DNA test for breed’s typical pathologies

How to use DNA tests for Genetic Diseases in Dog breeding program.

Utilizzo dei TEST sul DNA

Breed’s Typical pathologies:

You’ve all heard about each breed suffers from specific disease, even if sometimes they are only rumors and is not always correct, for example, you will have heard “the German shepherd has problem with his back legs”, or from more experts “suffer of hips dysplasia”. Well yes, in fact every breed has its “flaws”.

The luck on our side is today we have the opportunity to test DNA of our dogs and understand which of them can get sick or transmit the disease to their offspring!

To explain the question even to people who is not biologyst, and to explain how to use DNA tests, we must first talk a little about Genome and genetics.
In short, dog breeds, selected by man, have all a certain degree of inbreeding, i mean, some more distantly, some more closely, all the subjects belonging to a breed, are all related to each other, and this because to have a homogeneous typology of dogs, with a certain physic and certain aptitudes/characteristics to perform a certain task, it is customary to inbreed (to mate together dogs of the same “family” like father and daughter or two/half brothers, cousins and so on), and this is necessary especially at the beginning of the creation of a new breed, or rather it is customary to mate related dogs together, and inbreed more or less close and more or less often. In short, the breeding strategy in question has been used at least a little in all breeds. Moreover, unfortunately, sometimes happens a very titled stud, which many people “use” for theyr bitch, may be affected or carrier of a certain pathology, which in this way will inevitably spread like wildfire on all the lines where it will be used.

Here you can find an article of what i think about inbreeding in modern “pet dog”

Now, in simple terms, all mammals such as dogs, cats, humans… and so on, practice what is called sexual reproduction, in which half of the mother’s DNA and half the father’s DNA meet together and take part in the new life, building a new whole DNA, DNA of which genes are the “minimum logical units” which describe a characteristic of the subject to which they belong, and genes are redundant, because mom passes on her version of the (characteristic) gene, and dad passes his version, in the respective 50% of DNA that join together to form the new DNA of the son. What we have in our DNA is called GENOTYPE. What we “observe” from outside the subject, observed without “reading the DNA”, only by measuring parameters, doing tests, etc., is called PHENOTYPE.

What we see in the phenotype is the result of the interaction between mother’s and father’s genes for that trait, often mediated also by environmental influence. The traits most influenced by environment are those concerning behavior and character, wich is partly codified in the DNA, but is also partly learned and consequent to life experiences, modeled by what happens to a subject during growth and living, but a lot of other characteristics of a individual may be influenced by environement too. Let’s think about it doesn’t happend now for this little set of genes we are speaking of, And suppose only DNA will count, to make easier understand what genetically happend.

First of all we define locus as the locations in the genome which are known to be directly related to the expression of a defined phenotype, phenotyoe i remember is what we “see” on the living subject.

Now, as we need homogeneous traits in a breed, and having used inbreeding, many copies of genes in a locus can be HOMOZIGOUS within the breed (same identical “copy” of the gene passed both from mum and dad for a certain trait), i mean mother and father are relatives, even if they seems to be far in the pedigree, but looking back more generation over, they always  ave comon ancestors, and so they often pass the same copy of a gene to offsping, received probably from the same ancestors.
When, on the other hand, two different versions of the gene are passed from mother and father, then we speak of HETEROZIGOSYS, and in this case we must considerate gene dominance relationship to understand wich of the 2 genes in a locus will influece phenotype.

Let’s suppose now we can find 2 version of a gene in a locus (called alleles), describing a certain trait, and we will call them A and B, if the subject has 2 version of A (AA) or 2 version of B (BB) we have Omozygous A (or B), and we will see fenotype A (or B) on the living subject,
if we have mixed genotype (AB)  we can speak of HETEROZIGOSIS, and in this case we must considerate gene dominance relationship.

A has Complete dominance over B if heterozygote phenotype (AB) is indistinguishable from the homozygous phenotype of the dominant gene (AA).
For example shortcoated gene is full dominant over longcoated.
A has Incomplete dominance over B if heterozygote phenotype (AB) is distinguishable from the homozygous phenotype (AA) and the homozygous phenotype (BB) and usually the (AB) mixed phenotype it’s an intermediate phenotype between A and B phenotypes.
For example merle phenotype is Incomplete dominating over non merle.
This case is very useful as we are able to identify carriers for a pathology, even if for a lot of problems now we have DNA test, and is for these reason you are reading this article.

While dog has been breeded by man in the last 10-20 thousand years, a lot of mutations occoured, some of them can be dangerous for health, or are considerated “flaw” but we find it useful, for example the dachshund dwarfism is one of them. In wild dogs (wolves), and wild animal in general, i mean not managed by man, a new and useful mutation will fix in a specie every about 10 thousand year, in the same time we fixed a big number of mutation we find useful for breed’s jobs.

Probably some casual mutation caused also pathologies, almos most of them, not lethal for the fetus but compatible with life, are recurring in a lot of other mammals, but as we used to inbreed, each breed has it’s common and usual ones, fixed for error, for side effect, using inbreeding, while fixing other useful traits.

Usually genes associated to relative defect are recessive, as if it were dominant probably the subject carrying it, will not be able to access to reproduction. Even if some dominant pathologies may can claim on late age, and so can be passed throug generation the same way, but usually for the reason we just wrote before, we find more easily recessive pathologies in breeds.

So let’s now suppose we are screening DNA for a new testable recessive pathology, i mean we know the problem from a lot of time, like for degenerative myelopathy, but we just we have just recently developed DNA test to find carriers and affected from:

If we mate together 2 dogs carrier for a defected gene (with one healthy copy and one defected copy of the gene in the relative locus) we have 25% of chance to have a son homozygous for the defected gene (affected) , 25% a clear son and 50% a carrier one, just like parents.

Once, when the DNA test was not available, if the dominance of the right gene was full over the defected one, it could have been a problem to identify carriers, we only could imagine it as at least an affected son were born out of them.

Today we have this powerfull weapon, and we can read DNA and find carriers (and affected too),
but we have to learn to use it in the best way!

Unfortunately, some pathologies are still not testable, or not only monogenethic, like hips and elbow dysplasia for example, wich is multifactorial and polygenetic, even if there are ongoing study for solve the problem and find a schema, but in case the gene will follow mendelian rules, the rules explained just over there, these test are really powerfull and usefull for a breeder.

And we can surely say to test and use test in a good eway is a duty for a good breeder.

Given that each pathology must be studied, because it is not obvious it behaves in the same way, and in some pathologies healthy carriers can get sick, or the affected ones do not necessarily get sick, or for other it is still perhaps unknown what factor is trigger, both genetic and possibly environmental, because sometimes being genetically affected, or better omozygous for a certain mutation, as for example in degenerative myelopathy, is a necessary but not sufficient condition for contracting the disease. Maybe other genes are involved, but we are sure carriers and free from SOD1 mutation, will not develop the problem.

SO, supposing we have the “classic” recessive pathology, completely hidden by the healthy gene,

How to use those TESTS?

I wrote this article because sadly not all the breeder use test in a rightway, so we pass from dogs affected for easily DNA testable pathologies in  “home made” litters,  or out of litter raised up from unscrupulous breeders, in which the parents have not really been tested, or incorrectly reproduced, to people who go so far as to discard even “healthy carriers” from the breeding program.

Now, as i wrote before, the more inbreeding coefficient si higher, the more we run the risk to have omozygosys also for defected genes not necessary typical for the breed, if we consider casual mutations wich sometimes occour during DNA replication, the more we stop stud and bitches in the breeding program, the more we increase % of inbreeding in the breed, using always “about the same dogs”, so maybe we will sole one problem, the one we just discovered the test for, but we may cause one or more new problem to spread against the breed.

So it’s obivious in a breeding program sometimes we have to “use”not only free and carriers, but also affected, or better subject with omozigosyc defected gene, expecially at the beginning of a screening, because we run the risk to “cut off” too much dogs, loosing good subjects, and running also the risk to fix other mutations, other pathologies for wich we don’t yet have a test yet, throwing the baby out with the bathwater, and finding little or nothing in hand from a genetic point of view. Also because maybe in a few years, a new DNA test will be discovered for a pathology that was previously untestable, and we would be starting over again with the same iter, perhaps “throwing away” other good dogs, already leftovers from a first strong and disastrous skimming.

On the other hand, in pathologies with a recessive behaviour, if in a mating at least one of the two parents is free from mutation on both genes, the offspring will never run the risk of getting sick, and perhaps we will not lose what good things we have in a subject or in a bloodline.

Let us remember that perfection does not exist in nature, or rather perfection is precisely imperfection, which is not always a benefit in a subject, but in the end it always is for the species itself. In the dog we have put our hand to reproduction, and we are looking for perfection, which precisely because of how nature works we will never be able to arrive. Those who have been breeding for some time and have already become disillusioned will know that avoiding trouble 100% is not always possible, but they try anyway, and will also know that breeding is a compromise, where the pros and cons of a mating are weighed , and sometimes a possible problem can even be acceptable, in exchange for a more serious one.

In conclusion, DNA tests for recessive Mendelian transmission pathologies are excellent for containing the typical pathologies in the breeds, they are a must, by serious breeders, but they are necessary to find affecteds and carriers, and to breed them with a clear to avoid affected offpsring, not to “remove” from breedig all dogs wich are not clear, it will be a big mistake.

Good subjects must not be stopped, never, even if they are carriers and sometimes also affected, if obviously mated with a free partner.

If we want to completely remove the problem in our dogs, we know one of the parents it will mathematically pass the healthy version of the gene to the child, and therefore the child will at worst be a healthy carrier and will never develop the disease. Furthermore, if we want to keep a clean dog out of our line, free for that pathology mutated gene, at most in two generations, by testing the puppies and keeping one totally free, we could easily remove it without loose years and generations of farming.

Because of its ease of use, these tests allow us to keep the best subject in any case from other points of view, even if it were a healthy carrier, and at the same time keep the pathology in question under control, avoiding giving birth to dogs that could get sick of that disease, specific breed’s genetic disease.

This is right the strength of a DNA TEST and its correct use!