Baking Bread: The
Red Hen Approach to Genetic Disease
Originally published in Double Helix Network News, Vol. X No. 2, Spring 2002.
by
Remember the story of the Little Red Hen? She grew grain, harvested it, ground
it to flour, and used the flour to make bread. At each step she asked the other
barnyard animals if they would help. No one would. When the bread came out of
the oven wafting its wonderful aroma, everyone wanted some. The hen, refusing
to share with a bunch of freeloaders, told them to cluck-off.
The original purpose of this old fable was to teach children that if they want
a share of life's good things, they have a responsibility to contribute to the
process of producing them. While it might not seem so on the surface, this
lesson can be applied to dog breeders and canine genetic disease.
For breeders the "bread" is the results of hereditary disease
research. If we don’t participate in the process—not just in ones and twos, but
in dozens and hundreds—our dogs will only get crumbs. Of the nearly 400
identified hereditary diseases in dogs, nearly half have been identified in a
single breed only. If that breed is yours and you aren’t doing anything about
it, dogs will continue to suffer. Even if a disease occurs in multiple breeds,
we cannot assume that research on other breeds will help our own.
Determining incidence, mode of inheritance and developing screening tests are
vital to the effective control of genetic disease. Breeders hold the key to
accomplishing these goals: Data. None of these goals will be reached without
effort on the part of those who should be the most interested in the
preservation and improvement of the breed.
Listings of diseases reported in various breeds are nothing new, but they can
provide an inaccurate picture of what is going on. Lists of peer-reviewed
journal articles give no indication of how frequent any particular disease is
in a given breed, though some of the specific articles in such a listing might
do so. A published journal article indicates that someone had the interest or
(very important) funding to conduct research on that problem or to write up a
case study on one or a few affected dogs. Such articles may describe signs,
prognosis and treatment or investigate what goes wrong and brings about
disease, but they often do not include any detailed discussion of disease
frequency in a population. Very rare conditions can find their way onto such
lists and frequently encountered problems may not appear at all. If no one has
researched and published an article, the only ones who will know about it are
the breeders and the veterinarians who treat their dogs.
The author frequently encountered a frustrating “this does not happen in your
breed” attitude when she first started investigating Collie Eye Anomaly in
Australian Shepherds in the mid 1980s. Except for breeders who had affected
dogs or knew those who did and veterinary ophthalmologists experienced with the
breed, no one knew it was there. It wasn’t in the veterinary literature or
textbooks so it effectively did not exist. Sadly, dogs might be judged clear when
they were not, because vets did not know CEA occurred in Aussies and breeders
didn’t realize the necessity of checking all puppies at an early age. In 1991 a
peer-reviewed article was published on CEA in Aussies and the presence of the
disease became an established fact. Every so often, the author still hears of a
vet who has told an owner that CEA "doesn’t exist" in Aussies. When
this occurs, she gladly sends that vet a copy of the journal article.
Disease registries give a better indication of disease incidence, but they also
have their limitations. Unless all results of all examinations are submitted,
the results may be skewed. For example, many breeders will have Orthopedic Foundation of Animals (OFA) hip x-rays done to
screen for hip dysplasia. But those who discover that
the hips are bad may opt not to send them on to OFA, thereby skewing the
registry’s database toward unaffected dogs and giving a rosier picture of
disease incidence than is actually the case. How much rosier will depend on
what portion of negative reports is withheld.
Even in the case of a database which collects results of all exams, like
Penn-Hip and the Canine Eye Research Foundation (CERF), disease incidence will
only apply to the reporting population. If a breed is rare and few breeders
screen their dogs, the registry’s data will have little meaning. In
small-population breeds everyone needs to cooperate to see that most dogs get
screened.
Even in populous breeds, statistics may or may not be indicative of the whole
picture. As a group, show breeders are the ones most likely to utilize
screening programs, though that utilization certainly isn’t universal. Working
and performance breeders, depending on the breed and the disease, may or may
not participate. Those who breed dogs primarily to make money selling puppies,
whether on a large or small scale, rarely if ever bother with screening tests.
Those who have no intention of breeding are unlikely to screen unless the
health of their dog or one of its near relatives makes the test seem necessary.
In all of these situations, the resultant registry statistics apply only to the
sub-population of the breed that is being tested. If most show-bred dogs are
screened and reported, you will have a good idea of how frequent something is in
show dogs but you will know nothing about the pet population if those dogs come
largely from non-show breeders.
For many inherited diseases there is no standard, accepted screening test.
Epilepsy is a common inherited problem in a number of breeds for which there is
not yet any screening test. Therefore, there can be no registry to record data
on affected dogs.
Health surveys conducted by breed clubs can be a constructive way to gather
disease incidence data. Every breed should conduct them at intervals, but their
usefulness can be limited by design, participation and politics. Those who
develop the survey must have a good idea of what is going on in the breed
genetically and have the will to tackle all pertinent issues. If the question
isn’t asked, there will be no answer.
Response needs to be statistically significant. Not everyone must respond, but
if only a tiny percentage do or only one segment does so (e.g. pet owners vs.
breeders,) the results may not give a true picture of disease incidence. Some
parent clubs have rather small membership even though the breed is populous. In
such cases, if only members are polled even full response may provide
inaccurate data on the breed as a whole.
And then there is politics. Having been intimately involved with a breed health
survey herself, the author has had occasion to discuss the process with a
number others who have been involved in such surveys. Several individuals in
various breeds voiced frustration at survey results that were edited before
presentation or even suppressed at the demand of those with the political power
and, one presumes, personal motivation to do so.
If sufficient breeders and owners have cooperated with the data-gathering
process, good disease incidence statistics may be available. If the mode of
inheritance is known, it may be possible to determine the frequency of the gene
in the breed population. Steps can then be taken to reduce that frequency.
Unfortunately, the mode of inheritance often is not known.
Many inherited diseases—and recent research indicates this "most"
might be more accurate—do not have simple single-gene modes of inheritance.
Even if they do, genealogy data (pedigrees plus diagnostic information) must be
gathered on numerous affected dogs and their kin before the mode of inheritance
can be discerned.
CEA was presumed to be recessive in Collies, but when the disease first was
noted in Aussies we could not be sure it was the same in our breed. The author
gathered pedigrees and CERF reports provided by a number of people who owned or
produced affected dogs. These indicated that recessive inheritance in Aussies
was a strong probability. When a breeder donated two affected puppies, those
dogs were bred together. All the puppies from that litter were affected, thereby
proving the recessive inheritance in the breed. None of this could have been
accomplished without the willing participation of those who provided data to
build the genealogies and the breeder who made the puppies available. [Note:
Recent research is Collies indicated that inheritance did not show a strictly
single-gene recessive pattern. Given the variable presentation of the disease
it is probably polygenic. Some researchers believe that there is a single
recessive gene of major effect, one for which a dog must be homozygous to have
the disease at all. The Collie research may indicate that some combinations of
the other genes may result in an unaffected dog. Whether this holds true for
other CEA breeds remains to be discovered and warrants further research.]
Genealogies and biological samples are necessary to develop DNA screening
tests. Genealogies can be built from pedigrees and diagnostic paperwork alone,
but samples, usually in the form of blood draws or cheek swabs, must come from
several members of a family, those with the disease and some of their healthy
kin. Breeders are the ones who are most likely to have access to multiple
members of an affected family.
The author is presently attempting to assist VetGen,
a commercial laboratory, to gather data on Australian Shepherd families
affected with epilepsy, a common breed problem. In spite of the fact that there
are numerous affected Aussies (so numerous that one vet has told her that
Aussies "always" come up in discussions of epilepsy among her colleagues),
VetGen has been unable to get sufficient data over
the course of several years. While owners of sick dogs are usually willing to
provide whatever they can if it might help, those who own the parents or
siblings of the affected dog frequently are not. Without a screening test those
uncooperative individuals will be able to continue hiding behind a curtain of
deniability while the breed health crisis continues to get worse.
Progressive Retinal Atrophy (PRA), caused by a recessive gene, occurs in numerous
breeds of dog, including the Irish Setter. A DNA test
was developed for PRA in Irish Setters a few years ago that allows breeders to
know ahead of time if a dog will develop the disease as well as whether it
carries a single PRA gene and might produce affected offspring. But different
genes cause PRA in different breeds, so the Irish Setter
test will not work for others. Each breed needs its very own loaf of PRA-test
bread. The "recipe" (research and technology) for the Irish Setter
test might be used to develop a test for another breed but the
"ingredients," in the form of data, can come only from people in that
breed.
When the disease occurs in closely related breeds, as with CEA in Australian
Shepherds, Border Collies, Collies and Shetland Sheepdogs, the genetic cause
may be the same. But genes can be difficult to pin-point and sometimes the best
that can be achieved is a marker test. The markers are usually microsatellites, tiny bits of non-coding DNA that lie
between genes. They are highly polymorphic, which means they have many
different alleles, or forms. When DNA gets shuffled through the process of
recombination prior to the formation of eggs or sperm, things that are on the
same chromosome are likely to be passed on together. The closer together they
are, the more likely this will happen. If the gene itself is illusive,
researchers look for microsatellites that are close
to the gene. Desirable microsatellites will have a
particular allele associated with a particular allele of the gene, so the test
result will indicate whether the dog has a desirable or undesirable form of the
gene and whether it has one or two copies of it. Multiple markers are used as
back-ups to prevent false positive or false negative results in case gene and
marker go their separate ways during recombination. Markers are likely to be
breed-specific, so it is vital that each affected breed contribute to efforts
aimed at developing marker tests.
Last but hardly least comes money. Research does not happen without funding. Little
is available for research into canine diseases from governments and large
granting agencies unless affected dogs are being used as a model for a similar
human ailment. If we want a strictly canine problem researched, we need to put
our money where our mouth is.
The American Kennel Club’s Canine Health Foundation (CHF) and Morris Animal
Foundation (MAF) both regularly fund canine health research grants, as do a
number of single-breed clubs and health organizations. While single-breed
groups may not be able to gather sufficient funding on their own, they must get
involved. Who better knows the needs and concerns of a breed than those who
work with it and breed it? By teaming up with CHF or MAF or forming a coalition
with other like-minded groups even a small club can help fund important
research. With sufficient, energy, determination and cooperation, a club can do
it on its own.
The American Border Collie Association (ABCA), an organization of working
Border Collie owners and breeders, is largely responsible
for funding research into CEA at
We all have to start doing more to help bake the bread, both individually and
through our local and national clubs. The clubs must educate members about
genetic disease, encourage involvement in research and
the sharing of information with other breedersl. They
must also make monetary support of breed health research a regular item in
their budgets, not something done if and when the club might have some spare
change. National breed clubs should encourage members and regional clubs to
donate to MAF, CHF and breed health foundations.
Individual breeders, whether club members or not, also have responsibility for
seeing that the bred is baked, by compiling and sharing data on hereditary
disease in their dogs—with each other as well as with researchers—and by making
donations toward research a mandatory part of their personal budgets.
There are many Little Red Hens in the world of purebred dogs sewing, harvesting
and milling grain to bake the bread for genetic disease research. But they are
too few to see that all of our breeds get "fed." It's time the rest
of us stopped emulating the lazy animals in the Red Hen's barnyard, and pitched
in to help.
Copyright 2002 C. A. Sharp. All rights
reserved. C.A. Sharp
is editor of the "Double Helix Network News", the quarterly
newsletter for those interested in genetics and hereditary disease in the
Australian Shepherd.
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