By Carol Beuchat PhD
When computing the coefficient of inbreeding from pedigree data, how many generations of data should you use?
Ask ten breeders and I expect you will get at least five different answers. Many just do as they see others doing, some only have limited pedigree data and they use whatever is available, and often breeders rely on websites that provide COIs based on the data in that site's database, but for a modest number of generation (usually 8 or 10). I suspect lots of breeders don't know that the number of generations used actually matters.
Well, does it?
The coefficient of inbreeding is probably the single most useful statistic for animal breeding. It tells you about the degree of homozygosity due to inheritance of two copies of an allele from an ancestor on both sides of the pedigree. The key thing to know about this is that homozygosity matters in animal breeding. For many genes, the heterozygous state of an allele (e.g., Aa, versus AA or aa) is the most advantageous, a situation called "overdominance". Inbreeding results in loss of heterozygosity, producing homozygous genotypes, either AA or aa. Consequently, the advantages of heterozygosity are lost, and the resulting deleterious consequences for function are known as inbreeding depression.
Animal breeders documented the negative effects of inbreeding depression over a century ago. They also realized that outcrossing improved inbreeding depression by reducing homozygosity, the benefits of which are called "heterosis" or hybrid vigor. Awareness that the level of inbreeding in their animals affected their profit, animal breeders supported the development of the coefficient of inbreeding by Sewell Wright in the 1920s, which could estimate the level of inbreeding of any animal from pedigree data. To this day, COI remains one of the most powerful tools in the design of breeding plans that balance the negative effects of inbreeding with the benefits for consistency and quality.
Ask ten breeders and I expect you will get at least five different answers. Many just do as they see others doing, some only have limited pedigree data and they use whatever is available, and often breeders rely on websites that provide COIs based on the data in that site's database, but for a modest number of generation (usually 8 or 10). I suspect lots of breeders don't know that the number of generations used actually matters.
Well, does it?
The coefficient of inbreeding is probably the single most useful statistic for animal breeding. It tells you about the degree of homozygosity due to inheritance of two copies of an allele from an ancestor on both sides of the pedigree. The key thing to know about this is that homozygosity matters in animal breeding. For many genes, the heterozygous state of an allele (e.g., Aa, versus AA or aa) is the most advantageous, a situation called "overdominance". Inbreeding results in loss of heterozygosity, producing homozygous genotypes, either AA or aa. Consequently, the advantages of heterozygosity are lost, and the resulting deleterious consequences for function are known as inbreeding depression.
Animal breeders documented the negative effects of inbreeding depression over a century ago. They also realized that outcrossing improved inbreeding depression by reducing homozygosity, the benefits of which are called "heterosis" or hybrid vigor. Awareness that the level of inbreeding in their animals affected their profit, animal breeders supported the development of the coefficient of inbreeding by Sewell Wright in the 1920s, which could estimate the level of inbreeding of any animal from pedigree data. To this day, COI remains one of the most powerful tools in the design of breeding plans that balance the negative effects of inbreeding with the benefits for consistency and quality.
When COI is computed from pedigree data, the quality of the database is critical. COI cannot predict inbreeding due to an ancestor that is not in the pedigree database you're using. In dogs, much of the most significant inbreeding occurred very early in breed development. Many breeds also suffered population crashes during wars, especially WWII. In small populations, it's difficult to avoid breeding, so these events define the genetic resources of the breed forever into the future as long as the stud book is closed. The dogs we have today carry the genes passed down from the animals before them. Animals lost to breeding because of a bottleneck are genetically irrelevant. If we are interested in the genetics of today's dogs, only the offspring produced that carried on after a bottleneck matter. The gene pool then is as large and diverse as it will ever be, and if the stud book remains closed, some of that diversity will be lost every generation.
Registrations of some some sporting dog breeds wince about 1910. There two obvious population dips. One in the 1940s that probably reflects the effect of wars. The other is in about 1975, and the cause is unknown, but it could be an artifact of data collection or change in the ways dogs were registered. (from https://www.instituteofcaninebiology.org/kc-gundogs.html)
Both history and genetics indicate that the number of generations of pedigree data used to compute COI should matter, and indeed it does. But the number of generations used for COI in dogs is both variable and seemingly arbitrary. If we are interested minimizing the deleterious effects of inbreeding, then we should be working with COI data that tell us about actual levels of homozygosity, not relative to other dogs or by a subjective opinion of what is "good" or "bad". If we want useful information about inbreeding, we need to be producing COI values that inform us about actual levels of homozygosity.
[This is a bit of an aside, but it is crucially relevant here. Ideally, breeders should have pedigree data that are complete back to founders. By some oversight of breed or kennel clubs, most breeds do not have a complete database back to founders. This prevents breeders com computing what would be the most accurate estimate of inbreeding using data for genetic history. This is a problem we could (and should) solve, and it should be a priority for all stakeholders. Certainly, the kennel clubs could do a lot to help out this with, since they maintain the actual stud book. There is no benefit in blocking access to this information, so we have to ask why they do this. I'm sure many would urge the kennel clubs to get with the program and unlock a hugely valuable resource so breeders - and others including researchers and scientists - can get access.]
So, if we consider the nature of pedigree data (a record of ancestry and population history) together with the need for information about consequences of breeding strategies for population and individual genetics, the depth of pedigree data used in COI calculations should be based on things that matter for genetics, not some arbitrary number of generations.
When a complete pedigree database back to founders is not available, I propose that the most useful, non-arbitrary pedigree depth that should be used in estimates of inbreeding should reflect the timing of historical bottlenecks or the lowest historical population size for more recently recognized (or developed) breeds. This pins down a population of dogs (and their genes) as known ancestors from which all subsequent descendants descend. Breeders need to realize that the COI computed from this population assumes that the oldest generation (our bottleneck population) is comprised of dogs that are not inbreed and not related. This means tht the first generation of descendants from those dogs will have computed COIs of zero. For most breeds, we know this isn't true, but this is the same assumption used in any calculation of COI from pedigree data. What this means, however, is that the COI we calculate from these data represents the inbreeding that occurred from that generation to the present. This defines a specific pedigree depth for calculations of COI. Because many breeds went through bottlenecks at the same time, it allows for comparison of historical rates of inbreeding across breeds.
The other problem this specific "bottleneck" generation for calculation of COI solves is that of the "sliding" COI. If you use some arbitrary number of generations in calculation of COI, as would be the case for online databases and for many breeders that maintain their own databases (e.g., 5 or 8 or 10, for example), adding the most recent (new) generation to the database bumps off the oldest generation to keep the number of generations the same. The calculation of COI must include the historical inbreeding, so cutting off the bottlenecks and other generations where there was lots of inbreeding will result in lower COIs in today's dogs. Remember, the COI calculation assumes the oldest generation of dogs are not related and not inbred, which isn't true. Generation after generation, as you lose the early generations of inbreeding, it will look like inbreeding is going down in your breed - which of course it isn't - leading to the erroneous (and oft claimed) conclusion that "breeders are doing a great job at reducing inbreeding". (If you didn't know this about calculating COI, you need to dip into ICBs's FREE online course, COI Bootcamp. You don't know what else you don't know, and you should be able to see how making a simple mistake can result in nonsense when in fact you think you are being careful and responsible. The course is FREE. Just do it!)
Pedigree data for Basenji. *Year of breed recognition by the American Kennel Club (AKC). (from Dreger et al 2016 Whole-genome sequence, SNP chips and pedigree structure: building demographic profiles in domestic dog breeds to optimize genetic-trait mapping.)
We should be using historical bottlenecks as a "starting generation" in calculations of COI from pedigree data. It would be more informative to have pedigree data back to founders, but until the Kennel Clubs of the world decide that the very future of the breeds they register depends on breeders making smart decisions that will prevent further deterioration of gene pools. With a fixed starting generation, we really can see if breeders are adopting breeding strategies that are reducing the rate of inbreeding or, in the case of breeds undergoing genetic rescue, breeders can monitor progress without a large expense for DNA analysis.
Again, until Kennel Clubs step up to provide the data, it is up to breeders to work on creating databases complete back to bottlenecks, but they would gain a valuable tool for making breeding decisions that will reduce the risk of inbreeding depression and protect the health of the gene pool.
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