Estimated Breeding Values (EBVs)
and the Cavalier King Charles Spaniel
-
What
are EBVs? - Importance of objective data
- Can a dog's EBV change?
- How are EBVs to be used?
- Genetics of SM -- By Dr. Sarah Blott
- Related Links
- Veterinary Resources
What are EBVs?
An “estimated breeding value” (EBV) is a statistical numerical prediction of the relative genetic value of a particular dog (male or female) available for breeding. EBVs are used to rank breeding stock for selection, based upon the genetic risk of each dog with regard to one or more specified traits. An EBV therefore is a calculated estimate of heritability for each trait being considered, relative to the EBVs of other dogs in the breeding population.
EBVs for Cavalier King Charles spaniels are intended to be each dog’s genetic risk of disease – initially syringomyelia and early-onset mitral valve disease – relative to the rest of the available breeding stock.
EBVs are calculated by compiling as much objective information about each dog as possible, including health test data, together with its pedigree information and physical characteristics. The sum of this data is called the dog’s “phenotype” – what can be observed and measured with respect to the disease(s). A dog’s phenotype will consist of both genetic and non-genetic components.
The importance of using objective data
To be useful to breeders, EBVs must be accurate and unbiased. This accuracy applies to both the particular dog being examined as well as the breeding population as a whole. For EBVs to be accurate, the calculators constantly need as much information, particularly health test data, on as many Cavaliers as possible.
Can a dog’s EBV Change?
EBVs are based upon the data available for estimating them. As new information is collected, about the particular dog or its relatives, its EBV can be re-calculated to improve the accuracy of its estimate. Initially, an off-spring’s EBV is the sum of its sire’s and dam’s scores, divided by two. As more and more of the dog’s health test data and other information is acquired, the EBV will change.
How are EBVs to be used?
The EBV system is evolving and currently in its early stage, and presently only among Cavaliers in the United Kingdom. In the UK, once EBVs are assigned , breeders can compare the EBVs of the breeding stock, to determine which Cavaliers may be expected to best meet the SM and MVD breeding protocols when bred.
EBVs will be an important, objective (and hopefully unbiased) tool for breeders to use in the process of selecting breeding stock. Their aim is to improve the accuracy of breeding stock selection decisions, resulting in reducing the risk of genetic disease in each succeeding generation.
Genetics of SM
Genetics of Syringomyelia and Breeding Strategies
to Reduce Occurrence
By SARAH BLOTT, PhD (Quantitative Genetics), MSc (Animal
Breeding)
Genetics Department, Animal Health Trust, UK
Notes for the Cavalier King Charles Spaniel Clubs Liaison Meeting 18 May 2008
Syringomyelia is believed to be a complex disease, where the disease phenotype results from the effects of several genes plus environmental influences. The phenotype includes not only the affectation status of the individual but also clinical observations and measurements made from MRI scans. In order to determine the genetic basis of the disease two different approaches are being taken. The first uses a population-based approach, where phenotypic measurements and pedigree information are used to estimate the heritability of the disease. This requires that we have accurate phenotypic measurements, including MRI scans, on as much of the population as possible, together with pedigrees so that genetic relationships between individuals can be identified.
Where information exists on other diseases, such as Mitral Valve Disease, this can also be included in the analysis allowing genetic correlations between diseases to be established. It is important to know about correlations, or relationships, between diseases so that any selection strategies take account of the possible influence that selection against one disease may have on other diseases. The second approach to understanding the genetic basis of a disease is to use molecular genetics and gene mapping techniques to try to identify the underlying causative mutations. This approach is also being used to try to identify genes causing both Syringomyelia (SM) and Chiari Malformation (CM) in the Cavalier King Charles Spaniel (CKCS) and other toy breeds such as the Brussels Griffon. It is hoped that this will identify regions of the genome harbouring the genes causing these conditions.
Data collected by Penny Knowler and Clare Rusbridge is currently being used as the basis for the population-based analysis of heritability. Their database contains clinical observations for SM and CM on around 1,400 dogs and MRI scan results for around 700 of these dogs. We have also been given access to the full UK Kennel Club pedigree records for CKCS. This enables us to estimate the heritability of SM and the genetic correlations between SM and measurements made from the MRI scans. The information obtained from this analysis then allows us to derive estimated breeding values (EBVs) for all measured dogs as well as all dogs in the pedigree.
Once the results of the gene mapping studies become available it is hoped to bring this information together with the population analysis to facilitate the calculation of genomic breeding values (geBVs). Early estimates of the heritability of SM suggest it is around 0.7-0.8 (Preliminary estimate which may be subject to later modification) or that 70-80% of the variation between individuals is genetic in origin and about 20-30% is environmental. In the case of SM not much is known about the environmental influences and these may include in-utero or developmental effects. The heritability is sufficiently high, however, that genetic selection against the disease should be very successful. Heritabilities for Chiari Malformation, Cerebellar Herniation and Medullary Kinking are also very high. Genetic correlations between these traits and SM are positive and, interestingly, less than one. This suggests that different genes may be controlling SM and CM and that it will be possible to select against SM even if dogs have the malformation (CM).
One concern that we have at the present is that the estimates of heritability may be biased upwards. This is because the data has been ascertained on the basis of clinical cases. Most dogs will be MRI scanned because of concern that the dog may have SM or because the family or line is known to be afflicted by the condition. It is probably fairly rare that unaffected dogs from clear lines would be MRI scanned. We are taking various approaches to trying to iron out the bias, most based on modifying the statistical analysis, but it would also be beneficial if some dogs identified as unaffected could be MRI scanned. The plan is to then consolidate the estimated breeding values (EBVs) and try to estimate them for the entire UK registered population of CKCS. To help towards this aim we would like to collate the results of MRI scans coming from all clinics that are currently offering scans. We intend to set up a webpage where people can submit information directly and which gives details of where information can be sent by post. We hope to have this in operation in the next few weeks.
Estimated Breeding Values (EBVs) are the best measure available for complex traits of the genetic potential of individuals. The breeding value is the sum of the genetic effects and is the equivalent of an animal’s genotype at all the genes contributing to the disease. The EBVs for SM allow us to go from a dichotomous outcome (affected or unaffected) to an underlying continuous scale of liability. This gives us a much finer grading on which to evaluate dogs, leading to much more accurate selection. As an example, the figure below shows how EBVs compare with the A-F grading based on the MRI scans (gradings proposed by Clare Rusbridge). Grades A-C have more favourable (lower or more negative) EBVs while grades D-F are unfavourable. The gradings, however, do span a range of breeding values and some dogs graded A-C may have EBVs which suggest they can pass on a degree of disease risk to their offspring.
Using
EBVs allows us to distinguish between higher and lower risk dogs in the grading
categories A-C. EBVs can be calculated for most dogs even if they have not been
MRI scanned, as long as they are related to dogs that have been scanned. The
predicted EBV of an individual is half the EBV of its sire plus half the EBV of
its dam. All dogs will have an EBV at birth but the EBV may be modified by the
dog’s subsequent clinical record or MRI scan and by information coming from
other relatives.
The EBV becomes more accurate as information on offspring becomes available, because we start to gain insight into which half of the sire and dam genes were actually inherited when we see transmission of the genes to offspring. The accuracy of the EBV increases with numbers of offspring and this may take some time to achieve. In contrast, genomic breeding values (geBVs) provide a high accuracy from birth. By looking directly at the DNA genotypes we can see which genes were inherited from the sire and from the dam, without having to wait for offspring. Genomic breeding values can be used for accurate evaluation at an early stage, before the disease phenotype may be apparent and before a dog is used for breeding.
In
addition to selecting away from individual known diseases, such as
syringomyelia, it is important to consider the long-term health of the breed.
Population diversity and maintenance of diversity is important in order to
minimize the risk of future new diseases arising. We want to apply
state-of-the-art genetic selection techniques that use optimal contribution
theory to help avoid unequal representation of individuals in future generations
or ‘genetic bottlenecks’ occurring. This ensures that increases in inbreeding
and loss of diversity are minimized. Our aim is to develop internet-based tools
that allow breeders to have direct access to these state-of-the-art techniques
to help them make optimal selection decisions.
The Cavalier King Charles Spaniel will be the first dog breed in the world for which these techniques will be available. We also plan to explore different breeding strategies, based on computer modelling. This will help us to establish the time-scale over which the disease incidence can be reduced, the range of breeding values that should be used for breeding and the acceptable rate of diversity loss to minimize future disease risk. The immediate next steps in the project are to:
4 Widen our data collection effort to include information for as broad a section of the population as we can. We will be setting up a webpage which will give details on how information can be submitted to us.
4 Look at ways in which we can get a more accurate or unbiased estimate of the disease incidence.
4 Investigate whether SM could be caused by a single gene or whether the multiple gene (polygenic) model fits the data better.
4 Include information on Mitral Valve Disease (MVD) with the aim of producing EBVs for MVD.
We are also working towards the longer term aims of:
4 Modelling different breeding strategies and identifying the most appropriate strategy.
4 Carrying out molecular genetic analysis of SM and CM to identify the underlying genes, in collaboration with the University of Montreal, Clare Rusbridge and Penny Knowler.
4 Developing genomic breeding values (geBVs) for SM.
Dr. Blott may be contacted at Genetics Department, Animal Health Trust, , Lanwades Park Kentford, Newmarket, Suffolk CB8 7UU, telephone +44 1638 751000, fax +44 1638 555606, website: www.aht.org.uk
Related Links
SM Breeding Protocol
Board Certified Veterinary Neurologists
MRI Screening Protocol
Primary Secretory Otitis Media (PSOM)
Questions for Cavalier Breeders
Canine Health Testing Clinics
Dr. Clare Rusbridge:
Dr.
Rusbridge's Comprehensive Website
Dr. Rusbridge's Syringomyelia News Winter 2007 Research Update
Dr. Rusbridge's Syringomyelia News Autumn 2007 Research Update
Dr. Rusbridge's Syringomyelia News 2007 Research Update
Dr. Clare Rusbridge video DVD "Syringomyelia Seminar", contact penny.knowler@ntlworld.com
Veterinary Resources
Heritability of syringomyelia in Cavalier King Charles spaniels. Tom Lewis, Clare Rusbridge, Penny Knowler, Sarah Blott, John A. Woolliams. Vet.J. 183(3): 345-347 Mar. 2010. Quote: "Mixed model analysis of 384 Cavalier King Charles spaniels (CKCS), with a magnetic resonance imaging diagnosis for the presence or absence of a syrinx, in conjunction with the Kennel Club pedigree records of all dogs registered from the mid 1980s to September 2007, revealed a moderately high estimate of heritability of syringomyelia (h2 = 0.37 ± 0.15 standard error) when analysed as a binary trait. Inspection of cases where the disease segregated within families pointed to genes at more than one locus influencing syringomyelia. The availability of estimated breeding values for Kennel Club registered CKCS is a significant step in being able to select against syringomyelia, particularly given the difficulty of ascertaining the disease phenotype."
Optimisation of breeding strategies to reduce the prevalence of inherited disease in pedigree dogs. Lewis, T.W.; Woolliams, J.A.; Blott, S.C. Animal Welfare 19(Supp 1):93-98(6), May 2010. Quote: "One option for improving the welfare of purebred dog breeds is to implement health breeding programmes, which allow selection to be directed against known diseases while controlling the rate of inbreeding to a minimal level in order to maintain the long-term health of the breed. The aim of this study is to evaluate the predicted impact of selection against disease in two breeds: the Cavalier King Charles spaniel (CKCS) .... Heritabilities for mitral valve disease, syringomyelia in the CKCS ... were estimated to be 0.64 (± 0.07), 0.32 (± 0.125) ... respectively, which suggest encouraging selection responses are feasible based upon the estimation of breeding values (EBVs) if monitoring schemes are maintained for these breeds. Although using data from disease databases can introduce problems due to bias, as a result of individuals and families with disease usually being over-represented, the data presented is a step forward in providing information on risk. EBVs will allow breeders to distinguish between potential parents of high and low risk, after removing the influence of life history events. Analysis of current population structure, including numbers of dogs used for breeding, average kinship and average inbreeding provides a basis from which to compare breeding strategies. Predictions can then be made about the number of generations it will take to eradicate disease, the number of affected individuals that will be born during the course of selective breeding and the benefits that can be obtained by using optimisation to constrain inbreeding to a pre-defined sustainable rate.
