This article was written by Dr. Prof. Peter Friedrich, President of the VDH and ADRK show and IPO judge, and is being published with permission of the VDH and the ADRK
Dear Rottweiler Friends, The article on JLPP sets out in detail what is in this severe disease, how it is inherited, and how and why it must be fought. Although it is hoped that the disease is not yet widespread, complete testing of all breeding animals must continue. It is expressly emphasized that most adult dogs are carriers of the disease, even if they can not fall ill, because the disease had shown at a young age. As of November 1, 2016, breedings may only be carried out with animals that have been tested for JLPP. This means that of all the animals that are to be found in breeding use, an oral mucosa sample must be taken and evaluated, and the result must be entered in the pedigree. Assay vials can be requested at the Office. A sample (in duplicate) must be taken by an LG-breed warden, breeding judge or veterinarian. Together with the completed examination Orders, to be found on the ADRK websit (forms), send the sample to the laboratory Laboklin for investigation.
After presentation of the result, a copy will be sent along with the pedigree of the dog upon the entry to the Office. Before mating, the owner of the dogs involved must access the pedigree to verify that each pairing is permitted in the future. —ADRK Executive Board
by Peter Friedrich President of the German Kennel Club (Verband für das Deutsche Hundewesen - VDH), breed judge, w orking ju dge and m em ber o f the breeding co m m itte e o f the A llgem einer Deutscher R ottw eiler Klub (ADRK)
1. WHAT IS JLPP?
The Symptoms of Juvenile Laryngeal Paralysis and Polyneuropathy (JLPP) have become apparent in Rottweilers in recent years. I would like to begin with an outline of the Symptoms that are characteristic for this disorder and its typical progression.
I will Start by explaining where the term itself comes from. Neuropathy is a Word used to describe a severe disorder of the nervous System. The prefix “poly” indicates that neuropathies can affect many different parts of the body at the same time. In a healthy body, nerve structures control muscles and perform a ränge of complex additional functions. In its fully expressed form, polyneuropathy causes control over the muscles to be lost to an ever-greater degree until it is ultimately lost entirely. Pronounced Symptoms of paralysis of the larynx and the surrounding tissue comprise the second component of JLPP. The onset of the disease is typically marked by breathing Problems in affected dogs, especially during physical exertion or when they are excited. Dogs may cough when eating or drinking, and the sound of their bark often changes. This is followed, somewhat later, by a loss of coordination in the hind limbs and subsequently also the forelimbs. These Symptoms worsen until the dog is unable to move. The disorder typically appears either shortly after weaning age or in somewhat older juvenile dogs. The risk of misdiagnosis cannot always be eliminated. The disease causes immense distress to affected dogs. It is inevitably terminal; no eure exists. We can consider ourselves lucky, that its appearance can be avoided with absolute certainty. This Situation represents the best possible scenario for everybody seeking a Rottweiler puppy.
2. WHAT IS THE GENETIC BASIS FOR THE CONDITION?
Juvenile Laryngeal Paralysis and Polyneuropathy (JLPP) in Rottweilers is a hereditary disease.
Its mode of inheritance is monogenic autosomal recessive. It is caused, in other words, by a mutation in a single genetic locus which is not located on the chromosomes deciding a dog’s sex (so not on the X or Y chromosomes). The concept of recessiveness relates to the natural laws which determine whether genes trigger disease Symptoms or not. In Order to understand how this works, we need to remember that every inherited trait we see in a dog that is controlled by a single gene goes back to two alleles. These are alternative forms of the same gene, one passed down from the dog’s father and one from its mother.
In the illustrations below, I will show how the genes behind monogenic autosomal recessive disorders are inherited and expressed. Many other modes of genetic inheritance following entirely different principles also exist, but need not be explored here; as the focus of this article is on JLPP, aspects of genetics not relevant to its transmission can be ignored here. The following genetic constellations can occur in any dog, regardless of its sex.
3. WHAT WILL HAPPEN IF THIS IS IGNORED, AND WHAT ACTION MUST ROTTWEILER BREEDERS TAKE NOW?
Fortunately, a reliable DNA test has come onto the market. Discovering whether a dog’s genetic make-up is homozygous unaffected (“completelyclear” ),heterozygous (a carrier) or homozygous affected is now relatively straightforward and inexpensive. This test has demonstrated that the gene responsible for the disorder is present in our Rottweiler population: it has been shown that carriers exist. We don’t know how many fatal cases of the disease have already occurred. Attempting to trace the problematic genetic heritage of dogs back to particular ancestors does not represent a fruitful approach to the issue: the best way forward lies in the adoption of genetic testing. At this point, let us imagine, for the sake of argument, a scenario in which very few Rottweilers were carriers. If that were the case, some people might reject the Option of testing on cost grounds as well as for other reasons: measures to counteract a rare disease might strike them as disproportionate.
In their innermost selves, they might also harbour deep-seated fears that they would no longer be able to breed from one of their most successful dogs without restrictions. A few people might handle the resultant stress by going into denial and refusing to engage with the issue or find out more about it. Knowing nothing about the disorder, they would then not need to factor it into their thinking. If you are in any way tempted to react in this way, please consider changing your attitude, even if you find this difficult, for the sake of the Rottweiler. Please wake up to the fact that responsible, ethically justifiable and legally compliant dog breeding must necessarily rest on more solid foundations. The risk of the mutant gene slowly but steadily spreading throughout the population is unacceptably high. Over years, the number of carriers would rise higher and higher, and sooner or later the number of fatal cases of the disease would also rise drastically. We know all this. And we must draw the logical conclusions from what we have learned.
From now on, or, more accurately, after an appropriate transition period, to allow time for the necessary tests to be carried out, every single breeder may only breed from dogs that have been identified as homozygous unaffected (“completely clear”) or as carriers. Carriers may only be bred with homozygous unaffected (“completely clear”) animals. Flomozygous unaffected (“completely clear”) dogs may be bred with both homozygous unaffected (“completely clear”) dogs and with carriers.The procedure specified here ensures that NO more Rottweilers will develop JLPP.
To be clear: I want to stress here that it would not be at all wise to breed only from homozygous normal (“clear”) dogs and bitches. If that were to happen, genetic diversity would be severely reduced and it would be virtually impossible to stave off the negative consequences of inbreeding.
The ADRK Board has, quite correctly and after consultation with the breeding Committee, now adopted a resolution to this effect. It will go on to produce a list of authorized genetic laboratories of assured quality. Independently of any club regulations, the same duty to take action can also be derived from the German Protection of Animals Act which each and every one of us is bound by. But let this be clear: our desire to breed healthy, sociable, energetic, and fun-loving Rottweilers that are true to type comes from the bottom of our hearts. It is not something we do only for the sake of complying with legislation.
I perceive the same ethical duty to adopt precisely this approach in every country where Rottweilers are bred, be that Germany or any other nation. Diseases do not respect national borders.The suffering of animals does not stop at national borders. Friends of the Rottweiler across the world - on every continent and in every country - are challenged to act on this issue. Nothing and nobody can free any breeder from this duty. Whether the relevant local breeding regulations already contain provisions dealing with JLPP matters not a jot in this regard.
In conclusion, it may be noted that other dog breeds have already profited from the successful implementation of similar breeding programs. Several diseases with the same mode of inheritance have already been eliminated in this way, for example polyneuropathy in Greyhounds (a relatively similar form to the disease affecting Rottweilers) and progressive retinal atrophy (PRA) in Sloughis. Counter-measures against JLPP in Rottweilers are exceptionally likely to prove successful, not least because no other genetic tests are currently in routine use in their breeding.
The development of ever better and cheaper tools for the analysis of DNA have driven the development of a genetic testing industry that allows breeders to identify potential genetic defects before breeding. Through pedigree research and careful selection of tested animals, breeders can now produce a litter of puppies that is essentially guaranteed to be free of particular genetic disorders that plague the breed.
Breeders have adopted routine genetic testing with enthusiasm. Nevertheless, purebred dogs are in a bad spot. The list of genetic disorders is growing faster than the canine geneticists can identify the responsible genes, and the development of tests lags even further behind. DNA tests are powerful tools - they can reliably identify the presence of particular mutations, but it sure doesn’t feel like we’re winning this war. Is all of the effort and expense being invested in DNA analysis and testing actually improving the health of our dogs?
It began with hip dysplasia. Thirty or forty years ago the canine community could no longer ignore the proliferation of crippled young dogs and sought to ameliorate the situation through use of radiographic hip examinations as a screening mechanism for breeding. The concept was quite simple. Since the defective hip socket configuration and the consequent proliferation of crippled dogs was primarily the result of genetic inheritance, the solution seemed to be the elimination from the breeding population dogs exhibiting external symptoms and also those dogs whose hips were deemed faulty through the use of X ray examination.
And indeed there was a very significant element of success in this selection program. Having one’s breeding stock certified as free from dysplasia by agencies such as the Orthopedic Foundation of America ( OFA ) became the standard of breeder responsibility and there was statistical evidence of a broad improvement in the hip status of many breeds.
Anyone who knows me at all probably also knows how totally excited I am by the ability of molecular genetics to solve the mysteries inherent in the breeding of purebred dogs. In addition to allowing us to actually "breed for improvement" instead of just blithely throwing the term around, I firmly believe that if used wisely, this new store of knowledge represents out best hope for both preserving the sport of dog breeing for future generations, and for fending off our own personal Professor Moriarty in the guise of Ingred Newkird & Co. But actually using this new knowledge to our benefit, and to the benefit of dogs, often requires us to discard long-held and long-cherished beliefs.
Realizing that something we were taught years ago (and in many cases have passed on to the next generation of breeders) was based on an incorrect assumption, and may actually be flat-out WRONG, can be a difficult mental pill to swallow, and some people just can't seem to do it. For others, it provides an "Ah-HA!" moment, when the seemingly inexplicable suddenly becomes clear.
One such moment for me occurred a few years ago, when I learned that prenatal disruption (via genetics or environment) of a regulatory gene with the delightfully improbable name sonic hedgehog (SHH) often results in asymmetry, where the two sides of a dog don't exactly match. (It's a lot commoner than you'd expect, actually, and occurs in people to varying degrees as well. And symmetry in people has been linked to both beauty and longevity. Probably true in dogs as well.) More to the point, an asymmetric dog will invariably crab, as he has longer reach and more drive on one side than the other, causing his forward progress to eerily resemble that of a '63 Ford Fairlane with a bent frame. Yet stacked in profile the dog displays flawless balance, which has confounded judges and breeders since time immemorial. When I shared that discovery in a column a few years back, an amazing number of judges who read it made a point of telling me that it was an "Ah-HA! moment for them, too. (One told me that now whenever she sees a dog crabbing, she checks the elbows on both sides, and one is invariably set higher on the ribcage than the other.) An old dog show mystery solved by molecular genetics. Cool. I had another of those "Ah-HA! moments recently, when I stumbled upon a fascinating research paper while looking for something else entirely. (Happens to me all the time.) It seems that scientists have discovered that the size and shape of the mammalian mandible (or lower jaw) is controlled by a surprisingly large number of genes - over 15 have been identified to date. A little more digging revealed that an equally large number are involved in the development of the maxillary complex, or what we refer to as the upper jaw. The kicker is......they are different genes, and inherited pretty much independently. Which means, in terms expressed as simply as humanly possible: A DOG CAN INHERIT HIS UPPER JAW FROM ONE PARENT, AND HIS LOWER JAW FROM THE OTHER. Ah-HaH! Another dog-breeding mystery solved, and a long-cherished belief laid to rest. Putting this into an everyday breeding scenario, here's what too often happens. A young health-screened dog of quality with a magnificent head is widely used by breeders on bitches whos heads could use some improvement--depending on the breed standard, their muzzles could be a little shorter, or a little longer, or maybe a little more or less refined. But rather than the overall improvement in the first generation breeders are hoping for, they get maybe one nice bite (if they're lucky and depending upon what the bitch's parents looked like) and a basketful of "bad" bites. (What constitutes a bad bite varies from breed to breed, of course.) Soon the word goes round that this lovely-headed dog "throws bad bites" and his stock drops faster than Lehman Brothers. Happens all the time. And now we learn that it wasn't his fault at all, poor guy. Breeders have been laboring for years under the misconception that an off-bite is the result of an AR gene, and that some dogs are carrying a recessive gene that causes them to "throw bad bites." I've heard it said a thousand times over the years, and so have you. But it is simply NOT TRUE. Turns out there is no single AR gene for an undershot bite, or an overshot bite, either. There are literally dozens of genes involved, all inherited more or less independently. So, from this day forward (unless you are one of those people now recognized as incapable of changing a long-held opinion in the face of new evidence due to insufficient activity in the anterior singulate cortex and I'm wasting my time here) we can all stop blaming the poor stud dog. What is actually happening genetically is this: Given Mendel's Law of Independent Assortment, which is still scientifically valid after all these years, a percentage of the pups from an "unlike-to-unlike" breeding in the head department will inherit a larger percentage of the genes for a longer mandibular (under) jaw from one parent, and a larger percentage of the genes for a shorter upper maxillary (upper) jaw from the other, resulting in bites that are undesirable per a particular breed's standard. NEITHER parent is to blame - malocclusions of the jaw, we now know, are polygenic. Now, hopefully most of us already understand that there is a huge genetic difference between a MALOCCLUSION OF THE JAW and MISALIGNMENT OF INCISORS, which cause a reverse scissors bite in a dog whose jaws align according to the standard, and whose "puppy bite" is often perfect. Misalignment of incisors is usually caused by no more than the particular timing of the eruption of the individual permanent teeth - if it is off, the upper incisors will force the lower ones out, resulting in a reverse scissors. (That's why it's correctable with mere pressure.) There's no sense blaming this one on either parent, either: Research has shown there are more than FIFTY different genes that influence the development, and timing of eruption, of teeth. Some of these genes, it turns out, are involved in other processes and also code for traits that we've actually selected FOR over the years---the MITF gene, for example, which is involved in pigment development (parti-colored dogs are parti-colored because they carry a mutation on this gene) is also involved in toogh development and timing of eruption, which is likely why the parti-colored pups in a litter often get their teeth later than their solid-colored brethren. The RSPO2 gene is also involved in tooth development, and a mutation on this one is responsible for canine head furnishings. (And that's just two off the top of my head- no doubt there are dozens more, as we now know that genes "multi-task.)
The route to overall improvement in bites within a breed IS THE SAME ROUTE THAT HAS REDUCED HIP DYSPLASIA in several breeds over the last few decades ---- SELECTION.
This probably explains why wolves -uniformly long-muzzled, solid-colored, and generally free of head furnishings - rarely display the anomalies in dentition that plague purebred dogs. Now, I'm NOT suggesting for a moment that we should be trying to put a ''wolf head" on all our dogs, or to make them all solid-colored or clean faced-- to do so would seriously affect breed type in probably two-thirds of them, and not necessarily for the better. What I AM suggesting is that simply understanding that malocclusion of the jaw and misalignment of incisors both appear to be polygenic, rather than the result of a single recessive gene, allows us to make more informed breeding decisions. Breeding a male with a gorgeous head to a bitch who is lacking and expecting the resulting puppies to all end up with his head (and bite) is about as silly as breeding a dog who is OFA Excellent to a dysplastic bitch and expecting the resulting pups to all end up OFA Excellent. No one with half a brain would blame the sire in that situation, because (hopefully!) we now all understand that canine hip dysplasia is polygenic, and represents a threshold characteristic. The route to overall improvement in bites within a breed is the same route that has reduced hip dysplasia in several breeds over the last few decades--SELECTION. And as the German Shepherd breed has proven conclusively with its OFA ratings, you can do it without sacrificing breed type. Rather than discarding a quality health-screened male with a correct head per his standard who produces off-bites when bred to bitches with poor heads, it would make more sense to selectively linebreed off him, using only those offspring who inherited his head and petting out the rest. After three or four generations of this, the line should be homozygous for his head, the pedigree will have both depth and breadth in that regard, and malocclusions will be few and far between. What we'd be doing is simply combining time-honored animal husbandry practices with knowledge gained from cutting edge molecular genetics. It's the future of responsible dog breeding. However, refusal to change one's long-held beliefs regarding mode of inheritance (i.e. continuing to believe that there is a single recessive gene for "bad bites" and that a dog who produces one is "a carrier") as new information becomes available to us will untimately result in failure to improve. Why? Because the breeding techniques used to reduce or eliminate the incidence of a trait caused by an AR gene will always be different than those used to reduce or eliminate the incidence of a threshold trait caused by polygenics, where gene testing is not a viable possibility. And consistently producing sounder, healthier dogs is more important now than ever because, make no mistake about it, the wolf is at our door. See you at the shows, and remember to have fun out there!
If you already know a little about genetics then you'll probably be familiar with the following terms. Most of them crop up in the basic genetics taught at school, but just to make sure, we'll go through all the relevant ones anyway and have a look at how they are applicable to dogs.
Die Chromosomen, Gene und die DNS sind einige wichtige Fachbegriffe aus dem Bereich der Biologie. Doch was bedeuten eigentlich Chromosomen, Gene und DNS? Was steckt hinter den Begriffen? Und welche Erkenntnisse kann man durch sie gewinnen? Das alles erfahrt ihr in diesem Biologie-Artikel zur Genetik.