DCM in the
July 8, 2002 This is the third installment
in a series about dilated cardiomyopathy (DCM) in the Great Dane.
If you have not already done so, please take a look at installment
#1 and installment #2 for additional
Dr. Meurs's preliminary data, which strongly
suggests DCM in the Great Dane is an inherited X-linked recessive
trait, is hard to ignore. But what exactly is an X-linked recessive
trait? If you think back to your high school biology class, you'll
recall (hopefully) that females have two X chromosomes and males have
one X chromosome and one Y chromosome. At the time of conception,
the female provides one of her X chromosomes, and the male provides
either an X or Y chromosome. If the father gives an X, the offspring
will be female. If he gives a Y, the offspring will be male.
dilated cardiomyopathy an inherited disease?
Last week we covered some of the basics about dilated cardiomyopathy
(DCM) in general and how it relates to the Great Dane in
particular. Unfortunately Great Danes are the second most common
breed of dog to suffer from DCM. We're lucky in one respect, though.
Kathryn M. Meurs, a professor of cardiovascular medicine at
Ohio State's College of Veterinary Medicine, has been working in
recent years to identify the clinical features of DCM in the Great
Dane, to determine whether DCM is inherited in the breed, and if
it is inherited, to determine how it is transmitted from parent
to offspring. Dr. Meurs is also striving to identify a "marker
gene" that can be used to develop a blood test to screen for
DCM. Meurs's research has received substantial funding from the
AKC's Canine Health Foundation and support from the Great Dane Health
Foundation of America (GDHFA) and the Great Dane Club of America
In a recent paper that appeared in the Journal of the American Veterinary
Medical Association (JAVMA
2001; 218: 729732; Meurs, Miller, Wright) Dr. Meurs describes
a retrospective study in which pedigrees of Great Danes with confirmed
DCM "were assembled and examined for evidence of a specific
mode of inheritance." Systematic evaluation of pedigrees from
affected Great Danes suggested a strong family tendency. Various
modes of inheritance were considered in the context of the pedigrees.
An X-linked recessive mode of inheritance was determined to be the
most likely. Further work is underway to definitively identify the
mode of inheritance.**
What is X-linked recessive?
The sex chromosomes aren't the only pair of chromosomes that
make up a being. Humans have 23 pairs of chromosomes; dogs have 39.
Chromosomes carry genes, the principle unit of inheritance for individual
traits (for example, blood type). Each gene produces a product that
can influence the individual's appearance (for example, eye color)
or bodily function (for example, ability to digest food). Genes are
described both in terms of being present (carried) in an individual
and in terms of having influence (manifesting) in an individual.
chromosomes come in pairs, genes for each trait are found in pairs,
one coming from the mother and one from the father (genes on sex chromosomes
are exceptions, as you will see below). For many traits, there are
many possible versions of its gene. Often, one version of a gene will
be silent when paired with any other version. A gene version of this
type is called a "recessive gene" because it will only influence
what the individual is like if it is not paired with a more powerful,
or "dominant," version. For non-sex chromosomes, that means
the recessive gene must exist on both chromosomes in the pair in order
to manifest itself.
In the case of the sex chromosomes, however, the single X-linked (X-chromosome
linked) recessive gene will manifest itself in males because it is
"unopposed" by anything on the Y chromosome. This means
if a male offspring inherits an X-linked recessive gene from his mother
he will manifest that gene's influence. A good example of this in
humans is hemophilia. It is extremely rare for a woman to have the
recessive gene on both of her X chromosomes, but in affected families
she may carry the recessive hemophilia gene on one X chromosome. For
such a woman with a non-hemophiliac mate, her daughters have a 50%
chance of being hemophilia carriers like herself and 50% of her sons
will be hemophiliacs.
|Here's the bottom line on
the behavior of the X-linked recessive gene:
The trait will be manifested in any males who inherit the X-recessive
gene from their mother. (Their father has nothing to do with
it.) The trait will be manifested in females ONLY if they have
two copies of the X-recessive gene, one coming from their mother,
the other from their father. If females inherit one just copy
of the X-recessive gene, they will not develop the trait, but
they will be carriers.
Bringing this back to DCM,
Dr. Meurs's data suggests DCM is a recessive X-linked version
of an important gene related to the Great Dane heart. If this
is true, that means:
How might we predict DCM in our
Can you be certain that a given percentage of all pups from a carrier
female will inherit her DCM gene? No, and here is why. Inheritance
is like flipping a coin. If you only flip the coin once, then heads
or tails will occur 100% of the time. If you flip the coin twice,
you could easily get heads twice or tails twice, even though they
each have a 50% chance of turning up each time. It is only by flipping
the coin many times that you start to see the 50:50 odds
(Try the coin flip, if you can't picture this). This illustrates
why in some pedigrees DCM may appear more or less
than predicted, because Danes generally do not have large numbers
of pups. Only by studying many generations of related Danes can
the pattern be detected.
In addition, there are bound to be other influences on the DCM gene
besides its dominant counterparts, influences that can soften the
symptoms or make them worse. That is why all Danes with the symptoms
of DCM are not equally sick and do not die at the same age. These
influences could be completely separate genes, elements in the dog's
environment, and/or other factors. We are only beginning to understand
what causes DCM in Great Danes and much additional research will
have to be done to fill in the picture.
That said, you may use the charts below
as a general guide to what might be expected to occur in a breeding.
Keep in mind that in any single litter, it's unlikely the numbers
would exactly match these percentages. In a large sampling involving
multiple litters, however, the numbers would be much closer.
In a breeding, if the sire is positive for DCM and the dam
is positive for DCM, statistically here's what should happen:
100% of the puppies would be affected and at high risk for
Some additional information and comments:
- Remember that X-linked recessive
traits are overwhelmingly manifested in the male population (meaning
many more males are affected), yet it is the female chromosome
which provides the inherited defective gene.
- According to Dr. Meurs, DCM in
the Great Dane can develop from age 1 to age 10 (or older). For
breeding stock, or dogs at risk, she recommends screening with
echocardiography (ultrasound) every year. Early detection
and drug treatment may slow the progression of the disease.
- When/if abnormalities are observed
on an echocardiogram, Dr. Meurs recommends those dogs with suspect
findings be held out from a breeding program for 6 months to a
year. They should then be retested. If still abnormal, you may
want to avoid using them for breeding.
- Dr. Meurs emphasizes that the perfect
screening test does not exist. She would like to develop a noninvasive
diagnostic test to identify DCM at an early stage before a dog
is used for breeding. Her ultimate goal is to develop a genetic
test for DCM. She can't do this alone. She needs the support
of the Dane community.
- A brief Cardiomyopathy
Questionnaire by Dr. Meurs is available through the Great
Dane Health Foundation's website. You are invited to contribute
to the ongoing DCM study by filling out the survey and mailing
it directly to Dr. Meurs. Information gathered from the questionnaire
will be kept strictly confidential.
If you'd like to get more involved, Dr. Meurs is interested in
recruiting Great Danes from families with a history of DCM. She
states, "We particularly need to evaluate affected dogs as
well as their family members. Additionally, we are in great need
of healthy Great Danes that are at least 7 years of age who could
come to Ohio State for an echocardiogram and who would be willing
to donate a small blood sample. These animals will serve as 'healthy
controls' and their DNA will be compared to the DNA from the affected
Dr. Meurs can be reached at firstname.lastname@example.org
if you would like to inquire about participating. (I believe all
work-ups performed on Danes for this study are free of charge.)
- JP Yousha, chair of the Great Dane
Club of America's Health and Welfare Committee, has written an
informative article on the subject of heart disease in the Great
Dane. She provides information about various congenital heart
defects, discusses DCM, and elaborates on Dr. Meurs' research.
can be found on JP's website.
- Dr. Meurs will be speaking at the
Great Dane Club of America's 2002
National Specialty in Kentucky this October. She will
discuss DCM in the Great Dane, and provide us with an update on
her current work. Everyone is invited to attend.
Next week we'll hear from one breeder who has come forward to talk
candidly about her personal experiences with DCM. If you would like
to share your own comments, stories and/or insights, please drop
me a line.
Installment #1 || Installment
#2 || Next Installment >>
* Video tapes of the lecture "Dilated Cardiomyopathy
in the Great Dane," which was presented by Dr. Meurs
at the 2001 GDCA National Specialty, are now available. Please
contact Susan Hoke for
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