Genetic idiopathic epilepsy - Page 1

This is the same pedigree of my friend's dog who two weeks ago was euthanized due to severe epilepsy at the age of 2:The dog started to have grand mal seizures around 15 months. Otherwise healthy male.

\http://www.pedigreedatabase.com/german_shepherd_dog/dog.html?id=2139562-loki-vom-allegiancehaus


I have read that some severe forms of epilepsy that strike young dogs have a genetic link.  This is not to point fingers but to try and learn. Are there known carriers in this line that anyone is aware of? Or is the condition'sd DNA still widely unknown in GSD. Sadly we weren't able to swab the dog or get blood sample for researchers to learn from this dog.  My sign on name and the dog's name here is just a coincidence.  This household's cat's name is Loki!!!  If its easier you can pm me info. Again not to point fingers, but just trying to understand the condition that struck down this wonderful dog.

A few years back, there was a thread about a dog that was euthanized due to severe epilepsy. I've pulled it up, and  compared the pedigrees, but can't spot any links right off the bat. Maybe after I've had my coffee....

http://www.pedigreedatabase.com/german_shepherd_dog/dog.html?id=2139562-loki-vom-allegiancehaus&p=7-generation-pedigree

http://www.pedigreedatabase.com/german_shepherd_dog/dog.html?id=1924558-benvillarosa-all-that-jazz&p=7-generation-pedigree

Here's the link to the discussion about this dog. It was definitely genetic in his case.

http://www.pedigreedatabase.com/forum.read?mnr=674162-benvillarosa-all-that-jazz--pts-after-horrific-seizures

Here's a link to an excellent discussion about the disease, and how it is carried:

http://www.pedigreedatabase.com/forum.read?mnr=63837-epilepsy--from-german-bred-sires

If you do a search for epilepsy on this board, you'll find a LOT of threads, with a lot of information. I haven't had time to pick through them yet. The above thread mentions certain diseases (epilepsly in ghe GSD seems to be one) require several copies of the mutated gene to be present before the disease will show up. And, as you'll see from the thread about Jazz, there was a great deal of inbreeding in his pedigree.

The most important post from the above thread is the last one:
 

LilyDexter and Videx,

Back in the "old days" when the homegrown English lines started to experience epilepsy ( the dog mentioned above and I think one of the Delridge (sp) dogs) did not the GSDLeague purhase some of the dogs so Willis could study the mode of inheritance? It seems to me in the vet world we are often reinventing the wheel because there is no memory or research of what has come before.

Yes there are different kinds of epilepsy in different breeds. Historically in the GSD epilepsy was late onset (after 2-3 years of age) which is part of what made it difficult to remove from the genome since dogs had often been bred before it raised it's ugly head. If I remember right what Willis determined was that it had a threshold inheritance pattern.  For example 10 genes might be involved with a minimum of 4-5 before seizures would occur. Males appeared to have a lower threshold than females and started to fit at an early age and more severely. Since you guys are in England, you have the resource at your finger tips - email him.

Re the "ideal" situation of  a "picked clean" genome to produce the perfect dog - make haste slowly. Some interesting research has been done on Cystic Fibrosis and Tay Sachs diseases. The question posed was this - Since these are obviously fatal diseases why do they persist in the genome since truly fatal diseases breed themselves out of existence?  They went back and looked at the historical populations that that gave rise to these diseases and found in the case of  Tay Sachs those populations were subject to periodic epidemics of dysentry and similiar diseases. Tay sachs is an abnomality in how the body handles fluids and fats. What they found is a carrier with one copy of the gene actually would survive the dystentery epidemics because their bodies did not become dehydrated in the same way as someone w/o the gene. Re Cystic Fibrosis something very similar except the diease was TB. The CF gene increases mucus in the lungs. With one copy of the gene it actually is a protection vs TB. You think this might be handy to know now that we are facing an epidemic of drug resistant TB?  So yes make haste slowly - make sure you understand what the gene brings to the table and do not just off the hand label it bad gene.

His last point about 'bad genes' is one I'd like to elaborate on. Until recently, breeders thought that by inbreeding on their lines, they could eliminate alll recessive 'bad genes', resulting in a gene pool that was 'picked clean', to use VKF's terminology.

What geneticists have now discovered is the number of recessive genes in an animal is much, much larger that we thought. If you tried to eliminate all of these genes, you would  wind up with animals that were so lacking in genetic diversity that their health would be affected. The hidden diversity present in recessive alleles is a very important part of an animal's genetic makeup. You CANNOT eliminate it without severely damaging the health and longevity of your lines!

I think this fact is made abundantly clear by examining the American line GSD, which is very closely bred on Lance of Fran-jo and his progeny. These lines suffer from a number of diseases not seen in other lines that are less closely bred, or seen much less frequently: sudden deaths, mostly due to cardiac problems such as cardiomyopathy, aortic stenosis, etc; toxic gut syndrome, EPI, and gastric torsion/bloat.

As VFK says, those 'hidden' genes aren't always sitting there doing nothing. Some provide resistance to diseases.Some are harmless when only one copy of the gene is present. Then, breeders start mucking around with the lines, doing close inbreeding/linebreeding, and the dog winds up with three, four or more copies of the gene...and OOPS! We've got a full-blown disease we didn't know was present in our lines! Gee, WHERE did that COME from?

The genetic diversity is there for a reason, folks. Someone once came up with an oddball theory that said if you linebred very closely on your lines, by the seventh generation, you'd have a dog that was an exact copy of the wonderful dog you'd started out with and wanted to duplicate.

I think scientists tried this out in the lab, with mice or rats. By the seventh generation of close inbreeding/linebreeding, there were NO progeny left. The survivors were all too weak and sickly to reproduce!

So, how is a breeder going to get the qualities they want in their lines without linebreeding (which is REALLY just a form of inbreeding)?

Back in the early days of the GSD in America, I heard breeders used phenotype breeding. (The phenotype is the actual appearance of the dog, while genotype refers to the genes present.) If you wanted your lines to have more angulation or darker pigment, you would bring in an unrelated sire or dam that had those characteristics.

The Germans avoid too much inbreeding by only allowing dogs to mate that have no common ancestors for 5 generations. That's fine, that's a good system, BUT sometimes it backfires, if the same sire or dam is present too many times in 5th, 6th or 7th generation. Many German showlines have Palme v Wildstiegerland present many, many times in their pedigrees, and I am convinced this is what has caused both my female and her sire to have problems with allergies and yucky ears. It's not life-threatening, but it sure is annoying!

Okay, I'll get off my hobbyhorse now...time to go give Star her steriods and eardrops!  

" The Germans avoid too much inbreeding by only allowing dogs to mate that have no common ancestors for 5 generations."
This s not correct, the closest allowed linebreeding, although not used that often, is 2/3, not 5/5.

So sorry for the dog(s) involved;  this is a horrific disease.  Let's hope this gives breeders a little wake up call or at least a heads up...  Sorry for all involved.  Nan

Linebreeding or inbreeding itself is not problematic. A 2-3 is OK in most cases if the dam and sire were not linebred or inbred themselves.  Two animals with no common ancestors in their own pedigree inbred 2-3 or 3-3 seldom produce unhealthy offspring.  Repeated linebreeding on the same dogs or bloodlines for several generations will however come back to bite you and more importantly can produce some unhealthy and unfit animals.  It was common practice in cattle breeding to inbreed a promising bull for bull stud use to his own daughters and then after 30 or so such breedings if nothing harmful showed up he was deemed free of most harmful recessive genes.  In dog breeding however we can't eat our mistakes and in fact in cattle breeding unhealthy animals rarely make it to market size and many are killed (or destroyed if you like PC descriptors).  I won't inbreed on one individual and then take those inbred offspring and inbreed on another ancestor .. I like to reshuffle the deck often.  However in this thread the link to epilepsy and inbreeding is not clear or proven.

http://www.canine-epilepsy.net/cerc.html

http://www.akcchf.org/search/search.jsp

Susie, thanks for the correction. Most breeders don't breed closer than 4-4 or 5-5, so I wrongly assumed that was the standard.
Should have know better!

However in this thread the link to epilepsy and inbreeding is not clear or proven.

True, the dog in question is not inbred, and even has very little linebreeding. The epilepsy could be due to a cause other than genetics. However, take a look at the other thread in my first post, regarding Jazz. There has been a big problem with epilepsy in Alsatian-line GSDs in the U.K., and it's mostly due to breeders continuing to breed animals know to be affected. And as the quote from VFK says, Willis says it's a 'threshold' disease, requiring several genes to be present before it manifests. You are much more likely to have that happen with close linebreeding/inbreeding. And Jazz had that IN SPADES!

Linebreeding - 5 generations

• 3 - 3............................................. in Lornaville Chief Dancer
• 5,4,5,5 - 5,5..................................... in Lornaville Jasmine
• 5,5,5,5 - 5,5..................................... in Lornaville Ulysses
• 5,5,5 - 5......................................... in Lornaville Summer Mist
• 4,4,5,4 - 5,4..................................... in Lornaville Sea Bird
• 4 - 4............................................. in Lornaville Princess Royal
• 4 - 4............................................. in Lornaville Strong Choice
• 5 - 5............................................. in Lornaville Crystal Star
• 4,4 - 4........................................... in Lornaville Charlotte's Secret
• 3 - 3............................................. in Lornaville Special Secret
• 2 - 2............................................. in Lornaville Firestone Summer Mist

Indeed !!  This is some crazy wild inbreeding in the case of Jazz .. inbreeding 2-2 on a dog already inbred 2,3 and the 3-3 dogs were also highly inbred.  I can't sleep nights if I don't reshuffle the deck after a 2-3 or 3-3 inbreeding by doing a 5-5 or no ancestors in 5 generations breeding with those inbred individuals.  It can be much more complex than the explanation by Willis though.  There are diseases caused by copying mistakes in just one gene (too many copies of a gene can make it deleterious) for example.  A gene with one or less than 10 copies may give no disease or syndrome expression,  10 to 50 copies may predispose or cause late onset or mild symptoms, and 50-100 copies may cause full blown expression of the disease or syndrome.  Sometimes copying mistakes are related to inbreeding and sometimes they are spontaneous or environmental in nature.  Switching on or off of genes can cause a disease or syndrome to express or be dormant.  Some geneticists have advanced the theory that all individuals probably carry three or four genetic combinations that if fully expressed would kill us but through a combination of gene switching and the regulation of which genes are expressed by chance and the environment we survive or thrive to pass those same genes forward to our offspring.  Epigenetics and the mothers mitochondrial DNA are also involved in gene expression.