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LABOKLIN (UK)| Genetic Diseases | Dogs| German Shepherd KC DNA bundle (DM Exon2+F8+MDR1)
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new test:      Paradoxical Pseudomyotonia (PP) in English Cocker and English Springer Spaniels  
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German Shepherd KC DNA bundle (DM Exon2+F8+MDR1)

Test number: 8708

Price: £ 138.00 (including VAT) for all 3 tests

  1 ) Degenerative Myelopathy / Degenerative Radiculomyelopathy) DM (Exon 2) / SOD1

Breeds
Airedale Terrier , Alaskan Malamute , All Dog Breeds , American Eskimo , Bernese Mountain Dog , Bloodhound , Borzoi (Russian Wolfhound) , Boxer , Cavalier King Charles Spaniel , Canaan Dog , Welsh Corgi (Cardigan) , Chesapeake Bay Retriever , Cockapoo (English) , Cockapoo (American) , Fox Terrier , French Bull Dog , German Shepherd , Glen Of Imaal Terrier ( GIT ) , Golden Retriever , Goldendoodle , Pyrenean Mountain Dog (Great Pyrenees) , Hovawart , Pumi ( Hungarian Pumi / Pumik ) , Jack Russell Terrier , Kerry Blue Terrier , Labradoodle , Labrador Retriever , Lakeland Terrier , Northern Inuit (Tamaskan / British Timber Dog) , Nova Scotia Duck tolling Retriever ( NSDTR / Toller) , Pembroke Welsh Corgi , Poodle , Pug , Rhodesian Ridgeback , Rough Collie , Soft Coated Wheaten Terrier , Shetland Sheepdog (Sheltie) , Smooth Collie , Utonagan , Wire Fox Terrier .
Kennel Club
This test is part of the Official UK Kennel Club DNA Testing Scheme in Chesapeake Bay Retriever, French Bull Dog, German Shepherd, Nova Scotia Duck tolling Retriever ( NSDTR / Toller), Rough Collie, and Smooth Collie.

for UK registered dogs, Laboklin can send results of the tests which are part of the Official UK Kennel Club DNA testing scheme to the Kennel Club (KC) to be recorded and published as part of the Kennel Club scheme. Results will only be recorded and published by the KC if the result report includes the dog’s microchip or tattoo number along with either the dog’s registered name or registered number. Any test results that do not carry these identifying features will not be recorded by the Kennel Club.

In order to ensure that test results are sent to the Kennel Club, customers must also sign the declaration section on the order form to give Laboklin permission to do so.

important: When you sign the declaration, Laboklin will send the results to the KC on your behalf, and you do not need to send them to the KC yourself again to avoid unnecessary duplications.

The Disease
Canine degenerative myelopathy (also known as chronic degenerative radiculomyelopathy) is a progressive disease of the spinal cord in older dogs. The disease has an insidious onset typically between 7 and 14 years of age. It begins with a loss of coordination (ataxia) in the hind limbs. As of July 15, 2008 the mutated gene responsible for DM has been found present in 43 breeds including German Shepherds, Boxers, Chesapeake Bay Retrievers, Rhodesian Ridgebacks, and both breeds of Welsh Corgis. The disease is chronic and progressive, and resulting in paralysis.
Clinical Signs
Degenerative myelopathy initially affects the back legs and causes muscle weakness and loss, and lack of coordination. These cause a staggering effect that may appear to be arthritis. The dog may drag one or both rear paws when it walks. This dragging can cause the nails of one foot to be worn down. The condition may lead to extensive paralysis of the back legs. As the disease progresses, the animal may display symptoms such as incontinence and has considerable difficulties with both balance and walking. If allowed to progress, the animal will show front limb involvement and extensive muscle atrophy. Eventually cranial nerve or respiratory muscle involvement necessitates euthanasia. Progression of the disease is generally slow but highly variable. The animal could be crippled within a few months, or may survive up to three years
Trait of Inheritance
Tow alleles are invloved in Degenerative Myelopathy, A and G, therefore a test result can be A/A, A/G, or G/G.

Mode of inheritance is autosomal recessive with variable penetrance;

Inheritance : AUTOSOMAL RECESSIVE trait


 

Sire

 

Dam

 

Offspring

         
clear
clear
100% clear
         
clear
carrier
50%  clear + 50% carriers
         
clear
affected
100% carriers
         
carrier
clear
50%  clear + 50% carriers
         
carrier
carrier
25% clear + 25% affected + 50% carriers
         
carrier
affected
50% carriers + 50% affected
         
affected
clear
100%  carriers
         
affected
carrier
50% carriers + 50% affected
         
affected
affected
100% affected

 


Clear

Genotype: N / N [ Homozygous normal ]

The dog is noncarrier of the mutant gene.

It is very unlikely that the dog will show signs of the Degenerative Myelopathy

 

Carrier

Genotype: N / DM (Exon 2) [ Heterozygous ]

The dog carries one copy of the mutant gene and one copy of the normal gene.

It is very unlikely that the dog will show signs of the Degenerative Myelopathy

 

Affected

Genotype: DM (Exon 2) / DM (Exon 2) [ Homozygous mutant ]

 

The dog carries two copies of the mutant gene and therefore it will pass the mutant gene to its entire offspring.

The dog may or may not show signs of the disease
Description

SOD1-Gene

Please note that Exon 2 can be found in all dog breeds, there is another DM mutation in Exon 1 which can only be found in Bernese Mountain Dog, click here for more information.

For bernese Mountain Dog we have a special offer for both Exon 1 and Exon 2 at reduced price, click here for more details.

Sample Requirements
Buccal Swabs or 0.5 - 1 ml blood in EDTA Blood Tube
Turnaround
1 - 2 weeks

  2 ) Haemophilia A (factor VIII deficiency / F8)

Breeds
Boxer , German Shepherd , Labrador Retriever , Old English Sheepdog (Bobtail) , Rhodesian Ridgeback .
The Disease
Haemophilia A is one of the most important inherited disorders of haemostasis in Havanese Dogs. The underlying pathomechanism of Haemophilia A is a lack or decreased activity of factor VIII that plays a critical role in the coagulation cascade. Affected dogs present with hemorrhage that can vary from mild to severe depending on the degree of the disease. The clinical signs include haematomas of large sizes, bleeding of the nose, skin, muscles and joints. If the disease is severe and no precautions are taken, affected dogs can bleed to death after surgery or injury. In cooperation with Prof. Dr. Mischke (Tierärztliche Hochschule Hannover) LABOKLIN was able to identify a SINE insert in exon 14 of the factor VIII gene that is responsible for the lack of active factor VIII protein in Havanese Dogs.
Haemophilia A is a sex-linked disorder (x-chromosomal recessive). Male dogs express the disease when they have one mutated x-chromosome. The mutated x-chromosome comes from the bitch. In most cases female dogs are carrier of one mutated x-chromosome without being diseased (conductor). According to Mendel's Law of Inheritance, 50% of the male puppies of a carrier bitch will have the mutated x-chromosome and express the disease and 50% of the female puppies will be healthy carriers (conductors). Female dogs will be diseased when they have two mutated x-chromosomes (one from the mother, one from the father). In that case both, father and mother must have the mutated x-chromosome (e.g. diseased male dog bred to conductor bitch).
Trait of Inheritance
There are 3 possible genotypes:
1. Homozygous healthy:
Genotype female: N(X)/N(X),
Genotype male: N(X)/Y (homozygous healthy)
A dog like this is healthy and does not carry the mutated x-chromosome.
Offspring of this dog will not get the mutated x-chromosome.

2. Heterozygous carrier (only female):
Genotype female: N(X)/FVIII(X) (heterozygous carrier)
A bitch like this carries one copy of the mutated gene. It is unlikely that the bitch will suffer from haemophilia A, however there is a 50% chance that she will pass on the mutation to her offspring.

3. Homozygous affected:
Genotype female FVIII(X)/FVIII(X) (homozygous affected)
Genotype male FVIII(X)/Y (hemizygous affected)
Because of the x-chromosomal mode of inheritance, a homozygous affected female dog carries two mutated x-chromosomes and a hemizygous affected male dog carries one mutated x-chromosome. Female and male affected dogs have a high risk to express haemophilia A. The bitch will pass on the mutation to a 100% of her offspring and 50% of the offspring of the male dog will get the mutated x-chromosome.

Inheritance : X-LINKED RECESSIVE trait

 

Sire

  Dam   Offspring
        Males   Females
clear
clear
100% clear
 
100% clear
             
clear
carrier
50%  clear + 50% affected
 
50%  clear + 50% carriers
             
clear
affected
100% affected
 
100% carriers
             
affected
clear
100%  clear
 
100%  carriers
             
affected
carrier
50% affected + 50% clear
 
50% affected + 50% carriers
             
affected
affected
100% affected
 
100% affected

 


Male:

Clear

Genotype: N [ normal ]

The dog is noncarrier of the mutant gene.

The dog will never develop Haemophilia A (factor VIII deficiency / F8) and therefore it can be used in breeding and should only be bred to clear females.

 

Affected

Genotype: FVIII [ mutant ]

 

The dog carries the mutant gene and will pass it its entire female offspring.

The dog will develop Haemophilia A (factor VIII deficiency / F8) and will pass the mutant gene to its entire female offspring

Female:

Clear

Genotype: N / N [ Homozygous normal ]

The dog is noncarrier of the mutant gene.

The dog will never develop Haemophilia A (factor VIII deficiency / F8) and therefore it can be used in breeding and should only be bred to clear females.

 

Carrier

Genotype: N / FVIII [ Heterozygous ]

The dog carries one copy of the mutant gene and one copy of the normal gene.

The dog will never develop Haemophilia A (factor VIII deficiency / F8) but since it carries the mutant gene, it can pass it on to its offspring.

 

Affected

Genotype: FVIII / FVIII [ Homozygous mutant ]

 

The dog carries two copies of the mutant gene and therefore it will pass the mutant gene to its entire offspring.

The dog will develop Haemophilia A (factor VIII deficiency / F8) and will pass the mutant gene to its entire female offspring
Description

DNA test

The mutation responsible for haemophilia A can now be identified using our DNA-test. The test can be performed on dogs of any age and even puppies can be tested. The DNA test does not only differentiate healthy and diseased dogs, but furthermore identifies healthy carrier (female) dogs. This is of crucial importance for dog breeders.
To achieve a maximum reliability of the test result, we perform the DNA-test of each submitted sample in two independent test runs.

Sample Requirements
Whole blood in EDTA tube (0.5 - 1 ml) or Buccal Swabs.
Turnaround
2 - 3 weeks

  3 ) MDR1 Gene Varian / Ivermectin Sensitivity * (ABCB1)

Breeds
American White Shepherd , Australian Shepherd , Bobtail , Border Collie , Collie , Elo , English shepherd , German Shepherd , Kromfohrländer , Longhaired Whippet , McNab Shepherd (McNab Border Collie) , Miniature American Shepherd , Old English Sheepdog (Bobtail) , Rough Collie , Shetland Sheepdog (Sheltie) , Silken Windhound , Smooth Collie , Waeller (Wäller) , White Swiss Shepherd ( Berger Blanc Suisse ) .
Kennel Club
This test is part of the Official UK Kennel Club DNA Testing Scheme in Australian Shepherd, Border Collie, Rough Collie, Shetland Sheepdog (Sheltie), and Smooth Collie.

for UK registered dogs, Laboklin can send results of the tests which are part of the Official UK Kennel Club DNA testing scheme to the Kennel Club (KC) to be recorded and published as part of the Kennel Club scheme. Results will only be recorded and published by the KC if the result report includes the dog’s microchip or tattoo number along with either the dog’s registered name or registered number. Any test results that do not carry these identifying features will not be recorded by the Kennel Club.

In order to ensure that test results are sent to the Kennel Club, customers must also sign the declaration section on the order form to give Laboklin permission to do so.

important: When you sign the declaration, Laboklin will send the results to the KC on your behalf, and you do not need to send them to the KC yourself again to avoid unnecessary duplications.

The Disease
MDR1 is a genetic disorder found in many dog breeds. Affected dogs, when treated with certain common drugs such as Ivermectin and loperamide (Imodium), are unable to pump out these drugs from the brain resulting in poisoning and neurologic symptoms ranging from tremors, anorexia and excess salivation to blindness, coma and even death. Some of these drugs such as Ivermectins, which vets prescribe extensively for the treatment of parasite infections, are able to cause toxicity at 1/200th of the dose required to cause toxicity in healthy dogs.


Scientists discovered that these dogs lack a protein (P-Glycoprotein), which is responsible for pumping out many drugs and toxins from the brain, and that affected dogs show signs of toxicity because they are unable to stop drugs from permeating their brains. Researchers have identified that this condition is due to a mutation in the multi-drug resistance gene [MDR1].
 

LIST OF DRUGS THAT CAUSE SENSITIVITY TO DOGS WITH MDR1 MUTATION

Class A Do not use these drugs in dogs with MDR1 Gene Defect

Ivermectine substances "Anti parasites": (Diapec®, Ecomectin®, Equimax®, Eqvalan®, Ivomec®, Noromectin®, Paramectin®, Qualimec®, Sumex®, Virbamec®) 

Doramectine substances "Anti parasites":  (Dectomax® )

Loperamide substances "ant diarrheal ": (Imodium®)

Moxidectine substances "Anti Parasites" (Cydectin®, Equest®) 

Class B

Use only under close control of veterinarian

Cytostatics  "Chemotherapy": (Vinblastine, Vincristine, Doxorubicine, Paclitaxel, Docetaxel, Methotrexat, Vincristine)

Immunosuppressive: (Cyclosporine A)

Heart glycosides: (Digoxine, Methyldigoxine)

Opioids: (Morphium)

Antiarrhythmics: (Verapamil, Diltiazem, Chinidine)
 

Antiemetics (Ondansetron, Domperidon, Metoclopramide )
 

Antibiotics (Sparfloxacin, Grepafloxacin, Erythromycin)
 

Antihistamin (Ebastin)
 

Glucocorticoid (Dexamethason)

Acepromazine (tranquilizer and pre-anesthetic agent) *

Butorphanol "analgesic and pre-anesthetic agent" *

Other drugs: Etoposide, Mitoxantrone, Ondansetron, Paclitaxel, Rifampicin 

Class C  Can be used only in the permitted application form and dose!   Selamectin (Stronghold®), Milbemax®  and Advocate® .

* In dogs with the MDR1 mutation, acepromazine and butorphanol tend to cause more profound and prolonged sedation in dogs . It is recommended to reduce the dose by 25% in dogs heterozygous for the MDR1 mutation (MDR1 / N) and by 30-50% in dogs homozygous for the MDR1 mutation (MDR1 / MDR1).

Trait of Inheritance
Dogs that are homozygous for the mutation display, due to a non-functional transporter the ivermectin sensitive phenotype. They can show increased absorption of ivermectin and other substrates e.g. Digoxin, Vincristine, Doxorubicin, Cyclosporin A, Grepafloxacin, Dexamethasone and Loperamide (See list of drugs). Heterozygous animals (carriers) may show sensitivity to avermectins and other drugs. They are able to propagate the responsible mutation throughout the population and it is therefore important that carrier animals are detected prior to breeding.
Carriers mayhave sensitivity and should be treated with care

Inheritance : AUTOSOMAL trait
Description

This is a mutation-based gene test, which offers many advantages over other methods

The MDR1 gene variant can be detected, using molecular genetic testing techniques. By DNA testing the mutation can be shown directly. The testing is carried out by state of the art laboratory methods and therefore provides a very high accuracy. In general DNA tests can be done at any age. These tests identify both affected and carrier animals. The mutation can be shown directly, what clearly identifies homozygous affected animals. The genetic test offers the unique possibility to identify Ivermectin sensitive animals prior to treatment with Ivermectin and other drugs (see list).

* partner lab

Please note drug list may not be up to date. The WSU Veterinary CLinical Pharmacology Lab may have a more updated list https://vcpl.vetmed.wsu.edu/problem-drugs. Please note that there maybe other problem drugs which may have not been yet identified.

 
Further reading
Canine MDR1 MutationAcrobat file
WSU Problem Drug listHTML file
Sample Requirements
Whole blood in EDTA tube (0.5 - 1 ml) or Buccal Swabs.
Turnaround
2 - 3 weeks
Price for the above 3 tests
£ 138.00 (including VAT)

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