Longlease Bernese Mountain Dogs Cancer Information

Inbreeding And Its Effect On The Immune System

By Dr. Heather E. Lorimer

(Reprinted with permission)

All cat breeders know something about the dangers of inbreeding. We have all heard of (and many of us have seen) the tragic results of doubling up dangerous recessive genes. One way to avoid the recessive lethal genes is to outcross as much as possible. On the other hand, the line into which you outcross may carry the very same gene that you are trying to avoid.

However, it is quite possible to weed out genetic faults in even the most inbred lines. Scientists do this all the time; they have produced strains of mice, rats, and other animals that are so inbred as to be genetically identical. Each animal in one of these strains is the identical twin (aside from sex) of every other animal of that strain. These animals carry no lethal genes and are extremely healthy in every way except one. They must be kept in a nearly sterile environment, because their immune systems are not capable of fighting off a normal range of diseases.

The immune systems of all animals are absolutely dependent on genetic diversity. There are basically two kinds of immune responses:

There are cells called B-cells, that make antibodies which are capable of inactivating or killing foreign particles (such as bacteria or viruses) that enter the body.

There are cells called T-cells, which kill dangerous cells such as tumor cells infected with a virus.

In many respects these two systems are the same. These cells are very specific; one cell makes only one kind of antibody or is capable of recognizing and killing only one kind of dangerous cell. The most startling thing about this system is that for every kind of infection or every kind of cancer to which an animal could ever be exposed there is already a cell in the animal's body specific to that infection or cancer.

This means that there are probably millions of genes, each coded for a specific antibody or cell surface receptor, in every adult animal. The problem is that there is not enough room on the chromosomes for all these genes. We animals have a very clever method of circumventing this paradox: our immune systems' cells don't have complete genes for antibodies; instead, they have lots of little gene segments which the cell cuts and splices together to make a whole gene. Immune system cells are the only cells which alter their own DNA. If this happened anywhere but in the immunity genes, it would be very dangerous. In the immunity genes, however, it is essential: otherwise, we would not be able to fight very many diseases.

In the following discussion I have arbitrarily used an original (germ-line) DNA with six gene segments, each segment containing ten different choices (in real life there are many more). These six segments could produce 10x10x10x10x10x10 (one million) different antibodies. If both chromosomes of a cat or other animal have identical immune system gene segments, that animal has lost half of its potential antibody genes. If that animal is further inbred, it starts to lose other individual gene segments to a genetic phenomenon called "crossover." Each gene segment that is lost represents thousands of potential antibodies. In the above example, an animal with two entirely different chromosomes can make two million different antibodies, each specific for one kind of infection. An animal that has identical (homozygous) immune system chromosomes can make one million different antibodies. An animal that has lost one gene segment from crossover can make only nine hundred thousand antibodies. So we see that, in my example, the loss of one gene segment represents the loss of one hundred thousand potential antibodies. When this happens, the animal starts losing its ability to fight some diseases. If a group of animals are missing the same gene segments, as happens in inbred lines, suddenly whole catteries or whole bloodlines can be lost to infections that would normally have little effect on a normal cat.

A well-known example of this kind of sensitivity to disease, caused by a lack of genetic diversity, has occurred in wild and captive populations of cheetahs. Captive cheetah breeding programs have been plagued by low birth rates and high infant mortality. To add insult to injury, cheetahs have proved to be very susceptible to Feline Infectious Peritonitis (FIP). Most cats become infected with the virus that can cause FIP when they are exposed to it, but usually less than 10% of those cats will go to develop the usually fatal FIP. However, cheetahs exposed to the virus will experience a 50% mortality rate. Stephen J, O'Brien and his collegues examined the cheetah problem in an article published in the May 1986 issue of "Scientific American." They found that cheetahs are nearly identical genetically - so identical that individual cheetahs, born thousand of miles apart, did not reject skin grafts from each other (a trait which is normally seen only in identical twins). At some point in history, the cheetah population must have narrowed down to so few individuals that their immunological diversity was lost and, as a result, these big, beautiful cats are in danger of extinction.

We as cat breeders must protect our beautiful companions from this fate. We must be careful no to "fix" immunodeficiency when we are trying to "fix" type. Fortunately, this is not hard to do. When you want to bring a trait into your cats, such as size or ear set, go to more than one source. Remember, you won't lose type in an outcross unless the cat to which you're outcrossing lacks type. Most important, watch for the danger signs of excessive breeding. They are:

1. Low fertility in either males or females.
2. Small litter size (one or two kittens) on a regular basis.
3. Asymmetry, misaligned jaws, crooked noses, irregular eye-set.
4. Regular appearance of cancer in young cats.
5. Loss of a large proportion of cats to one disease. If 50% of a litter of kittens or of a group of adults dies of a simple infection, there is not enough immune system diversity in your line.

Authors note: June 1998. New information about the MHC complex indicates that lack of heterozygosity there may be an even bigger problem than is found in the antibody genes and TCR genes. More recent evidence indicates an even more serious problem with the immune system caused by inbreeding then the ones mentioned in this article. Some of this will be probably coming out in the next issue of the Cat Fanciers Journal.

Heather E. Lorimer, Ph.D.
Assistant Professor,
Genetics Department of Biological Sciences
Youngstown State University
Youngstown, OH 44555





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