The Institute of Canine Biology
  • HOME
  • Blog
  • Courses
    • COI BootCamp (FREE!)
    • Basic Population Genetics (FREE)
    • The Science of Canine Husbandry
    • Managing Genetics For the Future >
      • Syllabus - Managing Genetics for the Future
    • The Biology of Dogs (Open Reg )
    • DNA For Dog Breeders >
      • Syllabus - DNA for Dog Breeders
      • Open Reg - DNA For Dog Breeders
    • Understanding Hip & Elbow Dysplasia >
      • Open Reg - Understanding Hip & Elbow Dysplasia
    • Genetics of Behavior & Performance >
      • Syllabus - Genetics Behavior & Performance
      • Open Reg - Genetics of Behavior & Performance (Open Reg)
    • Strategies for Preservation Breeding >
      • Open Reg - Strategies for Preservation Breeding
    • Group Discounts
    • MORE FREE COURSES >
      • Quickie Genetics (Free!)
      • Heredity & Genetics (Free!)
      • Useful Genetics (Free!)
      • Basic Genetics Videos
  • Breed Preservation
    • Breed Status
    • Breeding for the future >
      • BFF Breed Groups
    • The "Elevator Pitch"
    • What's in the Gene Pool?
    • The Pox of Popular Sires
    • What population genetics can tell us about a breed
    • What population genetics can tell you...Tollers & Heelers
    • How to use kinship data
    • Using EBVs to breed better dogs >
      • How population size affects inbreeding
      • EBV Examples
    • How to read a dendrogram
    • Global Pedigree Project >
      • The Database
    • Finding the genes without DNA
    • How to read a heat map
  • Health Data
    • Bloat (Purdue Study)
    • Body Condition Score >
      • % Dysplastic vs BCS
    • Breed Comparions
    • Cancer
    • Cardiac
    • Cataracts
    • Caesareans
    • Deafness
    • Degenerative Myelopathy
    • Elbow Dysplasia
    • Epilepsy
    • Genetic Diversity
    • Genetic Diversity (MyDogDNA)
    • Hip Dysplasia >
      • Hip Dysplasia (Hou et al 2013)
    • Inbreeding Effects
    • Inbreeding (Gubbels)
    • Inbreeding (Dreger)
    • Lifespan
    • Litter size
    • Metabolic
    • mtDNA
    • Orthopedic
    • Mode of Inheritance
    • Patella Luxation
    • Thyroid
    • Portosystemic shunt
    • Purebred vs Mixed (UC Davis)
    • Purebred vs Mixed Breed (Bonnett)
    • Spay & Neuter Effects
    • Calboli et al 2008
    • Hodgman (1963)
    • Scott & Fuller (1965)
    • Stockard: Purebred crosses
    • Summers (2011)
  • Projects
    • How To Interpret Breed Analyses
    • Afghan Hound
    • More details about the Toller study
    • Belgian Tervuren >
      • Belgian Terv p2
      • Belgians- why population size matters
    • Bernese Mountain Dog
    • Boxer
    • Brussels Griffon
    • Bullmastiff
    • Canaan Dog >
      • Canaan analyses
    • Cesky Terrier >
      • Cesky genetic history
    • Chinook
    • Curly-coated Retriever
    • Doberman
    • Entelbucher Mountain Dog
    • Flatcoat Retriever
    • French Bulldog
    • German Shorthair
    • Golden Retriever >
      • Golden Retriever Pedigree Charts
    • Irish Water Spaniel >
      • IWS (6 Nov 17)
    • Labrador Retriever
    • Manchester Terrier
    • Mongolian Bankhar >
      • Research Updates
      • Bankhar 1
    • Norwegian Lundehund
    • Plummer Terrier
    • Otterhound
    • Portuguese Water Dog >
      • Portuguese Water Dog (pt 2)
    • Ridgeback
    • Schipperke
    • Standard Poodle >
      • The Problem With Poodles
      • 3poodle pedigree charts
      • 3Poodle Wycliff dogs
      • Poodle Genetics
    • Tibetan Spaniel
    • Tibetan Mastiff
    • West Highland White Terrier
    • Whippet
    • Wirehaired Pointing Griffons
    • UK KC Graphs >
      • UK KC Breed Status
      • UK Groups
      • KC Gundogs
      • KC Hounds
      • KC Terriers >
        • Terriers (select breeds)
      • KC Pastoral
      • KC Toys
      • KC Working
      • KC Utility
      • Australian KC
    • Breed outcrossing programs
  • Resources
    • Genetics Databases
    • Stud Books >
      • American Kennel Club stud books
      • Field Dog stud books
      • The Kennel Club (UK)
    • Learn
    • Videos about dog genetics
    • The Amazing Things Dogs Do! (videos) >
      • Livestock Management
      • Livestock guarding
      • Transportation, exploration, racing
      • Conservation & wildlife management
      • Detection Dogs
      • Medicine & Research
      • Entertainment
      • AKC/CHF Podcasts
    • Read & Watch
    • Bookshelf

Dog breeding in the era of genomic selection

11/26/2016

 
By Carol Beuchat PhD
Early dog breeding: selection on phenotype

For most of history, the creation of populations of different types of dogs was based on phenotypic selection, the preferential mating of dogs that displayed the desired traits.

It wasn't until about 200 years ago that we realized that we could select for desirable traits more efficiently if we understood that phenotype reflects genotype, and that genes are the raw material of selection. ​From there, it was easy to understand that if we had a way to know which genes were in a dog, we could predict much more accurately what traits it was likely to pass on to its offspring then if we just knew the phenotype.
Current dog breeding: selection on genes

​
In the mid-1900s we discovered the structure of DNA, the double helix, and the physical nature of genes. Then the race was on to identify the very building blocks of the genes themselves, the nucleotides. These create the language of genetics using only four letters, A, C, T, and G. 
We can now read these genetic instructions in the DNA code letter by letter, using a process called DNA sequencing. When the first human genome (the genome is the entire genetic content of an animal or plant) was sequenced, it took a decade and cost $30 billion dollars. Today, we can do the same thing in a matter of a day or two and it costs about $1,000. ​
Picture
Picture
There are changes in the structure of many breeds over the last hundred years of purebred dog breeding that reflect selection on phenotype alone.
The ability to read the genetic library of an animal has revolutionized animal breeding. Instead of trying to select for particular traits by evaluating phenotype, we can select specifically for the genes that result in or are associated with those traits. Now, we can run DNA tests on prospective breeding dogs that will tell us if an animal carries a particular disease-causing mutation, even though that mutation might have no effect at all on the dog that carries it. There are now dozens of DNA tests for known mutations in dogs, and the list will surely get longer.
The future of dog breeding: selection on genotype

Even as DNA testing has revolutionized how we breed dogs, we are still far from taking full advantage of the advances in molecular genetics. The DNA tests we now have allow selection against specific mutations, or for particular desirable traits like color, but DNA tests are not useful for complex traits that might involve dozens or even hundreds of genes. Instead, we could leverage the massive amount of information coded in the DNA if we could evaluate not just a handful of genes, but many hundreds or even thousands.

​The technology now exists to do this. It's called genomic selection.
​

Picture
A simple example of genomic selection
Let's say that you have a bitch that you plan to breed and you've identified several potential sires to consider, any of which you would be happy with based on conformation, temperament, and health testing.

You can select the sire that is likely to produce the highest genetic diversity in the puppies by comparing the genotypes of the potential parents. By comparing the DNA of two individuals, we can determine relationship coefficient, the actual fraction of genes that are shared by a pair of dogs. 


The chart with colored squares is a genomic relationship matrix with data for five Neapolitan mastiffs. The animal at the upper left (red square, FZ6D12) is a female.The other four dogs are males. An animal compared with itself has a relationship of 1 (red squares). In the comparison of the female to the four males, the intensity of green indicates their genetic similarity, with darker green indicating greater difference.  From this, you can see that of the four potential sires, the one right next to the female on the chart (PFZ43B01) is the darkest green. It is therefore the most different from the bitch and would produce puppies with the highest genetic diversity.

ICB is developing a tool that will allow breeders to take advantage of the tremendous amount of information coded in the genome. The ICB Breeder Tool will integrate the data from high-resolution, whole genome DNA analysis with pedigree, health, and trait data. These combined resources will provide breeders with the best information about the genetics of a dog that has ever been available. All in one database. 
Picture

​What's so cool about genomic selection?

a) Genomic selection allows you to select for (or against) the genes for a trait
The phenotype of a trait that you can observe or measure reflects the effects not just of genes, but of environment as well. A dog with the genes for large size might not achieve its full potential if its diet doesn't contain adequate nutrition. Using only phenotype for selection, we assume that what we can see tells us about the genes in the dog. But many traits are affected not only by genes but also environment, and we have no way to separate those two influences just by looking at phenotype. However, if we know which genes are associated with size, we can select directly for those, making breeding more efficient and predictable.

b) We can predict the traits of offspring despite uncertainty about ancestry
Historically, we have relied on pedigree relationships and information about the the traits of related dogs to predict what we might see in offspring. But we don't always have pedigree data, and selecting directly for the genes associated with a trait we want solves this problem.
c) Genomic data can be used to identify and fix errors in pedigree databases
Pedigrees carry an enormous amount of information about the relationships among dogs - if they are correct. But mistakes happen, parentage isn't always certain, and sometimes reporting isn't entirely honest. Not being able to trust a pedigree definitely limits how useful it can be. But genomic data can allow us to identify errors in a pedigree database and fix them (Munoz et al 2014). 
d) Genetic and pedigree information are more powerful than either alone
Just because we can "see" the genes we want to select for, don't throw those pedigree data away! Using both pedigree and genomic data together, we can make much better predictions about the genetic value of a dog for a particular trait. Together, they are more powerful than either alone (Aguilar 2010; Do et al 2014; Dreger et al 2016; Meuwissen et al 2011; Zhang et al 2015)). 
Picture
Picture
e) Genomics allow selection for or against traits that are not expressed
One problem with using phenotypic selection alone is that you can't select against disorders that only show up later in life. Many eye disorders, neurological and muscular dystrophies, epilepsy, and cancer foil efforts of breeders to improve health because they might not appear until later in life, after an animal has been bred. You also can't select efficiently on traits that are only expressed in one sex, like milk quality or cryptorchidism.
f) Genomic selection allows us to use information from many thousands of loci across all chromosomes
More information is definitely better. Before the advent of the modern SNP chip (pronounced "snip chip"), information from genomic markers called microsatellites was used in genetic prediction. Microsatellites have been used for selection and also for parentage verification for several decades, but the number of markers used is usually limited to less than 100. Using SNP technology, we can have thousands of markers on each chromosome, and the most recent version of the Illumina Canine High Density SNP chip has about 230,000. This provides vastly more information than can be obtained using a few dozen microsatellites. For this reason, SNP technology is overtaking microsatellites as the method of choice for genetic studies across the whole genome.
Picture
g) Genomic selection allows us to select for (or against) traits with low heritability
The expression of a trait usually reflects the effects of both genes and environment. Heritability is a way of measuring how much of the variation in the expression of a trait is due to genes versus environment. If heritability is low, then the effects of environment make it very difficult to select genotype on the basis of phenotype alone. Genomic data can solve that problem.
h) Genomic selection does not require knowing causative alleles
Dealing with traits that result from single genes is relatively straightforward. In many cases, we can identify the allele and develop a test, and we now have an arsenal of DNA tests that are now done on breeding stock. But far more traits are polygenic and we will probably never know all of the causative genes. In these cases, we can use statistics to identify suites of genes that are associated with particular traits, even without knowing exactly what the genes do. In this way, genomic selection has been used to accomplish amazing improvements in the traits of livestock animals, as well as sport and pleasure horses, and of course many crop species.

​Using a genomic breeding tool

ICB is introducing the first tool for genomic selection available to dog breeders that makes use of high-density SNP data (> 200,000 SNPs). It will report individual inbreeding, genomic relationship coefficients, allelic diversity, expected offspring genotypes and diversity, and clear/carrier/affected status for most known mutations. It will also report statistics for entire breeds and subpopulations such as genetic diversity, kinship, rates of inbreeding, loss of genetic diversity, and effective population size (Do et al 2014). Paired with phenotype information (e.g., health or disease records, conformation, temperament, behavior evaluations, etc), the ICB Breeder Tool can be used to produce estimated breeding values to improve the efficiency of selection for or against complex traits (Hou et al 2013).
The ICB Genomic Breeding Tool is currently in beta testing. You can read more about it HERE and HERE.

The whole genome DNA test will be available within the next couple of weeks, and we expect the Genomic Breeding Tool to be available around the beginning of the year. Watch this space for dates! 

​If you think your breed might be interested in participating in beta testing, please contact Dr Carol Beuchat at ICB. (carol@instituteofcaninebiology.org)

REFERENCES

Aguilar I, I Misztal, DL Johnson, A Legarra, S Tsuruta, & TJ Lawlor. 2010. A unified approach to utilize phenotypic, full pedigree, and genomic information for genetic evaluation of Holstein final score. J Dairy Sci 93: 743-752.

Do K-T, J-H Lee, H-K Lee, J Kim, & K-D Park. 2014. Estimation of effective population size using single-nucleotide polymorphism (SNP) data in Jeju horse. J Animal Sci 56:28.

Dreger DL, M Rimbault, BW Davis, A Bhatnagar, HG Parker, & EA Ostrander. 2016. Whole genome swquence, SNP chips and pedigree structure: building demographic profiles in domestic dog breeds to optimize genetic trait mapping. Dis Model Mech 17 (in press).

Eynard SE, JJ Windig, G Leroy, R van Binsbergen & MPL Calus. 2015. The effect of rare alleles on estimated genomic relationships from whole genome sequence data. BMC Genetics 16:24.

Hou Y, Y Wang, XLu, X Zhang, Q Zhao, RJ Todhunter, & Z Zhang. 2013. Monitoring hip and elbow dysplasia achieved modest genetic improvement of 74 dog breeds over 40 years in USA. PLoS One 8(10): e76390.

Meuwissen THE, T Luan, & JA Woolliams. 2011. The unified approach to the use of genomic and pedigree information in genomic evaluations revisited. J Anim Breeding & Genetics 128: 429-439.

Munoz PR, MFR Resende Jr, DA Huber, T Quesada, MDV Resende, DB Neale, JL Wegrzyn, M Kirst, & GF Peter. 2014. Genomic relationship matrix for correcting pedigree errors in breeding populations: impact on genetic parameters and genomic selection accuracy. Crop Science 54: 1115-1123.

Zhang Q, MPL Calus, B Guldbrandtsen, MS Lund, & G Sahana. 2015. Estimation of inbreeding using pedigree, 50k SNP chip genotypes and full sequence data in three cattle breeds. BMC Genetics 16:88.

Check out
ICB's online courses
​

*******************

Join our Facebook Group
ICB Breeding for the Future
...the science of dog breeding
*******************

Visit our Facebook Page
ICB Institute of Canine Biology
...the latest canine news and research

The New ICB Genomic Breeding Tool: the genomic relationship coefficient

11/23/2016

 
By Carol Beuchat PhD
"How related are these dogs??

Dogs that are more related are likely to be more similar genetically than less related dogs. B
reeders often want to know how related a dam and sire are because it tells them something about the traits likely to be expressed in a litter of puppies, and it also reflects the risk of inherited genetic disorders.

We can put a number on the degree of genetic similarity between a pair of dogs using the "Relationship Coefficient," which is the fraction of their genes that they share in common. 


For example, a parent and offspring should have a relationship coefficient of 0.5, because the progeny inherits half of its genes from each parent. A pair of dogs that are less related, like half-sibs or cousins, will be less similar genetically and have a lower relationship coefficient. 

You can estimate the relationship coefficient between a pair of dogs from pedigree data. Of course, you can never really know exactly which alleles have been inherited by a dog, so the relationship coefficient determined from a pedigree is just an estimate. You can get a far better estimate of genetic similarity by directly comparing the genes in the pair of dogs.

​Thanks to DNA analysis, we can now do this.
​
The Genomic Relationship Coefficient

ICB has been working on the development of new tools that will provide breeders with information about the genetic similarity of dogs by direct comparison of their DNA sequences. The resulting number for a pair of individuals is called the "genomic relationship coefficient". The higher this number, the more similar the DNA of the two dogs. (Identical twins would have a genomic relationship coefficient of 1.)

You might also be interested in the relatedness among the dogs in a group, or between two groups. Perhaps you want to compare dogs from two different subpopulations (e.g. bench vs field lines, UK vs US dogs, or dogs from different kennels). For this, you would determine the genomic relationship coefficients for every pair of dogs in the groups to be compared. If you only have a few dogs, this is relatively easy, but for more dogs the table of numbers gets big very quickly.

To make it easy visualize patterns in the relationship coefficients among larger numbers of dogs, we can use two graphical tools. The first is called a dendrogram, which is a type of pedigree tree that visually displays the magnitude of the relationship coefficient by the length of the branches. The other tool is called a "heat map", because it displays numerical values using different colors or variations in the intensity of color. Let's look at an example.
Below is the dendrogram and heat map produced from a "genomic relationship matrix - the table of all of the pairwise relationship coefficients for a random collection of Jack Russell Terriers, computed from DNA data. 

The IDs of the dogs are listed across the bottom and also down the right axis in the same order. The "Heatmap Color Key" in the upper left corner displays the colors that correspond to relationship coefficients from 0 to 1.

The row of red squares across the diagonal of the chart is each dog's relationship coefficient with itself, which is equal to one. The other squares are for each pairwise comparison of all of the dogs in the population. So, in the upper right hand corner, the first square compares dog PFZ44D01 with dog JRT_GT255. The square is a dark shade of blue, indicating that their genetic similarity is relatively low. In the middle of the graph you can see two turquoise squares, which indicate a pair of dogs that have a higher amount of genetic similarity. The reason there is a pair of squares on each side of the line of red squares is because the graph is a mirror image of itself along the diagonal. (Convince yourself of this by finding the IDs of the the pair of dogs for each of the turquoise squares.)
Jack Russell Terriers
Picture
Also displayed on this chart are dendrograms displaying the genetic relationships among the dogs determined by comparing their DNA. (Again, the dendrogram across the top is the mirror image of the one down the left axis, although the colors used for the groups are not the same.) If you look at the group of three dogs in the upper left corner (in green), you see that three of the dogs are closely related; the pairs of squares are turquoise, and the branches of the dendrogram that connect them are short. The fourth dog, on the end (PFZ44DO1), is less related to the other three, with a longer branch connecting it and a dark blue square.

This chart provides you with a lot of information about this particular population of Jack Russel Terriers. There is a group of 4 dogs that seem to be genetically distinct from all of the rest, three of which are very closely related. The rest of the dogs vary in relatedness in pairwise comparisons, but on average their genetic similarity is low.

Here is a more complicated example using data for Irish Wolfhounds. As before, there is a (tiny) row of red squares across the diagonal for each dog's comparison with itself. The patches of lighter color squares are for groups of dogs that are more closely related. You can also see that that these correspond to groups of dogs in the dendrogram that are connected by shorter branches. The dendrogram has used different colors for related clusters of dogs, making it very easy to pick out the groups.
Irish Wolfhound
Picture

You should see in the Wolfhound data that there are actually two large groups of dogs connected by the highest horizontal branch. I don't have any information about these dogs, but the two clusters might depict dogs from different countries, or perhaps lines that have been bred more or less independently for many generations. The shortest branches might be connecting the dogs in a litter. The overall lightness of the blue (compared, for example, to the graph for Jack Russell Terriers) indicates that the genetic diversity in this population of dogs is relatively low.

You can also use DNA data to explore the genetics within a line or even a litter of dogs. Of course, you would expect the puppies in a litter to be genetically similar although each will be different. If you created the genomic relationship matrix of a litter of six puppies, you might see something like the chart below, in which two of the pups are similar to each other but less like the others. You might get a litter like this from breeding two dogs that are not closely related, and just by chance some of the puppies were much more similar to each other than they are to the rest.
Picture


​Introducing: ICB's Genomic Breeding Tool

ICB's Genomic Breeding Tool is the most powerful genetic tool available to breeders today, providing information about:

  • genetic similarity of pairs of dogs by direct comparison of DNA
  • individual inbreeding coefficient of each dog
  • overall genetic similarity of the dogs in the population
  • identification of subpopulations or genetically similar clusters
  • genetic diversity of the population

The DNA analysis ICB uses for this compares uses the newest version of the high density Illumina CanineHD SNP chip. This analysis identifies more than 200,000 DNA nucleotides distributed across each of the dog's 38 autosomal chromosomes, the two sex chromosomes, and the mitochondrial DNA (mtDNA). The same DNA analysis also tests for most genetic mutations for which a test is available, as well as X and Y chromosome and DLA haplotypes. This is the highest level of genetic comparison available anywhere. (For comparision, MyDogDNA uses about 7,000 nucleotides for their breeding tool, and the UC Davis VGL genetic diversity test uses 33 microsatellites.)

The data produced for the ICB Genomic Breeding Tool can also be combined with pedigree data, which will allow breeders to infer the relationships among dogs for which DNA is not available. We can also superimpose health information on this, which will facilitate identifying lineages of dogs at greater risk of a particular disorder. (Read about how to do this here.)

The ICB Genomic Breeding Tool is currently in beta testing. The whole genome DNA test will be available within the next couple of weeks, and we expect the Genomic Breeding Tool to be available around the beginning of the year. Watch this space for dates!

​If you think your breed might be interested in participating in beta testing, please contact ICB.

Check out
ICB's online courses
​

*******************

Join our Facebook Group
ICB Breeding for the Future
...the science of dog breeding
*******************

Visit our Facebook Page
ICB Institute of Canine Biology
...the latest canine news and research

    Archives

    January 2025
    November 2022
    July 2022
    May 2022
    April 2022
    March 2022
    February 2022
    November 2021
    October 2021
    December 2020
    January 2020
    August 2019
    July 2019
    June 2019
    May 2019
    April 2019
    March 2019
    February 2019
    January 2019
    December 2018
    November 2018
    September 2018
    August 2018
    July 2018
    June 2018
    May 2018
    October 2017
    August 2017
    May 2017
    April 2017
    March 2017
    February 2017
    January 2017
    December 2016
    November 2016
    September 2016
    August 2016
    July 2016
    June 2016
    April 2016
    March 2016
    February 2016
    January 2016
    December 2015
    November 2015
    October 2015
    September 2015
    August 2015
    July 2015
    June 2015
    May 2015
    April 2015
    March 2015
    January 2015
    December 2014
    November 2014
    October 2014
    September 2014
    August 2014
    July 2014
    June 2014
    May 2014
    February 2014
    December 2013
    October 2013
    September 2013
    July 2013
    March 2013
    July 2012
    April 2012

    Categories

    All
    Behavior
    Border-collie
    Herding

Blog

News


About Us

Contact Us








Copyright © 2012-2017 Institute of Canine Biology
Picture
Picture