Genetics

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Introduction

NOTE: As we say elsewhere, the information on this website focuses on mini wire dachshunds but much of what is written may well apply to other breeds too.

It appears likely that Lafora in the mini wire dachshund population first appeared as a genetic mutation in the UK. There are several ways that a disorder, disease or positive trait can be passed down through breeding, and Lafora is an ’autosomal recessive genetic disease’, which means that two copies of an abnormal gene must be present in order for the disease or trait to develop. In other words, a dog must have two of the mutated genes, one from each parent to be ‘affected’, i.e. show some of the characteristics of the disease, whether these be minor or major. If a dog has only one Lafora gene, it will be a ‘carrier’. It will not be affected, but if bred to another carrier or affected, at least some of the puppies born will receive the two genes and thus be affected. Furthermore, Lafora is a ‘late onset autosomal recessive genetic disease’ which means that the signs only manifest themselves in middle to older age ( characteristically from the age of 5 upwards), which tragically means that many dogs may have bred from before it becomes apparent that they have a severe problem.

When research first started on Lafora in Mini Wires in the 1990’s it was estimated that around 5% of the UK population was ‘affected’ and up to 25% were carriers. We understand that it is possible that the % now may be much higher, around 12% as indicated by the recent results of the Controlled Testing programme.

Not all Lafora ‘affected’ dogs will go on to develop the most severe form of the disease. Some dogs are barely affected, and because of the characteristic myoclonus ‘jerking’ when confronted by sudden noise, movement or light may simply be thought of as being ‘nervous’

The Genetics of Lafora

To help understand how this works, let’s start with the basics of genetics. The following information is from the researchers of the AKC Canine Health Foundation, and from Medlineplus, the US National Library of Health, simplified as much as possible:

DNA (deoxyribonucleic acid) is the genetic material shared by all living organisms. It specifies which characteristics an offspring will inherit from its parents.  A Gene is a short piece of DNA and there are approximately 30,000 in each cell of the human body. The combination of all genes makes up the blueprint for the human body and its functions – A person’s genetic makeup is called a genotype.  Heredity is passed from generation to generation through the genetic characteristics passed on from parent to offspring. Sometimes at this point or, for example as the result of exposure to viruses, radiation, chemicals etc, a genetic mutation might occur, resulting in the development of a new characteristic which can be passed on to offspring

Genes are located on strands of DNA, just like beads on a string. The DNA strands make up the chromosomes. Chromosomes contain matching pairs of one copy of a specific gene – the dog has maybe 100,000 genes, arranged linearly along the chromosomes

Humans have 23 pairs of chromosomes, whereas dogs have 39 pairs of chromosomes. In either case, the offspring receives one of each chromosome pair from each parent. Thus it has TWO copies of each gene, one inherited from each parent. From now on, this article will refer only to dogs and puppies, but exactly the same information applies to humans.

Two of the chromosomes (the X and the Y chromosome) determine the gender of the puppies, called, unsurprisingly, the sex chromosomes:

  • Females have 2 X chromosomes.
  • Males have 1 X and 1 Y chromosome.

The dam (mother) always contributes an X chromosome to the child. The sire (father) may contribute an X or a Y. Therefore, it is the father that determines the gender of the child.

All the remaining chromosomes are called autosomal chromosomes.

Inheriting Disease

Inheriting a specific disease, condition, or trait depends on the type of chromosome affected (autosomal or sex chromosome). A mutation in a gene on one of these non-sex chromosomes can lead to an autosomal disorder.

It also depends on whether the trait is dominant or recessive. Dominant genes show their effect even if there is only one copy of that gene in the pair. Recessive genetic mutations only show their effect where both genes in the pair have the mutated characteristic, one from each parent.

Recessive inheritance means both genes in a pair must be defective to cause disease. Dogs with only one defective gene in the pair are considered carriers. However, they can pass the abnormal gene to their puppies.

Chances of Puppies Inheriting Lafora or other Genetic Disease

As stated above, Lafora is an autosomal recessive genetic condition which is late onset (i.e. the condition only becomes apparent later in life from age 5 years + in the case of Lafora)

If a puppy is born to a breeding pair who both carry an autosomal recessive change (mutation), each will have a 1 in 4 chance of getting the malfunctioning genes from both parents and developing the disease, in a mild or more severe form, i.e. being ‘affected’, a 1 in 4 chance of getting the non-malfunctioning genes from both parents i.e. being ‘clear’ and a 50% (1 in 2) chance of inheriting one abnormal gene, i.e. a carrier.

In other words, if four puppies are born to a breeding pair who both carry the gene (but do not have signs of disease), the statistical expectation (not exact for every litter) is as follows:

  • One puppy is born with two normal genes (normal)
  • Two puppies are born with one normal and one abnormal gene (carriers, without disease)
  • One puppy is born with two abnormal genes (at risk for the disease)

Without a DNA test, it is impossible to tell if a dog is carrying the recessive mutation unless:
1. One of his parents is affected, or
2. He is bred to another dog also carrying a copy of the gene, and one or more of the resulting pups is affected.

A recessive mutation can spread fairly rapidly through a population before breeders are aware of it, especially if the gene pool is small. Carriers, who will test normal all their lives, will be bred and pass the gene to half their offspring. If the disease is late-onset, like Lafora, many affected dogs will be bred unknowingly. An affected dog, carrying two copies of the gene mutation, will pass the trait to 100% of his offspring, as he does not HAVE the dominant gene in his chromosomal makeup to pass on. This spreads the gene even faster. The number of carriers will rise exponentially with every generation. By the time the first affected dog appears in a pedigree, many of the dogs in that pedigree will be carriers. It’s just that no one knew it. For each affected dog identified, both his parents, at LEAST two of his grandparents, two-thirds of his siblings, and all his offspring will be carrying the gene. Without a DNA test to identify the carriers, it is virtually impossible to eradicate a recessive disease from a gene pool.

This chart is a useful illustration of what this actually means: Lafora genetics RAG chart April 2011

There is Hope!

Now, this may sound like a lot of gloom and doom, but the good news is that IF we can collect enough data to identify affected and carrier dogs, we can eradicate hereditary cataracts in three generations without removing a single dog from breeding!

The link below, taken from information provided by the HEART group, working to eradicate genetic conditions from the Havenese dog, shows how you can start with an affected dog and produce an entire litter of Normal puppies (those NOT carrying a copy of the recessive gene) in three generations without producing ANY affected pups in the meantime read about the ♥ 3 generation breed out

This chart illustrates how important it is that tests are made available which can identify ‘affected’, ‘carrier’ and ‘clear’ dogs. If two carrier dogs, (who will never show any sign of the condition themselves) are unwittingly bred together, or a carrier bred to an affected dog, then affected puppies, as described above, will inherit a copy of the faulty gene from each parent. Because of this, it might seem  that the best way forward is to avoid breeding  any dog identified as either an ‘affected’ or a ‘carrier’ dog. However, by limiting the gene pool so severely, there is a very strong chance of either increasing the prevelence of equally dangerous and potentially fatal genetic traits, for example in Mini Wires,  IVDD (Back Disease) or as yet unknown conditions.

By knowing exactly what the characteristics are of any breeding pair, it is possible, in theory, to remove the faulty gene entirely from a population within three generations whilst allowing strictly controlled breeding of carrier dogs

If all dogs are tested, there would never be another Lafora affected dog.  Is there anyone who wouldn’t pay that to insure that his dog wasn’t going to suffer from epilepsy, blindness and eventual dementia?????

Unfortunately, because there are so many breeders (both hobby and professional) who either are not aware of the condition or are not willing to comply strictly with to such a programme, the chances are that it will take much longer to reduce and hopefully eventually prevent Lafora unless some very positive action is taken.  It is encouraging that there is progress now being made with reducing the incidence of the Cord1 gene, proven to be linked to PRA (Progressive Retinal Atrophy), which affects miniature long hair, mini smooths and the other dachshund varieties (including the mini wire) to a greater or lesser extent.

For this to work, we’ll need to identify affected, carrier and clear dogs, so even if there is no sign of the disease in a dog, it is just as important that they are tested.

So Now What?

Where does this leave puppy buyers?

The Mini Wire Hair Dachshund is an absolutely delightful dog, and a healthy, hearty little breed. The only way that breeders can guarantee against Lafora is through a responsible breeding programme.

Virtually all breeds have genetic problems – poodles have 24 heritable diseases documented ….. and of course there’s no guarantees at all with cross breed dogs.

In other words, don’t let this put you off buying a mini wire. There are plenty of breeders out there who are intending to get their dogs tested in the near future. For now, we’ll keep a record of those breeders who have advised us of the outcome of those tests, but we anticipate that eventually this will be part of a wider database. For more information contact laforadogs@btinternet.com

If you already have a mini wire – get it tested just the same. The chances are that it will be clear and provided you don’t intend to breed, there is no worry if it is a carrier. If, God Forbid, your dog is diagnosed as being affected then don’t panic. Check out our information sheet here and contact us for more information.

References:

  • Havanese Cataracts – article written by members of H.E.A.R.T. – Havanese Eye Angel Research Team, US based group, no longer apparently in existence 
  • http://www.nlm.nih.gov/medlineplus/ency/article/002048.htm and other articles from same source – medline plus website, US National Library of Medicine

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