CA: In the Beginning

NOTE: The below articles are helpful to get an overview of the problems we face, how we began, and how far we have come in working together.

Some of the important points:

    1. CA is not a single kennel problem
    2. CA is an autosomal recessive gene
    3. The closest common ancestor in pedigrees is not necessarily a carrier
    4. To keep our gene pool diverse, we should not discard dogs from breeding programs simply because they are related to a dog affected with CA.

CA - Dr. Bell & OESCA
Statement to the OESCA on Cerebellar Abiotrophy (Ataxia) in the Old English Sheepdog

Jerold S. Bell, DVM
Veterinary Genetic Counseling
PO Box 3399
Enfield, CT 06083
860-749-8348
860-749-4760 (Fax)
GeneticVet@aol.com

Background Information

Jerold S. Bell, DVM, is a clinical veterinary geneticist and small animal veterinary practitioner.  He was trained in genetics and genetic counseling at Michigan State University, the University of Missouri, and the Jackson Laboratory at Bar Harbor, Maine.  His Doctorate of Veterinary Medicine is from Cornell University. Dr. Bell’s faculty appointment at the Tufts University School of Veterinary Medicine is Clinical Assistant Professor.  He has been the course director of the Clinical Veterinary Genetics course since 1988.  He has also lectured on veterinary genetics at the veterinary schools of the University of Tennessee, the University of Missouri, and Cornell University.

Dr. Bell is a frequent lecturer to all-breed and individual breed dog clubs.  He is the national project administrator for numerous genetic disease control programs of pure-bred dogs.  He performs genetic counseling through Veterinary Genetic Counseling, and practices veterinary medicine at Freshwater Veterinary Hospital in Enfield, CT.

Statement to the OESCA on Cerebellar Abiotrophy (Ataxia) in the Old English Sheepdog

October 9, 1998

Since 1993, I have been contacted by owners of Old English Sheepdogs affected with a degenerative neurological condition affecting their gait.  At that time, the diagnosis, prognosis, progression, and heredity of the condition was unknown.  Through the work of Dr. H. Steven Steinberg with the cooperation of many breeders and veterinarians, the features of Old English Sheepdog cerebellar abiotrophy are being identified.  A scientific paper is being prepared with the results of the research.

My study of the heredity of CA in the Old English Sheepdog includes confirmed affected dogs from many kennels in the United States and England.  Two important aspects of the disorder for the breed include a defined mode of inheritance, and determination of the pedigree spread of the genetic defect in the breed.  Based on these studies, CA in the Old English Sheepdog is shown to be transmitted by an autosomal recessive gene with complete penetrance.  This means that affected dogs must inherit a defective recessive gene from both parents.  Parents of confirmed affected dogs are obligate carriers of the defective recessive gene.  Dogs who have one normal (dominant) gene and one defective recessive gene are normal, healthy dogs (regarding CA).  Their only difference is that they will pass on the defective gene to approximately half their offspring.  Being a recessive disorder, carriers can multiply for many generations without producing affected dogs, if they have not been bred to other carriers.  At this time, there is no test for carriers of CA in the Old English Sheepdog.

Identifying the genetic spread of the defective recessive gene requires epidemiological pedigree research.  It is a consensus among researchers that defective genes in breed related genetic disorders usually originate from a single mutation in an ancestral source.  Rarely is the ancestral source of a defective gene identified.  A tool of population geneticists is the identification of the closest common ancestor of a defective gene.  By studying the pedigrees of all obligate carriers of the defective gene, and finding the closest ancestor that relates to all of them, a minimal age of the defective gene in the population can be identified.  The focus of the closest common ancestor analysis is to find the genetic spread of the defective gene, and therefore, the breadth of the breeding population that is at risk for being carriers of the gene.

A fallacious use of the closest common ancestor analysis is to identify the ancestor as a carrier of the defective gene.  Due to the nature of dog breeding, top stud dogs tend to spread their genes widely, and therefore, become the central convergence points for bringing families together in ancestral pedigree analysis.  Consequently, individuals identified as a closest common ancestor are usually widely used stud dogs.  The identification of additional affected dogs will often change the closest common ancestor to a different individual on the pedigree map.  (For a more detailed description, see “Understanding the Relevance of the Closest Common Ancestor”, AKC Gazette, July 1993, p. 86.)

The closest common ancestor of the defective recessive gene causing CA in the Old English Sheepdog was an English Old English Sheepdog born in 1961.  I am told that he appears behind over ninety-percent of Old English Sheepdog breeding stock.  After studying pedigrees of today’s Old English Sheepdogs, it would not be surprising to find affected dogs from diverse backgrounds in America, England, Australia, Japan, or other countries.  With the identification of more affected Old English Sheepdogs around the country and the world, the closest common ancestor may move further back behind this dog, or not involve him directly.  However, additional affected dogs will not narrow the scope of the Old English Sheepdog gene pool that is currently at risk for carrying the defective gene.

As a rule, I do not identify the closest common ancestor when discussing the spread of the defective gene in a breed.  Identifying the closest common ancestor puts a focus on a single ancestor, who may or may not be a carrier, and is usually so far back in pedigrees that his influence on the breed cannot be modified.  The focus in genetic disease control must be on today’s breeding dogs, and what we can do to control the spread of defective genes and to produce quality, healthy dogs.

OESCA members have urged me to identify the closest common ancestor for CA in the Old English Sheepdog, so that the breeders can judge for themselves that almost everyone is at risk with this disorder.  I am reluctant to do so, for fear of worsening the finger pointing that has already taken place in the breed.  Two breeders, Joyce Wetzler and Linda Ruelle of Whisperwood kennels have produced CA in their linebreeding programs, have retired many dogs from breeding and have sacrificed dogs in search of answers concerning this disorder.  With the assistance of Dr. Tim Cujdik, and their desire for answers, the breed is no longer in the dark about CA.  Because of their openness in discussing their experience, many breeders have called CA a Whisperwood problem, and not a breed problem.  My research shows that the defective gene for CA had to be imported into the United States through several English imports.  These imported dogs also appear behind the majority of Old English Sheepdog breeding stock.  It is documented that the defective gene predates the existence of Whisperwood kennels.

The OESCA has asked for my advice in dealing with CA.  The important point is to not abandon your breeding programs, or make hasty, irreversible decisions concerning your breeding stock.  Wholesale spaying and neutering will do nothing but limit the genetic diversity in the breed.  The ancestral source of the defective gene is deep in the pedigrees of present day breeding dogs.  Therefore, the question is not who descended from this genetic background to receive the defective gene, but who has lost the defective gene in the generations since its introduction.  The vast majority of breeding dogs will not be carriers of this single defective gene.  Everyone breeding to a limited number of dogs identified as not carrying the defective gene will only limit diversity, and could propagate other detrimental recessives in the population.

I will be recommending to the board of directors a pedigree analysis service, so that owners can objectively determine the risk of their own dogs being carriers or producing affected dogs.  Through computing the average carrier risk of the population, the breed can work to lower that risk over time.  The breed should also pursue research toward identifying the defective gene, and developing a test for identifying carriers.  While cerebellar abiotrophy is an important disorder that concerns the Old English Sheepdog, it must be kept in perspective to the 40,000 to 100,000 genes present in the breed.  Breeders should not ignore the important features of form, function, and temperament of the breed, while attempting to control this and other genetic disorders.

Proposal to the Old English Sheepdog Club of America
A genetic disease control program for Cerebellar Abiotrophy (CA)

October 9, 1998

Cerebellar abiotrophy is shown to be an autosomal recessive genetic disorder in the Old English Sheepdog breed.  The pedigree background of the defective gene for CA traces back to dogs in England, whose descendants were foundation stock for the majority of Old English Sheepdog kennels in America and around the world.  There is no test for carriers, or way to identify carriers of CA, unless they produce an affected dog, or are the offspring of an affected dog.

In order to control the genetic spread and production of additional affected dogs, Dr. Jerold S. Bell is offering his services as a genetic consultant to the OESCA, its breeders, and owners.  Genetic disease control requires education, proper identifications, risk assessment, and support to keep the process positive and forward moving. Under this agreement, Dr. Bell’s role will include the following:

  • Obtain veterinary confirmation of the diagnosis of purported affected dogs brought to his attention.
  • Assist owners and breeders of suspected affected and carrier dogs. Honor the expressed confidentiality of breeders and owners pertaining to diagnoses in their dogs.
  • Establish a database to be used in the implementation of a relative risk pedigree analysis service for breeders.
  • At the request of the club, write regular releases for the OESCA, for publication in their newsletter, or other materials as the club sees fit.
  • Assist the club in establishing contacts with researchers who may be able to identify the defective gene causing CA, and thereby develop a test for carriers of CA.
  • Provide cerebellar abiotrophy genetic counseling to owners and breeders of Old English Sheepdogs. Such genetic counseling will be by return collect phone call, at no additional charge to the owners.

Release to the Old English Sheepdog Club of America

November 7, 1998

In the October release, the concept of the closest common ancestor was discussed. It was stated, “A fallacious use of the closest common ancestor analysis is to identify the ancestor as a carrier of the defective gene. Due to the nature of dog breeding, top stud dogs tend to spread their genes widely, and therefore, become the central convergence points for bringing families together in an ancestral pedigree analysis. Consequently, individuals identified as a closest common ancestor are usually widely used stud dogs.”  In viewing pedigrees of affected dogs, including the pedigree of the English dog Prospectblue Marie-Louise, many breeders have determined that the closest common ancestor for CA is Prospect Shaggy Boy.  As many breeders have early foundation stock out of him, they question why they are not seeing CA in their breeding programs.

Unfortunately, these questions originate from a faulty premise, and my original release was not studied in full. The sole use of the closest common ancestor analysis is to determine the minimum possible ages of the defective recessive gene in the Old English Sheepdog population. The determines the scope of the Old English Sheepdog gene pool that is currently at risk for carrying the defective gene. The analysis has nothing to do with carrier assessment. There is no evidence or indication that Prospect Shaggy Boy was, or was not a carrier. If he were not a prolific and influential breeding dog, then he would not be the closest common ancestor, because that is the prerequisite of being the closest common ancestor. It has to be a dog that is standing in a major crossroad of the ancestral pedigree, so that he can bring many diverging lines of descent together.

As an example of complex pedigree relationships, I can find six distinct ancestral pathways from obligate carriers to Prospect Shaggy Boy, each exclusive of each other, and through prolific foundation stock of many kennels. Without the diagnosis of Prospectblue Marie-Louise, one of these prolific breeding dogs would be the closest common ancestor for the defective gene, although any could be a carrier. I can find common ancestors behind Prospect Shaggy Boy who also are ancestors of all carriers, who are prolific and influential ancestors, and who do not require Prospect Shaggy Boy to pass on the defective gene. These ancestors also do not require the contribution of the six pathways to Prospect Shaggy Boy, and connect through other prolific sires and dams. The lesson here is that the only dogs whom we can say are carriers, are those who have produced affected dogs, or are the offspring of affected dogs. Any other conclusions have no basis in fact, and are what is commonly referred to as witch hunting.

Dogs who were carriers of the defective gene causing CA forty or more years ago have little to do with today’s carriers. A carrier passes on the defective gene to approximately half of its offspring. If an offspring receives the defective gene and is bred, then it will pass it on to half its offspring. No new defective CA gene is being created in the gene pool. Therefore, the question for all breeders is, “Have my breeding dogs been lucky enough to lose the defective gene over generations?” Carriers have been propagated for many generations.  The only time affected dogs can be produced is when two carriers are bred together. Even if this occurs, there is no guarantee that you will see an affected dog from such a mating, as there is only a twenty-five percent chance of inheriting the defective gene from both parents. If unknown carrier breeding stock have not produced affected dogs, it is because they have not been involved in matings to other carriers or produced confirmed affected dogs.

With the progress in molecular genetic identification of defective genes coupled with the recent generous donation to the AKC Canine Health Foundation, there is great hope for a test for carriers and pre-clinically affected dogs. In working with many breeds with autosomal recessive ataxia disorders over the past twenty years, this is the first time there has been hope for identifying the defective gene. Through a carrier test for GM-1 Storage disease in Portuguese Water Dogs, I administrated a program that brought the carrier frequency from more than 16% to less than 3% over the past 10 years, without a significant loss of genetic diversity.  I’m hopeful that CA will be less of a problem in your breed, and will not significantly disrupt your breeding programs to produce better Old English Sheepdogs.

The question concerning CA in the Old English Sheepdog gene pool are, what is the average frequency of the defective gene for the breed, and what are the risks of my own dogs being carriers? Some breeding programs that have seen affected dogs have a higher than average frequency of the defective gene. Many breeding programs will be free of the defective gene.  The proposed relative risk pedigree analysis service will identify the carrier risk of your own dogs, including the risk passed from the sire and dam.  The will allow each breeder to assess the risk of their own matings.

The relative risk analysis identifies the minimum objective risk in a pedigree based on relationships to obligate carrier and confirmed affected dogs. For this service to be of the most beneficial to all, I should have information on all affected dogs. If you own or bred a dog who you feel may be affected with CA, please contact me to go through confidential diagnosis verification.

In pedigree analysis or discussing proposed matings at this time, the most important issue is to try to prevent the creation of more affected dogs. It is up to individual breeders to make their breeding decisions. I have never recommended a mating, or given sanction to a mating to any breeder. I can only present the objective risk based on the knowledge of pedigree backgrounds.  We can hop that when dogs who are born today are ready for breeding over two years from now that we can test for carrier status. With that ability, a breeder can move from a carrier parent to a normal offspring in one generation of selection. Until that time, please do not sacrifice the breed with widespread spaying and neutering until we have more data on the present state of the breed concerning this single defective gene.

Reprinted with permission from Old English Times, December 1998, pp. 36-38.