DNA%20Testing%20and%20Marker%20Assisted%20Selection

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DNA Testing and Marker Assisted Selection

• R. Mark Thallman
• U.S. Meat Animal Research Center
• Clay Center, NE

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Applications of DNA Testing

• Parentage Verification
• Parentage Determination (Multisire)
• Traceback
• Qualitative Traits
• Color, polledness, genetic defects
• Quantitative Traits
• Most production and end product traits

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Commercially Available DNA Tests for Quantitative
Traits in Beef Cattle

• GeneStar Marbling
• Genetic Solutions/Bovigen
• GeneStar Tenderness 2
• Genetic Solutions/Bovigen
• TenderGENE
• Frontier Beef Systems/GeneSeek
• IGENITY L
• Merial/Quantum Genetics
• MMIG Mu-Calpain Tender
• MMI Genomics

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Overview

• Should I use DNA testing?
• Which DNA tests should I use?
• Which traits will DNA tests be most useful for?
  
• Which animals should I test?
• How should I use the test results?
• What should breed associations be doing about
  DNA testing?

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Should I Use DNA Testing?
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Benefits of DNA Testing

• Obtain evaluations earlier in the life cycle.
• Increased accuracy of selection, especially for
  traits that are expensive to measure,
  sex-limited, or measured postmortem.
• Get more benefit from each phenotype that is
  measured.
• Greater opportunity to select for traits with
  antagonistic genetic relationships (e.g., birth
  weight and growth rate).

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Cost of Testing
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Should I Use DNA Testing?

• This is a business decision that each breeder
  must make individually.
• It depends as much on the breeders role in the
  industry and marketing plan as it does on the
  cost of testing.

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They Just Use it as a Marketing Tool

• Not an acceptable excuse for not using technology

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They Just Use it as a Marketing Tool

• Not an acceptable excuse for not using technology
• They have said this about weights, EPDs,
  ultrasound, and every other new technology for
  genetic improvement.

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They Just Use it as a Marketing Tool

• Not an acceptable excuse for not using technology
• They have said this about weights, EPDs,
  ultrasound, and every other new technology for
  genetic improvement.
• If it is used successfully in marketing, it is
  influencing breeding decisions.

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They Just Use it as a Marketing Tool

• Not an acceptable excuse for not using technology
• They have said this about weights, EPDs,
  ultrasound, and every other new technology for
  genetic improvement.
• If it is used successfully in marketing, it is
  influencing breeding decisions.
• Over time, it seems that the early adopters of
  technology have benefited the most.

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Which DNA Tests Should I Use?

• A number of detailed questions about DNA tests
  should be answered before deciding which tests to
  use.

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Which DNA Tests Should I Use?

• The essential questions about a test are
• Does it work?
• Does it affect traits that you want to change?
• Does it segregate in your population?

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Independent Characterization of DNA Tests

• Standard resource populations of cattle with
  phenotypes for the desired traits
• Independent institution to conduct the
  characterization
• The National Beef Cattle Evaluation Consortium (
  NBCEC) has initiated such a process.

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Independent Characterization of DNA Tests

• The NBCEC provides DNA to the DNA testing
  company.
• The DNA testing company runs the test on the DNA
  and send the results to the NBCEC.
• The NBCEC analyzes the data and reports results
  in a standardized format as described above.

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Benefits of Independent Characterization of DNA
Tests

• Breeders have better information from which to
  decide which tests to use.
• DNA testing companies can market tests more
  effectively and with greater confidence.
• The process generates information that is needed
  in order for DNA testing data to be included in
  national cattle evaluation.

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The Debate On Characterizing DNA Tests for All
Traits

• If you do enough tests, something is bound to be
  statistically significant.
• The concern is that spurious results will show up
  in advertisements.
• This is a legitimate concern.
• One solution is to only analyze traits for which
  prior evidence of an effect exists.

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The Debate On Characterizing DNA Tests for All
Traits

• However, it is important to know effects on as
  many economically relevant traits as is
  practical.
• There must be some practical solution.
• But, I am outnumbered by my colleagues who think
  we should limit the analysis to only a few traits.

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What if a Test Has Not BeenCharacterized in My
Breed?

• Ideally, tests would be characterized in every
  breed in which they would be used.
• But, that is probably not realistic, so you may
  need to use data from another breed of the same
  biological type as your breed.
• It does not serve anybody if the cost of bringing
  a new test to market is unreasonably high.
• Tests are most likely to be characterized in
  breeds that are proactive in providing quality
  resource populations for the process and that
  tend to use and promote DNA testing technology.

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Realistic Expectations for Independent
Characterization

• We are unlikely to have enough data to answer all
  of the questions we have as clearly as we would
  like.
• Allele frequencies often work against us.
• But some information is better than none.
• If customers come to expect it, it will become
  routine.
• The process will improve with time.

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BIF Guidelines on DNA Testing

• Independent Characterization
• Standardized format for reporting results
• Format in which test results are reported
• Which animals to test
• Data acquisition for NCE
• Nomenclature
• Incorporation into NCE

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Which Traits will be Emphasized?

• Most interest is in traits that are difficult or
  expensive to measure
• Carcass traits, especially tenderness
• Feed efficiency
• Reproductive efficiency
• Disease resistance
• Tests for such traits are difficult to develop
  for the same reasons that they are difficult to
  select for conventionally
• It is also difficult to verify that they work

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Realistic Expectations

• DNA testing can increase the amount of
  information that each phenotype contributes.
• DNA testing can reduce the number of phenotypes
  needed.
• DNA testing can not replace phenotypes.

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Which Traits will be Emphasized?

• There is some merit in developing and using DNA
  tests for which phenotypes are routinely
  recorded.
• One of the benefits of DNA testing is the ability
  to break antagonistic genetic correlations.
• There could be benefit in tests associated with
  birth weight without affecting growth rate.

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Which Animals Should I Test?

• Influential sires
• Herd sire candidates
• Donor prospects
• Optimal testing strategy depends on whether the
  favorable allele is at high or low frequency

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How Should I Use the Test Results?
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Current Genetic Evaluation

• Currently, genetic merit is evaluated in the form
  of EPDs, which are computed from phenotypes on
  the individual and its relatives.

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The Myth
Pedigree
Phenotypes
Easy, Highly Accurate Evaluation of Genetic Merit
DNA Tests
Phenotypes
Phenotypes
EPDs
Progeny

• For a long time, breeders have been told that an
  animals genetic potential will be determined by
  simply testing a DNA sample, without any need for
  pedigree, phenotypes, progeny or EPDs.

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Consequences of the Myth

• Leads to the expectation that DNA testing will
  simplify cattle breeding

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A More Realistic Vision
NCE
Pedigree
Phenotypes
DNA tests
More Accurate Evaluation of Genetic Merit
Marker Adjusted EPDs
Phenotypes
DNA tests
Phenotypes
DNA tests
Progeny

• Under this scenario, phenotypes and DNA tests on
  the individual and its relatives are combined,
  through National Cattle Evaluation (NCE), to
  produce marker-adjusted EPDs, upon which
  selection decisions are made.

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Inclusion of DNA Test Results in National Cattle
Evaluation
ID Conv. EPD Acc. Residual EPD Test A Test B MA- EPD
1 50 .90 36 10 5 52
2 35 .90 44 -10 0 34
3 47 .20 49 -10 0 39
4 46 .20 47 0 -5 42
5 45 .20 42 10 5 57
6 44 .20 44 0 0 44
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Inclusion of DNA Test Results in National Cattle
Evaluation
ID Conv. EPD Acc. Residual EPD Test A Test B MA- EPD
1 50 .90 36 10 5 52
2 35 .90 44 -10 0 34
3 47 .20 49 -10 0 39
4 46 .20 47 0 -5 42
5 45 .20 42 10 5 57
6 44 .20 44 0 0 44
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The Myth of Additivity
Pedigree
Phenotypes
DNA Tests
Marker Effects Added to EPDs

EPDs
Phenotypes
Phenotypes
Progeny

• DNA test results affect low accuracy EPDs much
  more than they do high accuracy EPDs.

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They Dont Use DNA Test Results Optimally

• It is difficult to include DNA test results in
  NCE until we have sufficient data to work with.
• But, we wont get a lot of data until it starts
  going into NCE.
• So, we are starting to think about where we are
  going and starting to work on the things we can
  do now.
• This is not a legitimate excuse not to use the
  technology.

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Single Gene Selection
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Weighting the Information Obtained from Multiple
DNA Tests

• Hopefully, there will be too many tests available
  for breeders to make breeding decisions based on
  raw test results.
• Need to weight the relative emphasis on each gene
  by its effect and the relative importance of the
  trait.
• Each DNA test will be related to several traits.
• For the foreseeable future, DNA tests will only
  account for some of the genetics of any trait
  we will still need EPDs.

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Weighting the Information Obtained from Multiple
DNA Tests

• Breeding decisions will be based on output of
  National Cattle Evaluation (NCE), rather than on
  individual test results.
• NCE will have to be enhanced to accommodate DNA
  testing.

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What Should Breed Associations be Doing About
DNA Testing?

• Establish procedures for direct acquisition of
  DNA test results into breed databases.
• Develop policies that prevent selective reporting
  of results.
• Educate breeders on proper use.

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What Can You Do Now?

• Make it Standard Operating Procedure to have DNA
  tests independently characterized
• Generate data use DNA testing to the extent
  that it fits in your business
• Contribute to systems that allow test results to
  flow directly through breed associations into the
  NCE system

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Conclusions

• We have some difficult issues to deal with in the
  next few years
• All roads to genetic improvement go through
  National Cattle Evaluation
• DNA testing will become an important component of
  genetic improvement