|
Degenerative Myelopathy Testing
A reprint from
www.caninegeneticdiseases.net/DM/DMtest.htm
A DNA Test for DM
The collaborative efforts of Dr
Joan Coates and Dr Gary Johnson and associates at
the University of Missouri and Dr Kirsten
Lindblad-Toh and Dr Claire Wade and associates at
the Broad Institute at MIT/Harvard have resulted in
identification of a mutation that is a responsible
for the development of Degenerative Myelopathy in
many breeds of dogs.
The DNA test for DM is now
available from OFA, and also DDC Veterinary. This test clearly identifies
dogs that are normal (have 2 normal copies of the
gene), those who are carriers (have one normal copy
of the gene and one mutated copy of the gene), and
those who are at much higher risk for developing DM
(have 2 mutated copies of the gene - designated
affected/at risk). The age of onset of symptoms can
vary from 6 to 15 years of age or older, and some
dogs who are genetically at risk for DM will die
from other causes before any DM symptoms appear.
Factors that may influence the age of onset of
symptoms are the topic of current research - at this
time we cannot predict which of the genetically at
risk dogs will have an early appearance of clinical
signs, and which will have a delayed onset.
A
relatively high percentage of dogs in several breeds
have the predisposing mutation. With the testing
done thus far (thru February 2011), the frequency of
the mutation is over 70% in Boxers, Pembroke Welsh
Corgis, and Wire Fox Terriers. There are another 10
breeds where the mutation frequency is over 40%. For
breeds with a high frequency of the DM mutation, it
will take wise use of the test and several
generations to maintain a healthy and diverse gene
pool while reducing the prevalence of DM. It is
important for breeders and owners to keep in mind
all the traits present in an individual dog, and not
to simply breed a test result. We encourage breeders
to DNA test potential breeding stock and consider
the results of the DM test as part of their
evaluation and decision-making process.
A reprint from
www.caninegeneticdiseases.net/DM/DMtest.htm
Understanding the
DNA Test for Degenerative Myelopathy
We
have discovered a mutation in a gene which is
associated with development of degenerative
myelopathy (DM). In that gene, the
DNA occurs in two possible forms (or alleles). The
“G” allele is the predominant form in dogs that
seldom or never develop DM; you can think of it as
the “Good” allele. The “A” allele
is more frequent in dogs exhibiting clinical signs
of DM; you can think of it as the “Affected”
allele.
Summary: “A” allele is
associated with DM; “G” allele is not associated
with DM.
Since an individual dog inherits
two alleles (one from the sire and one from the dam)
there are three possible test results: two “A”
alleles; one “A” and one “G”
allele; and, two “G” alleles.
Summary: Test results can be
A/A (affected/at risk), A/G (carrier), or G/G
(normal) .
Microscopic examination of a
section of spinal cord (following euthanasia) is the
"gold standard" for diagnosing and confirming DM. We
do not have the opportunity to examine cord samples
from all the dogs that have died or been euthanized
due to DM, but for those cords submitted for
evaluation, and where the cellular changes have been
consistent with a diagnosis of DM, the dogs have had
a DNA test result of A/A in all but
2 individuals. There is additional work being done
to better understand these 2 exceptions, but it is
clear that the vast majority of real DM cases do
have the A/A test result.
Summary: Dogs that test A/G or G/G are very unlikely
to develop DM. Dogs that test A/A are likely to
develop clinical signs of DM at some point as they
age. Additional research now in
progress is focused on understanding why some A/A
dogs show clinical signs of DM at 7 or 8 years of
age while others only begin to show clinical signs
at 14 or 15yrs or older, or may die from some other
cause without developing recognized clinical signs
of DM.
The
“A” allele is very common in some breeds. In these
breeds, an overly aggressive breeding program to
eliminate the dogs testing A/A or A/G might be
destructive to the breed as a whole
because it would eliminate a large fraction of the
high quality dogs that would otherwise contribute
desirable qualities to the breed. Nonetheless, DM
should be taken seriously. It is a fatal disease
with devastating consequences for the dogs and a
very unpleasant experience for the owners who care
for them. Thus, a realistic approach when
considering which dogs to select for breeding would
be to consider dogs with the A/A or
A/G test result to have a fault,
just as a poor top-line or imperfect gait would be
considered faults. Dogs that test A/A
should be considered to have a worse fault than
those that test A/G. Dog breeders
could then continue to do what conscientious
breeders have always done: make their selections for
breeding stock in light of all of the dogs’ good
points and all of the dogs’ faults. Using this
approach over many generations should substantially
reduce the prevalence of DM while continuing to
maintain or improve those qualities that have
contributed to the various dog breeds.
Summary: We recommend that dog
breeders take into consideration the DM test results
as they plan their breeding programs; however,breeders
should not over-emphasize this test result.
Instead, the test result
is one factor among
many in a balanced
breeding program.
Additional Information on DM,
Description of Clinical signs, and cell
description
in photos
Degenerative Myelopathy, Disease Basics
DM Research
Schraderhaus K9
|
