“Health Testing” in Dogs is Limited

health_testing_chihuahua

“Health testing” is not health testing. It is disease testing. No test will ever tell you that your dog is healthy.  Health is more than simply the absence of known diseases which have a name and a definitive DNA test.

Plenty of diseases that are serious and pervasive in breeds have no DNA test and some diseases like idiopathic epilepsy have no diagnostic test or conclusive diagnosis tool at all save the elimination of other suspected causes.

There are also countless conditions which have no name, and likely never will, caused by mutations that no one will ever search for or realize are responsible for some negative aspect in your breed, your line, or even unique to just one of your dogs.  New, rare, and orphan disease paths often never get diagnosed or given names because they never reach a critical mass of victims such that anyone would notice a pattern or invest in the incredible overhead necessary to establish a cause and find a gene.

Maybe it’s an allergy to a food or drug they will never try or when they do it just gets written off as an idiopathic adverse reaction.  Perhaps it’s a late-onset disease path that just gets chalked up to old age.  And what if there’s a new mutation in your dog that is recessive or semi-dominant and it’s never doubled up on because your dog’s descendants are never inbred and the new mutation eventually disappears due to genetic drift.

Or maybe it’s a condition that breeders choose to hide and bury versus advertise and seek community awareness of, allowing diseases to proliferate and catch new victims unaware.

There are over 19,300 protein-coding genes in dogs and yet there are fewer than 200 Canine DNA tests, most of which are unique to just one breed and look at only a fraction of one gene.  Few breeds have more than 3 DNA tests and many have none at all.  How can we claim to have robust “health testing” in dogs when the number of tests we have is less than 1% of the number of genes?  We can’t claim that in good faith and we shouldn’t because the degree of our ignorance is even worse than the unknown and untested 99+%.

There are over 2.8 billion base pairs in the haploid canine genome which is carried fully in each dog sperm and egg, so 5.6 billion base pairs define each individual dog, which means that there are 11.2 billion bases {G,A,T,C} of DNA in every dog’s genetic recipe.

There are Canine DNA health tests that tell you about only one base. One base out of 11,200,000,000.  Other tests look at changes, additions, or deletions in anywhere from a handful of base pairs to several thousand base pairs.  But no DNA test looks at more than a tiny almost insignificant fraction of the code that makes up a dog.  Even if you applied every single DNA test available on the market you’d scarcely cover a noticeable portion of the canine genome.

Let’s look at the current DNA Disease Test offerings in Border Collies as an example.

Here's 1 pixel out of an image with billions of pixels.  What is the image of?

Here’s 1 pixel out of an image with billions of pixels. Like doing one DNA test. What is the image of?

Neuronal Ceroid Lipofuscinosis (NCL) is a rare recessive disease in the family of lysosomal storage disorders which leads to progressive degeneration of the eyes and brain resulting in severe impairment and early death. There is no treatment or cure.  Only 3% of Border Collies are believed to be carriers of this disease and fewer than 1 in 1,000 litters will produce affected puppies.

NCL in Border Collies is caused by a single base substitution (from a C to a T) in the CLN5 gene located on canine chromosome 22.
1 change out of 11,200,000,000.

5 pixels out of billions. Like doing 2 DNA tests. What do you know about the whole image?

5 pixels out of billions. Like doing 2 DNA tests. What do you know about the whole image?

Trapped Neutrophil Syndrome (TNS) is a is a relatively uncommon recessive disorder where the white blood cells that are produced in the bone marrow are unable to progress into the blood stream depriving the dog of an effective immune system.  There is no treatment or cure.  It is thought that 10% of the Border Collie population might be carriers.

TNS in Border Collies is caused by a 4 base pair (GTTT) deletion in the VPS13B gene on chromosome 8.
4 removed out of 5,600,000,000.

4 more pixels revealed by doing another DNA test.  Where is this image taken?

4 more pixels revealed by doing another DNA test. Where is this image taken?

Multi-Drug Resistance 1 (MDR1) is a semi-dominant mutation that causes a clinical sensitivity to a number of common drugs (including Ivermectin) by impairing the transport of those drugs out of the canine brain allowing for a toxic buildup of the drugs upon administration of sufficient doses, which can lead to neurological dysfunction and death.  No pedigreed Border Collies have been documented to carry the MDR1 mutation although one suspected rescue Border Collie was identified within the pool of dogs used to study the prevalence of the mutation in herding breeds and was not included in the results and a handful of others out of thousands tested globally have been found with the mutation.  The prevalence of the  mutation present in much higher concentrations in Border Collie relatives like Australian Shepherds and Collies.

MDR1 in herding breeds is caused by a 4 base pair deletion (ATAG) in the ABCB1 gene on chromosome 14.
4 removed out of 5,600,000,000.

Even adding a few thousand more pixels with a big DNA test like CEA doesn't give us a lot of information about the big picture with billions of pixels.

Even adding a few thousand more pixels with a big DNA test like CEA doesn’t give us a lot of information about the big picture with billions of pixels.

Collie Eye Anomaly / Choroidal Hypoplasia (CEA) is a recessive disease which impairs the proper formation of a layer of cells below the retina of the eye causing various degrees of blindness.  There is no treatment or cure.  Just over 2% of Border Collies will present with Chorodial Hypoplasia, about a half of a percent will have Colombomae, and less than 1 in 1,000 will have retinal detachment.

CEA in Border Collies is caused by a 7799 base pair deletion in the NHEJ1 gene on chromosome 37.
7.8k removed out of 5,600,000,000.

None of the diseases which there are currently DNA tests for affect even 1 in 100 Border Collies.  The sum total of the Border Collie genome we get a look at when we do all of these tests is only 7808 base pairs out of 5.6 BILLION.  That’s a glimpse of 0.0000014 of the genome.  Just better than One-one-millionth.  That’s like looking at 1 hair off of the heads of 10 healthy young people and trying to say something profound about who they are.

That’s like taking one word out of the world’s longest book (Marcel Proust’s In Search of Lost Time at 1.2M words) and trying to ascertain the plot.  That’s longer than two Bible’s worth of words or two read throughs of the entire Lord of the Rings series.  More than all of the Harry Potter books combined.  Just ONE word out of all those words.

Look at the series of photos and tell me what they signify, where and when they were taken.  By the time we get a good chunk of information from the sizable CEA test, we might guess that the red cross has something to do with health, and it does, but that doesn’t even begin to inform us about the greater picture.  I selected the most recognizable and apropos snippet out of an image of 3.8 billion pixels.  If we were to look at all of the image at once, the area you see above would barely even register as one pixel on the screen.

everest_basecamp_1

Even with hundreds of times more information than is available to any breeder today, we have a decent idea of what we’re looking at but we have little context to make definitive claims about what we’re seeing and the greater picture. We might even be able to take a good guess about what we’re seeing and where it’s located based upon our extensive outside knowledge. But what’s given to us in the photo is still quite limited.

everest_basecamp_2

As we zoom out, we can begin to see how small the information we had at the beginning really was although just how small in relation to the 3.8 billion pixel image is not yet clear. Research and context with information we can learn outside of the isolation of this image can be used to guess the location. But that itself is a lesson, we need a frame of reference and research outside of the limited DNA tests to even begin to put them into context and to use the information to assess health in our dogs.

everest_basecamp_3

Out initial data is but a small speck, although we can now guess that we have a camp along the edge of a glacier.

everest_basecamp_4

Only now can we confirm that this glacier is the Khumbu Glacier that is located in the Khumbu region of northeastern Nepal between Mount Everest and the Lhotse-Nuptse ridge. The series of tents we saw before is the Mt. Everest base camp. But even now we are not even looking at 1/4th of the 3.8 billion pixels in the complete image.

complete_mt_everest_zoomed_out

The complete view of Mt. Everest and the Khumbu Glacier taken from the Pumori viewpoint. I obviously can’t recreate the entire 3.8 billion pixel image here, but you can view it in its entirety with a great interactive zoom and pan feature at the Glacier Works website.

 

When we look at DNA results we MUST understand that we are only looking at a tiny fraction of what makes up our dogs and an even smaller speck of what makes up a breed.  We need to think bigger than a few DNA tests.  We need to breed away from disease slowly and methodically, not cut it out with a hatchet. This will mean breeding dogs that are carriers and even possibly affected. It means devising a breeding plan BEFORE you test when you can be rational and circumspect about the results instead of acting rash after you test.

We need to appreciate that no dog is free of deleterious genes and that we don’t earn the right to inbreed with abandon simply because two or three DNA tests came back favorably.  We also need to appreciate that we are breeding not just for one litter but for the breed as a whole and that means not being capricious with genetic diversity. We have to breed for what we don’t know as well as breed for what we do know.

We need to realize that all closed gene pools eventually dry up and that every year from when most breeds had their books closed a century ago we lose genetic diversity and condense all sorts of dangerous genes like reducing sauce on the stove.  There’s a balance to be had between an ideal flavor that’s not too bland and watered down and not too condensed and congealed. Most breeds are already over-cooked and beginning to scald.

We need to appreciate the whole animal and its place within its breed and within the species of canis lupus familiaris. Disease testing has a place in this calculus, but we can not afford to over-react to the results of a tiny handful of tests that look at a minuscule speck of the genome and slash and burn our already genetically depleted breeds because of it.

We need to open the stud books and we need to regularly bring in new blood–even if just a few dogs per generation across an entire breed–via appendix registries and routine outcrossing. We need to move beyond the fascism of “pedigree” and realize that we can still have our breeds and mix them too. We can keep every single aspect of our breeds that we value and not doom them to deplorable health outcomes (except of course when we value them for their disease).

Health testing isn’t another kudo to add to your dog’s resume. It’s a tool to be used with the entire breed in mind and few breeders are using it that way. The test-result-as-ribbon mentality is poisonous to the genetic health of breeds and its incorporation into the “I’m a superior breeder because I health test!” mantra is patently bogus. You aren’t an ethical breeder if you paid for a DNA test that tells you about one rare gene that will only affect 1 in 1000 dogs, but you continue to propagate genetic and structural disease that affects every single dog you and everyone else in your breed produce.

You don’t need a health test to determine that Bulldogs, Pugs, and Shar Peis are diseased messes. You don’t need DNA to tell you that Rhodesian Ridgeback breeders will continue to place appearance above health. And no suite of DNA tests gives you the license to inbreed your line, use that popular sire, or reject any and all out-crossing without the dogs you produce having to suffer the consequences.

There’s no DNA test for stupid, and you don’t need one to conclude that the greater dog fancy both show and work, is corrupt and decadent and destroying the legacy we have inherited from our ancestors by continuing to live in the ignorance that plagued them and shaped their behavior. Except we have no excuse. We should know better and if we want to pass along a thriving canine legacy to the next generation we need to be better, act better, and breed better.

It’s not enough to health test, any more than Mt. Everest can be understood by a few pixels. Or even 3.8 billion of them. Even our best image is wholly insufficient to appreciate that reality. In dogs, we need to do more of the hard work, to actually climb that mountain and make hard choices and be practical and pragmatic and circumspect and a lot less dogmatic. No one would give you an award for looking at a really nice photo of Everest, but that’s exactly what the breeding culture is asking you to do by treating disease testing as a seal of approval. Don’t fall for it.

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About Christopher

Christopher Landauer is a fifth generation Colorado native and second generation Border Collie enthusiast. Border Collies have been the Landauer family dogs since the 1960s and Christopher got his first one as a toddler. He began his own modest breeding program with the purchase of Dublin and Celeste in 2006 and currently shares his home with their children Mercury and Gemma as well. His interest in genetics began in AP Chemistry and AP Biology and was honed at Stanford University.