By Carol Beuchat PhD
Even 100 years ago, breeders of domestic animals realized that continuous inbreeding resulted in deterioration in the quality of their stock. To remedy this, every few generations a relatively unrelated animal would be crossed in to the population to freshen up the gene pool and reduce the level of inbreeding. In fact, the coefficient of inbreeding was devised in the 1920s as a way to estimate the level of inbreeding so breeders would know when it was time to do an outcross.
Many modern dog breeders follow a similar regime, breeding close for a few generations then out to a relatively unrelated dog. But is this as effective as we think it is?
For one thing, our dogs are much more inbred than they were a century ago. Many breeds have average levels of inbreeding above 20%, and too many are even higher. With such high levels of inbreeding and low genetic diversity, the dogs in a breed can all be more similar genetically than half- or even full siblings - or even more. How much can you expect to gain from an "outcross" that really amounts to close inbreeding?
For one thing, our dogs are much more inbred than they were a century ago. Many breeds have average levels of inbreeding above 20%, and too many are even higher. With such high levels of inbreeding and low genetic diversity, the dogs in a breed can all be more similar genetically than half- or even full siblings - or even more. How much can you expect to gain from an "outcross" that really amounts to close inbreeding?
One way we can get an idea of the potential benefits of an outcross is by using simple mathematical models of population genetics (Windig & Doekes 2018).
Researchers have simulated various outcrossing strategies for the Saarloos Wolfhond (a cross between a wolf and German Shepherd created in about 1935) and an unrelated "donor" breed. The Saarloos Wolfhond has been a relatively small breed since it was founded, with about 25 litters produced per year and high rates of inbreeding. In the last decade or so, genetic disorders have become a problem and signs of inbreeding depression (smaller litters) have appeared. Because of this, an outcross project was started in 2016.
The researchers assessed the consequences of four types of crossbreeding schemes on inbreeding.
1) A single outcross with no backcross;
2) A single outcross with backcross;
3) Repeated outcrosses with backcrossing;
4) Continuous outcrossing.
For each of these scenarios, they ran multiple simulations to produce information on the degree of variation that might be produced in a real, randomly breeding population.
The F1 from a cross of the recipient (Saarloos) and the unrelated donor breeds will have an inbreeding coefficient of 0%.
The researchers assessed the consequences of four types of crossbreeding schemes on inbreeding.
1) A single outcross with no backcross;
2) A single outcross with backcross;
3) Repeated outcrosses with backcrossing;
4) Continuous outcrossing.
For each of these scenarios, they ran multiple simulations to produce information on the degree of variation that might be produced in a real, randomly breeding population.
The F1 from a cross of the recipient (Saarloos) and the unrelated donor breeds will have an inbreeding coefficient of 0%.
They found that a single outcross followed by one or more generations of backcrossing reduced the beneficial effect of the outcross and sometimes even increased the rate of inbreeding. In the cross breeding, the first generation receives 50% of alleles from each of the donor and recipient parents. But in subsequent backcrosses, half of the donor genes are lost on average, so that after a few backcrosses the remaining donor contribution was inconsequential.
This result is not unexpectded, but it should give pause to those that undertake a crossing program that consists of a single donor cross followed by serial backcrosses. Kennel clubs typically prefer 3 backcrosses before admitting the descendants of a crossbreeding program to the studbook. But the simulations show that the required backcrosses essentially flush the donor genes from the recipient gene pool and there is no net benefit. Indeed, there are multiple examples of crossbreeding programs that failed or produced little benefit because the introduced genetic variation was subsequently lost.
This result is not unexpectded, but it should give pause to those that undertake a crossing program that consists of a single donor cross followed by serial backcrosses. Kennel clubs typically prefer 3 backcrosses before admitting the descendants of a crossbreeding program to the studbook. But the simulations show that the required backcrosses essentially flush the donor genes from the recipient gene pool and there is no net benefit. Indeed, there are multiple examples of crossbreeding programs that failed or produced little benefit because the introduced genetic variation was subsequently lost.
Regular outcrossing was the most effective strategy for reducing the rate of inbreeding in the Saarloos Wolfhond, but still the outcomes of the simulations were highly variable. The scenario of regular outcrossing generally reduced the rate of inbreeding, but the inbreeding rates were highly variable, and in some simulations all of the donor genetic contribution was lost.
What this study clearly showed is that using outcrossing to reduce the rate of inbreeding requires careful management in order to ensure success, and the benefit achieved will be small unless crossing is done on a regular basis. One key to success is to follow outcrossing with strategies to increase the effective population size. Otherwise, inbreeding will quickly return to previous levels.
This outcross simulation used a completely unrelated (fictitious) breed as a donor. For breeders that are crossing to what they hope are relatively unrelated dogs in their own breed, the benefit will be much less if the level of relatedness among individuals is high.
This outcross simulation used a completely unrelated (fictitious) breed as a donor. For breeders that are crossing to what they hope are relatively unrelated dogs in their own breed, the benefit will be much less if the level of relatedness among individuals is high.
The authors of the study also addressed an issue often raised by breeders in discussions of outcrossing.
| "The unwanted introgression of (unknown) deleterious alleles from a donor breed is often used as an argument against outcrossing. Since probably all animals carry recessive deleterious alleles, this may indeed be the case. However, the opposite, introgression of beneficial alleles is possible as well. The chance that different alleles are present in the donor breed depends on how closely related the breed is." (Windig & Doekes 2018) |
This study highlights the difficulty in reversing the effects of inbreeding and loss of genetic diversity in closed populations of dogs. While simple in concept, genetic rescue is complex and challenging, and undertaking a program without an effective plan for maintaining the added diversity will likely achieve little. Fortunately, the authors point out, the efficiency and chance of success can be improved using "genomic-assisted selection". For this, microsatellites (STRs) have largely been replaced by next-generation sequencing using high-density (> 100,000) SNP genotyping, which now produces vastly more detailed information at a reasonable cost.
This cutting-edige technology as well as the necessary expertise to design an effective outcrossing program is now available to dog breeders, offering them the possibility of reducing the burden of genetic disorders in dogs in future generations.
Ironically, the modern solution to the problem of genetic disorders in dogs goes back to the time-tested method used a century ago- the regular introduction of new genes into the gene pool. These days, the rehabilitation is more difficult because the levels of inbreeding are very high, but we can improve the chances of success using population genetics and genomics.
This cutting-edige technology as well as the necessary expertise to design an effective outcrossing program is now available to dog breeders, offering them the possibility of reducing the burden of genetic disorders in dogs in future generations.
Ironically, the modern solution to the problem of genetic disorders in dogs goes back to the time-tested method used a century ago- the regular introduction of new genes into the gene pool. These days, the rehabilitation is more difficult because the levels of inbreeding are very high, but we can improve the chances of success using population genetics and genomics.
REFERENCES
Windig JJ & HP Doekes. 2018. Limits to genetic rescue by outcross in pedigree dogs. Journal of Animal Breeding and Genetics 135:238-248.
To learn more about the genetics of dogs, check out
ICB's online courses
***************************************
Visit our Facebook Groups
ICB Institute of Canine Biology
...the latest canine news and research
ICB Breeding for the Future
...the science of animal breeding
ICB's online courses
***************************************
Visit our Facebook Groups
ICB Institute of Canine Biology
...the latest canine news and research
ICB Breeding for the Future
...the science of animal breeding
