HOW TO BREED SENSIBLY WITH DNA TESTS
French Bulldog Clubs should look at any DNA test that is specific to the French Bulldog with regard to the numbers affected, the severity of the disease concerned, the impact on the animals health and well being and decide whether any animals need to be removed from the gene pool. Many breeders erroneously consider that affected dogs cannot be used. But the beauty of having a DNA test is that, in the main, no animal needs to be lost to the gene pool.
Club members need to understand a) how these diseases are inherited; b) how to sensibly use this information; and c) not lose any valuable breeding stock unnecessarily.
The vast majority of DNA tests currently available (>90%) deal with simple recessive diseases.
Simple recessive DNA diseases - possible matings
Normal/clear dogs are shown as ‘AA’
Carriers (heterozygous) are shown as ‘Aa’
Affected dogs are shown as ‘aa’
Where ‘A’ = normal dominant allele and ‘a’ = affected recessive allele. One allele comes from each parent.
As ‘A’ in this case is a dominant normal gene, all un-highlighted matings are acceptable.
Matings highlighted in red are not advised and should not occur.
Matings highlighted in pink are high risk but may be required from time to time. If done, all progeny should be DNA tested prior to sale.
There is 1 reasonably significant DNA disease test available to the French Bulldog at this time, which is largely being underutilised. There are also tests for colour dilution, mainly for blue, but as this is not considered a major issue by many, it is less frequently tested (or used as a selection criteria for breeding). More tests are constantly being developed. Some of these may cover obscure diseases, while others may cover significant diseases within the breed.
HC (hereditary cataract) HSF4 gene—this is an early onset cataract disease, usually affecting both eyes which is seen within the first 2-3 years of life and is progressive (ie. they go blind). These cataracts can be removed surgically, which is expensive, but the dog should have reasonable vision afterwards. This condition can be tested and the affect, carrier and normal dogs readily sorted out.
Cataracts occur in many breeds, some are early onset, some are late. The incidence in the French Bulldog does not appear to be high in Australia. However the consequences of a young dog going blind where this can be avoided, should have breeders test for this condition when doing genetic profiles.
DM (degenerative myelopathy) is a disease that occurs at the other end of a dog's life. There are no confirmed cases of DM worldwide in the French Bulldog up to this point. I do not recommend testing for DM in the French Bulldog. DM is a very old gene that is widespread in the canine population and turns up in many breeds (over 120 I believe at last count) as well as cross bred dogs, yet only 17 breeds have been proven to develop the disease - of which the French Bulldog is not included. There are obviously other mitigating factors that turn these dogs from “at risk” to affected that are not present in these unaffected breeds.
The number of cases of DM and HC are under reported. Use of the Health Report can assist us in ensuring we are improving the overall health of the breed as well as giving us more accurate statistics.
SNIP tests—when DNA testing SNIP tests are now available that will test all known (and recognised) diseases in any breed. These will also test for parentage (where generational data exists). It is now cheaper to test this way than for individual disease testing. Current costing is around $60-65 for 1 disease and around $135 for 3-4 diseases plus parentage.
Dr Karen Hedberg BVSc
Concern about genetic testing Degenerative Myelopathy (DM) in French Bulldogs
Dr. Jerold Bell, Adjunct Professor Tufts University, and Chair of the Hereditary Disease Committee of the World Small Animal Veterinary Association, has recently circulated a letter about DM testing in French Bulldogs (see below). According to his research and communication with international neurologists there has never been a confirmed case of DM in this breed, and yet the test is recommended in several countries.
French Bulldogs do have spinal problems, but these are generally due to widespread prevalence of vertebral abnormalities and not DM. Testing - and then perhaps eliminating dogs from the breeding stock based on test results - is not a beneficial strategy for the population.
Part of the problem of wrongly recommended tests may be related to the unfortunate use of language for some genetic tests. Results of allele frequencies may be reported as 'clear', 'carrier', or 'affected'. In fact, 'affected' in this case means 'genetically affected' and may or may not relate to clinical disease, as in the case of DM in French Bulldogs, at least as far as we know.
Discussions like these are crucially needed as part of better genetic counselling.
DEGENERATIVE MYELOPATHY DOES NOT OCCUR IN FRENCH BULLDOGS
JEROLD S BELL DVM Dept Clinical Sciences, Cummings School of Veterinary Medicine at Tufts University
This article is written in response to the misinformation and gene pool destructive genetic testing that is currently going on in the French Bulldog breed regarding degenerative myelopathy (DM). DM is a specific genetic disease that causes fatal spinal cord degeneration in older dogs. It has a complex mode of inheritance which requires more than one gene pair having to combine to cause a clinically affected dog. Several different disorders mimic the clinical signs of DM. Therefore, a confirmed diagnosis can only be made through a pathological examination of the spinal cord.
Dr. Joan Coates and her associates at the University of Missouri have conducted clinical and pathological research on DM since 2007. Due to the complex neuropathological changes observed in affected dogs, pathologists from around the world have sent spinal cord slides to UMo. for confirmation of a diagnosis. Sporadic cases have been pathologically confirmed in 34 different breeds and in mixed breed dogs, but the majority of clinical cases occur in only a handful of breeds. DM has never been pathologically confirmed in the French Bulldog.
Several peer-reviewed published studies document the neurological disorders present in the French Bulldog breed. A 2017 study reviewed all French Bulldogs presenting with neurological disease to the Alfort University Veterinary Hospital in France between 2002-2016. No cases of degenerative myelopathy were diagnosed in the breed. The most common condition causing neurological signs in the breed was intervertebral disc disease at 45.5% (5% of all French Bulldogs seen) with two-thirds of the cases involving the hind legs. The rest of the neurological conditions diagnosed included spinal arachnoid diverticula (7.3%), brain tumors (7.2%), compressive spinal cord disease (5.5%), spinal tumors (2.0%) and syringomyelia (1.7%). Other conditions included infectious, toxic, metabolic and ischemic disease. A study of French Bulldogs in the UK showed similar results with zero dogs being confirmed with DM. The vast majority of diseases causing neurological signs in the French Bulldog cause similar clinical signs to DM and are treatable diseases. Assigning a misdiagnosis of a fatal disease such as DM prevents a proper workup and treatment that can likely save a dog’s life.
I personally take some blame for the misunderstanding of whether DM exists in this breed. During the 2009 French Bulldog Club of America National Specialty health seminar, I included an analysis of a 2009 FBCA breed health survey. The survey was filled out by owners and 2.3% indicated that their dog was diagnosed with DM. (The PowerPoint with the health survey statistics and a description of DM are still present on the internet.) We now know there are no confirmed French Bulldogs with DM. There are French Bulldog owners who believe that their dogs have DM and have Facebook and other social media pages dedicated to their dogs. On several of these, serial videos of the dogs actually rule out a neurological diagnosis of DM.
The most confusion concerning DM is associated with the genetic test for the sod1 mutation. In 2008, researchers at the University of Missouri and the Broad Institute identified a recessive mutation in the sod1 gene that is homozygous (carrying two copies) “at risk” in all pathologically confirmed DM affected dogs. A genetic test for the sod1 mutation is available from several dog DNA testing laboratories including the University of Missouri (OFA testing). As DM is a complexly inherited disease, dogs must have a mutation in another (yet unidentified) gene or genes in addition to being homozygous for the sod1 mutation to become clinically affected. Based on the lack of confirmed cases in the French Bulldog breed it is probable that the breed lacks other causative genes necessary to produce clinical DM.
The sod1 mutation is an ancient mutation in the dog genome and is the most frequent mutation identified in the genetic screening of mixed-breed and purebred dogs. Mars/Genoscoper testing finds that the sod1 mutation frequency is 7.77% in all mixed-breed dogs tested, and 5.41% in all purebred dogs tested. In several breeds the frequency of the sod1 mutation is over 90%, but no members of the breed have ever been diagnosed with clinical DM. In worldwide testing of French Bulldogs, 2-5% test homozygous “at risk” for the sod1 mutation, and 18-33% test as heterozygous carriers. However, the presence of the sod1 mutation is of no consequence to any French Bulldog as DM is not a clinical disease in the breed.
Due to misdiagnoses, misconception and misinterpretation of sod1 testing, several national French Bulldog parent clubs call for pre-breeding sod1 testing. This erroneous call places an enormous pressure to restrict the breeding of healthy, quality French Bulldogs. It severely restricts the genetic diversity of the breed by selecting against up to one-third of all dogs for breeding. In addition, a sod1 homozygous “at risk” test result places a significant and unnecessary emotional burden on owners who believe that their family member will develop DM and die from the disease. Unless and until DM is proven to be a significant clinical disease in the French Bulldog breed, no French Bulldog should be tested for the sod1 mutation and no breeding decisions should be made based on the results of sod1 testing. French Bulldog breeders should concentrate on selecting for quality breeding dogs that are free of validated breed-specific disease liability genes and genetic disorders.
Mayousse et. al. Prevalence of neurological disorders in French bulldog: a retrospective study of 343 cases (2002–2016). BMC Vet Res. 2017;13:212.
O’Neill et al. Demography and disorders of the French Bulldog population under primary veterinary care in the UK in 2013. Canine Genet Epidem. 2018;5:3
Ryan et. al. Prevalence of thoracic vertebral malformations in French bulldogs, pugs and English bulldogs with and without associated neurological deficits. Vet J. 2017;221:25–9.
Inglez de Souza et. al. Evaluation of the influence of kyphosis and scoliosis on intervertebral disc extrusion in French bulldogs. BMC Vet Res. 2018;14(1):5.
Donner et. al. Frequency and distribution of 152 genetic disease variants in over 100,000 mixed breed and purebred dogs. PLoS Genet. 2018;15(1):e1007938.
Zeng et. al. Breed Distribution of SOD1 Alleles Previously Associated with Canine Degenerative Myelopathy. J Vet Intern Med. 2014;28:515-521.
This article can be reproduced with the permission of the author JEROLD S BELL DVA Dept Clinical Sciences Cummins School of Veterinary Medicine Tufts University Massachusetts USA