THE CO-EFFICIENT OF INBREEDING (COI)

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WHAT MAKES A BREED?

GENETICALLY SIMILAR DOGS

COI measures the common ancestors of dam and sire, and indicates the probability of how genetically similar they are. Dogs inherit two copies of any gene; one from each parent. Calculating the COI of any litter measures the probability of an allele being homozygous due to an identical gene being passed down to the puppies in that litter along both the dam and sires lines from single common ancestors. Homozygous genes can be good or bad; identical genes have created the look and traits of the Labrador, but, in a different gene, it may also contribute to lower fertility, smaller litters (i.e. for each 10% of COI), one less puppy) inherited diseases and potentially a shorter lifetime.

There are now three methods of testing for Genetic Diversity:

1) Traditional Pedigree COI 2) Genetic testing of specific SNPs 3) Genetic Testing of 200,000+ SNPs

ALLELE

The gene-pair is called an ‘allele’.

HOMOZYGOUS

When the gene pair is identical, it is called ‘homozygous’.

HETEROZYGOUS

When the gene pair is not identical, it is called ‘heterozygous.’

The coefficient of inbreeding for dogs is not a measure of health. It is a measure of the probability of inherited matching copies of a gene. Homozygosity is not inherently bad.

Which genes are homogenous is important to know. For example, Beagles are homozygous for the coat color genes a(t) a(t) and k(y) - There are no known deletrious effects of being homozygous on these locii.

It is not how MUCH homozygosity that matters...it is WHICH genes are homozygous. COI does not tell us that. Again, it measures the probability of inheriting matching copies of a gene.

Embark's COI from 200,000 plus SNPs is going to reflect both non-harmful duplication of some genes and potentially harmful duplications of others.

Pedigree COI

Parent/offspring: 25%

Full sibling: 25%

Grandparent/grandchild: 12.5%

Half sibling: 12.5%

Great grandparents/great grandchild: 6.25%

First cousin: 6.25%

Read as: 12.5% COI - there is a one in 12.5 chance that any particular locus would have two copies of the same allele, and 12.5% of all of the genes in an animal will be homozygous.

To help lower COI average in our breed, most breeders used "outcross" breeding rather than the closer breeding shown above.

The breed average COI using Pedigree Calculations is 6.5%. Choosing a Breeding Pair that will produce litters with COIs under that has been the goal.

Until very recently, Breeders relied upon pedigrees to determine COI. Using at least 10 generations, there were calculators to let us know what the COI of each litter produced by a pair of Labradors would be estimated to be.

The calculator would say that statistically, two full siblings mated together would have a 25% COI. But, it could actually be much lower or even much higher. Without any way to test 200,000 plus genes we were guessing at a litter's COI.

To compensate for this "guessing", Breeders used COI calculations together with Genetic Health Testing for diseases we knew were found within our Breed. We also moved towards using "outcross breeding" to lower COI; this simply means we paired together dogs with no common ancestors within the last 4 to 6 generations. Over time, we began to see COI averages for the Breed move lower. (Note that Breeders whose dogs compete in Breed Conformation Shows will still use inbreeding or line-breeding every few generations.)

Recently, the ability to test the Genetic Diversity of our dogs through companies like Embark or Wisdom have become possible. Breeders are moving towards using these companies for their younger dogs. Panel testing also covers the Health Tests for the relevant diseases so this is an overall improvement on how we are able to determine which dogs to breed and which to sell as pets.

Example of Pedigree COI

Note: These are not the full results and are shown as an example.

Genetic Diversity

Wisdom Panel - Wisdom Panel uses a genetic diversity measurement based on specific markers within a pet's DNA, known as single nucleotide polymorphisms (SNPs)

"A measure of genetic diversity (also known as heterozygosity) is distinct from the traditional definition of coefficient of inbreeding (COI). COI is typically based on recent pedigrees and is associated with the probability of inheriting two copies of the same allele (or sometimes a large genomic chunk of inherited gene variants) from common ancestors. Diversity scoring is based on genetic testing at several genomic locations that are informative of overall variability within a population.... Both methods of determining genetic diversity measure an association with inbreeding rather than directly measuring inbreeding itself. In addition to recent family inbreeding, both measures reflect long-term population “inbreeding.”

Embark Panel - uses 200,000+ markers

"There are three ways to quantify the coefficient of inbreeding (COI):

(1) Using a pedigree,

(2) Trying a small set of polymorphic markers

(3) Testing a genome-wide marker panel.

"We use nearly all of our 200,000+ markers to identify segments of chromosomes that are highly likely to have been inherited from a common ancestor. In comparison, tests that evaluate only small parts of the genome, or estimate homozygosity based on “identity by state,” can miss long inbreeding tracks (sometimes entire chromosomes). With over 200,000 markers spaced throughout the genome, our test uncovers long (and short) inbreeding tracks...."

Because Panel Testing is testing genetic material and therefore able to give us more information, the COI average is different than that of Pedigree COI.

Wisdom Panel, is actually a test of Genetic Diversity and separate from the traditional COI. Embark tests 230,000 SNPs and is obviously going to report a higher COI than Pedigree COI.

These differences have caused a headache for breeders (who had been doing what was within their power previously) as their puppy family sends off a DNA test to Embark or Wisdom and the COI is higher than they had been told by their Breeder. I once had a puppy tested by its owner for whom Embark stated COI was 19% vs the 0% calculated by the traditional pedigree calculations done before the breeding.

It is important for pet owners to remember a few things as they read their results.

Breeders used the tools at their disposal; DNA testing for relevant diseases and the Pedigree COI Calculators.
Breeders used that same Pedigree to mate their dogs using Outcross Breeding and were lowering the average COI for the breed before panel testing was available as a tool.
In order for a litter to be a Labrador litter, there IS going to be a degree of inbreeding - after all, that is how a breed is created. Even mixed breeds can have a high COI depending upon the community from which they come.
It is in a Breeder's best interest to protect not only their own litters but the health of the breed as a whole. We produce these litters because we love and want to protect the breed.
COIs are not the be-all and end-all of a dog. They’re just one measure and NOT a measure of an individual dogs health. A COI of only 1% does not guarantee health and fitness it simply lowers the chance of having inherited a double dose of defective genes.
The coefficient of inbreeding for dogs is not a measure of health. It is a measure of risk of inherited matching copies of a gene. Homozygosity is not inherently bad.
The result is going to be different depending upon the methodology. A PEDIGREE COI of 25% is a mating of full siblings or Father to Daughter/Mother to Son. In GENETIC COI, the percentage is accumulative over ALL generations of breeding and therefore HIGHER than the PEDIGREE COI and is based in part on an “across all purebreds” basis.

The Average COI using DNA for all pure breeds is 20%

Embark reports that its database reflects a COI average for Labradors of 11%. (Note: Each puppy in a litter may have a different COI in DNA COI as inheritance is random.) As with the testing of human DNA for ancestral inheritance, as their database grows, the estimate will become more accurate.

The coefficient of inbreeding for dogs is not a measure of health. It is a measure of risk of inherited matching copies of a gene. Homozygosity is not inherently bad.

It is not how MUCH homozygosity that matters...it is WHICH genes are homozygous. COI does not tell us that. Again, it measures the risk of inheriting matching copies of a gene.

Embark's COI from 200,000 plus SNPs is going to reflect both non-harmful duplication of some genes and potentially harmful duplications of others.

Wrapping it up

ISSUES TO CONSIDER WITH DOG DNA GENETIC TESTING

While the FDA regulates the human DNA testing there is no regulatory body for dog DNA testing).

Sending DNA samples to multiple companies can result in widely varying results from the breed or mix of breeds to familial relationships and disease related mutations.
Resending a sample from the same dog to the same company can result in a different result
Purebred dogs can be deemed as "mixed breed" to the extent that Wisdom Panel states: Wisdom Panel Canine DNA tests are not intended to refute” known ancestry....Because there is only one purebred tree model in the 11 considered, the statistical process inherently favors mixed ancestry.
How you fill out your information appears to affect the results...for example, a veterinary group sampled a Purebred Registered Poodle submitting it to several companies as a Purebred; results came back as purebred Poodle. When the same DNA was submitted to the same companies as a mixed breed, the results were Labrador retriever, Pembroke Welsh Corgi, Shih Tzu, Tibetan Spaniel and Miniature Poodle.