Sunday, May 29, 2011

Cancer, Autoimmune disease and MHC diversity-should we blame vague toxins and food or inbreeding and closed registries?

It is common among proponents of certain types of diets and supplements (raw diets, the "evolution" diet, and many types of herbal supplements) to claim that cancer and autoimmune diseases are caused by unidentified "toxins" in commercial foods, vaccines or simply toxins from the environment. Unfortunately, some breeders and even some veterinarians, particularly the "CAVM" crowd, have bought into these ideas, and sometimes try to require new puppy owners to feed specific foods, delay or avoid vaccinations and sometimes avoid certain types of exercise in an attempt to avoid problems that have a strong genetic basis.

Many ideas about breeding dogs date back to the Victorian era when little to nothing was known about genetics and their relationship to the function of the immune system, and ideas of pure blood and avoiding undesirable mixing of different breeds were considered to be the appropriate way to "improve" dogs and other animals. Unfortunately, these ideas were institutionalized and perpetuated through kennel clubs and many breed clubs in the form of policies that allow and even encourage inbreeding (often called "line breeding") and specifically prohibit out-crosses for any reason. The only way to try to eliminate a problem under this system is to eliminate individuals carrying the undesirable genes, which may remove one problem, but is likely to further constrict the gene pool and cause other problems at the same time. While the "holistic" veterinary medicine crowd tries to blame toxins and vaccines, and the large kennel clubs do their best to ignore the underlying problems with their policies, scientists have been working hard to identify the reasons why some breeds are so much more susceptible to certain types of cancer and autoimmune diseases than other dogs or less inbred dogs are.

The underlying genetics associated with susceptibility to several autoimmune diseases and cancers have been discovered in the last few years. While we have known that certain breeds have much higher incidences of certain diseases than others for years (some diseases are named for the breeds which they occur in most frequently), the complexity of the immune system and the genetics associated with it means that only recently have we started to unravel how this affects the health of our pets. There are two main types of Major Histocompatability   Complex (MHC) genes in vertebrates-which are also one of the most polymorphic sets of genes in vertebrates-which are involved with identifying different proteins (antigens) and presenting them to the immune system as "self" or "non-self". This is how the immune system regulates which things to attack and remove (bacteria, cells infected by viruses, cancer cells, etc.) and which things to leave alone (normal cells, harmless proteins from food and the environment).  In general, having a larger number of diverse MHC genes means that the immune system is better equipped to identify and distinguish good and bad antigens in the body.

In the last few years, researchers have identified varying MHC diversity in different dog breeds. Although it is probably still quite early to use MHC haplotype testing to test for suceptiblity to most diseases, such testing is starting to become available. Many studies have been done identifying specific problems and relationships of specific MHC haplotypes with specific diseases. Some examples include; Autoimmune Hemolytic anemia, Hypothyroidism, Canine Masticatory Myositis, Toller arthritis (a disease similar to Lupus), Canine chronic superficial keratitis, and Doberman Hepatitis. These are just a few of the heritable autoimmune diseases which occur in dogs, and active research continues. MHC diversity is also important for detecting and eliminating cancers, and a lot of research has been done into transmissible tumors in an attempt to discover a way to fight
Devil facial tumor disease in Tasmanian Devils. This research is helping to show how many types of tumors in addition to transmissible tumors evade the immune system. Some inheritable diseases have unsurprisingly been discovered to be unrelated to the MHC genes as well.

This body of research is providing both a broad knowledge of how limited gene pools increase the risk of autoimmune disease and cancer, and which specific genes affect susceptibility to specific diseases. While this line of research will result in specific tests for many of these diseases, eliminating carriers from the population may further restrict genetic variability and is very likely to cause other problems. It would be a much better idea to try to increase diversity in HLA haplotypes first, before eliminating undesirable genes. In some cases, this may mean outcrosses from other breeds to introduce the desirable genetic diversity. In the rare casees that this has been tried, the kennel clubs and breed organizations have not reacted positively. Another problem is that often kennel clubs and breed organizations fund genetic research on purebred dogs, which may deter criticism from organized veterinary medicine.Even worse, the "holistic" or CAVM crowd enthusiastically promote a wide variety of diets, supplements, and even antivaccine nonsense while ignoring the growing body of evidence of genetic problems in purebred dogs. "Holistic" indeed.

For further discussion of these issues in dogs and other animals, see these thoughtful posts;
Pedigree dogs Exposed-How to breed dogs with stronger immune systems.
Border Wars-Inbred Mistakes.
Desert Wind Hounds-MHC, DLA, WTF?
Retrieverman-Misunderstanding the concept of inbreeding tolerance.


  1. Excellent article, I'll spread it.

  2. This is an amazing article because the Akita was used in an MHC study at U.C. Davis in 1998. The ultimate goal of the 1998 study was to establish a genetic database for disease association studies of the major histocompatibility complex (MHC).

    The first part of the study concentrated on a database for both the Akita and Weimaraner breeds, and the development of several promising microsatellite genetic candidate markers within the canine MHC region. Variation occurs between individuals at each of these DNA markers (alleles), and work is in progress to determine the number of different alleles present in normal purebred dogs, Dr. Neils Pederson said. “Only with this knowledge of the allele types in the normal population can differences be detected between the normal group and those with immune mediated disease.”

    Dr. Angles and Dr. Pedersen looked at the diversity of alleles (or segments of genes) that occur alternately at a given location. In the sample group of 100 Akitas, they found a diversity of only six alleles at one MHC gene--a very low variance for what was believed to be unrelated donors. The biggest surprise was that one allele, an allele of the DRB1 gene, was found in 70% of the dogs. In this group of genes, heterozygosity improves disease resistance; this lack of variation in the MHC is considered to be a major risk factor for autoimmune disease. Because the allele was found in healthy Akitas (as well as those with VKH-like syndrome and myasthenia gravis), and is known to occur in other breeds, it may not provide a definitive marker for autoimmunity.

    It is known within the Akita community that inbreeding was practiced by the early breeders--one breeder claiming to have used her male 57 times to her own bitches!!! She could take credit for ruining an entire breed but she saw nothing wrong with inbreeding.