Controlling Genetic diseases

When a genetic disease appears in Italian Greyhounds we consider how it happened, what can be done to control its spread and how to keep future generations free from affectation. In order to understand what is happening when a genetic "epidemic" appears we need to acquire a little knowledge about the basics of population genetics.

WHAT IS GENETIC FREQUENCY?

Genetic Frequency is the percentage of a gene that is within a population. For purposes of explanation we will assume a gene pool of 100 dogs. Using PRA as an example let's assume that 16% of our population is PRA affected. How many would be considered carriers (meaning - what is the gene frequency of PRA for the breed)?   If the population is 100 and 16% are affected... the probability is that the carrier rate of the PRA gene would be 48%. The gene frequency would be 40% within the population.   For the sake of simplicity, formulas have been left out. There are websites that can explain the mathematical formulas.

WHAT DOES EFFECTIVE POPULATION MEAN?

The effective population is the number of dogs actually being bred in relation to the size of the gene pool. For example, if a population contains 100 individuals with an equal number of males and females randomly mated to each other with the same number of offspring replicating each parent ... then the EFFECTIVE population is also 100. Of course this isn't the actual case in dog breeding. Dog breeders are highly selective as to which animals will be bred. Sometimes one individual male will be used disproportionally (i.e. popular sire) in comparison to the general number of available males. An extreme example would be a popular sire that could be mated to every female in the population within a single generation. If this were the case our effective population would be 50%...with every dog carrying half of a single father's genes with the maternal half varying genetically.

With that kind of breeding, of course, the gene pool will not be large, even if the population contained a thousand unrelated females. Such extremes are rarely if ever seen. But in some breeds, limited gene pools with limited number of individuals from that population being bred can become a cause for concern. An effective population of 500 is generally considered to be the limit to declare a species directly threatened by extinction...even if that population contained seventy thousand dogs.

HOW SELECTION WORKS:

If dogs were randomly bred (no popular sires) the frequency of genes (good or bad) would remain unchanged. For example, if 10% of the dogs in a breed are affected by PRA, ( approx 32% gene frequency for PRA), and breeders failed to intercede in order to reduce this frequency, then the frequency will remain the same. However, if breeders select only obvious cases against PRA (eg. PRA affected dogs are not bred) which is a relatively weak approach...then the gene frequency will decrease.

Therefore..a weak selection would result in a slow decrease of frequency. Conversely...too a strong selection would result in a more rapid decrease. An overwhelmingly strong selection (removal of all affected, carriers and possible carriers) could cause an initial decrease of PRA, but might INCREASE other potentially dangerous genetic defects.

Why is a smaller gene pool at a larger risk in a selection process than a larger gene pool? What could happen to the gene frequency? If one could take a coin and toss it 1000 times - (i.e. large gene pool with lots of genetic diversity) there is a close to 50% chance of heads and 50% chance of tails. But if the coin is only tossed 10 times (small gene pool with little diversity), the results may be surprising - perhaps 40% heads and 60% tails.

In a small population this means that the gene frequency of around 40% in the next generation might have increased to 45%, because of this random effect. This phenomenon is called random drift. If the impact of this random drift gets stronger than the impact of the selection - natural or artificial - then the changes of the gene frequency could very well be the opposite to what may have been desired.... despite  the selection.

In a large gene pool with lots of diversity, random drift can have a small impact on local populations and overall little effect on the population as a whole. The smaller the effective population ... the larger the risk of producing a large deviation from the expected value of the gene frequency.

What does all this mean? If a dog breed does not have large enough effective populations then high frequencies of unpleasant genetic problems will continue to pop up. With a little bad luck breeders might also have difficulty attempting to reduce these problems with selection. However, if breeders ensure that there are large enough effective populations in their breed, genetic diseases will not pop up as a common problem in the entire population. Also...as a bonus, inbreeding depressions and compromised immune systems could be avoided.

INBREEDING AND GENE POOLS.

It is extremely important that breeders begin to think of an entire breed's gene pool as a Community Well. When a breeder sells an intact animal to another breeding home, that transaction begins to directly affect every other breeder's future breedings. How so? A good example would be when a large portion of breeders rush to use one or two males for breeding purposes in exclusion of all other males in the breeding population.

The largest problem is in convincing people to view these problems not as individual situations but as problematic for the entire breed. Some breeders may say, "I have bred in this way for many years and have not had any problems". While their breeding may be an "outcross" to a popular dog, with everyone else using the dog, the next and future generation will find it difficult to find unrelated dogs. When other equally good dogs are ignored in favor of a single popular, winning dog ...the gene pool loses valuable genes from those dogs not selected for breeding. When those genes are lost... there is no way to get them back.

A too small gene pool will continue to decrease in diversity every generation. What will happen in each future generation? In the beginning, not much at all. It isn't until the degree of inbreeding reaches a certain critical level that the real problems begin to manifest and by then it is usually much more difficult to take corrective action. It is much better to start working against these problems before the symptoms appear.

Every educated breeder knows that inbreeding means an increased risk of doubling up on harmful or lethal recessive genes. All breeders know that each dog will carry a few harmful recessive genes.

Some people think that the inbreeding clears out the harmful recessives and leads to a healthier breed for the future. Inbreeding doesn't clear out anything in itself. Inbreeding has to be combined with a strong selection in order to clear out any undesirable genes. Here is one nightmare scenario. It is possible that a breeder could heavily inbreed with strong selection to weed out all "undesirable" genes and that the resulting pups might need to live in a completely sterile environment... as their immune systems would be almost be non-functioning. There is also the added spectre of nightmare mutations that could crop up to topple a so-called "perfect" house of genes!


SOLUTIONS FOR LIMITED GENEPOOLS

If a breed is already so inbred that clear signs of inbreeding depression have begun to appear (for instance a high rate of autoimmune problems, cancers or increase of genetic diseases) what could be done to correct this? If there are unrelated lines in other countries, of course, the best solution would be to import.

Some breeders will hesitate to outcross because they are afraid that "Type" will be gone for ever. Some breeders believe that line breeding is the only way to get Type. It is true that by using inbreeding quicker results can be obtained in this area. But it is possible to achieve the same result without inbreeding. Unfortunately inbreeding is a very tempting shortcut for breeders. Most of the genes that are doubled up by inbreeding have absolutely nothing to do with type. In most limited gene pool populations, type has already been set and therefore breeding type to type - regardless of the parent relation will keep type.

A common objection against out-crossing is that new harmful recessives could be introduced into the breed. True..it is a chance that may need to be taken. What we do know, though, is that each dog carries at least one or more harmful recessive genes - regardless of its status as inbred or out-crossed. Some breeders believe it is better to have a more inbred population with fewer genetic diseases in order to more easily keep those diseases more firmly under control. Maybe there are even tests available for those diseases. However, it is better to have lower frequencies of several different harmful recessives than to have a higher frequency of one single recessive. If population "A" has a single genetic defect that has a 50% frequency in the breed, then a puppy born in that population would have a 25% chance of showing that genetic disease.

In another example...perhaps population "B" has 5 diseases that have a 10% frequency for each disease (50% frequency for 5 diseases). The risk for a puppy to show a genetic disease in population B is 5% . We get considerably less chance of a health problem in a population B which has lower frequencies for several different kinds of diseases than for population A with a major disease at the same frequency as population B.

All of the above leads to one unavoidable conclusion. If breeders fail to maintain a large enough effective population, then high rates of unpleasant genetic problems will continue to increase. If a gene pool is too small...additional difficulties in attempting to reduce these problems with selection may occur. The moral of the story is to think twice about breeding to an overwhelmingly popular stud. A couple of winning dog show ribbons are not worth the possible nightmare epidemic of genetic disease two or three generations down the line.