Victory over a genetic condition?
By Dominique Vincent, Vet
In collaboration with Sally Clegg, Dalmatian breeder
Translated from French by Joanne Sullivan and Sally Clegg
In 1973, Dr. Robert Schaible, a geneticist and Dalmatian breeder, crossed a Dalmatian bitch with a Pointer in the belief that a single gene is responsible for the over-production of uric acid, which causes the formation of stones ( a potentially crippling condition) in approximately 25 % of male Dalmatians. This “Backcross Project” triggered fierce arguments within the American Kennel Club (AKC), which lasted for almost 35 years. However, in 2008, Dr. Danika Bannasch discovered a recessive mutation. All Dalmatians are homozygous for this mutated gene, except Dr. Schaible’s bloodline, known as “LUA”, which had retrieved this “wild” gene. As a result, The Backcross line was finally registered by the AKC in 2011 and, at present, five litters have been whelped in Europe, the firstof which in France.
An uphill struggle against genetic conditions
Imprudent use of inbreeding in order to fix certain characteristics as quickly as possible (in particular, coat and conformation), combined with the limited number of champions available for breeding and the search for an exaggerated type, has led to the development of genetic conditions. Indeed, this was something that Dr. B. Denis and Dr. G. Leroy reminded us of at the World Science Program in 2011.
It is not enough to content ourselves with alleviating the symptoms of these conditions. On the contrary, this resolves nothing. However, recent measures taken by the administration of the Stud Books do allow us some hope. The Société Centrale Canine (SCC) records health details concerning debilitating hereditary illnesses on birth and pedigree certificates, whilst the British Kennel Club will no longer register litters resulting from close breeding and recommends testing potential parents for the hereditary diseases particular to their breed.
Dr. Schaible’s underlying idea when dealing with an old genetic condition (which has therefore been accepted as unavoidable) was to turn back the clock using the simple, tested method of cross-breeding and we believe that his work, driven by a dogged determination for almost 40 years, deserves to be broadcast.
The work of Dr. R. Schaible
The concept of a “pure” race
This unique crossing with a Pointer caused a scandal which was, in many ways, a huge misunderstanding, especially since the Pointer almost certainly played a role in the initial creation of the breed. Furthermore, a study commissioned by the AKC (N. Fretwell 2010: Molecular genetic Analysis of Backcross Dalmatians Conpared to AKC, UK Dalmatians, Pointers and other breeds) did not find any genetic traces of the Pointer.
A non-schismatic preservation project
The “Backcross Project” aimed quite simple to re-introduce a “wild” gene lost through the process of selection. It was a case of careful borrowing and was in no way intended to create a split in the breed. The re-introduction of the gene will spread over a period of decades in such a way as to preserve the genetic variety of the breed. There are two Stud Books in the USA: the AKC book and the UKC (United Kennel Club) book, in which the “LUA” bloodline is entered and which is culturally associated with health. With this in mind, UKC breeders recommend avoiding breeding heterochrome dogs (blue eyes) as statistics show a positive correlation between blue eyes and deafness.
The follow-up of the “Backcross breeding” concerning uricosuria (high levels of uric acid in the urine) was based on a very simple urinary test. When refrigerated, “LUA” urine stays clear, whereas “HUA” (High Uric Acid) urine, which is over-saturated with urates, becomes cloudy due to the precipitation of crystals.
The opposition’s key arguments are largely refutable
The first claim is that the formation of stones depends as much on precipitation factors as on the level of uric acid in the blood. A study commissioned by the AKC is currently being carried out to investigate this (Dr.Bartges) but the process risks being both long and unfruitful as there are a great many factors to be considered. But as Dr. Schaible quite rightly points out, “First things first. The primary factor needs to be addressed: that is to say the over-saturation of the urine with urates.”
Secondly, some believe that the Dalmatian’s spots could suffer detrimental effects. However, whilst it is true that the spots of “LUA” Dalmatians can sometimes be mixed with white (“frosted”), this defect is not unique to them. It already exists within the breed and can be improved by selection. Moreover, although “LUA” spots can often be a little smaller, they nevertheless conform to the size required by the Standard.
Finally, there are concerns over the introduction of new genetic conditions. However, through necessity the bloodline is now sufficiently closely -bred for us to be able to conclude that, since we are now on the 15th generation, any harmful mutations would have be revealed by now. Furthermore, the Pointer is a very reliable breed and has been used in cross-breeding before.
2008: The mutation is discovered
In 2008, Dr. Danika Bannasch discovered the recessive mutation which affects the gene SLC2A9 on chromosome 3 and is responsible for preventing uric acid from being transported to the liver and kidneys, where it would usually be transformed into a blood-soluble product. In Dalmatians, this mutation goes back so far that every Dalmatian carries two copies of this recessive gene (recessive homozygous).
A direct correlation between pigmentation and uric acid levels
According to Dr. Bannasch, the mutation of the gene SLC2A9 could be linked to the selection of dogs with the aim of producing better defined spots. Dr. Schaible’s hypothesis is that the speed at which pigment cells migrate is controlled by one (or even several) genes situated on the same chromosome as the SLC2A9 gene and, whilst the correlation of these genes may not seem to serve any purpose, the fact that there are so close together probably explains their simultaneous transmission.
The correlation between the SLC2A9 gene and pigmentation is also very interesting when you consider that deafness in Dalmatians is linked to a pigmentation defect in the inner ear of polygenetic origin, in which the SW gene causes the white coat to invade the coloured coat. This may well lead us to start asking questions… It should be noted that the hearing test results from the first “Lua” litters born in Europe are really excellent, but, nonetheless, statistical studies (Animal Health Trust Newmarket) have been set in motion to judge whether these results are significant.
A genetic test is now available
Developed in the USA, a buccal smear test is now available in France which will no doubt help to prevent the harmful evolution that we have seen with the Dalmatian from affecting the Australian Sheepdog and the Black Russian Terrier, 35% of which appear to be carriers of this mutation.
2009: The project is presented at the WAFDAL convention
The World Association for Dalmatians (WAFDAL) brings together all of the official Dalmatian clubs. However, until the convention in 2009, the project had remained confined to the USA and only the AKC newsletter displayed any evidence of the fierce quarrel, episodes of which were passed on to me by Sally Clegg, an English breeder living in France since 1988. Indeed, this is how Stocklore Forrest Windsong (Wendy) came to be imported to France in 2009. During the bi-annual convention in Oslo, under the subject of Health and Breeding, the French delegation presented the project, emphasizing the need for international cooperation in order to ensure the genetic variety necessary for the project’s success. It was also an opportunity to pay homage to Dr. Bannasch, who travelled to Oslo to show her research.
2011: The project receives international recognition
In 2009, two female and one male “Lua” Dalmatians were officially imported to the UK. For three generations, the pedigree of their descendants will be marked with an asterisk, indicating special monitoring. This will involve conformation to the Standard as well as health, e.g. deafness (BAER electro-diagnosis or brain stem analysis), hip status (even though the breed has an excellent record as far as this is concerned) and character. In 2011, the AKC registered the “Lua” bloodline: under pressure from an increasing number of AKC members, the committee was obliged to accept the registration of the bloodline, thereby giving it international recognition. (The UKC is not a member of the FCI.) In 2012, five litters were born in Europe: in France, in the UK and in Germany, with one male puppy being exported to Finland. In addition to this, a stud dog, Stocklore Forrest Wizard (Merlin) is soon to be used in Italy.
The “Backcross Project”, founded on a true love of the breed that united clear sight, rigour, impartiality and a long-term vision for the future, is now in the hands of well-advised people. Moreover, it is just reaching its adolescence and opening up to the world. Let us hope, above all, that it is able to remain true to its inspiration.
This article was originally published in the SCC’s publication “Cynophilie française” (2eme TRIM. 2012). Translated from French by Joanne Sullivan and Sally Clegg