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I decided to set
up this page in an effort to share with you my understanding of
what the current DNA test for Copper Toxicosis (CT) is all about,
and what it means.
Early in 1996 we
and many other breeders around the world began submitting samples
to various laboratories for DNA testing for CT in Bedlingtons.
Since then, there
has been much confusion in that many times the DNA results were
not supported by the liver biopsy results which have always been
the more definitive test. Now, the various laboratories have changed
protocols, and will not venture so far as to even call a dog affected,
carrier or non-carrier. What breeders get now are merely numbers
representing the alleles found using the microsatellite marker C04107.
It is important
to remember at this point that the actual gene has not been identified.
This is merely a linkage test, the value of which depends on the
breeder finding a link in their pedigrees to an affected dog.
Chart of inheritance:
| Sire |
Dam |
Puppies |
| 1-1 |
1-1 |
All 1-1 |
| 1-1 |
1-2 |
1-1 and 1-2 |
| 1-1 |
2-2 |
All 1-2 |
| 1-2 |
1-1 |
1-1 and 1-2 |
| 1-2 |
1-2 |
1-1, 1-2 and 2-2 |
| 1-2 |
2-2 |
1-2 and 2-2 |
| 2-2 |
1-1 |
All 1-2 |
| 2-2 |
1-2 |
1-2 and 2-2 |
| 2-2 |
2-2 |
All 2-2 |
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The above illustrates
what should happen in breedings when the allele numbers of the parents
are known. To make any sense of these numbers, the breeder must
find out what the 1's and 2's mean in his or her individual bloodline.
It is not correct to automatically assume that a 1-1 dog is a non-carrier
(commonly called clear) and a 2-2 dog is affected. There have been
enough cases of the opposite to prove this.
Following are some
examples of how to find the link in a pedigree (these are actual
cases).
| Case 1:
Puppy in question has a DNA result of 1-1
Sire: DNA 1-2 and was biopsied unaffected
Dam: DNA 1-2 and was biopsied unaffected
At one year of age, the puppy was biopsied and found
to be affected. Therefore we can assume that the
"1" from both the sire and the dam are the so-called
"bad" genes. Because both the sire and dam had biopsied
normal, that meant their "2" had to be good.
Therefore, any puppy that was DNA 1-2 from this
breeding would be a carrier (bad "1" and good "2") and
any puppy that would DNA 2-2 would be clear (non-carrier)
as both 2's would be good. |
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| Case 2:
Puppy in question has a DNA result of 2-2
Sire: DNA 2-2 and was biopsied unaffected
Dam: DNA 2-2 and was biopsied unaffected
At one year of age the entire litter of five puppies
(all DNA 2-2) were biopsied unaffected except for one
puppy. Since there was an affected puppy, we know
that both parents are carriers, yet we cannot tell which
is the bad and which is the good gene. They are both
identified as "2". We should also note here that
two carriers bred together can produce affected, carrier
and non-carrier puppies! That means that of the four
unaffected puppies in this litter, some may be carriers
and some may be non-carriers (clear). |
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To illustrate further,
let's suppose you bred the two puppies from the above cases together,
(this is only hypothetical):
| Parent 1: DNA 1-1 biopsied affected
Parent 2: DNA 2-2 biopsied unaffected
Offspring: All puppies will have a DNA result of
1-2. We already know from our above cases that the
"1" would be bad as that parent biopsied affected.
We also know that either one or both "2"s from
Parent 2 are good since that dog biopsied unaffected.
For the resulting puppies then, the unfortunate ones
that inherited the bad "2" will be affected and
the fortunate ones that inherit the good "2"
will be unaffected, but carriers.
In either case all the puppies will have the same
DNA result ... that being 1-2. The only way to tell
then if any are affected is through the liver biopsy.
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In many bloodlines
and in many countries, breeders have managed to find links in pedigrees
and what has been found is that, usually, the allele number "1"
is linked to the "good" gene and the "2" is linked to the "bad"
gene.
We wish to stress
however, that this is not always the case. Every bloodline can be
different. It is no good to assume that a 1-1 dog is a non-carrier
or a 1-2 dog is a carrier or a 2-2 dog is affected simply because
of the numbers. A link must be found in the pedigree in order for
it all to make any sense.
To further the point.
There is an actual stud dog that has a DNA result of 1-2 and was
test bred and proven to be a non-carrier (clear). That means he
is producing offspring with good "1"s AND "2"s.
One last point ...
please remember, that according to the laboratories, even if a link
can be found in your pedigrees, it is only 95% certain. They
still recommend that breeders continue to liver biopsy all dogs.
This is only our
understanding of the current DNA testing protocol for CT in Bedlingtons.
We still continue to use the DNA test as we believe it has some
value, yet we also continue to have a biopsy performed on all our
dogs as we also believe in being safe. The results from both tests
used in tandem can many times give encouraging results.
Please take this
information in the spirit it is being provided. This is not meant
to accuse anyone of anything, merely to provide what we hope is
useful information.
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