from Charles Born, Past President, American Spaniel Club
As our members know the validity of the merle pattern and associated health issues in the Cocker Spaniel have concerned breeders for some time now. After some progress, in 2009 the ASC Board began a concerted effort to identify and understand the depth of the issue and what to do. In addition to our request to the AKC for Z registration status on merle Cockers which has been approved, at the direction of the ASC Board of Directors I asked the ASC Foundation to conduct a three-part study that included:
- Researching the evidence showing whether merle is or is not a Cocker Spaniel color.
- Researching the scientific evidence that the merle color can produce significant health issues.
- Developing an approach for educating breeders, owners and the general puppy buying population on the results of their investigations
The Scientific Research Committee assisted by the Grants Committee was tasked with conducting this study by ASCF President Dee Torgerson-Rismyhr. This combined task force was led by Doug McFarlane, a long-time Cocker fancier and English Cocker breeder and judge and a former member of ASC Board and many other Spaniel Boards and joined by Karen Yager, a PhD geneticists and Clumber breeder. You can read about their approach and methodology in the full study report.
My layman’s summary of their report is as follows:
- Is merle a Cocker Spaniel color?A peer-reviewed and validated scientific study of six different breeds with a merle mutation found the gene to be exactly the same in all the six breeds. The study concluded that the merle mutation predates all dogs and is behind all breeds—quite possibly going back to their wolf ancestors.
- Is the merle mutation a health risk? While not every single merle Cocker has health issues, the preponderance of health issues directly and specifically associated with the merle genetic mutation has been identified in the peer-reviewed scientific studies highlighted in the study by the task force.
- Lastly, education.We are starting this education with our members by providing the results of the study conducted by the task force and providing an open forum for questions and dialogue. I wanted a study that was absent of opinion or bias and strong on scientific fact; my deepest gratitude goes to the committee and the ASCF for delivering on this. American Spaniel Club members will have opportunities for Q&A with the task force through their Zone Representatives and other forums. The details of this will be in the Bulletin coming out in March.
It is the opinion of the American Spaniel club Board of Directors that the breeding of this mutation should be stopped for the obvious health reasons identified in the study. Our standard is already clear that this pattern is a confirmation disqualification. We hope that through a combination of education and the tracking made possible with the Z registration we are providing information and knowledge to current breeders and to future generations of breeders to make informed choices.
Charles Born, President, American Spaniel Club, Feb. 2011
American Spaniel Club Foundation
Merle Color In Cocker Spaniels
Prepared by ASCF Scientific Research Committee
Douglas P. McFarlane, BS Mathematics, MS Computer Science
Karen L. Yager, BS Microbiology, Ph.D. Developmental Biology (Genetics)
- The Board of the ASC asked the ASCF to take on the task of researching the hereditary aspects and related issues of Merle Cocker Spaniels. The specific hypothesis presented to the ASCF was that the Merle color was not a Cocker Spaniel color but was instead introduced into the gene pool by a specific breeding that occurred in the 1980s.
- The ASCF tasked the Scientific Research Committee, assisted by the Grants Committee, with conducting this study with the goal of confirming this hypothesis
- The Study objective was defined and approved by the ASCF Board and work began early in 2010
The study was separated into 3 specific goals
- Goal #1: Determine if scientific evidence can be provided to prove Merle is not a Cocker Spaniel color. If yes, provide such scientific evidence.
- Goal #2: Provide scientific evidence the Merle color can produce significant health issues
- Goal #3: Develop recommended approach to educating breeders, owners and general puppy buying population the results of the investigations and facts determined from goals 1 and 2
The Committee reviewed:
- Prior work done by ASC members
- Numerous published scientific studies
- Articles discussing Merle color issues
Findings and conclusions were based on scientific evidence presented in peer reviewed published reports
- Each goal is presented and the findings are summarized in this report. Based on the findings, conclusions are drawn and provided in this report
- Specific details of the findings and research reference material is provided as an appendix
What is a Merle color?
Merle is a pattern with patches of intermingled colored and white hairs and other patches of solid color such as red or black.
Heterozygous & Homozygous genes
Each gene is made up of two representative alleles – one inherited from the maternal source (mother) and the other inherited from the paternal source (father)
When a gene is homozygous, both alleles for that gene are the same (ie both the mother and father contributed the same version of the gene)
When a gene is heterozygous, each allele is different
Phenotype & Genotype
Phenotype – An observable physical characteristics of an organism as determined by both genetic and environmental influences
Genotype – The genetic make-up of an organism as opposed to its physical characteristics
A mutation is a permanent change in the DNA sequence of a gene
Cryptic Merle Mutation
A cryptic Merle is a dog that does NOT present with the overt Merle phenotype but does possess the Merle genotype. It has the potential to produce Merle offspring, but the mechanism by which this occurs is unknown
An abnormal condition in which the number of neutrophils in the bloodstream is decreased. Neutrophils are a type of white blood cell that defends the body against bacterial infection. Neutropenia affects the body’s ability to fight off infections
Retrotransposon & SINE
SINE is a short interspersed element and are “jumping genes” that belong to the retrotransposon class of mobile genetic elements
These genes are capable of propagating in a host genome by a ‘copy and paste’ mechanism
Most SINE insertions occur within regions of the genome that have no functional significance
Occasionally they can insert into regions where they can interrupt a necessary gene as is the case for Merle
Goal #1: Determine if scientific evidence can be provided to prove Merle is not a Cocker Spaniel color. If yes, provide such scientific evidence.
- The gene mutation responsible for Merle patterning in dogs has been identified
- The results of a study done at Texas A & M in 2006 were published in the Proceedings of the National Academy of Science (PNAS), a highly respected scientific journal
- The PNAS paper is entitled: Retrotransposon insertion in SILV is responsible for Merle patterning of the domestic dog. L. A. Clark, J. M. Wahl, C. A. Rees, and K. E. Murphy. 2006 January 31; 103(5): 1376-1381
- The study focused on six breeds: Collie, Border Collie, Australian Shepherd, Cardigan Welsh Corgi, Dachshund, and the Great Dane
Specific Findings of this Study
- The SILV gene locus was chosen as a potential gene for Merle based upon the research that previously showed black hair color in mice dilutes with age. The SILV gene locus was investigated for any mutations in the Shetland sheepdog
- A SINE, a short interspersed element, was found inserted in the SILV gene locus
- This SINE insertion segregated with the Merle phenotype in multiple breeds and was absent from dog breeds that lack Merle patterning
- The mutation was identical at the DNA level, (with the exception of two point mutations), in all breeds analyzed in this study
- The SINE is a retrotransposon, and has a poly A tail. The cryptic mutation was found to have a longer poly A tail, the actual Merle mutation has a shorter poly A tail. During replication, the process can ‘fail’ and shorten the longer poly A tail in the cryptic mutation, and result in the shorter poly A tail. This then leads to the disruption of the SILV gene, and the manifestation of the Merle patterning
Discussion of the Findings of this study:
- The SILV gene is expressed early in a developing embryo, and is within cells that become numerous different cells and tissues in the adult. Because of the widespread expression in different cells and tissues, this leads to the wide range of hearing and eye problems, as well as other organ systems defects such as the skeletal, cardiac, and reproductive systems
- Finding the mutation was identical in each breed analyzed, and comparison of when each of the six different breeds historically emerged, the data indicates that the Merle mutation most likely existed prior to the establishment of different dog breeds. This means that it is likely that the predecessor to ALL dog breeds had the Merle mutation. The sequence data analysis was statistically significant
- The normal function of the gene is unknown; the researchers hypothesize that it is involved in the biogenesis of pre-melanosomes, which differentiate and give rise to skin and eye tissue, and many different body tissues
- The researchers applied for a patent for the Merle mutation
Implications & Conclusions for Cocker Spaniels
- Based upon this significant research, the Merle gene mutation was present before dog breeds emerged. This would include the Cocker Spaniel
- A DNA test is commercially available, as reported in the AKC Gazette article from August 2010 (IDEXX Reference Laboratories). The PNAS paper references a second company, Vita-tech, located in Canada
- An ASC member obtained DNA samples of Merle Cocker Spaniels. The DNA results showed two were heterozygous Merles, one was a homozygous Merle. One can therefore conclude that the Merle mutation identified in the PNAS paper is the same mutation for Merle Cocker Spaniels
- There have been individuals who have theorized that the Merle mutation was introduced into the Cocker Spaniel by a breeding with a Merle Australian Shepherd, that occurred in the 1980’s
- We cannot scientifically conclude that the Merle gene was introduced by this breeding.
- The statistically significant findings in the PNAS paper would indicate the mutation was present before individual dog breeds diverged
- We do not have DNA samples from dogs from this reported breeding, nor do we have samples from the parents of this reported breeding. Without DNA samples, the testing cannot be performed
- If the progeny of this breeding were then backcrossed with Cocker Spaniels, following 6 breedings or approximately 10 years, all progeny would test 99% pure Cocker Spaniel. i.e. If we could test every single Cocker Spaniel, even those with the Merle mutation, if they have only been bred with Cocker Spaniels, would test pure at the DNA level for Cocker Spaniel DNA
- The AKC can identify all progeny down the multi-generational line back to these two parents. This confirms parentage but NOT carriers of the Merle mutation
- For these reasons, proving the Merle gene was introduced by this breeding is not possible. Furthermore, there is no possibility of scientifically proving Merle color is not a Cocker Spaniel color
Goal #2: Provide scientific evidence the Merle color can produce significant health issues.
- There are a number of articles that describe significant health issues that may arise when breeding Merle dogs
- The AKC-Canine Health Foundation (AKC-CHF) lists Merle as a disease for which there is a genetic test. The AKC-CHF has therefore concluded that Merle is detrimental to the breeds
- Based on the PNAS paper from 2006, the mutation for Merle is a disruption of the of pigmentation gene SILV. If this mutation is present, it can result in numerous health issues since the disruption occurs early in the development cycle and those cells then form many different body tissues which then can lead to a wide range of auditory and eye abnormalities. This can occur in both homozygous and heterozygous dogs. The research identified both the mutation and the ‘cryptic’ (phantom) mutation.
- A referenced study with Dachshunds, studied the hearing capacity for Merle phenotype homozygous and heterozygous dogs and found that over 50% of homozygous dogs and just over 30% heterozygous dogs have auditory problems ranging from mild to severe deafness. All control dogs having no mutation for Merle had normal hearing
- One can conclude that breeding a Merle to a non-merle can result in health problems nearly as frequent as breeding Merle to Merle (30% vs., 50%)
- In other cited studies, the homozygous genotype can be sub-lethal and is associated with multiple abnormalities of the skeletal, cardiac, and reproductive systems
- Common problems cited in an article in the AKC Gazette, dated August 2010 include cyclic neutrorpenia, white spotting and deafness, deafness and blindness, and color dilution alopecia.
- Cyclic neutorpenia occurs in collies which can result in loss of pigment and internal, life threatening infections
- Significant linkage has been identified that produces blindness and deafness in both heterozygous and homozygous dogs.
- The homozygous of double merles have a much higher incidence of eye and ear abnormalities
- A study lead by Dr. George Strain included several breeds of dogs of which 40 were homozygous (double Merle) and 113 dogs were heterozygous. The results were conclusive.
- 29 of the 40 were Catahoula, a breed with no white markings – only 2 were deaf in both ears and 1 was deaf in 1 ear
- Of the remaining 40, 11 dogs included 5 Aussies, 3 Collies, 1 Sheltie, 1 Corgi, and 1 Great Dane and 4 were deaf in both ears and 3 in one ear
- Only 1 of the 113 dogs was deaf – leading to the conclusion that heterozygous dogs are not prone to deafness
- Breeding Merle dogs introduces risk that offspring may have significant health issues including but not limited to blindness, deafness and color dilution alopecia and other problems leading to death
- This is especially true for homozygous offspring resulting from breeding Merle to Merle
- For significant health reasons, breeding Merle to Merle is strongly discouraged
- Breeding Merle to non-merle has similar health risks although the incidence is reduced
- The existence of the “cryptic” mutation introduces significant risk because it is not evident visually. Therefore, if you do NOT know the Merle status of a male you are planning on breeding to, a responsible breeder should perform a DNA test for the Merle mutation as a cryptic Merle may not show Merle phenotype but can produce Merle offspring
Goal #3: Develop recommended approach to educating breeders, owners and general puppy buying population the results of the investigations and facts determined from goals 1 and 2.
Target audiences for education should include, breeders, owners, puppy buyers
Develop key messages for each target audience
- Basic description of the Merle pattern
- Basic education on the genetics of breeding better dogs
- Specific education on the genetics of breeding Merle dogs (Merle to Merle, Merle to black or red)
- Existence of the Cryptic mutation
- Value of DNA testing for Merle mutation
- Health consequences of Merle breeding
- Basic description of a Merle pattern
- Value of DNA testing of their pets
- Specific education on genetics of Merle
- Existence of Cryptic mutation
- Potential existence of consequences (i.e. health issues)
- Alternative treatment options for specific health issues
- Basic description of the Merle pattern
- Value of DNA testing of their potential pets
- Simple explanation of genetics and gene mutation
- Potential for puppy to contract certain diseases
- Existence of potential significant health risks involved with Merle puppies
- Practice of breeding Merle cockers is not approved and is strongly denounced by the parent club – American Spaniel Club
Determine best outlets to maximize coverage of each for target audience
- Internet – websites, social networks,
- ASC, ASCF, selected Zone Club websites
- Print – articles and advertisements for cocker magazines, cocker club newsletters, ASC Bulletin
- On-the-shelf Powerpoint presentations, including speaker notes for broad decimation to clubs, gatherings, etc.
Resume & Credentials
Douglas P. McFarlane
- Long time breeder of English Cocker Spaniels
- Past President of English Cocker Spaniel Club of America (ECSCA)
- Board member of ASC, ASCF, ECSCA
- Scientific Research Chair of ASCF
- ECSCA Member – 32 Years
- Life Member ASC
- BS Mathematics, MS Computer Science
Karen L Yager
- Breeder of Clumber Spaniels
- Genetic Chair of the Clumber Spaniel Club of America (CSCA) Genetic Health Committee
- Member of Scientific Advisory Committee for CSCA
- Grants Chair of ASCF
- BS Microbiology, Ph.D Developmental Biology (Genetics)
- Retrotransposon insertion in SILV is responsible for Merle patterning of the domestic dog. L. A. Clark, J. M. Wahl, C. A. Rees, and K. E. Murphy. 2006 January 31; 103(5): 1376-1381.
- Decoding Coat Color. Leslie Crane Rugg, Eva Saks. AKC Gazette August 2010: 22-23.
- STRAIN’S PAPER
- Prevalence of Deafness in Dogs Heterozygous or Homozygous for the Merle Allele. G.M Strain, L.A. Clark,J.M. Wahl, A.E. Turner, and K.E. Murphy. J. Vet Intern Med 2009; 23:282-286.
CANINE HEALTH FOUNDATION WEBSITE
- Linkage and Direct DNA Canine Genetic Tests offered 5/06/10. List of Diseases for Which DNA testing is offered. Merle, All-Breeds, Vita-Tech: p. 2.