# Genetic testing



## scooterscout99 (Dec 3, 2015)

Article from NPR.

https://www.npr.org/sections/health...rise-about-shortcomings-of-dna-tests-for-dogs

It links to an article in Nature calling for regulation of pet genomics testing.

https://www.nature.com/articles/d41586-018-05771-0

I expected this to be about the tests that are used on mixed breed dogs to determine heritage. But it is about testing for genetic markers of disease. This issue is new to me (never heard of a down side of genetic health screening).

A quote from the Nature article touches on a recent topic on the PF:

“Can an owner, who might want to breed their pet and sell the offspring, keep any results secret (as they can currently) or should they be required to divulge this information to buyers?”


----------



## spicandspan (Apr 21, 2018)

The Nature article makes an excellent point. Genetic screening is intriguing but we don't know enough about genetics to really understand what the results mean. This issue is happening in human medicine too. Genetics are incredibly complex and it's rare for a disease to have only a couple of linked genes. Some, like heart disease, may have dozens of linked genes.


----------



## Vita (Sep 23, 2017)

*Some thoughts*



scooterscout99 said:


> ...A quote from the Nature article touches on a recent topic on the PF:
> 
> “Can an owner, who might want to breed their pet and sell the offspring, keep any results secret (as they can currently) or should they be required to divulge this information to buyers?”


I wish they had expanded rather than touched on that area. I've found a degree of resistance, excuses, enabling, denial and even anger, by pointing out that deceit by omission, while not common among the best among the show dog/breeder crowd, is not that uncommon either. It's been discussed here before, see this thread from 2009: Breeder Transparency

Here's a previous post of mine on another thread of one way to do quick research at OFA on a particular dog. If you have Excel, it takes all of five minutes or less to research which testing has been done, and which tests are glaringly omitted (link). 

In those cases, ask the breeder for copies of tests not published; they may even be published elsewhere. Or not. The 'not' would bother me. Is their dog clear of a particular genetic disorder? Or is it a carrier? 

I've given a great deal of thought, done a lot of advanced reading and spoken to several breeders in the poodle show world. It's fascinating _and_ complicated in how decisions are made. 

I'll share here what I've learned; skip it if you're not interested. 

*******​
Say for example, 

Poodle A is clear of a genetic disorder on a specific test. 
Poodle B is a carrier. 

Breeding Poodle A to Poodle B isn't necessarily a deal breaker for the breeder; it takes two carriers for the genetic problem to manifest itself. There may also be advantages:

Breeding Carriers of Canine Recessive Diseases- Why It Should be Considered, from Paw Print Genetics. 

Excerpt:

_"The major concerns in placing breeding limitations on carriers revolve around the loss of genetic diversity through the unintentional creation of a genetic bottleneck; a well described phenomenon associated with a rapid decrease in population size."_

There is a hard science behind good breeding, as well as the social science of how people act. A responsible breeder will sell the carrier pups to the general public with agreements to sterilize.

But for a breeder's own program, what if one of the carrier pups is a stunningly gorgeous poodle that could win a five point major hands down? 

The breeder might show it - but then not use it as a stud except to other well-known breeders who are educated (and ethical) about the risks of producing more carriers. 

The benefits? Their Poodle B (carrier) mates with Poodle A (non-carrier) and statistically half of the pups are non-carriers - but also are perfect show quality poodles. The rest can be sold with sterilization agreements to the public - or on a very limited basis, to a knowledgeable breeder willing to take the chance on a carrier pup that is _also_ show quality for their own breeding program with the hope of breeding to their own Poodle A and get genetically clear show prospects. 

Fascinating, at least to me, and smart breeders know and do this more often than we think. As the Paw Prints article stated, it also helps reduce the bottleneck and reduction of genetic diversity mentioned earlier. 

I don't think this strategy is for the faint-hearted, however, and should be implemented with caution only by knowledgeable, transparent breeders who have a sound program with specific goals. 

It's specifically not for the person who buys and takes their carrier poodle to championship _with the long term goal of using it source of income rather than improving the breed,_ as a stud dog service, and they omit or gloss over the DNA health tests. 

(Side thought: The best breeders support their dogs, not the other way around. For someone looking for championship fame & glory and stud income from that poodle, they'd be wise to start off with one that's not a carrier and _not_ expect their profits to exceed their expenses.) 

The unwitting and uneducated purchaser of their champion stud service thinks everything is fine & dandy because the breeder hasn't revealed their champ is a carrier, OR, the purchaser hasn't tested their own dog and may be clueless about testing and the stud owner doesn't insist on this b/c they just want the money. If purchaser's bitch is also a carrier, the result is half of those unlucky pups are sold to unlucky buyers, whom a few years later, have a blind dog, etc., and wonder how someone could be so cruel and irresponsible.


----------



## lily cd re (Jul 23, 2012)

scooterscout thanks for sharing this interesting material.


spicandspan this is probably semantics at work but I would say we know plenty about genetics, but we don't have sufficient data about genomics (which is really what we are looking at here) to understand all of the implications of the data we do have. Even in humans the database still needs more points of information (i.e. more genome sequences with clinical information attached to it and metadata analysis that reveals real causal relationships between a variant(s) at one or more loci and a clinical condition). The depth of the database in animals other than humans is deeply limited. There are not enough individual genomes and not enough clinical findings associated with those genomes to make more than cursory conclusions.


In the meantime the bottom line I think is not so much about breeders and testing as it is about the sad story of Petunia who was euthanized in the belief by her owners that she had the canine equivalent of ALS when her clinical findings were actually also consistent with a number of readily treatable spinal conditions.


If we, as purchasers of puppies, do our due diligence in searching for a litter out of appropriately screened parents then we have some reasonable degree of certainty about the health prospects of our dogs. What about the huge number of people like Petunia's owners who are willing to buy into the sell of for profit companies who claim to be able to sell all sorts of definitive information on their dogs' hereditary and health status?


----------



## scooterscout99 (Dec 3, 2015)

Thanks Lily CD, I thought that you might know more about this topic. Perhaps the key point is to recognize the vendors of some of the tests for who they are.

Vita, I read your explanation and appreciate it. It’s unfortunate that some breeders withold web publication of OFA results. 

An earlier thread mentioned the cost involved. I don’t think that it’s unreasonably high, maybe $15/each, hips & elbows were $40. The tests that my boy (who may never be bred) had at a health day sponsored by an AKC club, had the OFA fees discounted to $7.50. For those who’ve never done this, there’s a box on the OFA form that you check whether or not you will allow the results to be published publicly. It’s a little nerve wracking knowing that the results will be made public shortly after the owner is informed. But no harm done to responsible breeders, as they won’t breed a dog that is short in any of the recommended health screenings.


----------



## Johanna (Jun 21, 2017)

Some things to keep in mind:


Genetic diseases are not necessarily due to simple dominant/recessive gene characteristics. Hip dysplasia, for example, is result of the action of more than one gene.


A wide variety of environmental factors can modify the effect of genes. 



Breeding a dog who has tested clear to one that is a carrier does not necessarily result in a 50/50 split in the resulting puppies. They could all be clear or all be carriers, or any combination thereof. While it is not a "disease", monorchism is an easily observable trait that reveals how much the results can vary. I once bred to a whippet male who had both testicles and had a litter of five males none of which had both testicles!


----------



## lily cd re (Jul 23, 2012)

Vendors wouldn't exist if they didn't have a "product" to market and consumers willing to buy the product. It seems important to support non-profit scenarios for research such as through vet schools for animal health and academic medical schools for human research. Not that those institutions are flawless, but better than an entity with interest in the success of the product doing all the research to determine the value of what is being sold.


And Johanna, your comments, especially as regards the whippet litter illustrate how we can think we know what is going to happen, yet be surprised at what actually does happen. Even in simple patterns of inheritance where there is a single locus and only two alleles involved with a recessive that is abnormal it doesn't mean that only 25% of outcomes will be unfavorable. When I was in graduate school the genetics department did a lot of counseling for families with disorders like Tay Sach's disease (an autosomal recessive). I remember seeing affected families in elevators with three little children all of whom looked to be affected with a pregnant mom and worried looking dad.


----------



## spindledreams (Aug 7, 2012)

I have a dog who tested as a carrier for the SOD1 mutation. In some breeds this mutations is associated with DM a deadly, often late onset neurological disease. However some breeds exist that will nearly all test positive for this mutation and they have NO cases of DM known in their breed. 
DM does exist in poodles but so few have been tested for the mutation we currently don't know if it always goes hand in hand withe the SOD1 mutation or not. 
Sooo knowing that two copies MAY be associated with DM or may only be associated with DM in one or two related breeds what would be the ethical thing to do with my dog?


----------



## Vita (Sep 23, 2017)

Johanna said:


> Some things to keep in mind:
> Genetic diseases are not necessarily due to simple dominant/recessive gene characteristics...


So true. The Full Poodle Disease Panels test for:

~ Degenerative Myelopathy
~ GM2 Gangliosidosis (Poodle Type)
~ Neonatal Encephalopathy with Seizures
~ Osteochondrodysplasia
~ Progressive Retinal Atrophy, Progressive Rod-Cone Degeneration
~ Von Willebrand Disease I

Until recently, it was thought that if a dog was as a carrier of one of these diseases, it would not manifest the symptoms. However, *Peppersb* shared this in March, Von Willebrand's Disease -- New Research. 




Johanna said:


> ...Hip dysplasia, for example, is result of the action of more than one gene...


Yes. Recently I began reading more about this, learning about the usefulness of Vertical Pedigrees on that thread. 

It has a link to a wonderful, easy to understand article with a chart explaining it. OFA changed the link, however, from offa.org/blah blah to ofa.org/blah blah, so this is the newer link to 
Collecting and utilizing phenotypic data to minimize disease: A breeder’s practical guide. 




Johanna said:


> ...Breeding a dog who has tested clear to one that is a carrier does not necessarily result in a 50/50 split in the resulting puppies. They could all be clear or all be carriers, or any combination thereof...


Yes, true; statistically each pup has a 50% chance, but one could certainly hit the lucky lottery with all clear, or the opposite. Sorta like odds for _each_ individual Powerball ticket is one in 292 million; you could wipe out your saving buying as many as you can afford but this doesn't increase your chances of winning. Or buy one for the first time in your life and win.



scooterscout99 said:


> ...Vita, I read your explanation and appreciate it. It’s unfortunate that some breeders withold web publication of OFA results.
> 
> An earlier thread mentioned the cost involved. I don’t think that it’s unreasonably high, maybe $15/each, hips & elbows were $40... For those who’ve never done this, there’s a box on the OFA form that you check whether or not you will allow the results to be published publicly. It’s a little nerve wracking knowing that the results will be made public shortly after the owner is informed. But no harm done to responsible breeders, as they won’t breed a dog that is short in any of the recommended health screenings...


I couldn't agree more. I see publishing the flaws of some of their poodles as a huge asset, not a liability. To me, it says that the breeder is working their program and has the integrity to share both good and bad information. I've studied several breeders of standards and toys (just for the fun of it, ha-ha, I'm a nerd!) and some have been doing this for years. 

When the aunts, uncles, sibs and half-sibs are also listed, it helps in putting together a vertical health pedigree as aforementioned, ideal for studying hip dysplasia in particular.


----------



## spicandspan (Apr 21, 2018)

Yes Catherine genomics is a better term. In any case, it's a complicated topic. These articles on Science Based Medicine go into some detail on the challenges with 'precision medicine' and genetic testing.

https://sciencebasedmedicine.org/tag/genomic-analysis/


----------



## lily cd re (Jul 23, 2012)

I do know of a couple of instances where treatment decisions tailored to the patient's specific circumstances has made a difference in outcomes. The one that will always stand out in my heart and mind involved the father of a student of mine. The dad had esophageal cancer and the traditional chemotherapy protocol for esophageal cancer had not yielded any significant improvement. Histological and genetic analysis of the tumor showed it not to be a typical esophageal tumor and that it was more like as I recall a colon cancer. They changed the treatment protocol to one that was known to work well for the tumor type that dad's cancer looked like. The night the class was taking their lecture final was the day dad was having some scans and tests done to look at whether there had been any improvement. Normally I don't allow students to have phones accessible during exams but I told this student he could leave his phone out and go out in the hall to answer it if he heard from his parents. The call came and he went out in the hall. He had been there for a while so I was concerned and went into the hall to find the young man with tears rolling down his cheeks, but they were tears of joy and relief. The tumor had shrunk significantly enough that he was now going to be able to have surgery to remove what remained.


----------

