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CHROMODANE PART I
To
understand this genetically transmitted disease,
we must first understand the workings of the normal canine hip. This is the first in a series of articles addressing canine hip
dysplasia. What follows is written from the perspective that the readers
of the series are conscientious breeders who are the guardians of the
genetic pools that constitute their breeds. While this series of
articles will not replace a stack of veterinary medical texts, it is a
relatively in-depth look at the whole problem of canine hip dysplasia.
Furthermore, the series is designed to be retained as a reference. When
you finish reading it you will have a sufficient background to make
rational breeding choices and will be able to discuss the subject from
an informed basis with your veterinarian. You may not like what you
read, but you will be more competent to deal with the problem.
Hip dysplasia is one of the most controversial and widespread problems
in the dog fancy. So many old-wives tales, anecdotes, misconceptions and
even lies abound that one of the goals of this series of articles must
be to lay things out to the reader as they are, supported with some
scientific basis.
Let's start with a hypothetical scenario, but one which too many of us
have faced:
He's major-pointed; he moves like a dream; that head piece may just be
the best you have ever bred. In short, this boy typifies everything that
is good about your breed and is the culmination of many years of hard
work, hopes, tears, frustration and all the ups and downs, joys and
heartaches common to the fancy. Now it is time to X-ray his hips so that
you can not only use him in your breeding program, but advertise him at
stud. This is one boy that is going to make it, and we are talking
national specialty here.
Problem - the radiographic results come back with a diagnosis of canine
hip dysplasia-severe. What should you do?
More among us than will admit have had this experience, and most of
those who haven't have seen it happen to other breeders concentrating on
similar bloodlines. Now back to our hypothetical scenario: You never
suspected a thing. The dog never appeared to be in pain and his gait was
what won him his major points. You have invested time, money and your
hopes on this animal, and it all has been for naught! Now is the time
for hysteria and self-blame: What went wrong? Could this
have been prevented? Was he not fed correctly? Was he kept
on an improper surface while growing? What is this disease that
keeps reappearing in the most conscientious of breeding programs, and
which frustrates our attempts to eradicate it?
The first step in understanding canine hip dysplasia is to recognize it
as not just one disease but many diseases, which together result in
degenerative effects on the hip joint. An extremely complex disorder,
hip dysplasia is now thought by some to be the most noticeable
manifestation of a systemic condition that can affect not only the hip
joints but also those of the elbow, shoulder and event the joints
between the vertebrae 1. Whatever else might result from the systemic
conditions of this polygenic and multifactorial disease, hip dysplasia
remains a common, usually painful and often debilitating disease.
"Efforts by dog breeders and veterinarians to reduce the prevalence
of the disorder have proven marginally effective."
While there is much that we do not know we do know that canine hip
dysplasia is a genetically transmitted disease. If you need to, or if
you disagree at this point, please re-read that statement. We will be
repeating it throughout this series of articles, and this concept is the
basis for determination of fitness for breeding. The genetic concept of
heritability is a complicating factor and is one reason why hip
dysplasia remains so controversial. So often when you breed you get more
than you see. Without resorting to too much math, heritability is equal
to the statistical variance due to genetic influence divided by the sum
of the statistical variance due to the genetic influence plus the
variance due to the environmental influence. It is easier to comprehend
the mathematical notation than the statement of the equation: H2 =
heritability index Vgenetics = variance due to genetics
Venvironment = variance due to environmental influences
Thus, heritability is defined as an estimate of how much environmental
factors play in the expression of the inherited genes. A high
heritability index means that environmental considerations are not as
important as genetic elements. The numerical value or heritability index
is a function not only of breed type but of the population from which
the data is extracted. "Studies of hip dysplasia genetics have
indicated that the disease is polygenic and multifactorial, with
estimates of heritability index in the range of 0.2 to 0.3"3
For instance, in a 1986 Swedish study, the heritability of hip dysplasia
in German Shepherds was 0.40 in Sweden, but only 0.25 in the British
Isles during the same time period. The difference between breeds may
also reflect their levels of inbreeding. The more inbreeding, the lower
the heritability index because inbreeding reduces the total genetic
variability-that is, the gene pool is smaller. Inbreeding is not a bad
word. It only becomes problematic when undesirable genetic traits are
concentrated within the gene pool. By definition, every purebred dog of
any given breed is highly inbred, or else it would look like a feral
dog. We frequently hear that the problem with the American Kennel Club
purebred dogs is that they are inbred. We should hope so, otherwise we
could never fix type to the point where there were discernible
differences between breeds. On the other hand, we would hope that the
concentrated gene pools for the various breeds would have been
concentrated from stock exhibiting only desirable genetic traits. We
would hope that our field, bench and obedience champions would be fit to
contribute to the gene pool. Of course, we know that is not true, or
there would be no purpose in writing this article. 4,5,6 (diagram
based on reprint from the Journal of the American Veterinary
Association, Vol.196, No.1,pp.59-70. "New concepts of coxofemoral
joint stability and the development of a clinical stress-radiographic
method for quantitating hip joint laxity in the dog," by Gail K.
Smith, V.M.D., Ph.D.; Darryl N. Biery, D.V.M.; and Thomas P. Gregor,
B.S.) To further complicate matters
is the fact that the pattern of inheritance indicates that more than one
gene is involved. Hip dysplasia is polygenic (involves many different
genes) and multifactorial (influenced by many non- genetic factors).
This makes sense when you think of the complexity of the various
structures involved. Every cell in the body, except for sex cells,
carries two copies of each gene and each gene codes for a specific
characteristic. One very simple example is eye color: If the
cell's two sets of genes for a specific characteristic are exactly
alike, then the animal is homozygous for that characteristic. If
the two genes are different, i.e., heterozygous, then one copy of the
genes could code for blue eyes and the other could code for brown eyes.
Let's complicate the matter even further. If the animal carries two
different copies of the same gene for eye color, only one copy can be
expressed in any given eye. Closer to home, in humans for example, a
child born to parents heterozygous for eye color (both parents have a
blue-eyed gene and brown-eyed gene) will have a one-in-four chance of
having blue eyes. This is because the gene for blue eyes is recessive
and both copies for that code for blue eyes must be present before that
characteristic can be expressed. On the other hand, if the child has
brown eyes, we don't know what type of genes for eye color he or she
has. This is because the gene for brown eyes is dominant and is able to
"mask" the physical expression of the blue-eyed gene.
Alternatively, the child could have only the genes that code for brown
eyes. It is beyond the scope of this article to address the various
"odd" eye color combinations, but co-dominance and variable
penetrance may be what we are dealing with in canine hip dysplasia.
What you have just read is an example of phenotype vs. Genotype.
Phenotype is the physical expression of a genetic characteristic.
Genotype is genetic composition of the organism. Using our eye-color
example, the child with two different copies of the gene will express
the brown-eyed phenotype, but his or her genotype will be heterozygous.
Let's add to the complexity once again. Co-dominance of genes is a
situation where neither gene is dominant. A clear example illustrating
the concept of genetic co-dominance is flower color. A snap dragon
homozygous (both copies of color genes exactly alike) for white petals
crossed with a snap dragon homozygous for red petals will produce a
flower with pink petals, not a flower with either white or red petals or
a mixture of red and white petals. Many researchers feel that hip
dysplasia may be a mixture of dominant, recessive and co-dominant genes.
Quite probably, this is one of the reasons why isolation of the
causative genetic factors of canine hip dysplasia has been so elusive.
The concepts that you need to be clear on as we leave this mini-course
on genetics are: heritability index; genetic and environmental
variability; dominant vs. Recessive genes; homozygous vs. heterozygous;
genetic co-dominance; and most importantly that hip dysplasia is
genetically inheritable and is polygenic and multifactorial. In short,
you can get it in your breeding program when you bred from animals that
did not show it.
Before we can discuss an abnormal process (disease), we need to first
understand the normal process. In this case, we must be able to answer
the question, "What is a normal hip, what makes it normal, and how
does it get that way?"
First, what is the hip? The hip joint is a main weight-bearing joint
consisting principally of a ball and socket. This joint connects the
pelvis to the lower extremities. The ball is on the end of the femur
(thigh bone) and the socket (acetabulum) is part of the pelvis. Note
from figure 1 how the femoral head fits into the acetabulum in the
normal hip joint. This will be key to all our discussions from this
point forth. A true ball-and-socket joint has three degrees of freedom,
that is, it supports rotation about three different axes. The canine hip
joint is unusual as a ball-and-socket joint in that it has a fourth
degree of freedom. The femoral head may be displaced laterally from the
acetabulum. While this is the genius of this joint, allowing the
attached appendage a full range of motion, it can also create a problem
if there becomes too much laxity in the joint. Note the fourth degree of
freedom in Figure 2, which provides for the femoral head (ball) to move
directly away from the acetabulum (socket). From Figures 1 and 2, it
should be obvious that much lateral displacement of the femoral head
from its seat in the acetabulum will produce high joint stresses during
weight bearing. This joint laxity will be a major consideration for the
changes it causes in the joint mechanics as we progress through this
series of articles.
The acetabulum is formed from the embryonic process of fusion of the
ilium (top of the hip), the ischium (lowest part of the hip) and the
pubis (below the ilium but above the pubis) and the acetabular bone.
Most researchers feel that normal development requires close conformity
(close, tight fit) between the acetabulum and the femoral head
throughout their growth period. In other words, the joint must fit
tightly, deeply and snugly. This is how a puppy's hip starts out-dysplastic
and non-dysplastic puppies' hips are indistinguishable. The first six
months of life seem to be the most critical growth period when the depth
of the socket must be maintained. It is believed that the depth of the
socket in the growing puppy may be in part a function of the amount of
stress the femoral head can produce on the immature acetabulum. Think of
it as a thumb pushing into a ball of clay. The harder the thumb pushes,
the deeper the indentation in the clay. Much as a knife edge
concentrates force onto a relatively small surafce area (and a pin of a
diameter equal to the width of the knife edge even more), the two
phenotypic traits that maximize the forces between these two developing
bony structures are a small femoral head and a long femoral neck. Note,
however, that the normal acetabulum is well-formed in utero, thus the
stress may only serve to maintain that socket depth.
To cushion the force between these two bony surfaces, there is a truly
remarkable substance called articular cartilage. This cartilage is
similar to a hard sponge with a slick hard surface facing the interior
of the joint. In the normal joint, articular cartilage is able to change
its shape slightly when force is applied to it, thus spreading and
distributing force more evenly into the subchrondal bone directly
beneath the articular cartilage. This is of major importance to the
long-term integrity of the joint.
Holding everything in place is another structure that does more than
just enhance the stability of the joint. The joint capsule is a fibrous
structure filled with synovial fluid that surrounds, isolates and
protects the joint. This joint capsule is essential to proper
development and functioning of the joint. This structure is similar to
the rubber grease bladder around a ball joint in the front suspension of
your car. The cushioning effect of the grease with the fluid pressure of
the grease and the elasticity of the bladder helps to stabilize the
joint. The bladder helps keep out contaminants. This function becomes
even more important as the joint ages and surfaces become worn. The
joint capsule contains the all-important synovial fluid, the most
important ingredients of which are nutrients, which diffuse into the
joint from the blood supply, and hyaluronic acid (HA). The tissues
within the joint extract nutrients from the synovial fluid in which they
are bathed.
Hyaluronic acid has a critical function: to provide lubrication. This
slippery and viscous substance prevents rapid erosion of the articular
cartilage and the surfaces of the femoral head and the acetabulum. A
membrane called the synovial membrane lines the inside of the joint
capsule, providing further isolation of the joint space. Should the
synovial membrane become injured or ruptured, white blood cells release
enzymes and oxygen radials (free radicals) that attack and destroy
hyaluronic acid. When this occurs, the loss of HA reduces the
lubrication that prevents friction and limits erosion of the articular
cartilage. Even worse, loss of HA allows the enzymes from white blood
cells to join forces with oxygen free radicals and attack the articular
cartilage. Free radicals play a major role in degenerative arthritis.
The ball-and-socket (coxofemoral) joints of an affected puppy
radiographically appear to be structurally and functionally normal at
birth. The hips of an affected puppy are indistinguishable from a normal
puppy at birth. This is an important point to remember. As an affected
puppy grows, the hip joint undergoes severe structural alterations. The
changes result from joint laxity and adulteration/destruction of the
constituents of the synovial fluid and subsequent loss of lubrication
and nourishment, which serve to reduce the regenerative and elastic
(force-absorbing and distributing) properties of the articular
cartilage. The normal joint retains its tightness and close fit. Whereas
in the genetically dysplastic-to-be puppy, the acetabular rim and
femoral head become eroded.
Remember that the acetabular depth is partially a function of the small
"footprint" of the femoral head which concentrates force into
a small surface area. As the femoral head is flattened, the coxofemoral
joint no longer fits snugly. Excessive force is applied unevenly,
especially at the edges of the flattened femoral head. Visualize this
joint looseness as the difference between the impact of a boxer's fist
when the punch is thrown with the glove already in contact with the
opponent's jaw as contrasted with an initial stand-off distance of say
20 inches. In the first case, little impact force is transmitted and no
damage is done; in the second, there may be a knock-out. In the joint,
the increase in stress results not only in abnormal wear of the
articular cartilage, but causes tiny micro-stress fractures to appear in
the subchondral bone. The body attempts to heal these fissures, causing
the acetabulum to become filled in, i.e., made shallower. It is this
cycle of damage and repair (osteophyte formation) that leads to
deformation of the joint, and degenerative hip disease.
Conclusions: Hip dysplasia is not something a dog acquires; a dog either
is genetically dysplastic or it is not. Initially, the hips of affected
and normal puppies are indistinguishable. Later in life, an affected
animal can exhibit a wide range of phenotypes, all the way from normal
to severely dysplastic and functionally crippled. You should take away
from this article the idea that hip dysplasia is genetically inherited.
Never believe a fellow breeder or fancier who claims there is no hip
dysplasia in his or her line. Never believe breeders who claim that if
their breeding lines carried the genes for hip dysplasia they would be
able to see it in their animals' gaits. This just is not true.
Although work has been started to find the genetic markers for the
disease, we have as yet no method of genetic analysis that can tell
breeders whether their dogs are dysplastic or not. We only have physical
expression of the disease, and an effort to "back door" into
clear stock for breeding purposes. Breeders must come to understand that
the only way to reduce the incidence of hip dysplasia is by trying to
breed from as few animals that have progenitors, siblings, get, or get
of siblings that had clinical manifestations of hip dysplasia.
Obviously, a great amount of information is lacking to make a rational
breeding choice. These are hard words to have read, but much of our
problem has come from thousands of years of less than natural selection
resulting from the domestication of the dog.
In our second article in this series we will address in greater detail
the parts nutritional, environmental and other factors play in
mitigating or increasing the physical expression of canine hip dysplasia. Thank
you to Daphne Black who sent an article about Unilateral Hip Dysplasia, which led to this detailed article.
See this site about Unilateral
Hip Dysplasia
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