DogsArk
Cavalier King Charles Spaniel
GENETIC DASHBOARD
SYNOPSIS
Inbreeding in the Cavalier King Charles Spaniel is very high, with most dogs greater than 25% (equivalent to a cross of full siblings). There is very little genetic diversity in this sample of dogs, so apart from a handful of dogs that might be useful, there is little breeders can do to bring down levels of inbreeding. It would be worth sampling dogs from several different populations worldwide to evaluate how much genetic variation there might be geographically. It is definitely worth also sampling dogs from puppy mills, which might have lower levels of inbreeding and might represent different lines than the dogs produced by Cavalier breeders. However, restoring genetic and physical health to this breed will require crossing to dogs that can reduce homozygosity and restore genetic diversity of the breed. The breed-specific traits can be restored in backcrosses in a breeding program designed to protect the introduced diversity.
Breeders can use the DogsArk breeding tool for genomic data of individuals as well as an overview of the genetic status of the population. Kinship coefficients can identify the dogs that are genetically most valuable and prevent over-representation of genetically restored dogs in subsequent generations. Updating these data on a regular basis will provide breeders with the information they need to guide the breed back to genetic and physical health. Finland has begun a cross breeding program, and it would be ideal if breeders can create a population of dogs in the US that can provide dogs with good type for outcrossing, and vice versa. Submitting Embark files to DogsArk for as diverse a sample of dogs as possible will be valuable for tracking the outcome of a crossbreeding program.
SUMMARY
The Dogs and Data
The summarized here are extracted from the pages for this breed on DogsArk, the ICB Breeder Tool.
The information below is based on data obtained from Embark Vet for 51 Cavalier King Charles Spaniels (CKCS). The dogs are anonymous and nothing is known about their origin, but most were probably from the US. There is no health information for these dogs.
I processed the data using standard protocols for SNP data from the Illumina HD (high density) Canine Bead Chip. The analyses were performed using Golden Helix SNP and Variation Suite software. The algorithms the software uses are sourced to published studies validating their output. All information is from the DogsArk website (https://dogsark.org/breedertoolpages-2/cavalier-king-charles-spaniel/)
Inbreeding (F)
Genomic inbreeding in CKCS is among the highest of any breed (Dreger et al 2018), and averaging 36.5% in this sample of dogs. Even the lowest level of inbreeding in this sample of dogs was 26.9%, greater even than the average expected in a litter produced by full siblings with unrelated parents.
Fixation Index (Fis)
In a randomly breeding population, the average Fis (fixation index) would be zero. Fis of individual dogs is determined as their F minus the average F of the population. Therefore, a value of Fis greater than zero indicates that the parents of the dog are more closely related than the average in the population, suggesting purposeful pairing of closely related dogs.
Fixation Index (Fis)
In a randomly breeding population, the average Fis (fixation index) would be zero. Fis of individual dogs is determined as their F minus the average F of the population. Therefore, a value of Fis greater than zero indicates that the parents of the dog are more closely related than the average in the population, suggesting purposeful pairing of closely related dogs.
The average Fis in this population is close to zero (0.025), but there are some really high values (up to 0.279), that reflect choice of mating pairs more closely related than average in this population.
In a randomly breeding population, the average Fis (fixation index) would be zero. Fis of individual dogs is determined as their F minus the average F of the population. Therefore, a value of Fis greater than zero indicates that the parents of the dog are more closely related than the average in the population, suggesting purposeful pairing of closely related dogs.
The average Fis in this population is close to zero (0.025), but there are some really high values (up to 0.279), that reflect choice of mating pairs more closely related than average in this population.
Kinship (K)
The level of inbreeding in a litter of puppies is predicted by the degree of relatedness or genetic similarity of the parents. This is quantified by the kinship coefficient (K); that is, the kinship coefficient of a bitch and sire (the parents) is equal to the predicted (average) inbreeding in their hypothetical litter.
The mean kinship (mK) for a dog is the average of all of the potential pair-wise kinship coefficients in the population of interest. Dogs that are closely related to many others in the population (e.g., offspring of a popular sire) will have a high mK; dogs carrying alleles that are uncommon in the population will be genetically less similar on average to the rest of the population and, for them, mK will be relatively low.
In a randomly breeding population, we would expect the histograms for inbreeding and mean kinship to be similar. The histogram of mean kinship for the animals in this population of Cavaliers is similar to that for inbreeding. The average mean kinship is 0.299, which is less than the average level of inbreeding (36.5%). This means that levels of inbreeding could be reduced somewhat by taking advantage of parental pairings that were less related. Note that the average includes three very low values, so the median mK is somewhat higher than the mean but still less than the average inbreeding.
The level of inbreeding in a litter of puppies is predicted by the degree of relatedness or genetic similarity of the parents. This is quantified by the kinship coefficient (K); that is, the kinship coefficient of a bitch and sire (the parents) is equal to the predicted (average) inbreeding in their hypothetical litter.
The mean kinship (mK) for a dog is the average of all of the potential pair-wise kinship coefficients in the population of interest. Dogs that are closely related to many others in the population (e.g., offspring of a popular sire) will have a high mK; dogs carrying alleles that are uncommon in the population will be genetically less similar on average to the rest of the population and, for them, mK will be relatively low.
In a randomly breeding population, we would expect the histograms for inbreeding and mean kinship to be similar. The histogram of mean kinship for the animals in this population of Cavaliers is similar to that for inbreeding. The average mean kinship is 0.299, which is less than the average level of inbreeding (36.5%). This means that levels of inbreeding could be reduced somewhat by taking advantage of parental pairings that were less related. Note that the average includes three very low values, so the median mK is somewhat higher than the mean but still less than the average inbreeding.
Observed Heterozygosity (Ho)
Heterozygosity is a measure of the amount of genetic variation in a population. Inbreeding, selection, and genetic drift can result in the loss of alleles from the gene pool, which will be reflected in lower heterozygosity. If every locus is heterozygous, the observed heterozygosity (Ho) will be 0.5.
The data for observed heterozygosity (Ho) in this population of Cavaliers indicate substantial loss of genetic diversity (mean = 0.268). This is consistent with high inbreeding and also probably reflects low diversity in the foundation dogs and historical bottlenecks.
Identifying Dogs of High Genetic Value
The individuals in a population that are genetically most valuable have the lowest mean kinship. In Cavaliers, there is a single individual with very low mK (approx. 0.05; CKCS-1005), and for all but a few dogs, mK exceeds 0.25.
Runs of Homozygosity (Inbreeding)
The location of inbreeding on the chromosomes of each dog is visualized in this chart, in which blocks of inbreeding (“runs of homozygosity”) are indicated in blue. There are regions that are homozygous in most individuals (seen as vertical stripes, e.g., on chromosome 6 and 11). This might reflect selection across all individuals for a trait of interest located near those blocks of homozygosity. Runs of homozygosity are more likely to harbor deleterious mutations. So breeders should consider selecting mating pairs strategically to minimize homozygosity in offspring by avoiding potential parents with shared regions of homozygosity.
Heterozygosity is a measure of the amount of genetic variation in a population. Inbreeding, selection, and genetic drift can result in the loss of alleles from the gene pool, which will be reflected in lower heterozygosity. If every locus is heterozygous, the observed heterozygosity (Ho) will be 0.5.
The data for observed heterozygosity (Ho) in this population of Cavaliers indicate substantial loss of genetic diversity (mean = 0.268). This is consistent with high inbreeding and also probably reflects low diversity in the foundation dogs and historical bottlenecks.
Identifying Dogs of High Genetic Value
The individuals in a population that are genetically most valuable have the lowest mean kinship. In Cavaliers, there is a single individual with very low mK (approx. 0.05; CKCS-1005), and for all but a few dogs, mK exceeds 0.25.
Runs of Homozygosity (Inbreeding)
The location of inbreeding on the chromosomes of each dog is visualized in this chart, in which blocks of inbreeding (“runs of homozygosity”) are indicated in blue. There are regions that are homozygous in most individuals (seen as vertical stripes, e.g., on chromosome 6 and 11). This might reflect selection across all individuals for a trait of interest located near those blocks of homozygosity. Runs of homozygosity are more likely to harbor deleterious mutations. So breeders should consider selecting mating pairs strategically to minimize homozygosity in offspring by avoiding potential parents with shared regions of homozygosity.
Population Genetic Structure
Based on the data for kinship coefficients, there is some apparent genetic structure in the breed, shown here as about five subgroups. Even though the animals in the population are all closely related, this chart identifies subgroups that can indicate where to find pairs of least-related dogs.
Based on the data for kinship coefficients, there is some apparent genetic structure in the breed, shown here as about five subgroups. Even though the animals in the population are all closely related, this chart identifies subgroups that can indicate where to find pairs of least-related dogs.
This chart can also be used to identify least-related dogs based on kinship coefficients. All 51 dogs are listed across the top of the table and down the left axis, and the number in each cell indicates the kinship coefficient for that pair. For easier viewing, the cells are coded as: K < 0.0625 (6.25%; green, equivalent to a cross of first cousins), K = 0.125 (12.5%; yellow, half-sib cross), and K > 0.25 (25%; red, full sib cross). The red diagonal represents each dog compared with itself. The chart shows that there are just a few dogs that could produce litters with average COI less than 5%; otherwise, all other pairings would produce average levels of inbreeding between 6 and 12% (inbreeding levels produced by mating first cousins and half siblings, respectively).
As described elsewhere (see www.DogsArk.org), this dendrogram can be used to identify dogs at genetic risk of particular disorders or traits without knowing the genes involved. This can be especially useful when a polygenic genetic influence is expected. It requires only that the individuals with the trait of interest be identified. (See my post about how to read dendrograms.)
For more information about using kinship coefficients in dendrograms to evaluate the potential expression of heritable traits see Cool tricks with Kinship Coefficients, part 1: "Is this dog really an outcross?".
For more information about using cluster analysis and dendrograms to explore genetic patterns in disease and traits in a breed, see “Cool tricks with kinship coefficients, part 3: “How can I manage a disease without a DNA test?”
Finding Genetic Diversity in a Breed
The limited number of animals in this dataset might not be representative of the larger population of the breed worldwide, which would include dogs outside the US, as well as dogs from pet and high volume breeders. Breeders might find dogs with relatively low relatedness to this population.
Potential Impacts of Breeding Strategy on Health
If the population examined here is representative of the larger breed population, it indicates that there is little useful genetic variation in this breed that can be exploited to reduce levels of inbreeding. Of course, it would be worth doing a survey of other populations, but knowing the history of this breed, breeders are unlikely to find populations of dogs that could be exploited to make a significant genetic improvement in the breed.
Under the circumstances, breeders should initiate a crossbreeding program that is strategically designed to restore both genetic diversity and the structure of the skull that is predisposing for development of syringomyelia of Chiari syndrome. To do this, the dogs to be used in cross breeding should be carefully selected after considering the specific issues to be remedied in the program.
As described elsewhere (see www.DogsArk.org), this dendrogram can be used to identify dogs at genetic risk of particular disorders or traits without knowing the genes involved. This can be especially useful when a polygenic genetic influence is expected. It requires only that the individuals with the trait of interest be identified. (See my post about how to read dendrograms.)
For more information about using kinship coefficients in dendrograms to evaluate the potential expression of heritable traits see Cool tricks with Kinship Coefficients, part 1: "Is this dog really an outcross?".
For more information about using cluster analysis and dendrograms to explore genetic patterns in disease and traits in a breed, see “Cool tricks with kinship coefficients, part 3: “How can I manage a disease without a DNA test?”
Finding Genetic Diversity in a Breed
The limited number of animals in this dataset might not be representative of the larger population of the breed worldwide, which would include dogs outside the US, as well as dogs from pet and high volume breeders. Breeders might find dogs with relatively low relatedness to this population.
Potential Impacts of Breeding Strategy on Health
If the population examined here is representative of the larger breed population, it indicates that there is little useful genetic variation in this breed that can be exploited to reduce levels of inbreeding. Of course, it would be worth doing a survey of other populations, but knowing the history of this breed, breeders are unlikely to find populations of dogs that could be exploited to make a significant genetic improvement in the breed.
Under the circumstances, breeders should initiate a crossbreeding program that is strategically designed to restore both genetic diversity and the structure of the skull that is predisposing for development of syringomyelia of Chiari syndrome. To do this, the dogs to be used in cross breeding should be carefully selected after considering the specific issues to be remedied in the program.
