On my previous post entitled “Why is inbreeding bad?” I noted that one of the real issues with inbreeding is an impaired immune system as the result of losing diversity and heterozygosity in MHC/DLA haplotypes.
The MHC stands for the Major Histocompatibility Complex. The MHC is cell surface molecule that is encoded by a relatively large gene family. The MHC molecule controls some of the actions of the leukocytes, “the white blood cells.” As you might remember from your high school health class, leukocytes are the blood cells that act as police, taking out infectious diseases and foreign materials, including cancerous cells.
Possessing a greater diversity in MHC haplotypes allows the organism a heightened ability to control what leukocytes do when exposed to a variety of challenges to the immune system. Reduced diversity winds up restricting the immune system’s ability to fight disease. Possessing a heterozygous MHC haplotypes also provides greater immune resistance than possessing homozygous MHC haplotypes.
In humans, the MHC is called the human leukocyte antigen system, usually abbreviated as HLA. In dogs, it is called the dog leukocyte antigen system, which is abbreviated at DLA.
One cannot look at an organism and tell what its MHC haplotypes are. It’s not like looking at fur or hair color.
And as a result, these haplotypes are very easily lost within a closed registry system. Often, the haplotypes not lost entirely within a breed or strain, but because of the popular sire effect and continuous linebreeding from “the best,” a huge percentage of the population in any one breed can be quite homozyous in its MHC haplotypes.
This has real health and welfare effects. Autoimmune diseases are becoming more and more common in purebred dogs. Some breeds are highly susceptible to cancer, which might be partially the result of the decrease in MHC diversity of dogs within the closed registry system. Allergies are also likely implicated to this reduction in MHC diversity and heterozygosity. The MHC also has some effect upon reproductive cells, which is one reason why certain breeds and strains have issues with fertility.
So what can be done?
Well, the easy answer is to do away with rigid closed registry systems and allow the different dog breeds to exist as very genetically diverse populations.
However, it is possible to breed for great MHC diversity in domestic dogs, even within the closed registry system.
To understand how this is possible, we will have to change species again.
Take the San Nicolas population of the island fox (Urocyon littoralis). This population is considered the least genetically variable of all sexually reproducing animals.
However, despite its lack of genetic diversity, this population of island fox has relatively diverse MHC haplotypes.
How does it do this?
Well, a study led by Andres Aguilar (2004) found that the San Nicolas foxes likely were able to maintain their diverse MHC haplotypes through what is known as balancing selection. Balancing selection occurs when population keep multiple alleles actively maintained at frequencies that are higher than the mutation rate. It almost always happens within populations in better for an organism to be heterzygous for certain alleles than homozygous for them.
As we have seen with MHC haplotypes, it is better to be a heterzygote, so there is a strong selection pressure for the foxes to keep their MHC haplotypes diverse.
One way in which they likely do this is that they choose mates that have MHC haplotypes that are different from their own.
This might sound a little crazy, but even humans have innate mechanisms that are designed to keep our MHC haplotypes diverse.
There is a famous study in Switzerland that asked women which men were most attractive by smelling the shirts the men had slept in for two nights. Almost without exception, the women selected the men who had different MHC haplotypes from their own. The pheromones that are connected with sexual attraction in humans are also giving out genetic information such as what MHC haplotypes a potential mate might have. And it’s so innate that women are able to obtain this information without understanding exactly what they are responding to.
It’s likely the same way in island foxes, which, like humans, typically reproduce within a bonded pair system. Foxes, like all wild dogs, are pretty particular about their mates. After all, the survival of their offspring is dependent upon having a partner that can provide for them.
Domestic dogs, for whatever reason, don’t seem to be as particular about their mates, and thus, it has been easier to selectively breed them. Wolves and other wild dogs very rarely inbreed, but it is relatively easy to get dogs to inbreed and to do so for multiple generations.
And as a result, it has been easier for different breeds to lose their MHC haplotypes.
Further, it is not just the mere number of haplotypes a breed possesses. Heterozygosity has proven to be more important in determining immune health than just possessing a certain number of haplotypes.
That means that within an inbred population, there has to be some conscious effort to maintain both diversity and heterozygosity.
That is pretty hard to do when one is breeding for physical or behavioral traits– and the immune system genes cannot be readily ascertained.
Well, we do have a solution. Genoscoper currently offers an MHC II test, which would allow breeders to see what haplotypes their dogs posess and what to do with them. Mars Veterinary also offers a test that examines the MHC (among other things). It is called Optimal Selection from Wisdom Panel, and it was initially tested with breeders affiliated with the Dandie Dinmont Terrier Club of America (A NEW GENETIC BREEDING TOOL ON THE HORIZON (1)). Over a two year period, this selection tool has allowed Dandie Dinmont breeders to increase their litter sized from 2.75 to 4.0 puppies per litter. Dandie Dinmonts are a rare terrier breed that has issues with genetic diversity, and these tests could be a boon for breeds that have very small founding and effective populations.
So science now allows for us to do with domestic dogs what the San Nicolas island foxes were able to do on their own. We can maintain relatively inbred populations and still keep the MHC haplotypes diverse and heterozygous.
However, here are some caveats:
First of all, virtually no dogs are bred without some eye to competition. Competition, whether in show or working trials, has a selection pressure of its own, and a breeder has to considered a wide variety of issues before choosing which dog to breed with which other dog. As I’ve noted before, MHC haplotypes are hard to see, so how many breeders would choose diversity and hetrozygosity of MHC haplotypes over the ability of the dog to win in the show ring or in the trial? I would like to think that very few breeders would choose immune health over ribbons and titles, but that’s probably not the case. Keeping the MHC diverse and heterozygous is a long-term project, and it requires a bit more dedication and discipline to breed for than physical or behavioral traits.
Further, breeders have to balance a wide variety of issues when selecting which dogs to breed, and MHC haplotype diversity alone should not be the sole criteria. Other issues with temperament and hereditary diseases have to be considered in light of the MHC.
Finally, many of these breeds have either entirely lost MHC haplotypes or certain haplotypes are very rare within the breed.
You cannot do DIY balancing selection when you don’t have the haplotypes in the first place.
Even if we might have these tools, one should keep in mind that it is much more cost effective and easier to try to maintain genetic diversity within breeds and strains in the first place. It makes much more sense to keep breed registries more open and then operate selective breeding principles within much more diverse populations. Breeding within much more diverse populations requires some understanding of how different traits are inherited, but one can readily learn these skills. It is not rocket science, but one can figure it out. If people living thousands of years ago0–before there was even a Mendelian theory of inheritance– were able to produce so many different types of dogs, then we surely can.
DIY balancing selection can be a tool within conservation genetics, but I think it has to be paired with a fundamental understanding of how population genetics works.
Otherwise, you’re going to get into silly arguments with people who think that you can just inbreed and inbreed without consequence. No rare dog breed can be saved in the long term if its immune system doesn’t work properly.
It’s really that simple.
In the end, selecting for diverse and heterozygous MHC haplotypes within a limited gene pool is less preferable than trying to maintain genetically diverse strain. We have intentionally reduced genetic diversity within dog breeds and strains, yet as a population, dogs remain one of the most genetically diverse of all domestic animals. We have the ability to correct some of the errors without resorting to sophisticated genomic technology, but because the dog culture at large values purity and homozygosity at all costs, we are left looking at the only other option available.
Inbreeding requires so much scientific knowledge and acumen to pull off correctly that it really shouldn’t be done. And the validity registry systems that ultimately reduce dog breeds to inbred populations needs to be questioned.