner Sennenhond. (http://www.bernersennen.nl/)

8.6 Appendix 6: A-, B- and C-List Dutch Shepherd Dog and references

A-List

Discipline Condition - -

B-List

Discipline Condition Orthopaedics Hip Dysplasia (HD) 1, 3, 4, 7, 8, 9

C-List

Discipline Condition Cardiology Hypertrophic cardiomyopathy (HCM)8

Behaviour Behavioural problems7*

Dermatology Atopy,3

Endocrinology Cushing’s disease 8 Hypothyroidism 2,3

Gastroenterology Inflammable bowel disease3

Hematology Hemolytic anemia8

Neurology Epilepsy 7, 9 Cerebellar hypoplasia 3 Malignant hyperthermia 5 Masticatory Myositis 3

Oncology Hemangiosarcoma 8 Mammary gland tumors 8 Lymphoma 8 Iris tumor 8

Orthopaedics Elbow Dysplasia 1, 3, 8

Ophthalmology Atresia of lacrima puncta 8 Cataract 8 Disctichiasis 8 Pannus 3 Pectinate ligament abnormality (different kinds) 8 Goniodysplasia 2, 4, 8, 9, Retina Dysplasia 8

Reproduction Cryptorchidism 3

* possibly associated with hypothyroidism or thyroiditis.

References

1. Orthopedic Foundation for Animals (OFA): offa.org

2. Nederlandse Herdershonden Club. www.hollandseherder.nl

3. www.dutchshepherds.us/health

4. www.americandutchshepherdassoc.org/health.html

5. mydogdna.com

6. Mia Mäkinen and Outi Laitinen, Health survey of Dutch Shepherd dogs in Finland. Suomen Eläinlääkärilehti – Finsk Veterinärtidskrift (2004) 110 (5) 239-247

7. Dodds, W.J. Guide to congenital and heritable disorders in dogs. (The Humane Society Veterinary Medical Association, 2011)

8. Database rashonden Finland: http://jalostus.kennelliitto.fi/

9. Vereniging voor de Hollandse Herder. www.vereniginghollandseherder.nl/

8.7. Appendix 7: A-, B- and C-List Cavalier King Charles Spaniel and references

A-List

Discipline Condition Cardiology Mitral valve disease 2, 3, 4, 5, 12, 13, 14, 37, 58, 61, 62

Neurology Chiari-like malformation(CM) # 2, 3, 14, 15, 23, 34, 36, 45, 49, 65, 66 Syringomyelia (SM) 2, 13, 14, 15, 23, 30, 31, 34, 42, 44, 45, 46, 54, 59, 66

B-List

Discipline Condition Otolaryngology Primary Secretory Otitis Media (PSOM) 3, 7, 8,

Endocrinology Diabetes Mellitus 2, 4, 13, 47, 51

Hematology Autoimmune thrombocytopenia 3, 4, 13, 39, 70 Macrothrombocytopenia 12, 14, 28, 70 71

Ophthalmology CKCSID (keratoconjunctivitis sicca and ichtyosiform dermatosis) 1, 3, 11, 14, 35, 55 Reproduction Susceptibility to Pyometra (intact females) 3,16

C-List

Discipline Condition Cardiology/ Aortic Thromoembolism 4, 13, 50 Pulmonology Susceptibility to Angiostrongylus vasorum infection 15, 18 Pneumocystis pneumonia 3, 12 (susceptibility to Pneumocystis carinii infection) Mitral valve prolaps (MVP) 24, 60 Patent ductus arteriosus 12

Dermatology Ichthyosis 5, 12

Endocrinology Chronic pancreatitis 14, 19, 20 Cushings disease 14 NB1 Hypomagnesiamia 24 Hypothyroidism 4, 12

Gastroenterology Exocrine pancreatic insufficiency 3, 20

Hematology Hypereosinophilia64 Undefined immunodeficiency syndrome 12

Otolaryngology Abiotrophic sensorineural deafness 14 Congenital deafness 14 Eosinophilic stomatitis 14 Reverse sneezing 22

Nephrology Chronic Kidney disease 10, 14 Juvenile Renal dysplasia (JRD)1

Neurology Cerebellar infarcts 14, 15, 17 Cervical scoliosis 15 Degenerative myelopathy 1 Dens abnormalities 15, 36 Episodic Falling Syndrome (EF/EFS) 1, 3, 14, 12, 52 Episodic collaps (hyperexplexia) 13, 15 Facial nerve paralysis 15 Fly catching 15 Granulomatous meningoencephalomyelitis 15 Hydrocephalus 15 Idiopatic epilepsy 2, 14, 15 Idiopatic facial palsy 15 Malignant Hyperthermia 1 Masticatory Muscle Myositis 3, 26 Muscle Hypertonicity 3, 29, 67 Muscular Dystrofie 1 Idiopatic Vestibular syndrome 15 X-linked Myopathy 3 Oncology Anal sac gland carcinoma 14 Brachycephalic airway obstruction syndrome BAOS #, 2, 3, 5,12, 14, 57 Diffuse large B-cell lymphoma 14 Extranodal (T-cell) lymphoma 25 Liposarcoma56 Mammary tumors 14, 16 Meningioma43 Squamous cell carcinoma 14 Ophthalmology Congenital lacrimal occlusion 22 Cataracts 2, 3, 4, 6, 12, 13, 14 Cherry eye 14 Corneal dystrophy 2, 3, 4, 6, 12, 13, 63 Distichiasis 4, 6, 12, 13 Entropion 4, 12, 13 Epithelial-stromal dystrophia 5 Exposure keratopathy syndrome # 2, 6 Macroblepharon # 2, 6 Keratoconjunctivitis sicca (KCS) 1, 3, 4, 6, 12, 13, 14, Microphtalmia 2, 4, 5, 6, 13 PRA (general) 2, 4, 13 Retinal dysplasia 2, 4, 6, 12, 13

Orthopaedics/Neuro Elbow luxation 27 surgery Hip dysplasia (HD) 2, 9 Inguinal/scrotal herniation 12 Intervertebral disc disease 14, 15, Hernia nucleus pulposus type I 15 Patellar Luxation 4, 13 Shoulder dislocation 12 Temporomandibular joint dystrophy 3, 32

Urology Hyperuricosuria 1 Urate Stones 1 Xanthinuria 3, 5, 14, 21, 33, 40

# = related to breed standard

References

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36. Bynevelt M1, Rusbridge C, Britton J. Dorsal dens angulation and a Chiari type malformation in a Cavalier King Charles Spaniel. Vet Radiol Ultrasound. 2000 Nov-Dec;41(6):521-4.

37. French AT, Ogden R, Eland C, Hemani G, Pong-Wong R, Corcoran B, Summers KM. Genome-wide analysis of mitral valve disease in Cavalier King Charles Spaniels. Vet J. 2012 Jul;193(1):283-6. Epub 2011 Nov 2.

38. Forman OP1, Penderis J, Hartley C, Hayward LJ, Ricketts SL, Mellersh CS. Parallel mapping and simultaneous sequencing reveals deletions in BCAN and FAM83H associated with discrete inherited disorders in a domestic dog breed. PLoS Genet. 2012 Jan;8(1):e1002462.. Epub 2012 Jan 12.

39. P. Eskell, J. Haggstrom, C. Kvart, A. Karlsson. Thrombocytopenia in the cavalier King Charles spaniel. J Small Anim Pract, 35 (1994), pp. 153–155

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8.8 Appendix 8: A-, B- and C-List Maine Coon Cat and references

A-List

Discipline Condition Cardiology/Pulmonology Hypertrophic Cardiomyopathy 1, 2, 6, 8, 9, 10, 11, 12, 13, 15, 17

B-List

Discipline Condition Neurology Spinal Muscular atrophy (SMA) 3, 6

Orthopaedics/Neurosurgery Hip Dysplasia (HD) 1, 6

C-List

Discipline Condition Cardiology and Pulmonogy Peritoneopericardial diaphragmatic hernia (PPDH) 25

Dermatology Hepatocutaneous syndrome 23

Hematology Erythrocyte Pyruvate Kynase Deficiency 4 Immune-mediated heamatological disease 19

Otolaryngology Congenital Deafness in white coated cats 6 Polypus otitis media 29

Nephrology Renal cyst 14

Neurology Myopathy – Laminin alpha-2 deficiency 6, 22

Orthopaedics-Neurosurgery Bicipital tenosynovitis and Glenoid dysplasia18 Cranial crucial ligament rupture (CCL) 5,6 Fibrodysplasia ossificans progressive (FOP) 26 Polydactyly 6

Oncology Basal cell carcinoma 24 Cutaneous neuroendocrine (Merkel cell) malignant carcinoma 27 Primary feline hemangiosarcoma 20 Rhabdomyosarcoma 21

Reproduction Cryptorchidism 6

Urology Congenital (double) urethral stricture 28 Uroliths 16

References

1. Gough, A. & Thomas, A. Breed predispositions to disease in dogs and cats. Second Edition, Wiley-Blackwell (2010)

2. Mia TN Godiksen, Sara Granstrøm, Jørgen Koch, Michael Christiansen. Hypertrophic cardiomyopathy in young Maine Coon cats caused by the p.A31P cMyBP-C mutation - the clinical significance of having the mutation. Acta Veterinaria Scandinavica 2011, 53:7

3. Leslie A. Lyons. Feline Genetics: Clinical Applications and Genetic Testing. Top Companion Anim Med. 2010 November; 25(4): 203–212.

4. Robert A Grahn, Jennifer C Grahn, Maria CT Penedo, Chris R Helps, Leslie A Lyons BMC. Erythrocyte Pyruvate Kinase Deficiency mutation identified in multiple breeds of domestic cats. Vet Res. 2012; 8: 207.

5. Cassandra M. Ruthrauff, Leigh E. Glerum, Sharon D. Gottfried. Incidence of meniscal injury in cats with cranial cruciate ligament ruptures. Can Vet J. 2011 October; 52(10): 1106–1110.

6. Rapport. Testerink-Baas, E. Erfelijke afwijkingen bij raskatten. St. Platform Verantwoord Huisdierenbezit (2010).

7. Kittleson MD, Meurs K, Munro M. Re: Association of A31P and A74T polymorphisms in the myosin binding protein C3 gene and hypertrophic cardiomyopathy in Maine Coon and other breed cats. J Vet Intern Med. 2010 Nov-Dec;24(6):1242-3

8. Fries R, Heaney AM, Meurs KM. Prevalence of the myosin-binding protein C mutation in Maine Coon cats. J Vet Intern Med. 2008 Jul-Aug;22(4):893-6.

9. Gundler S1, Tidholm A, Häggström J. Prevalence of myocardial hypertrophy in a population of asymptomatic Swedish Maine coon cats. Acta Vet Scand. 2008 Jun 18;50:22.

10. Meurs KM, Munro MJ, Kittleson JA, Liu SK, Pion PD, Towbin JA. Familial hypertrophic cardiomyopathy in maine coon cats: an animal model of human disease. Circulation. 1999 Jun 22;99(24):3172-80.

11. Longeri M, Ferrari P, Knafelz P, Mezzelani A, Marabotti A, Milanesi L, Pertica G, Polli M, Brambilla PG, Kittleson M, Lyons LA, Porciello F. Myosin-binding protein C DNA variants in domestic cats (A31P, A74T, R820W) and their association with hypertrophic cardiomyopathy. J Vet Intern Med. 2013 Mar-Apr;27(2):275- 85.

12. Freeman LM, Rush JE, Meurs KM, Bulmer BJ, Cunningham SM. Body size and metabolic differences in Maine Coon cats with and without hypertrophic cardiomyopathy.Freeman LM1, Rush JE, Meurs KM, Bulmer BJ, Cunningham SM. J Feline Med Surg. 2013 Feb;15(2):74-80. Epub 2012 Sep 21.

13. Trehiou-Sechi E1, Tissier R, Gouni V, Misbach C, Petit AM, Balouka D, Sampedrano CC, Castaignet M, Pouchelon JL, Chetboul V. Comparative echocardiographic and clinical features of hypertrophic cardiomyopathy in 5 breeds of cats: a retrospective analysis of 344 cases (2001-2011). J Vet Intern Med. 2012 May-Jun;26(3):532-41. Epub 2012 Mar 23.

14. Gendron K1, Owczarek-Lipska M, Lang J, Leeb T. Maine Coon renal screening: ultrasonographical characterisation and preliminary genetic analysis for common genes in cats with renal cysts. J Feline Med Surg. 2013 Dec;15(12):1079-85. Epub 2013 Jun 4.

15. Casamian-Sorrosal D1, Chong SK, Fonfara S, Helps C. Prevalence and demographics of the MYBPC3- mutations in ragdolls and Maine coons in the British Isles. J Small Anim Pract. 2014 May;55(5):269-73. Epub 2014 Mar 7.

16. Hesse A1, Orzekowsky H, Frenk M, Neiger R. [Epidemiological data of urinary stones in cats between 1981 and 2008]. [Article in German] Tierarztl Prax Ausg K Kleintiere Heimtiere. 2012 Apr 24;40(2):95-101.

17. Godiksen MT1, Granstrøm S, Koch J, Christiansen M. Hypertrophic cardiomyopathy in young Maine Coon cats caused by the p.A31P cMyBP-C mutation--the clinical significance of having the mutation. Acta Vet Scand. 2011 Feb 9;53:7.

18. Scharf G1, Steinbüchl S, Messmer M, Ohlerth S. Glenoid dysplasia and bicipital tenosynovitis in a Maine

coon cat. J Small Anim Pract. 2004 Oct;45(10):515-20.

19. Best MP1, Fry DR. Primary immune-mediated thrombocytopenia and immune-mediated neutropenia suspected in a 21-week-old Maine Coon cat. Aust Vet J. 2014 Jul;92(7):250-3.

20. Roof-Wages E, Spangler T, Spangler WL, Siedlecki CT. Histology and Clinical Outcome of Benign and Malignant Vascular Lesions Primary to Feline Cervical Lymph Nodes. Vet Pathol. 2014 May 30.. [Epub ahead of print]

21. Miller AD, Steffey M, Alcaraz A, Cooper B. Embryonal rhabdomyosarcoma in a young Maine coon cat. J Am Anim Hosp Assoc. 2009 Jan-Feb;45(1):43-7. 22. Poncelet L, Résibois A, Engvall E, Shelton GD. Laminin alpha2 deficiency-associated muscular dystrophy in a Maine coon cat. J Small Anim Pract. 2003 Dec;44(12):550-2.

23. Kimmel SE, Christiansen W, Byrne KP. Clinicopathological, ultrasonographic, and histopathological findings of superficial necrolytic dermatitis with hepatopathy in a cat. J Am Anim Hosp Assoc. 2003 Jan-Feb;39(1):23-7.

24. Green ML, Smith J, Fineman L, Proulx D. Diagnosis and treatment of tracheal basal cell carcinoma in a Maine coon and long-term outcome. Green ML1, Smith J, Fineman L, Proulx D. J Am Anim Hosp Assoc. 2012 Jul- Aug;48(4):273-7. Epub 2012 May 18.

25. Banz AC, Gottfried SD. Peritoneopericardial diaphragmatic hernia: a retrospective study of 31 cats and eight dogs. J Am Anim Hosp Assoc. 2010 Nov-Dec;46(6):398-404.

26. Yabuzoe A, Yokoi S, Sekiguchi M, Momoi Y, Ide K, Nishifuji K, Iwasaki T. Fibrodysplasia ossificans progressiva in a Maine Coon cat with prominent ossification in dorsal muscle.Yabuzoe A J Vet Med Sci. 2009 Dec;71(12):1649-52.

27. Patnaik AK, Post GS, Erlandson RA. Clinicopathologic and electron microscopic study of cutaneous neuroendocrine (Merkel cell) carcinoma in a cat with comparisons to human and canine tumors. Vet Pathol. 2001 Sep;38(5):553-6

28. Zotti A1, Poser H, Chiavegato D. Asymptomatic double ureteral stricture in an 8-month-old Maine Coon cat: an imaging-based case report. J Feline Med Surg. 2004 Dec;6(6):371-5.

29. Cook LB, Bergman RL, Bahr A, Boothe HW. Inflammatory polyp in the middle ear with secondary suppurative meningoencephalitis in a cat. Vet Radiol Ultrasound. 2003 Nov-Dec;44(6):648-51.