Say I was to take 2 completely unrelated rabbits from 2 genetically distant breeds, and crossed them.
If I take that F1 outcrossed offspring and breed it to a littermate, what are my chances of them suffering from inbreeding depression?
I imagine the odds would be more in my favor than if I did a same-breed littermate breeding, since the parents are unlikely to share any deleterious recessive alleles.
Feedback and any resources that explain this specific phenomenon further would be much appreciated.
"Inbreeding depression" is a term for a theoretical decline in fitness in a population resulting from the increased expression of harmful recessive genes. It is a term applicable to populations, not individuals, and is related to the
potential of increasing prevalence of harmful recessives in the population, with the
potential result that more and more individuals will be conceived with the harmful alleles in the homozygous state (and thus suffer the harm, meaning they are less reproductively fit).
Note that this increase in prevalence and homozygosity of harmful alleles is
potentially, not
necessarily, a result of inbreeding. The size of the population substantially impacts risk, with an increasing population size corresponding to a decreasing risk. There are a number of other factors that play into the passing of certain alleles to the next generation as well, some of which encourage a problem, while others do not. These include the proportion of harmful alleles present in the population to begin with, their linkage (genetically or behaviorally) and/or interaction with other alleles, selectivity patterns in mate choice, and possible secondary and tertiary effects of the allele in its homozygous and heterozygous states.
The classic example of a persistent problematic allele is the allele that in the homozygous state causes sickle cell anemia in humans, but which in the heterozygous state confers resistance to malaria. Thus this harmful allele is maintained in populations at risk for the latter disease (but not usually in populations that are not at risk). Inbreeding, in this case, would obviously be likely to result in "inbreeding depression."
But in the case of a harmful allele that does not confer any benefits in the heterozygous state, it is just as likely that its prevalence will decrease in the population over time. Matings between individuals that are heterozygous for the harmful allele will produce, on average, 25% offsping homozygous for the harmful allele. Assuming that the allele is harmful enough to impact reproductive fitness (which is the definition of harmful in discussions of populations), that means the breeding of the original hetrozygotes will contribute 25% fewer offspring to the breeders of the next generation than the breeding of indivuduals that are not both heterozygous: in this way, the allele may decrease in prevalence. If mating is truly random, that might take a long time, but it's what would likely happen.
These scenarios assume no linkages and random mating, which probably never actually happens in real life. But in any case, a responsible breeder typically does not randomly mate their stock. In fact, for a breeder, inbreeding is a powerful way to expose and eliminate harmful recessives. Individual animals expressing traits caused by harmful alleles, and those individuals' parents, are removed from the breeding stock by a careful breeder, thus actually reducing the prevalence of harmful recessives rather than increasing them.
No matter what foundation stock you begin with (unless it is a highly inbred closed population already selected for optimum genetics), you may have harmful recessives lurking in your stock. You can outcross constantly to try to avoid their expression, and be constantly surprised at unpredictable results, and constantly bring the same or new harmful recessives into the herd; or you can inbreed selectively and actually eliminate or at least reduce the prevalence of harmful recessives in the herd, while increasing the prevalence of traits you
do want.
According to a description by
Yazawa, Umezawa, Kuramasu and Miyajima (1985) of the establishment of two inbred rabbit strains for laboratory purposes, breeding siblings together without seeing problems you might identify as inbreeding depression is possible for
at least 20 generations (the length of the project at the time of reporting, encompassing 103 breeding pairs, between 1 and 10 pairs per generation, from 1967-1982) . Unfortunately, for me, anyway, the text of the article is in Japanese, but you can read the abstract and see the breeding performance data chart here:
https://www.jstage.jst.go.jp/article/expanim1978/35/2/35_2_203/_pdf/-char/en
The direct, concise answer to your question is that crossing F1 siblings will not produce problems unless they both just happen to carry the same harmful allele. And if they do, I would not be inclined to call it "inbreeding depression," as that relates to population-level matters, and connotes breeding of multiple close relatives over time, not just one generation. I also would not predict that problems would be any more likely for same-breed or different-breed crosses, unless maybe you start with stock that is already extremely closely related, such as two related individuals of a very rare breed.