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Embark’s Test for Genetic Coefficient of Inbreeding (COI) Brings A New Tool to Breeders
F or millennia, dog breeders have intentionally bred relatives as a way to fix traits in a lineage. A century ago, Sewall Wright devised the coef- ficient of inbreeding (COI) as a way to mea- sure inbreeding, a statistic still popular today. Like humans, dogs tend to be 99.8-99.9% genetically similar to other members of their species. Even other species can exhibit simi- larities—dogs and humans are 64% similar at the base pair level. But genetic variation is the spice of life, and the 0.1-0.2% of the genome that differs encodes a myriad of variation. Some of these variations we have intentionally perpetuated, like body shape, coat color, and behavior. Unfortunately, other less desirable variants confer potentially harmful effects on health, longevity, and reproductive success. Harmful mutations come in three main varieties; recessive, dominant, and additive. The harmful dominant and additive mutations are quickly weeded out in large, outbred popu- lations. This occurs because the individual car- rying these mutations has a reduced fitness. Recessive mutations, on the other hand, are different. A harmful recessive mutation might “break” a gene. This has little or no conse- quence if an individual has a working copy of the gene from his or her other parent. How- ever, this can have disastrous consequences when an individual inherits two broken copies. Outbred individuals almost never inherit two broken copies. Therefore, natural selection or breeders cannot effectively select against them
unless there is a genetic test for the mutation. For example, if a mutation is at 1% frequency in an outbred population, any given dog has a 0.01% chance of inheriting two copies of the mutation—clearly a very small chance. As such, every dog popula- tion—or in the context of purebred dogs, every dog breed—contains an abundance of rare recessive mutations that were either present in a founder individual or arose spon- taneously in the dog population sometime afterwards. These rare mutations are hardly ever problematic for outbred individuals because they almost always inherit at least one working copy; however, they can cause real problems for inbred individuals—animals that arise from the mating of closely related parents. Let’s consider what happens with dogs in a mother-son mating. A mother passes along 50% of her genome to each pup, so each rare (<1% frequency) recessive muta- tion carried by the mother has a 50% chance of being transmitted to a son. Offspring from a mother-son mating would, therefore, have a 25% chance of inheriting two bad copies of the mutations that have been passed down to the son. This is a greater than 100-fold risk compared to an outbred dog! Inbreeding in dogs has real consequences. Research in the Embark Co-Founder Adam Boyko Lab has shown that a 10% increase in inbreeding can lead to a 6% reduction in adult size (poor growth) and a six- to ten-month reduction in lifespan. Reduced litter size and fertility are also likely. These risks occur from both classical inbreeding and from drift in small populations where every individual is a not-so-distant relative. Assessing these risks depends on accurately quantifying the likelihood that mutations will be identical-by-descent, or inherited from the same ancestor.
56 | SHOWSIGHT MAGAZINE, JULY 2021
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