Speculative from a very well versed owner:
ME is known or suspected to be genetic in a number of dog breeds. In most breeds it seems to be recessive, though dominant in a few. To understand what this means, for any simple trait, any sexually reproducing organism (any mammal, like a dog or a human, for instance) has two genes which control the trait. One of these two was randomly taken from the two genes the mother had for the trait, and the other of the two was randomly taken from the two genes the father had for the trait. There can be variants of these genes, some of which may be harmless, some of which may be beneficial, and some of which may be harmful, such as a gene for ME.

In a gene for a recessive trait (which ME commonly seems to be), the trait will be expressed only when both genes the individual has are for the trait. If the individual has only one of the gene, it will not show the trait, but it can still pass it on to some of its offspring. What this means is that for a recessive trait, both parents have to carriers of the gene to have any offspring that have the trait. If only one of the parents has the gene, then none of the offspring will have the trait, but typically about half of them will still have a gene for it and can pass it on to their own offspring. It is only when one of these offspring is bred with another dog with the gene that some of their offspring may have the trait. This is the tricky thing about a recessive trait, because it can skip generations, making it hard to spot. If each parent has one gene for a recessive trait, then typically about a fourth of the offspring will have two of the gene and have the trait, about half will have one of the gene and not have the trait but be able to pass it on, and about a fourth will have none of the gene and not be able to pass it on.

EXAMPLE: What this suggests is that for the mother, she probably has one recessive gene for ME, as the father also probably did, allowing 1 pup with ME, with several of the rest probably being carriers for the gene (no way to tell which ones at present, until a genetic test is developed, hopefully in not many more years).

In the previous litter the mother had, the father then probably had no ME genes, so that none of the pups would have ME, but probably about half the pups were carriers for it. The probabilities I have mentioned are really only the average for many litters. They are the most likely for any single litter, but
for any single litter, any possibility is possible, though many are unlikely.

That is, for two parents with one recessive gene each, on average, one fourth of the offspring will have 2 of the gene and the trait, half will be carriers, and one fourth will be free of the gene. But due to random chance, it is possible to have an entire litter with 2 of the genes, or an entire litter with just 1 of the gene, or an entire litter with none of the gene, even though these are less likely possibilities. It is exactly the same as flipping 2 coins, where there is a probability of one half of 1 head and 1 tail, a probability of one fourth of 2 heads, and a probability of one fourth of 2 tails. But unless you flip a coin many times and count the results of each type, you will not likely get close to these probabilities.

To get back to the mother and her pups, the implication of this is that she should be fixed, as well as the father, along with all the pups, to try to prevent more spread of the ME gene. A few of the pups are probably not carriers, but since there is currently no way to tell, it is best to err on the side of caution and fix them all.

Leigh Anne Clark, Ph.D.
Assistant Professor
100 Jordan Hall
Clemson University
Clemson, SC 29634-0318

The above is important for the following reasons:
1) Request for cheek swabs — more samples needed/requested. Following parameters only apply: the dog must have been diagnosed at the age of one or before.
2) ANY BREED may be submitted. Focus is still on GSD as that is the initial grant parameter. IE more GSD samples are still needed. “We” are going to start looking at the other breeds.
3) The coffers have run dry. SNP research is expensive. The cheek swabs will cost you virtually nothing. Please visit your vet, explain what the purpose is, and chances are strong they will be sent free of charge or minimal expense. Please take that savings and send it to Leigh Anne at the address above. If you can send more, please do so. I will be sending a nominal monthly donation. It will take all of us working together to move forward. Stop-starts due to coffers running dry are to be avoided … even if you can only spare a one time small donation, please do it today.

Why this is important:
Being able to map the genes involved will ultimately lead to the ability to develop a test so that breeders can know before breeding which sire and dams are carriers or if they are in fact clear.

Please Note: Leigh Anne runs a tight ship out of necessity (expense). Thus, please know that no direct results will be made available. Your affected dog,,, and you,,, can play a huge part in the advancement of this scientific endeavor to (eventually) eliminate this insideous disorder. That’s a feel good for you and a win-win-win for everyONE!

Permission to cross-post:
Please also share with your breeders in case they too know of other affecteds in their line to which you may not have knowledge.
–   USA dogs only (it’s the shipping, timeline aspect)
–    Your DVM will know how to take the cheek swabs. Minimum three (3).

Congenital ME would be present from birth, but would not necessarily be obvious for some time. There are some dogs who simply cope with it by regurgitating and immediately reswallowing, so you wouldn’t know that there’s a problem. Over time, however, as the esophagus stretches more and more the problem becomes obvious. It is also possible, of course for ME to occur later in life – sometimes as a result of being anaesthetized or as a side issue of MG.

From another DVM:
I had a lovely talk today with Dr. Leigh Ann Clark at Clemson Univ today about ME genetics. Dr. Clark is a geneticist (not a vet), who is doing a study to find the genetics of ME. She collects buccal (the inside of the cheek) swabs on dogs with congenital ME (NOT acquired ME), so if your dog has congenital ME and you haven’t contacted her about sending a sample, PLEASE do so. The more dogs she can study, the closer she will be to finding answers to the genetics and hopefully, the information that will help prevent this disease in pedigreed lines. Here are some of my notes (pls realize that this is not coming from Dr. Clark, just my notes from our conversation).
1. Congenital ME (not due to vascular ring, persistent right aortic arch):
Congenital ME (at least in GSDs) seems to be an autosomal dominant trait with incomplete penetrance. This means that in order to have congenital ME, a dog has to have inherited the mutation from one of its parents. A dog needs only ONE copy of the mutation to have ME. This is different from most of the genetic disorders that people might be aware of, such as cystic fibrosis, Tay Sachs, etc, which are autosomal recessive and require two copies for expression. Huntington’s disease is an example of an autosomal dominant disorder in humans. Incomplete penetrance simply means that an individual can have the gene, but not express the trait (i.e., not develop ME). I’m not sure if there’s a component of variable expression as well, since some dogs are able to outgrow ME.
2. Dr. Clark’s lab only has funding to continue the study for a few months this summer. It costs the lab $1000 per month for the supplies needed to conduct the study; not including labor costs. She applied for funding from the Canine Health Foundation (part of the AKC), but was denied because there was not perceived to be enough interest.
3. Why this research is important: We love our dogs, and wouldn’t trade them for the world, but we also would never willingly choose to have a dog be born with ME if it could be avoided. Identifying the mutation can impact breeding programs so that dogs with the ME mutation aren’t bred. With enough research and education, congenital ME in certain breeds could be nearly stamped out.

This is very scary to hear, that breeders would still breed parents and siblings of a dog with megaesophagus. They need to be educated very badly, or else put out of business. Either they understand absolutely nothing about genetics, in which case they should not be breeding animals, or they do not care and are only interested in the money, when they should even more not be breeding animals. They need to understand that a lot of these problems are caused by recessive genes, which means they can skip generations and spread the gene with no outward signs.

An ME dog owner asked breeders what they would do if they produced a ME pup.
–   Would they continue to breed the parents?
–   Would they breed the siblings?
A majority of them said yes they would. It was stated that just because a pup has ME, the siblings don’t have it.
What about passing on the carriers? It is a really scary thought.

Speculative from an ME dog owner well versed: A lot of these breeders are probably in denial. If a dog has a problem caused by a recessive gene, this means BOTH parents have to be carriers, meaning they can produce more such puppies. Of the offspring of two such carriers, statistically, about half will be carriers, about a fourth will have the outward problem, and about a fourth will be free of the gene. This means that breeding the parents again is bad news, and breeding the pups is very unwise, since about half can pass it on. As far as trying to know the mode of inheritance, there are 2 main modes, recessive and dominant, though occasionally there is something that is sort of a combination of the two. Basic inheritance is not that hard to understand. Any simple trait in a sexually reproducing species on this planet is governed by 2 genes of a particular type, one being taken randomly from the pair the mother has, and one being taken randomly from the pair the father has.

In most cases, if there are variations of the gene, then only one gets used. Of course, for most traits in a particular species, both genes in a pair are identical, so it doesn’t matter which gets used. All these identical genes are part of what makes a particular species unique. But again, if an individual inherits two variations of a gene for a particular trait, then typically only one gets used. The one used basically dominates the other, meaning the other is recessive with respect to this other gene variant. What this means is that the recessive variant can only be realized if there are two of them, one from each parent. This then implies that if the trait is realized, then each parent possesses as least one of the gene, though if neither parent expresses the trait, then both probably have only one of the gene and are simple carriers. A dominant gene, on the other hand, will be expressed even if there is only one, which means only one parent has to have it for an offspring to get it. There are implications of this which make it fairly straightforward to guess whether a potential genetic problem is recessive or dominant. If an offspring shows up with a problem caused by a dominant gene, then one or both parents should also exhibit the problem. If neither parent exhibits the problem, then the gene is almost certainly not dominant, meaning it has to be recessive, or else some cross between dominant and recessive, where each of the two genes is used to some extent, rather than only one. Also, the frequency of offspring which exhibit a problem differs between dominant genes and recessive genes. If you have one parent with a single dominant gene, then about half the offspring, on the average, should exhibit the problem. But if both parents have a single recessive gene, then about a fourth of the offspring, on the average, should exhibit the problem. So if a large fraction of the offspring have the problem, that suggests a dominant gene, while a small fraction suggests a recessive gene. If only 1 or 2 out of a large litter have such a problem, it is likely recessive.

As far as particular breeds, some breeds are known to have higher proportions of particular problems than others, not merely higher absolute numbers. This should not be surprising at all. A bad mutation has to start somewhere, and if it starts in a particular breed, it is likely to spread more in that breed,
since breeders only breed within the breed. It may spread to other breeds by accidental breeding. And other breeds may have different mutations, though they may have similar outward expressions. Megaesophagus may well be caused by different genes in some different breeds, or even different genes in the same breed, because the action of the esophagus is a complex procedure, governed by many types of genes, and so any one of those going bad may lead to a problem with the esophagus getting enlarged. Such variations may well account for the variations in severity seen in many dogs on this list, from mild to very severe.
German shepherds in particular are known to have a higher percentage of various problems than a number of other breeds. Goldens are another such breed with an oversized share of problems. Much of this is clearly due to too much inbreeding. Inbreeding per se is not bad, as long as the dogs bred do not happen to have any bad genes, particularly bad recessive genes. But once bad recessive genes appear, it easy for them to get spread around a limited gene pool, where a relatively small number of dogs are repeatedly bred, since a lot of the population may already be carriers before there are enough carriers to mate with each other frequently, when the problem will start to show up more. A particular number of dogs with problems will suggest that a far larger number are carriers.