Article – DNA Testing for MPSIIIB in the Schipperke.

Dr Jeff Sampson gave a talk on MPS111B at the AGM. It is reproduced here.
DNA Testing for MPS IIIB in the Schipperke.
Dr Jeff Sampson

Introduction
MPS IIIB is a simple inherited disease in the Schipperke caused by a recessive mutation in a single gene; a DNA test for the presence or absence of this mutated gene in an individual dog has been available for some time. DNA testing of an individual dog will have one of three possible outcomes, depending on the genotype (the genetic make-up) of the tested dog:

Normal
A normal (clear) dog has two copies of the normal gene. The dog is genetically normal and will not develop the clinical condition. If a normal dog is bred from, it will only pass a normal gene onto its offspring, the status of these offspring will then depend on the gene copy that it inherits from its other parent.

Carrier
This is a dog that has one normal gene copy and one recessive, mutant gene copy. A carrier will be clinically normal and will not develop MPS IIIB because the function of the normal gene copy will over-ride the presence of the recessive, mutant gene copy. If a carrier is bred from, its progeny will have a 50% chance of receiving its normal gene copy and a 50% chance of inheriting its mutant gene copy. Again the status of these progeny will depend on the gene copy they inherit from their other parent.

Affected
An affected dog has two copies of the recessive, mutant gene and will eventually become clinically affected. If bred from, an affected will pass a mutant gene copy onto each and every one of its offspring.

Breeding Outcomes
Normal to Normal
Since both parents have only normal gene copies, each of the offspring will inherit a normal gene copy from the dam and a normal gene copy from the sire and e both genetically and clinically normal.

Normal to Carrier
If a normal dog is bred to a carrier then each puppy will have a 1 in 2 chance of being normal and a 1 in 2 chance of being a carrier, but none of the puppies will become clinically affected, because carriers are clinically normal.

Carrier to Carrier
Each of the puppies from such a mating will have a 1 in 4 chance of being normal, a 1 in 2 chance of being a carrier and, importantly, a 1 in 4 chance of being affected.

Affected to Normal
All of the puppies from such a mating will be carriers because each puppy will inherit a normal gene copy form its normal parent and a mutant gene copy from its affected parent

Affected to Carrier
Each puppy will have a 1 in 2 chance of being a carrier and a 1 in 2 chance of being affected.

Affected to Affected
All puppies will be both genetically and clinically affected and will eventually succumb to the disease.

Breeding advice and the use of the DNA test

There a simple breeding rules that need to be followed and if all breeders follow these rules, then the mutant gene responsible for MPS IIIB will be removed from the UK Schipperke gene pool.

• DNA test all potential breeding stock before they are bred from. DNA testing can be done early in a dog’s life so dogs should be .DNA tested long before a decision is made about breeding.
• If a dog is shown to be normal (clear) by DNA testing, then there are no breeding restrictions.
• If a dog is DNA tested as a carrier, then such a dog can be bred from, but the breeder should carefully select its mate. A DNA-tested carrier should not be bred to an untested dog, another carrier or an affected dog. An untested dog should not be used on a carrier because there is absolutely no idea what gene copies such a dog possesses; a carrier should not be mated to another carrier or another affected dog because the probabilities that such mating will produce an affected dog (1 in 4 for a carrier and 1 in 2 for an affected) are simply too high to contemplate such matings.
• However a DNA tested carrier can be mated to a DNA tested normal dog . None of these puppies will become clinically affected because the worst a puppy can be from such a mating is a clinically normal carrier. If a breeder does choose to mate a DNA tested Carrier to a DNA tested normal dog, then, ideally, all of the progeny should be DNA tested to identify the normal puppies and the carrier puppies.

Following such breeding advice will allow breeders to reduce the frequency of the mutant gene in a responsibly way which will have minimum impact on the breed’s population structure. Owners of carrier bitches will be able to breed them to normal dogs and select a clear bitch puppy to continue their breeding programmes. I have a couple of thoughts on this process. The chief point is that breeders should not necessarily rush to achieve this clear bitch puppy. Don’t just choose any normal dog for your carrier bitch, select a dog that you would have liked to use anyway, that is also a normal dog. Likewise, don’t select a normal puppy just because it is normal, it has to be a puppy that you would have chosen anyway, that is also normal. If the normal puppies in a litter are below your own standards, then repeat the mating until you get a normal puppy that fits your exacting standards to develop your breeding programme.

Finally, a word about what to do with DNA tested affected dogs. Such dogs normally develop clinical symptoms between 2- 4 years of age and so an affected dog can reach sexual maturity. My own view is that such dogs should not be bred from. The prevalence of affected dogs is likely to be extremely low in the UK Schipperke population and so their removal from the breeding population will have minimum impact. However, if someone has compelling reasons to breed from an affected dog, then it absolutely imperative that such a dog is mated to a DNA tested normal dog. As we have seen above, such a mating will produce an entire litter of clinically normal carriers.