WORK ON MERLE GENE: 2005 (Historical Information)

Dr Keith Murphy and his Lab have just published their ground breaking work on the Merle gene. Thanks to the Great Dane folks who helped out with samples. Thanks to the GDCA and the Board of Directors who supported this work and the efforts of JP Yousha to keep Great Dane research at the forefront. Our club, GDCA is listed as a forward thinking example of a Club by the AKC and CHF for the progressive work done on research and distribution of information to GDCA members, and general public via the GDCA website. (Thanks to Nancy Lerch and JP for work on this also) Here is the link.
http://www.pnas.org/cgi/content/abstract/0506940103v1 [click on abstract free]
It will be possible in the future to have a test for carriers of this gene, and if they carry one or two copies. This is an exciting break through. Dr Murphy and his team hope to move onto work on the Harlequin gene next. These are exciting times. Dr Murphy lab has also been looking at genes involved in DCM in Great Danes, Dobes and Boxers.

Neil O'Sullivan
Chair Health & Research committee GDCA

In simple English<G>, this papers means, in a nutshell, that they have discovered the merle gene & the specific mutation that causes merling, and this is the SAME gene IN ALL DOG BREEDS, and a very, very ancient mutation. There will soon be a commercially available gene test for merle. This will be useful in many way, not only so-called "cryptic" merles (dogs who are merles but don't look it), but for telling if our "merles" are heterozygous or homozygous, and finding out the same answer about many Harlequins, especially those "light marked" Harlequins, many of whom are actually "double merles." Read on if this subject interests you. 

Dr. Keith Murphy of Texas A&M University (TAMU) and his colleagues have discovered the exact gene and the specific mutation that causes merle coloring in dogs. This is the same mutation be it Collies or Danes, Dachshunds or Catahoulas, which implies it is a very ancient gene as it's universal in the breeds that have the merle pattern (SILV retrotransposon). Merle is an incomplete dominant gene that in the heterozygote (the dog with one merle and one non-merle gene) results in a dog that has a coat that appears "mottled" or "marbled" and is usually normal clinically (i.e. does NOT have debilitating defects). While in the homozygote or "double merle" (a dog who has two copies of the merle gene), the dog is typically predominantly white and normally DOES have various defects as a result of getting two copies of this beautiful, but somewhat "deadly" gene. 

Thus, the double merle dog nearly always has defects; sensory defects of eyes and ears predominate, but others may also be present. In the Great Dane the dog with only one copy of the merle gene is usually reported to be normal. When one merle-bearing dog is bred to another such merle-bearing dog, double merles, the dogs with various debilitating defects, are produced. Since all Harlequins have at least one copy of the merle gene, most "light marked harls" have two copies, as do nearly all white Danes, we need to learn which of our "harls" and their relatives are "what" as to merling. It matters indeed that we know which of our dogs are "single" vs. "double" merles because defects result and various dogs with different gene constellations cannot be safely bred the same way (even though we have called them in the past the same thing, Harlequins). We need to know which dog is what as to these dominant & recessive white spotting genes.

And so it's very important that we help support the development of a gene test for both merle and harl genes. Merle is the only canine color gene definitely associated with producing defects, so it's important to know as much as we can about this gene and the other "white spotting" genes (like Harlequin and Piebald) that can influence it. Dr. Murphy's lab is currently pursuing the production of a commercially available test for merle; an affordable test for merle is something that every breeder (including Dane breeders who have Harlequin/Merle/White/Mantle, etc. dogs) can benefit from, as already this research has shown what many expected, that not all Harlequins are "created equal." And this lab is also immediately seeking funding to be able to search for the answer to "what is Harlequin?" 

Some Harlequin dogs in this research tested as double merles, while others (the majority) are "normal" or single merles. It's typical that the Harlequin dogs normally "show marked" or "heavily marked" are expected to be "single" (heterozygous) merles, whereas the Harlequins considered "lightly marked" or that are mostly white are most likely to be the double merles (the homozygotes). But we need to develop the research on Harlequin to know for sure what we are dealing with here. As to merles, the dogs who are predominately colored, who usually are some shade of grey (with some black and some white spots), are typically "single" merles and should be completely normal. However the dogs referred to as "whites," "lightly-marked Harlequins," and "merlikins" may carry two copies of the merle gene and such dogs should not be considered the "same" as normal Harlequins or normal merles, are most likely going to have various defects, and most definitely should NOT be considered in the same context for breeding, as they carry an entirely different set of genes (genotype). See http://www.gdca.org/health/deafness.htm 

This is one reason to test all Harlequins and other Harlequin family dogs for MERLE; to see just how many merle genes each member of the Harlequin family carries. And it's a good reason also to help see the Harlequin gene developed. Another is that our family of non-merle-bearing dogs, the Mantles and blacks, for example, may very well be able to carry the Harl gene and not "show" it in the absence of the merle gene. Harlequin appears to be a dominant modifer of merle, which means that Mantles, for example, can carry Harlequin sight unseen. Merle is nearly always seen (but for possible cryptic merles), however Harlequin, an independent merle modifier, may be carried "sight unseen" by dogs of the Harlequin family (such as Mantles). SO we really need to work in this area to learn more. 

Again, to summarize, merles when "doubled" are dangerous, as defects are usually found that can affect quality of life by restricting the normal range of sensory development and other important characteristics found in wholly normal dogs. Dane rescue is nationally associated with a predominance (more that 80%) of Harlequin bred dogs: whites, merles, "harl blacks" and various dogs referred to as "harlies" are our national rescue issue. To develop and use tests for the merle gene and the harl gene can go a long way to improving breeding in the Harlequin color family of Danes. To know more here is a chance for us all to improve the condition of many Danes, to help all interested breeders better themselves and their breeding programs, and to reduce or even eliminate the suffering of dogs in the future, as well as help produce more of the desirably colored puppies for breeders "of color." 

HARLEQUIN GENE PROJECT:

This research is ongoing and really is MOMENTOUS. Merling is the only known dog gene for color associated with defects in the dog. This research will provide all Dane breeders the chance to have more direct and specific information about how to breed properly and well. This laboratory has already taken the first major step to provide us the answers to "what is merle?". And the same lab is currently pursuing funding ($60,000 is needed) to elucidate the Harlequin gene (we have the dogs needed already to complete the study). We as Dane breeders need to see this further research on the Harlequin gene, a seperate, dominant, modifier of merle. Our blacks and Mantles may differentially carry the harlequin gene sight unseen. Our "whites" which are mostly double merles, may or may not carry one or even two copies of the harl gene. Until we learn what all these various "looks" (our multitudinous phenotypes) are IN REALITY, we will continued to be limited in our ability to produce litters knowledgeably. 

It's estimated to take no more than a year's research and this *very* reasonable funding (only $60,000 total is sought with an expectation of finding the Harlequin gene within a calendar year), to achieve the same marvelous results for Harlequin as have already been achieved in merle by this research group. I can only hope those who care about Harlequin phenotype will support the search for the "other" dominant white gene now that merling has been solved by this team! Anyone who wishes privately to contribute to this work can do so by contacting the CHARITABLE TRUST of the GDCA and specifying the donation is to be used specifically toward research into the Harlequin gene. This is a major step forward as still a major Health & Welfare issue for this breed! 

JP YOUSHA (2005)
H&R COMMITTEE, GDCA
danehealth@gdca.org
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