This has been bothering me for a while, and I won't write a long discourse about it now, but we really do need to think about this.

​Breeding programs usually focus on producing dogs that conform to the breed standard. The usual strategy is to use inbreeding to "fix" the traits for type so they are reliably produced every generation. The problem with this is that it assumes there are separate genes for each of these traits, and reproducing the trait is accomplished by producing homozygosity in the relevant genes.

I am reminded of this problem every time I see one of the breeds that demonstrates what I am calling "brachycreep" - shortening of the muzzle, doming of the head, spacing of the eyes farther apart - physical changes on a trajectory towards a brachycephaic head. I have talked about this before, moaning about the loss of a decent muzzle and skull on the Newfoundland, but you can see the same thing in other breeds. Many purebred dog breeds are becoming versions of the Pug. (This is no doubt how the Pug originally came by its breed-defining appearance.) This is an unintended consequence of the way we breed, altering by inbreeding the very traits we want to preserve. ​

The problem, however, is that traits can be the result of many genes, these might interact with yet more genes (epistasis). Most importantly, however, it might be the heterozygous state (two different alleles) of a gene that produces the desired phenotype. So inbreeding that produces homozygosity can in fact prevent the expression of a desired trait. This would not be unusual in animal genetics. In fact, homozygosity could be the reason many traits are being pushed to extremes, even though breeders are not selecting for extreme phenotypes. Crossing two dogs with moderate traits and heterozygous for the relevant genes, could produce offspring with homozygosity and extreme traits. Inbreeding generation after generation does cannot preserve type, because the composition of the gene pool is continuously changing. The notion that inbreeding is preserving type is easily falsified on first principles.

Does your breed have brachycreep?

The Cavalier King Charles Spaniel suffers from a number of serious health conditions. Syringomyelia and Chiari malformation are common in the breed and cause painful neurological issues. A disorder of the heart valve disease is also widespread in the breed, causing heart murmurs and, ultimately, congestive heart failure. 

The gene pool of the breed has been reduced over the years by bottlenecks and popular sires. As a result, the breed suffers from extremely high inbreeding (35-40%) and loss of genetic diversity, so mitigating the health issues by selective breeding within the breed is unlikely to be successful.

The health and welfare issues have drawn enough attention that a lawsuit in Norway banned breeding, and several European countries are also placing restrictions on breeding. However, several kennel clubs have initiated cross-breeding programs with the hopes of introducing new genetic diversity and eliminating the health issues. It will be several years before the outcomes of these efforts are apparent, but the steps are being taken and there is reason to hope that this wonderful breed can be restored to good health.

I have added the Cavalier King Charles Spaniel to the DogsArk Breeder Tool using Embark DNA data so that breeders can take advantage of the advanced analyses that are possible with these data, and I summarize the some of this information below. The DNA data are for anonymous dogs and do not contain information about health and trait markers. However, Embark data submitted by breeders can be incorporated into the analyses (see how here). For an example of what those analyses would look like, check out the Labrador Retriever on the menu of Breeds. 

Below I summarize the information about genetic status of the breed from the DogsArk breeder tool. Note that analyses that require data for specific genes or mutations are currently absent, but they can be added with the submission of Embark DNA analysis to DogsArk.

SYNOPSIS
These analyses were prepared using the DogsArk Breeder Tool.

​​Inbreeding in the Cavalier King Charles Spaniel is very high, with most dogs greater than 25% (equivalent to a cross of full siblings from unrelated parents). There is very little genetic diversity in this sample of 51 dogs, so apart from a handful of dogs that might be useful, there is little breeders can do to bring down levels of inbreeding by breeding within this population. 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 and casual breeders not breeding for show; both might have lower levels of inbreeding and might represent different lines than the dogs produced from show lines 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 Breeder Tool for analysis of genomic data of individuals as well as an overview of the genetic status of the breed or population. Kinship coefficients can identify the dogs that are genetically most valuable and also 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, Norway, and Sweden have begun cross breeding programs, and it would be ideal if US breeders can create a population of Cavaliers 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 information summarized here is extracted from the pages for this breed on DogsArk and 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 or trait information for these dogs. 
 
I processed the data using standard protocols for SNP data from the Illumina HD Canine Bead Chip (high density, >200,000 SNPs). 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)
Data for inbreeding, kinship, and heterozygosity are summarized in the table and displayed in the set of four graphs below. I will summarize each briefly below.

Genomic inbreeding in CKCS is among the highest of any breed (42.1%, Dreger et al 2018; 41.1%, Bannasch et al 2021 ), 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. ​

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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.

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 be able to find dogs among these 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 selected after considering the specific issues to be remedied in the program .  
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