Genetic Testing For Inherited Polyneuropathy In Leonbergers

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I am sure this is not the right place for this but do not know where to put it, please fell free to move.

The Test results interpretation is a very interesting read.

Genetic Testing for Inherited Polyneuropathy in Leonbergers

Brief Disease summary

http://www.cvm.umn.edu/vbs/prod/groups/cvm...news_211819.pdf

LPN1 Genetic Test Result Interpretation

Clear: Your dog is clear of the LPN1 gene mutation. This means that your dog has two copies of the normal gene

(this is also referred to as being homozygous normal). However, this result does not rule out the possibility that your

dog could have, or be a carrier for, a different polyneuropathy mutation that this test cannot detect.

At Risk: Your dog has one copy of the normal form of the gene and one copy of the mutated form of the LPN1 gene

(this is also referred to as being heterozygous). Our research indicates approximately 50% of dogs with one copy of

the LPN1 gene develop clinical signs of LPN, but whether it is due to this single copy of the LPN1 gene itself, or is

a different form of neurological disease entirely, is not yet known. The average age that owners first notice clinical

signs in these at risk dogs, if they develop at all, is 6 years. Additionally, these dogs typically have much milder

clinical signs than dogs with two copies of the LPN1 mutation. Having one copy of the mutated form of the LPN1

gene does not rule out the possibility that a dog may have younger onset of a different polyneuropathy caused by a

mutation not detected by this test. LPN1 at risk dogs will, on average, pass the LPN1 gene mutation on to half of

their offspring.

Affected: Your dog has two copies of the LPN1 gene mutation (this is also referred to as being homozygous

affected). Affected dogs typically develop neurological disease at or before 3 years of age, and clinical signs tend to

be more severe than those observed in at risk (heterozygous) dogs. Affected dogs will pass one copy of this

mutation on to all of their offspring.

Further Information

We are testing for a specific DNA segment deletion in a specific gene; therefore this can be referred to as a gene

mutation test. This situation is different from other types of genetic tests that describe only the identification of a

DNA marker that could be very far away from the true disease gene, and not be as highly predictive as desired.

We have designated the letter D to indicate the mutant (LPN1) form of the gene and N to indicate the normal form

of the gene. A dog's particular combination of N or D forms of the gene is known as its genotype. The genotype of a

normal dog is designated as N/N and is clear of the mutation. N/N dogs do not have LPN1, however, some do

develop neuropathy with similar clinical and histopathological signs due to other as-yet-unidentified mutations.

Dogs with the D/D genotype are affected with LPN1. All dogs with the D/D genotype to date have developed

clinical signs of neurologic disease, typically by 3 years of age or younger. Dogs with the D/N genotype are

currently considered at risk. At present, approximately 50% of dogs with the D/N genotype develop signs of

neurologic disease and the average age that clinical signs are first noted is 6 years. However, D/N dogs typically

present with less severe clinical signs than D/D dogs.

Due to other causes of neuropathy in Leonbergers, the exact mode of inheritance of the LPN1 form of neuropathy

cannot yet be stated for certain. For example, it is possible that LPN1 is dominantly inherited, with a dose-

dependent nature to the disease (more copies = worse disease). However, it also possible that LPN1 is recessive,

and that only D/D dogs have this form of neuropathy, while D/N and N/N dogs with clinical signs have another form

of neuropathy.

With either inheritance model, producing a puppy with severe, early-onset LPN caused by the mutant LPN1 gene

would require that both parents be either at risk (D/N) or affected (D/D). Given all the above considerations, our

best estimates of the chance of any given puppy with severe, early-onset LPN1 (i.e., with the D/D genotype) being

born from a litter produced by parents of all possible genotypes is indicated in the following table.

Chance of a severe, early-onset affected (D/D) puppy being born

from parents of known genotypes

Sires genotype

N/N D/N D/D

Dams genotype

N/N 0% 0% 0%

D/N 0% 25% 50%

D/D 0% 50% 100%

Chance of an at risk (D/N) puppy being born

from parents of known genotypes

Sires genotype

N/N D/N D/D

Dams genotype

N/N 0% 50% 100%

D/N 50% 50% 50%

D/D 100% 50% 0%

Matings indicated in red will produce D/D puppies, and are not recommended.

Another way of understanding the implications of the LPN1 results on breeding is that breeding a D/N sire to an

N/N dam can only produce puppies that are D/N or N/N. On the other hand, breeding a D/N sire to an D/D dam

gives a 50% chance that a puppy will have severe, early-onset LPN1, since puppies will be either D/N or D/D. All

puppies from the mating of two D/D parents will be D/D, and thus susceptible to the severe, early-onset form of

LPN1.

We do not recommend selecting dogs for breeding based solely on their being N/N for the LPN1 gene.

Such a drastic strategy, although more quickly eliminating the possibility of producing D/D and D/N dogs, also has

the undesired result of potentially constricting an already small breeding pool. This may result in the loss of some of

the outstanding traits expected of superior lines of Leonbergers. Immediate removal of all D/N dogs could also lead

to an increase in other deleterious traits or diseases. A breeding program that utilizes D/N dogs can be logically

implemented by mating to N/N dogs and retaining N/N puppies with most or all of the other highly desired

characteristics for future breeding. D/N puppies could also be retained for breeding if they possessed other

exceptional qualities and were mated with only N/N dogs. Long term, the ideal goal would be to minimize

production of any D/N dogs in each successive generation. There is no chance of producing a D/D puppy if it is

known that at least one of the parents is N/N.

It is important to remember that this LPN1 test is diagnostic for only one of possibly several genetic risk factors for

polyneuropathy. Thus, it is still possible that affected offspring with a different genetic form of polyneuropathy

could occur, even from a mating of two dogs that both have been tested N/N for the LPN1 mutation. To that end,

we also recommend that both dogs in a breeding pair be free of any signs of neurological disease, regardless of

genotype, because this test can only detect one polyneuropathy mutation.

Outlook and Treatment

Coming soon.

For additional information please refer to the following website:

www.vdl.umn.edu/vdl/ourservices/canineneuromuscular

**We encourage all owners to share their dogs test result with their breeder, as well as submitting them to the

Leonberger Health Foundation LPN1 database.