Demystifying InbreedingJuly 29, 2021 - 10 minutes read
Most of us first learned about inbreeding in a high school history class. You remember the one – the textbook example was the pedigree of a royal family and usually included gory details about the health problems that resulted when relatives married each other.
The moral of the story was that inbreeding is a bad thing that frequently led to geopolitical disaster. But as with many things in science, our perspective on inbreeding is more nuanced than that. Let’s start with the basics: measuring inbreeding in an individual is a way to assess how much that individual’s parents are related to one another.
There are two main ways to do this. The first is through pedigrees just like in high school history. Basically, you can (and many breeders do) make a family tree for an individual that goes back as far as you can and use this information to determine if the sire (male parent) and dam (female parent) shared any ancestors. You can use the number of shared ancestors to calculate an inbreeding statistic.
Typically, inbreeding calculated from pedigrees ranges from 0% (no shared ancestors) to 45% (a whole lot of them). The important thing to know about this method is that inbreeding calculated from pedigrees is highly influenced by incomplete data. If you don’t go back enough generations or if you don’t have information about some family lines, you’re likely to underestimate inbreeding.
Advances in sequencing technology have provided us with a more reliable way to estimate inbreeding. When we sequence a dog’s genome, we determine the genetic information present on both copies of every chromosome. This genetic information includes both coding regions (genes) and non-coding regions. The important thing is that these regions come in pairs. When the two copies are different, like a pair of mismatched socks, we call that region of genetic material heterozygous. When the socks match, they’re called homozygous.
We use information about heterozygosity and homozygosity to calculate a statistic called the coefficient of inbreeding (COI). While there are several ways to do this, the basic idea is to determine how frequently across the genome the paired genetic material is the same or different. Going back to the sock analogy, if every sock in the drawer is paired to an identical match, there is a lot less genetic diversity than if all the pairs are mismatched.
When a high proportion of the genetic material matches, the coefficient of inbreeding is higher, and we can conclude that the individual is descended from ancestors who were related to each other.
The Inbreeding Spectrum
The coefficient of inbreeding statistic ranges along a continuum from 0% to 100%. Any given individual is on this spectrum. So what’s it all mean? Let’s explore some typical values and how they are used and interpreted.
Zero percent means that there is no evidence of shared ancestors in the dog’s genomic sequence data and thus no inbreeding. If you took two unrelated dogs and bred them, and then bred a brother-sister pair from the resulting litter, the coefficient of inbreeding would be 25%. You’d end up with an even higher number if the sire and dam were themselves related farther back.
Mixed breed dogs, on average, tend to have a coefficient of inbreeding around 5% (see references below for more details). This is not always the case; breeding related mixed breed dogs together can result in high COI puppies, just as in purebreds. The average COI for purebred dogs is ~20%. Specific breeds can be higher or lower than this value. For some breeds, the average coefficient of inbreeding can approach or even pass 40%. Because these are average numbers, individual COI can vary. For example, some breeding lines may have more genetic diversity than others.
It’s worth noting that zoo-based, species conservation programs have set a target COI at 10%. This means that they want to design breeding programs that will keep the level of inbreeding at or below this level. While this metric is a bit arbitrary, it can be useful when comparing the inbreeding consequences of various pairings.
Health Consequences of Inbreeding
Many of us are interested in knowing whether or not inbreeding is going to lead to health issues in our animals. Research suggests that there can be health consequences of inbreeding (see references below for more details). Higher levels of inbreeding are associated with shorter life spans, for example.
But again, this is an area with some nuance. Remember that a low coefficient of inbreeding indicates higher heterozygosity, in other words, more genetic variation. Typically, this means that the individual has lower “genetic risk” and more “genetic options” when it comes to responding to environmental change or disease exposure.
A good example is the “Major Histocompability Complex” (MHC) region in the human genome. This part of the genome is responsible for our immune system response. More variation in this region means that the individual is able to recognize a wider variety of pathogens and defend against them. Less variation means that the individual might be more susceptible to certain bacteria or viruses.
If one individual has a higher coefficient of inbreeding than another, it doesn’t mean that their health is definitely going to be worse. However, if you consider averages, a group of individuals with a higher-than-average COI is more likely to display negative health consequences than a group with lower-than-average COI.
The key thing to remember is that there is no magic number for the coefficient of inbreeding below which the level of inbreeding is fine and above which it’s bad. Inbreeding is a way to understand genetic diversity, it exists on a spectrum, and its consequences can be influenced by environmental factors as well.
At the Dog Aging Project, we expect that the genetic portion of our research will reveal genetic markers for specific health conditions. If so, then these markers could ultimately be like human genetic tests and provide similarly important information to guide breeding and veterinary care decisions for dogs.
Body size, inbreeding, and lifespan in domestic dogs. Yordy J, Kraus C, Hayward JJ, White ME, Shannon LM, Creevy KE, Promislow DEL, Boyko AR. Conservation Genetics (2020) 21:137-148
Whole-genome sequence, SNP chips and pedigree structure: building demographic profiles in domestic dog breeds to optimize genetic-trait mapping. Dreger D, Rimbault M, Davis B, Bhatnagar A, Parker H, Ostrander E. Disease Models & Mechanisms (2016) 9 : 1445–1460.