DNA Testing and Marker Assisted Selection R. Mark Thallman U.S. Meat Animal Research Center Clay Center, NE

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

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

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?

Should I Use DNA Testing?

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).

Cost of Testing

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.

They Just Use it as a Marketing Tool Not an acceptable excuse for not using technology

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.

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.

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.

Which DNA Tests Should I Use? A number of detailed questions about DNA tests should be answered before deciding which tests to use.

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?

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.

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.

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.

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.

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.

What if a Test Has Not Been Characterized 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.

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.

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

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

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.

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.

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

How Should I Use the Test Results?

Current Genetic Evaluation Currently, genetic merit is evaluated in the form of EPDs, which are computed from phenotypes on the individual and its relatives. Pedigree Phenotypes Progeny EPDs Phenotypes Accurate Evaluation of Genetic Merit NCE

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

Consequences of the Myth: Leads to the expectation that DNA testing will simplify cattle breeding

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

Inclusion of DNA Test Results in National Cattle Evaluation ID Conv. EPDAcc. Residual EPD Test A Test B MA- EPD

Inclusion of DNA Test Results in National Cattle Evaluation ID Conv. EPDAcc. Residual EPD Test A Test B MA- EPD

The Myth of Additivity: Pedigree Phenotypes Progeny EPDs DNA test results affect low accuracy EPDs much more than they do high accuracy EPDs. Phenotypes Marker Effects Added to EPDs DNA Tests +

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.

Single Gene Selection

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.

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.

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.

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

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