Breeding Strategies for Managing Genetic Traits
Jerold S Bell DVM, Clinical Associate Professor of Genetics
Tufts
Cummings School of Veterinary Medicine
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With each new generation of dogs, breeders ask, “How can I continue
my line and improve it?” Aside from selecting for conformation,
behavior and ability, breeders must consider how they are going to
reduce the incidence of whichever genetic disorders are present in
their breed. There are no answers that will fit every situation.
There are, however, guidelines you can follow to preserve breeding
lines and genetic diversity while reducing the risk of producing
dogs that carry defective genes, or are affected with genetic
defects.
Autosomal Recessive Disorders
In the case of a simple autosomal recessive disorder for which a
test for carriers is available, the recommendation is to test your
breeding-quality stock, and breed carriers to normal-testing dogs.
The aim is to replace the carrier breeding-animal with a
normal-testing offspring that equals or exceeds it in quality. You
don’t want to diminish breed diversity by eliminating quality dogs
from the gene pool because they are carriers. As each breeder tests
and replaces carrier dogs with normal-testing dogs, the problem for
the breed as a whole diminishes.
For some disorders there are tests known as linkage-based carrier
tests, which can generate a small percentage of false positive and
negative results. When using these tests to make breeding decisions,
it’s advisable to first determine whether the results correlate with
the test results and known genotypes of relatives.
When dealing with a simple autosomal recessive disorder for which no
carrier test exists, breeders must assess whether each individual
dog in their breeding program is at high risk of being a carrier.
This requires knowledge of the carrier or affected status of close
relatives in the pedigree. An open health registry that is supported
by the parent club makes it easier for breeders to objectively
assess these matters. By determining the average carrier-risk for
the breeding population, breeders can select matings that have a
projected risk which is lower than the breed average.
If breeding a dog that is at high risk of being a carrier, the best
advice is to breed to a dog that has a low risk. This will
significantly diminish the likelihood that affected dogs will be
produced, and can reduce by up to half the risk that there will be
carriers among the offspring. Using relative-risk assessment as a
tool, breeders should replace higher-risk breeding dogs with
lower-risk offspring that are equal to or better than their parents
in quality. Relative-risk assessment allows for the continuation of
lines that might otherwise be abandoned due to high carrier risk.
Breeding a dog only once and replacing it with an offspring allows
breeders to improve their chances of moving away from defective
genes and also limits the dissemination of defective genes. When
dealing with disorders for which carriers cannot be identified, the
number of offspring placed in breeding homes should be kept to a
minimum.
Autosomal Dominant Disorders
Autosomal dominant genetic disorders are usually easy to manage.
Each affected dog has at least one affected parent, but it can be
expected that half of the offspring of an affected dog will be free
of the defective gene. With disorders that cause death or
discomfort, the recommendation is to not breed affected dogs. To
produce the next generation of a line, a normal full sibling of an
affected dog can be used, or the parent that is normal can be used.
A problem with some autosomal dominant disorders is incomplete
penetrance. In other words, some dogs with the defective gene may
not show the disorder. Roughly half their offspring, however, may be
affected. If a genetic
test is available, this is not a problem. Otherwise, relative-risk
assessment can identify which dogs are at risk of carrying
incompletely penetrant dominant genes.
Sex-Linked Disorders
For sex-linked (also known as x-linked) recessive defective genes
for which carrier tests exist, breeders should follow the same
“breed and replace” recommendations as are outlined above in the
discussion of autosomal recessive disorders. If there is no
test, the defective gene can be traced through the pedigree. If a
male is affected, he would have received the defective gene from his
carrier mother. All of his daughters will be carriers, but none of
his sons. By using relative-risk assessment to breed him to a female
that is at low risk of being a carrier, you can prevent affected
offspring, and select a quality son for replacement.
There are rare instances in which a female is affected with a
sex-linked disorder. In such cases, she would have received the
defective gene from both parents; specifically, an affected father
and a mother who is either a carrier or is affected herself. If an
affected female is bred, all the sons will be affected, and all the
daughters would be carriers, so affected females clearly should not
be bred. A normal male that is a littermate to an affected female,
however, would be able to carry on the line without propagating the
defective gene.
Sex-linked dominant disorders are managed the same way as autosomal
dominant disorders are. The difference is that affected males will
always produce all affected daughters.
Polygenic disorders
Polygenic disorders are those caused by more than one pair of genes.
Most polygenic disorders have no tests for carriers, but they do
have phenotypic tests that can identify affected dogs.
With polygenic disorders, a number of genes must combine to cross a
threshold and produce an affected dog. These are known as liability
genes. In identifying a dog’s liability for carrying defective genes
for a polygenic disorder, the breadth of the pedigree (that is,
consideration of all siblings of individuals in the pedigree) is
more important than the depth of the pedigree (consideration only of
parent-offspring relationships.) A clinically normal dog from a
litter that had one or no individuals affected with hip dysplasia
(which is a polygenic disorder) is expected to carry a lower amount
of liability genes than a dog with a greater number of affected
littermates. This is why it is important to screen both pet and
breeding dogs from your litters for polygenic disorders. Information
on the siblings of the parents of potential breeding dogs provides
additional data on which to base your breeding decisions.
Genetic disorders without a known mode of inheritance should be
managed in the same way as polygenic disorders. If there are
multiple generations of normalcy in the breadth of the pedigree,
then you can have some confidence
that there are less liability genes being carried. If a dog is
diagnosed with a genetic disorder, it can be replaced with a normal
sibling or parent and bred to a mate whose risk of having liability
genes is low. Replace the higher-risk parent with a lower-risk
offspring that equals or exceeds it in other aspects, and repeat the
process.
Genetic tests are extremely useful tools to help manage genetic
disorders. Even when there is no test, or a known mode of
inheritance, much can still be done to reduce the incidence of
affected and carrier animals. The use of these guidelines can assist
breeders in making objective breeding decisions for genetic-disease
management, while continuing their breeding lines.
(This article can be reproduced with the permission of the
author.
Jerold.Bell@tufts.edu)
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