The value of Coefficients of Inbreeding

Post date: Dec 19, 2013 7:22:6 PM

Dr. Tom Lewis and Dr. Sarah Blott, the Kennel Club Genetics Centre, AHT

The Coefficient of Inbreeding (COI) is a probability that at any gene in an individual both copies are identical by descent (IBD) – that is they are both identical copies of a single ancestral allele (a variant of a particular gene) which have been inherited via both the mother and father.

Importantly, the COI makes no assumptions about which particular genes may be IBD, or the ancestral sources. All individuals carry some mutant alleles (which are usually harmless as they are partnered by a “normal” allele). Therefore it makes no difference which common ancestor a particular mutation may have been inherited from. Given the COI describes the probability of IBD at each gene it is a useful indicator of risk – the higher the COI, the greater chance a gene is IBD and the greater the risk that it is a mutant allele that is IBD.

The COI is an estimate, derived from the pedigree, of actual IBD. Thus, discarding pedigree information, for example just taking 5 generations, hampers the ability to estimate this reliability. It is crucial to take note of the amount of pedigree used in the calculation of a COI to gauge its reliability – information that is clearly available from the KC's Mate Select. For example, a COI of 13% using 15 generations of a pedigree will be a more reliable indicator than a COI of 12% using four generations of pedigree, and as a result the former may be a “safer bet”.

It matters little whether a dog has a COI of 2.8%, 3% or 4%, since direct comparison of dogs' COI is futile – the dogs already exist and hopefully are healthy (COI represents risk – not a prediction of disease).

Standardisation of the amount of pedigree (usually tantamount to discarding pedigree information) used in COI calculation simply trades reliability of the estimate of IBD for the ability to directly compare individuals.

Furthermore, inappropriate focus on the COIs of individuals distracts us from our main objective – the monitoring of the rate of inbreeding at a population or breed level, i.e. the way in which the breed average COI is changing over time. This informs of the genetic influence ancestors have on the entire population, rather than to particular individuals and describes the risk that the frequencies of mutant alleles will increase. Mutant alleles at a higher frequency in a population lead to a greater chance that a disease appears to suddenly emerge. Thus, diseases or mutations do not come to light “by chance”, but are precipitated by a high rate of inbreeding.

If we think of the management of inbreeding as a means of managing diversity and reducing the long-term risk of disease in breeds then we need to accurately measure the rate of inbreeding.

We know that truncating the pedigree when calculating COIs leads to an underestimate of the rate of inbreeding in a breed. We can then be deceived into thinking the breed has an acceptable rate of inbreeding when, in fact, it does not.

One of the purposes of Mate Select is to help breeders manage the rate of inbreeding in their breeds, not just the COIs of individual dogs. To assist in this purpose it is intended to provide additional tools, such as the facility to track genetic contributors.

Given there are multiple selection objectives when breeding dogs (incorporating various aspects of health, temperament, type, etc.), COI can and should only be one of a number of considerations the breeder wishes to take into account. Inevitably the breeder must balance some concerns against others, but breeders have always done this.

We would certainly not condone using COI as the only selection objective. However, considering the potential COI of litters from a series of hypothetical matings (i.e. ahead of time) alongside the breed average COI (a feature of Mate Select) can help breeders more easily take into account the genetic diversity both of individual dogs and the wider breed.

December 2013

Reproduced with permission.