An analysis of the Coefficient of Inbreeding of Lafora DNA tested Mini Wires

Post date: Nov 20, 2014 5:51:34 PM

Now that we have nearly 500 Lafora DNA test results from a 4 year period, of which 357 have a result of “Clear”, “Carrier” or “Affected”, we thought it would be interesting to look at the breeding of Affected dogs and compare it with Clear dogs. We therefore collated the Coefficient of Inbreeding (COI) data from the KC's Mate Select database for all the dogs with Affected and Clear Lafora results.

We wanted to see whether there was a statistically significant difference in the average COI of the two groups.

One of the concerns that has been expressed about the reliability of the KC's COI calculations is that, for imported dogs, there is insufficient pedigree information and their COI is often reported as 0%. We therefore decided to exclude any dogs with a COI reported as 0% or any dog with an import as its parent.

This left us with 48 Affected dogs and 141 Clear dogs.

We asked three independent statisticians (2 members of the Operational Research Society and a Chartered Statistician) to analyse the data and tell us what it revealed.

Having looked at the data independently, they then summarised their analysis for us.

The conclusions were:

• • the mean COI of Lafora Affected dogs is statistically significantly higher than the mean COI of Clear dogs

  • COI is a poor predictor of whether or not a dog will be Affected or Clear

  • the higher the COI value of any particular dog, the higher is its risk of being Lafora Affected

The histogram below shows the variations in COI for Affected and Clear dogs; the mean COIs being 17% and 12% respectively. It is evident from the data that there are some Affected dogs with low COI values and some Clear dogs with high COI values.

Arguably, this analysis tells us what we already know about the risks of inbreeding; the more inbred a dog is, the higher the risk of harmful genetic mutations coming together in a single dog. What we have here is the data to prove that 'theory' in relation to Lafora Disease.

A further analysis was done by separating the COI results into deciles (for Clear dogs) and calculating the probability of a dog being Affected given its COI decile. This is shown in the chart below. Clearly, if there was no association between COI and being Affected, this probability should be equal for each decile. However, we actually see an increasing trend in the probability of being Affected as the COI deciles increase.

It is also worth noting that the samples of dogs tested are not random, they were self-selected and may not be representative of the wider UK population of Mini Wires. Nevertheless, our DNA test data shows nearly 1 in 10 dogs to be Affected and breeders (and buyers) simply should not be taking the risk of producing further Affected puppies when a reliable DNA test can prevent this.

The advice for breeders and buyers remains the same in relation to Lafora:

• • the Lafora DNA test should be used to ensure there is no risk of Affected puppies being produced; i.e. at least one of the breeding pair MUST have been tested Clear

  • puppy buyers should only buy a Mini Wire from a breeder who has used the DNA test to ensure their puppies will not be Lafora Affected

Our advice regarding inbreeding is based on the KC's information on its Mate Select website and the FCI's guidance on breeding strategies:

• • breeders should aim to breed with dogs so that the COI of the resulting puppies is lower than the current Breed Average COI (9.9%)

  • breeders should be very wary of using so-called Popular Sires because of their potential to significantly reduce the genetic diversity in the breed (the FCI recommends that no stud dog should sire more than 5% of a breed's puppies during a 5 year period)

The current Breed Average COI for Mini Wires is 9.9%. It is interesting to note that 59% of the dogs DNA tested Clear or Affected for Lafora (in our selected sample of 189 dogs) have a COI higher than the breed average. Additionally, 10% of these dogs had COI values greater than 25%, the level which equates to matings the KC will no longer register, such as Father-Daughter, Mother-Son and Brother-Sister.

We are grateful to statisticians Jane Parkin, Sophie Carr and Nigel Marriott for their help with the analysis of our Lafora Data.