CANINE HEREDITARY DISEASE AND DNA TECHNOLOGY
Over the years there has been a shift in the profile of diseases seen by veterinarians. Improvements and developments of antibiotics and more effective vaccines have controlled many of the infectious diseases that caused problems in the past. As the frequency of these infectious diseases has declined, there has been a relative increase in diseases that have a genetic basis.
Inherited diseases result from mutations or changes to one or more genes that make up the canine genome. There are two kinds of gene mutation that can occur: a dominant and a recessive mutation. In simple dominant diseases, affected offspring inherit just one copy of the mutant gene from either the father or mother. In simple recessive diseases, affected offspring have 2 copies of the recessive mutation, one inherited from the father and one
inherited from the mother. Offspring that have one recessive mutant gene and one normal version of the gene are termed carriers; such individuals will not be clinically affected by the condition that results from the recessive mutation. However, a carrier will pass on the recessive mutant gene to approximately 50% of its offspring, the other 50% receiving the normal version of the gene.
Some inherited diseases are however more genetically complex resulting from mutations of more than one gene. These are called polygenic inherited diseases such as hip and elbow dysplasia, epilepsy, and inherited cardiac disease and cancer. However, the vast majority of canine diseases are a result of recessive mutations in specific genes.
Around 400 inherited diseases have been recognised in the canine population most of which have a human equivalent. This interests the scientists because it has been realised that 75% of the genes that are in humans also appear to be in dogs. Pedigree dog breeds are essentially like closed human populations and, therefore, research in finding gene mutations in dogs also helps research in human conditions.
Over the past few years, canine molecular biologists have laid the foundations for a whole new era of informed dog breeding. The recently published map of the canine genome together with its component markers provides an invaluable resource to start addressing inherited diseases in dogs. The vast majority of canine diseases are a result of recessive mutations in specific genes. The availability of the map greatly facilitates that search for the genes that cause inherited disease. Once disease genes have been identified, relatively simple DNA (Deoxyribonucleic Acid) based tests can be developed to identify the presence of a mutant, diseased gene in a DNA sample. The availability of such tests will provide for the first time, a method of identifying carriers of recessive mutant genes.
Breeding Programmes
Being able to identify carriers will have an immense impact on breeding programmes. The removal of carriers from the breeding stock is not always the ideal solution because although you are minimising the spread of the mutant gene, you may also be removing positive qualities that the breed requires in order to maintain its overall health; in other words, you could be throwing the baby out with the bath water. The availability of a DNA test allows much more subtle manipulation of breeding programmes to reduce the frequency of a particular mutation whilst retaining some of the positive features present in affected lines
If a bitch is identified as a carrier using a DNA test, rather than removing this bitch from the breed's gene pool, potential mates can be screened to identify that they are clear. If a clear dog and a carrier bitch are mated approximately half of the offspring will be carriers and the other half will be totally clear of the disease gene, so there will be no clinically affected puppies in the litter. The litter can then be DNA tested with a cheek swab at about four to five weeks of age to show which of them are carriers and which of them are genetically clear puppies. Once identified, the genetically clear puppies can be bred from in the future, thereby removing the mutant gene from the breeding population, but at the same time retaining the many positive features the line has to offer.
The availability of a DNA test also means that under some circumstances genetically affected dogs can be bred from. If an affected dog is mated to a DNA tested clear mate all the offspring will be carriers but not clinically affected in any way. If one of these carrier progeny is subsequently mated to another clear mate, then approximately half this second generation will be clear and will be identifiable by DNA testing. Thus a breeder can go from an affected dog to a clear dog in just 2 generations using a DNA test driven selection process.
There are now about 50 DNA tests available for different conditions and for different breeds. The majority of these have been developed in the USA.
OES PNA PROJECTS in America
Information from Ann Lapp, OESCA Health And Research Committee, Chairperson.
The Old English Sheepdog Club Of America is supporting research through The American Kennel Clubs Canine Health Foundation in two major areas.
1. The Genetics of Cerebellar Degeneration. Dr Natasha Olby, North Carolina State University.
Old English Sheepdogs are affected with hereditary cerebellar degeneration (abiotrophy). The condition causes ataxia (inco-ordination) which begins late in life and is inherited as a recessive trait. While not necessarily fatal ataxia results in frequent falls and injury and seriously comprises the dog's quality of life. The delayed onset and recessive inheritance of this disease means that the trait can be widespread in the population and difficult to eliminate without a DNA test for carriers. Through the efforts of OESCA, over 350 blood samples and numerous tissue samples from OES continue to provide essential data for Cerebella Ataxia (CA) research. There is still a critical need for blood and tissue samples from affected dogs and from relatives of affected dogs. OES breeders and owners, or the veterinarian of the owners wishing to provide samples should be instructed to make direct contact with Dr Olby. (Note. Dr Olby is a Cambridge University UK graduate)
2. Investigation of Candidate Loci For Progressive Retinal Atrophy, Dr Simon
Peterson-Jones, Michigan State University.
Progressive retinal atrophy (PRA) is a common cause of blindness in purebred dogs. It is an inherited disease and there are several different forms resulting from defects in different genes. Most forms are due to a defect in a single gene and are inherited in an autosomal recessive manner. PRA has become a problem in OES and Papillon breeds. In both these breeds, dogs develop the disease in middle age and slowly and progressively lose vision. A number of different genes have been identified as the cause of PRA and these are being researched in the OES and Papillion. A DNA test
will then allow breeders to identify carriers of the disease and this will prove very
valuable in eradicating PRA from their breed.
If someone has a dog with PRA or a closely related dog (immediate family such as parents, siblings & offspring) contact Dr Simon Peterson-Jones to be included in the study. Both researchers work directly with OESCA members and their animals when needed. Research is progressing on schedule with expectations that results will be forthcoming.
If someone outside of the USA would like to make a financial contribution to either of these health studies, you may do so through OESCA Health and Research, contact Ann Lapp Pettiboneoes@aol.com or phone 715-878-4861
The next possible areas of OESCA supported research will probably be directed to cancer research or autoimmune research.
What is happening in the UK.
In Great Britain, the British Veterinary Association has operated a hereditary eye disease-screening programme for over 30 years. OES are listed as suffering from 3 types of Hereditary Cataract. The checks are voluntary but conscientious breeders do this with their breeding stock. The results are published in the Kennel Club's quarterly issue of the Breed Records Supplement along with litter registrations and hip scoring
results.
The dogs, which are eye-screened, are either affected or clear but with recessive genes we have no way of knowing which dogs are the carriers until affected offspring are produced. We are now seeing failures in the OES results and hearing of more dogs being affected and of puppies failing litter screening.
The OES Breed Council was made aware of worsening eye problems in the breed in April 2003.
In January 2004,1 wrote an article in the Greater London OES Club's magazine "Yours Faithfully" no 41 about recessive genes and hereditary eye disease to try and educate and inform the readers of the possible dangerous situation. Close breeding and a shrinking gene pool could cause the problem of hereditary cataract to become much worse in the next few generations.
The Kennel Club in its remit to promote the health and welfare of pedigree dogs is embracing the new DNA technology and through The KC Health Foundation will provide top up funding for research projects leading to the development of DNA tests.
In the last 2 years, the KC has granted £500.000 funding for research. This included money for the Animal Health Trust's research into Hereditary Cataract in the Staffordshire Bull Terrier and American Cocker Spaniel.
The OES Health committee commenced fundraising to try and further the research for a DNA test to be developed and now with the OES Breed Council, a Seminar is planned for Sunday 23rd October 2005. Dr Jeff Samson, the Kennel Club's Genetics Co-ordinator will talk on DNA testing for Hereditary Diseases in Dogs and answer any questions. Tickets cost £10 and are available from the OES Breed Council website www.oesbreedcouncil.org.uk
The OES Health committee has already spoken to Dr Cathryn Mellersh of The Animal Health Trust and she has agreed to take on our plight. There is also the
possibility of researching one other condition at the same time which has yet to be decided. The Animal Health Trust requires a blood sample, a copy pedigree and any other health certificates i.e. Eye Test and Hip Score and any other test relevant to your OES. Send these in confidence to the address on the AHT form which can be printed from the Breed Councils website, www.oesbreedcouncil.org.uk Dr C Mellersh is pleased to receive the blood samples now and will store them until there are enough to start the research.
Groups of possibly 10 related dogs make a good family gathering. Urgently required are 20 affected animals. We need at least 100 blood samples for an effective outcome. If anyone in Europe can help with this research by submitting blood samples and the pedigree^ information you will be helping your beloved breed to be more healthy and when a DNA Test is available it will benefit the OES Breed worldwide as will the American DNA research which is currently being undertaken.
The OES Health committee has written to all the UK OES Breed Clubs to help with fundraising efforts and donating money towards this research. The Breed Council's website will monitor the fundraising efforts.
We have this opportunity now to embrace this new scientific technology for the benefit of the whole breed the world over. The Kennel Club is offering to help with the funding and as more research projects get off the ground, the research is going to be quicker and cheaper.
If Breed Clubs, whether in the UK or in the countries of Europe, America or Australasia contributed towards this cause, together with donations from exhibitors, breeders and pet owners of Old English Sheepdogs, the money raised would result in a DNA test being available for future generations of healthy OES.
What a wonderful legacy this would be to the breed from the present day OES enthusiasts who hold the breed in trust for the future generations of Old English Sheepdog lovers to come.
Helen Harris July 2005
For further information or questions please contact Helen Harris. Tel 020 8776 1437
Email helen. harris8@ntl world, com
or Mr Ray Owen. Email owen@amblegait.freeserve.co.uk
Donations to be sent to "OES Health."
C/O Mr Trevor & Mrs Pauline Mills,
The Willow Tree
Tile Kiln Green
Great Hallingbury
Bishops Stortford ;
CM22 7TQ
Tel 01279 656256 Email kerjalee@aol.com
The information for this article has been compiled with the help from reliable sources on the Internet, The Animal Health Trust, The Kennel Club Website www.the-kennel-club.org.uk and the Dog Press.

Menu