Genetic Mutations Identified in English Shepherds

Multidrug resistance 1 (MDR-1) is a gene which influences how a dog reacts to some medications.  Affected dogs have two defective copies of this gene (genotype = Mutant/Mutant) and do not produce a protein that protects their brains from certain drugs.  When administered to a dog with the MDR-1 mutation, those drugs accumulate in the brain and can cause seizures, ataxia, or even death.  About 15% of English shepherds are affected by the MDR1 mutation.  Dogs that are carriers (Mutant/Normal) have some increased sensitivity to those same drugs, though they can tolerate higher doses than affected dogs can.  The list of drugs that cause the symptoms includes Ivermectin (a worming medicine), Loperamide (Imodium), several anti-cancer agents, Cyclosporin, Acepromazine (tranquilizer) and Butorphanol (pain killer).  Ivermectin is the active ingredient in many heartworm preventives but is at low enough levels that it is safe for even Mutant/Mutant dogs.  For an exhaustive list of drugs that should be avoided or used only very carefully, see the Washington State University Veterinary Teaching Hospital website.

Other genetic diseases recently discovered in English Shepherds include Collie Eye Anomaly (CEA), Progressive Retinal Atrophy – Progressive rod-cone degeneration (PRA-prcd), a few carriers of Hyperuricosuria (HU), and possibly Degenerative Myelopathy (DM).  

No cases of Degenerative Myelopathy have been diagnosed in the breed though a few dogs have tested to be carriers of a mutation associated with risk for DM.  There is some thought that the gene being tested for may only indicate a susceptibility to the disease, and that another gene or genes actually determine if the disease ever develops.  More work needs to be done to clarify how this disease is passed on.

Collie eye anomaly produces a malformation in the eye that can make a dog blind.  The degree of seriousness varies widely, even in affected dogs (genotype=mutant/mutant), so that they may have perfectly normal vision, or they could go blind as puppies.  CEA can be diagnosed in young puppies (< 6 weeks) by looking at the retina and optic nerve connection in the dog’s eye.

Progressive retinal atrophy is a gradual degeneration of the rods followed by the cones in the eye.  Symptoms usually begin around five years of age.  Rods degenerate first, and that leads to night blindness.  Then the cones degenerate until the dog is blind.

MDR1, as well as other genetic diseases, can be tested for.  Below are portions of reports for DNA tests for two English shepherds, showing that one is not a carrier for MDR1, CEA, or PRA-prcd, the other is not a carrier of MDR1, but does carry CEA.  Neither dog is affected by either disease.

This canine’s DNA showed the following genotype(s):
Disease                                                    Gene                      Genotype                           Interpretation

Collie eye anomaly                                   NHEJ1                              WT/WT                                       Normal

Multidrug resistance 1                            ABCB1                              WT/WT                                       Normal

Progressive retinal atrophy,
Progressive rod-cone degeneration       PRCD                              WT/WT                                       Normal

Another dog:
This canine’s DNA showed the following genotype(s):

Collie eye anomaly                                    NHEJ1                              WT/M                                           Carrier

Multidrug resistance 1                            ABCB1                                WT/WT                                       Normal 

Progressive retinal atrophy,
Progressive rod-cone degeneration       PRCD                               WT/WT                                       Normal          

NOTE:   WT = wild type (normal); M = mutant

Hyperuricosuria is a disease that predisposes a dog to have elevated levels of uric acid in the urine, which can result in stones, urinary tract infections, and other painful symptoms.  While an actual case of hyperuricosemia has not been reported in English Shepherds, one of the genetic testing companies has found at least four carriers of this mutation in the breed.