by Kris Hazelbaker @2015

 

 

Introduction

CEA?  PRA-prcd?  MDR1?  What?

You may have seen these terms bandied about, but what do these acronyms mean for you and your dog?

These are the initials for some specific genetic disorders in dogs: Multi-Drug Resistance type 1 (MDR1), Collie Eye Anomaly (CEA), Progressive Retinal Atrophy (PRA, the progressive rod-cone degeneration type), and Degenerative Myelopathy (DM)… now you know why people shorten the names to initials — the full names are a mouthful!   These four genetic diseases are ones we KNOW are found in English Shepherds and for which there are specific tests, to tell you whether or not your dog carries the disease-causing gene.  Only the MDR1 gene has been widely tested for in English Shepherds, and we have some feel for how extensive it is in the breed.  The world of genetics is expanding quickly, however, and we are learning more and more about what genetic-based diseases our English Shepherds may have, and how we can manage those diseases.

Basic Genetics 

Every dog gets a complete set of genes from each parent, so has two copies of each gene.  Those could be the same, or could be different.  If both copies are the same, it’s called being “homozygous”; if they are different, it’s called “heterozygous”.  Those terms just mean “the same” (hom0-) or “different” (hetero-).

The four genetic diseases known to affect English Shepherds are all caused by “recessive” genes.  That means that a dog needs to inherit the same mutation (bad gene) from both parents before it is affected by the disease.   In genetic terms, there are three possible combinations of genes.  Dogs can be:

  1. Normal/Normal – inherit two normal copies of the particular gene and not be affected by the disease;
  2. Normal/Mutant – inherit one normal copy and one mutant copy of the gene, and be a carrier of the disease but not affected themselves;
  3. Mutant/Mutant – inherit two copies of the mutation, and be affected by the disease.

Genetic testing will tell you which combination of genes your dog possesses.  Dogs that are Normal/Normal are not at risk for the disease and can not pass it on to their offspring; dogs that are Normal/Mutant are not at risk for the disease but their offspring may be (and should be tested); dogs that are Mutant/Mutant are at risk for the disease and will pass on the damaged gene to their offspring.

Liz Palika’s Bones

 

Available Genetic Tests

Multi-Drug Resistance 1 – this is a genetic mutation that originated sometime before the collie breeds fully differentiated from each other.  The mutation is found in most of the collie breeds, including English Shepherds; about 15% of English Shepherds carry the MDR-1 mutation.

The MDR-1 gene makes a dog sensitive to a whole list of drugs, including Ivermectin, Moxidectin, “Ace”, “Bute”, and several others.  Washington State University Veterinary School discovered the gene that causes this disease.  They publish a flyer that lists the drugs that can be a problem and how common the disease is in various breeds.  It can be found here:  http://vcpl.vetmed.wsu.edu/docs/librariesprovider17/default-document-library/vcplflier.pdf.   Dogs can carry two copies of the mutation, one copy of the mutation and one normal gene, or two normal genes.  Those who carry two copies are most sensitive to the listed drugs.  With one copy, there is some sensitivity, but much less than with two copies.  Dogs with two normal genes are not noticeably sensitive to those drugs.

Collie Eye Anomaly – is a genetic mutation that affects the retina, the vascular layer of the eyeball, and sclera of the eye. It can be a mild disease or cause blindness.  There is some evidence that there are other genes that determine how severe this disease is.  As far as I know, to date, no English Shepherds have been diagnosed with blindness caused by CEA.  No one knows if this is because they also have the modifying genes that make this a mild disease in ES, or if it just hasn’t been diagnosed and reported, or if the genes are so uncommon in the breed that affected dogs are very rare (both parents have to pass the gene on to produce an affected dog).  To date, very few ES have been tested for CEA, but of those tested, at least one carrier was found.  A carrier has only one copy of the damaged gene, along with a normal copy of the gene; carriers are not affected by the disease.  Unlike with the MDR1 mutation, carrying one copy of this mutation doesn’t seem to have any effect on the dog.

Progressive Retinal Atrophy (progressive rod-cone degeneration) – In this disease, the rods and cones of the retina gradually deteriorate.  The rod cells fail first, and this results in night blindness.  The cone cells are slower to deteriorate, but eventually fail, and the dog is then completely blind.  Symptoms are not seen until the dog is a young adult so cannot be clinically diagnosed in puppies.  Similarly to CEA, the progression and severity of the disease can vary from breed to breed.  To date, no English Shepherds have been diagnosed as affected by PRA-prcd; but, also like CEA, very few dogs of our breed have been tested.  Of those ES that have been tested, a couple were found to be carriers, with one copy of the mutation; these dogs are not affected by the disease but may pass the damaged gene on to their offspring.

Kris Hazelbaker’s Fae

 

Degenerative Myelopathy – This disease is similar to multiple sclerosis in people, causing degeneration of the nerve sheaths, first in the spine and then spreading.  Early signs that a dog is affected include weakness, trouble with balance, and a “drunken sailor” gait.  As the disease progresses, the dog eventually cannot walk and may develop incontinence.  It is apparently not painful for the dog.  Onset of the disease, for affected dogs, can be in middle age (8 years old or so), or very late (12 to 14 years old).  Some dogs will die of other causes before DM affects them.  Like CEA, there is some indication that other genetic modifiers influence how early the disease appears, but those modifiers have not been identified.  DM was identified in English Shepherds in the initial studies that discovered the gene but, to my knowledge, no ES have been diagnosed as affected with DM.

  

Summing It All Up

What does all this mean?  First, it means that breeders can know the genetic status of their dogs for these diseases.  Second, testing means that owners or puppy buyers can know a little bit about how to manage their dog (in the case of MDR1 in particular).  And, breeders can avoid producing puppies that will be affected by any of these diseases if they use test results to help guide their selection of breeding pairs.

Breeders who know the status of their breeding stock in relation to these diseases can choose matches that will not produce affected puppies.  For instance, if one of the prospective parents carries PRA-prcd (tests as normal/mutant for PRA-prcd), breeding that dog to a dog that is not a carrier (normal/normal) eliminates the risk of producing an affected pup.  Half of the puppies from this cross may inherit one copy of the damaged gene but no puppies will have two copies.

Several genetic labs test for these diseases.  Here are some labs and the tests they offer.

Testing Lab \  Disease -> MDR1 CEA PRA-prcd DM
Washington State University X
Canine Genetic Disease Network (through OFA) X
Paw Print Genetics X X X X
Opti-Gen X X
Animal Genetics X X X
VetGen X