Genomic technology is useful for improving beef cattle. It’s easy to become overwhelmed when thinking about genomics because the process involves thousands to millions of genotypes known as BIG DATA; therefore, it is important to understand that the results of the process is improving the accuracy of an animal’s expected progeny difference (EPD) as to be able to rank animals for selection. Genetic improvement is typically measured as an increase in EPD over many years. For example, the average yearling weight in a breed of cattle such as Angus was -13 in 1972 and it improved to +87 lbs in 2012 (Figure 1). This improvement is a result of selection for growth by the breeders for 40 years. The more accurately the calculation of EPDs can be accomplished, the faster the rate of genetic improvement can be observed by breeders using EPDs for mating decisions

Thomas, Milt

English

DigitalCommons@University of Nebraska

University of Nebraska - LincolnDigitalCommons@University of Nebraska - LincolnRange Beef Cow Symposium Animal Science Department2013Sorting Through the Science, Marketing, andRealities of DNA Tools for Genetic PredictionMilt ThomasColorado State UniversityFollow this and additional works at: http://digitalcommons.unl.edu/rangebeefcowsympThis Article is brought to you for free and open access by the Animal Science Department at DigitalCommons@University of Nebraska - Lincoln. It hasbeen accepted for inclusion in Range Beef Cow Symposium by an authorized administrator of DigitalCommons@University of Nebraska - Lincoln.Thomas, Milt, "Sorting Through the Science, Marketing, and Realities of DNA Tools for Genetic Prediction" (2013). Range Beef CowSymposium. 311.http://digitalcommons.unl.edu/rangebeefcowsymp/311	   99	  Proceedings, The Range Beef Cow Symposium XXIII December 3, 4 and 5, 2013, Rapid City, South Dakota   Sorting Through the Science, Marketing, and Realities of DNA Tools for Genetic Prediction  Dr. Milt Thomas John E. Rouse Chair of Animal Breeding Department of Animal Sciences Colorado State University Milt.Thomas@colostate.edu  Important acronyms:  DNA = deoxyribonucleic acid EPD = expected progeny difference gEPD = genome-enhance expected progeny difference MBV = molecular breeding value NBCEC = National Beef Cattle Evaluation Consortium 50K = jargon for the BovineSNP50 chip containing 50,000 genotypes   Genomic technology is useful for improving beef cattle. It’s easy to become overwhelmed when thinking about genomics because the process involves thousands to millions of genotypes known as BIG DATA; therefore, it is important to understand that the results of the process is improving the accuracy of an animal’s expected progeny difference (EPD) as to be able to rank animals for selection. Genetic improvement is typically measured as an increase in EPD over many years. For example, the average yearling weight in a breed of cattle such as Angus was -13 in 1972 and it improved to +87 lbs in 2012 (Figure 1). This improvement is a result of selection for growth by the breeders for 40 years. The more accurately the calculation of EPDs can be accomplished, the faster the rate of genetic improvement can be observed by breeders using EPDs for mating decisions.    Why genomics:  We now use genomics as the DNA-tool to improve accuracy of EPD rather than a few genotypes. Genomics means “all the DNA information”. In practice, it is a term meaning genotyping a large number of loci across all 30 cattle chromosomes. It is important to measure the entire genome as there are 25,000 to 30,000 genes in cattle and many of the economically relevant traits are polygenic (i.e., regulated by many genes). For example, weaning weight is influenced by thousands of genes, so we need lots of genotypes on many chromosomes to effectively estimate an animal’s molecular breeding value (MBV) for weaning weight. An MBV is a numeric value for an animal. There is a statistical process that will estimate a positive or negative value for each genotype. Adding up all the pluses and minuses will equate to an animal’s MBV.   MBVs are being estimated from genotypes on a laboratory chip known as BovineSNP50 (Figure 2). Within each well, this chip has 50,000 genotypes so it is 	   100	  commonly called the 50K chip. DNA from 24 animals is placed in the individual wells on the chip and a computer system reads the genotypes for each animal. Zoetis and GeneSeek are two prominent companies that provide cattle genotyping services using the chips manufactured by Illumina, Inc. There are now more than 10 SNP-chips on the market. Another prominent chip is what is known as BovineSNPHD. The HD is an acronym for high density meaning there are ~800,000 SNP genotypes on the chip.   The process of calculating EPDs has evolved a lot over the past 50 to 60 years. The statistical models started with pedigree-based (i.e., animal) models and added multi-trait, multi-breed, and now genome-enhanced (gEPD) procedures. There are two types of gEPD procedures 1) MBV and 2) genomic relationship matrix. The MBV procedure is being used by several beef cattle breed associations, while the dairy industry primarily uses the genomic relationship matrix process. The dairy industry, particularly Holstein, quickly translated genome technology into the calculation of their EPD. The first bovine genome sequence was completed in 2004, Illumina manufactured BovineSNP50 in 2006, and the first Holstein genetic evaluation including genomic information was completed in 2008. Several USDA and university scientists were involved in this technology translation, which was greatly helped by the fact that semen from Holstein bulls was readily available to supply DNA for genotyping. In Holstein, this process has worked great as it improves accuracy of non-parent EPD to the point that the 6 year sire-proofing process can be minimalized. The adoption of this technology for beef cattle breeds has been much slower. Specifically, breed associations have been working with the National Beef Cattle Evaluation Consortium (NBCEC) as to acquire genotypes on several thousand sires as to develop a resource large enough conduct the statistics of estimating MBV. For many beef cattle breeds, this process has taken several years. Nonetheless, accuracy is improved by adding MBV to the EPD system. In a recent presentation at the American Society of Animal Science meeting, NBCEC scientists from Iowa State University (Saatchi and Garrick) reported accuracy values in the 0.2 to 0.4 range in Hereford cattle when varied numbers of genotypes were used in simple models to calculate the MBV. These observed levels of accuracies are encouraging and an improvement to the levels initially estimated via genomic technology in beef cattle.  What does a gEPD program look like?  Several beef cattle breed associations have implemented or are working to implement gEPD programs. These include Angus, Red Angus, Simmental, Gelbvieh, Hereford, Limousin, Brangus, Brahman, etc. Each of these breeds first gathered DNA samples from > 1,000 animals for 50K genotyping and used this as a training population, which helped assign the plus and minus numeric value to each genotype. For those breeds that have established training populations, additional animals are now being genotyped and their MBV predicted based on the training population. The MBV of each animal is then being included into the multi-trait EPD calculation. For breeders, it’s a simple process. They submit DNA samples in the form of a hair, blood, or semen sample and payment to the breed association office and get back the gEPD via breed association website. Behind the scenes and over several months, the samples were sent to a lab for DNA extraction, genotyping, MBV calculation, and then the MBV included in the multi-trait EPD calculation. Please note that the gEPD is not a new EPD added to the suite of traits published by a breed association, rather it’s an improvement in accuracy of the currently published EPDs. As genomic research progresses, the MBV 	   101	  technology may be used to publish EPDs for traits that are difficult or very expensive to collect. Examples of such traits are feed efficiency, grazing distribution, health (i.e., bovine respiratory disease), etc. gEPD for these types of traits may always be of low to moderate accuracy, but are extremely valuable in addressing industry-wide challenges.   Evolution of DNA technology:  DNA technology is advancing at a pace very similar to computer technology. DNA is very simple as its repeating units of AGCT, which have a reverse complement of TCGA. The Watson-Crick base-pairing allows this biological process to be easily computerized, which meshes well with the data systems of breed associations. In 2004, the first cow sequenced was Dominette, an inbred Hereford. The process cost approximately $50 million dollars with the bill being paid by National Institutes of Health, USDA, and several other partners. Today genome sequences can be completed for approximately $5,000 and there is a global project called, “1000 bull genomes” http://www.1000bullgenomes.com/ working to complete the sequence on this many bulls. With all this sequence, comes massive knowledge of genotypes that can be placed on chips. There are currently more than 10 genotyping chips being marketed that range from 3K to 800K in their density. The 800K chip is frequently called BovineSNPHD with the HD meaning “high density” (i.e., 800,000 genotypes across the 30 cattle chromosomes). With knowledge of so many genotypes, the chip products and companies selling genotyping services are competing; thus, genotyping costs per animal are becoming much cheaper. Typical costs of genotyping/animal are approximately $250, $100, and $45 for the HD, 50K and lower density chips. Competition in the genomics market is a beneficial to the beef industry. However, we all must realize that DNA technology, and the translation of these technologies, will continue to rapidly evolve.   How do we keep up with advancing technology:  The most prevalent challenge to the segments of the beef industry working with genotyping technology will be deciding the most cost effective genotyping platform (i.e., which chips and which genotypes to use with their EPD system?). In parallel, how will breeding organizations manage these BIG DATA, which quickly makes files terabytes in size (i.e., 1012 bytes). As in the history of developing EPD, breeders and breed improvement committees of breed associations must work hard to understand the technology and how to best use it for genetic improvement. This will be a challenge as everyone must realize that the federal funding for NBCEC has been eliminated and the base-funding for animal agriculture research at land grant universities has not kept pace with the value of the dollar for decades. Thus, new partnerships among the beef industry, USDA, and universities must be formed.  Please note that a cooperative relationship for management of big data was established in September of 2013 between the USDA-ARS and the Colorado State University Agricultural Experiment Station. The groups provided funding to start to construct a database to manage genomic data to parallel phenotypic information now stored in A-GRIN (http://nrrc.ars.usda.gov/A-GRIN/main_webpage/ars?record_source=US), which preserves germplasm for livestock. The partnership is reaching out to breed associations for participation and long-term sustainability and use of the database.    	   102	   Figure 1. Yearling weight genetic trend in Angus cattle 1972 to 2012.    Figure 2. BovineSNP50 from Illumina, Inc. A genotyping chip with 24 wells that each contains DNA probes for 50,000 genotypes. 

Sorting Through the Science, Marketing, and Realities of DNA Tools for Genetic
Prediction

UNL | Libraries

University of Nebraska - Lincoln
DigitalCommons@University of Nebraska - Lincoln
Range Beef Cow Symposium Animal Science Department
2013
Sorting Through the Science, Marketing, and
Realities of DNA Tools for Genetic Prediction
Milt Thomas
Colorado State University
Follow this and additional works at: http://digitalcommons.unl.edu/rangebeefcowsymp
This Article is brought to you for free and open access by the Animal Science Department at DigitalCommons@University of Nebraska - Lincoln. It has
been accepted for inclusion in Range Beef Cow Symposium by an authorized administrator of DigitalCommons@University of Nebraska - Lincoln.
Thomas, Milt, "Sorting Through the Science, Marketing, and Realities of DNA Tools for Genetic Prediction" (2013). Range Beef Cow
Symposium. 311.
http://digitalcommons.unl.edu/rangebeefcowsymp/311
	   99	  
Proceedings, The Range Beef Cow Symposium XXIII 
December 3, 4 and 5, 2013, Rapid City, South Dakota 
 
 
Sorting Through the Science, Marketing, and Realities of DNA Tools for Genetic 
Prediction 
 
Dr. Milt Thomas 
John E. Rouse Chair of Animal Breeding 
Department of Animal Sciences 
Colorado State University 
Milt.Thomas@colostate.edu 
 
Important acronyms:  
DNA = deoxyribonucleic acid 
EPD = expected progeny difference 
gEPD = genome-enhance expected progeny difference 
MBV = molecular breeding value 
NBCEC = National Beef Cattle Evaluation Consortium 
50K = jargon for the BovineSNP50 chip containing 50,000 genotypes 
 
 Genomic technology is useful for improving beef cattle. It’s easy to become 
overwhelmed when thinking about genomics because the process involves thousands to 
millions of genotypes known as BIG DATA; therefore, it is important to understand that the 
results of the process is improving the accuracy of an animal’s expected progeny difference 
(EPD) as to be able to rank animals for selection. Genetic improvement is typically measured 
as an increase in EPD over many years. For example, the average yearling weight in a breed 
of cattle such as Angus was -13 in 1972 and it improved to +87 lbs in 2012 (Figure 1). This 
improvement is a result of selection for growth by the breeders for 40 years. The more 
accurately the calculation of EPDs can be accomplished, the faster the rate of genetic 
improvement can be observed by breeders using EPDs for mating decisions.  
  
Why genomics:  
We now use genomics as the DNA-tool to improve accuracy of EPD rather than a 
few genotypes. Genomics means “all the DNA information”. In practice, it is a term meaning 
genotyping a large number of loci across all 30 cattle chromosomes. It is important to 
measure the entire genome as there are 25,000 to 30,000 genes in cattle and many of the 
economically relevant traits are polygenic (i.e., regulated by many genes). For example, 
weaning weight is influenced by thousands of genes, so we need lots of genotypes on many 
chromosomes to effectively estimate an animal’s molecular breeding value (MBV) for 
weaning weight. An MBV is a numeric value for an animal. There is a statistical process that 
will estimate a positive or negative value for each genotype. Adding up all the pluses and 
minuses will equate to an animal’s MBV.  
 
MBVs are being estimated from genotypes on a laboratory chip known as 
BovineSNP50 (Figure 2). Within each well, this chip has 50,000 genotypes so it is 
	   100	  
commonly called the 50K chip. DNA from 24 animals is placed in the individual wells on the 
chip and a computer system reads the genotypes for each animal. Zoetis and GeneSeek are 
two prominent companies that provide cattle genotyping services using the chips 
manufactured by Illumina, Inc. There are now more than 10 SNP-chips on the market. 
Another prominent chip is what is known as BovineSNPHD. The HD is an acronym for high 
density meaning there are ~800,000 SNP genotypes on the chip.  
 
The process of calculating EPDs has evolved a lot over the past 50 to 60 years. The 
statistical models started with pedigree-based (i.e., animal) models and added multi-trait, 
multi-breed, and now genome-enhanced (gEPD) procedures. There are two types of gEPD 
procedures 1) MBV and 2) genomic relationship matrix. The MBV procedure is being used 
by several beef cattle breed associations, while the dairy industry primarily uses the genomic 
relationship matrix process. The dairy industry, particularly Holstein, quickly translated 
genome technology into the calculation of their EPD. The first bovine genome sequence was 
completed in 2004, Illumina manufactured BovineSNP50 in 2006, and the first Holstein 
genetic evaluation including genomic information was completed in 2008. Several USDA 
and university scientists were involved in this technology translation, which was greatly 
helped by the fact that semen from Holstein bulls was readily available to supply DNA for 
genotyping. In Holstein, this process has worked great as it improves accuracy of non-parent 
EPD to the point that the 6 year sire-proofing process can be minimalized. The adoption of 
this technology for beef cattle breeds has been much slower. Specifically, breed associations 
have been working with the National Beef Cattle Evaluation Consortium (NBCEC) as to 
acquire genotypes on several thousand sires as to develop a resource large enough conduct 
the statistics of estimating MBV. For many beef cattle breeds, this process has taken several 
years. Nonetheless, accuracy is improved by adding MBV to the EPD system. In a recent 
presentation at the American Society of Animal Science meeting, NBCEC scientists from 
Iowa State University (Saatchi and Garrick) reported accuracy values in the 0.2 to 0.4 range 
in Hereford cattle when varied numbers of genotypes were used in simple models to calculate 
the MBV. These observed levels of accuracies are encouraging and an improvement to the 
levels initially estimated via genomic technology in beef cattle. 
 
What does a gEPD program look like? 
 Several beef cattle breed associations have implemented or are working to implement 
gEPD programs. These include Angus, Red Angus, Simmental, Gelbvieh, Hereford, 
Limousin, Brangus, Brahman, etc. Each of these breeds first gathered DNA samples from > 
1,000 animals for 50K genotyping and used this as a training population, which helped assign 
the plus and minus numeric value to each genotype. For those breeds that have established 
training populations, additional animals are now being genotyped and their MBV predicted 
based on the training population. The MBV of each animal is then being included into the 
multi-trait EPD calculation. For breeders, it’s a simple process. They submit DNA samples in 
the form of a hair, blood, or semen sample and payment to the breed association office and 
get back the gEPD via breed association website. Behind the scenes and over several months, 
the samples were sent to a lab for DNA extraction, genotyping, MBV calculation, and then 
the MBV included in the multi-trait EPD calculation. Please note that the gEPD is not a new 
EPD added to the suite of traits published by a breed association, rather it’s an improvement 
in accuracy of the currently published EPDs. As genomic research progresses, the MBV 
	   101	  
technology may be used to publish EPDs for traits that are difficult or very expensive to 
collect. Examples of such traits are feed efficiency, grazing distribution, health (i.e., bovine 
respiratory disease), etc. gEPD for these types of traits may always be of low to moderate 
accuracy, but are extremely valuable in addressing industry-wide challenges.  
 
Evolution of DNA technology: 
 DNA technology is advancing at a pace very similar to computer technology. DNA is 
very simple as its repeating units of AGCT, which have a reverse complement of TCGA. The 
Watson-Crick base-pairing allows this biological process to be easily computerized, which 
meshes well with the data systems of breed associations. In 2004, the first cow sequenced 
was Dominette, an inbred Hereford. The process cost approximately $50 million dollars with 
the bill being paid by National Institutes of Health, USDA, and several other partners. Today 
genome sequences can be completed for approximately $5,000 and there is a global project 
called, “1000 bull genomes” http://www.1000bullgenomes.com/ working to complete the 
sequence on this many bulls. With all this sequence, comes massive knowledge of genotypes 
that can be placed on chips. There are currently more than 10 genotyping chips being 
marketed that range from 3K to 800K in their density. The 800K chip is frequently called 
BovineSNPHD with the HD meaning “high density” (i.e., 800,000 genotypes across the 30 
cattle chromosomes). With knowledge of so many genotypes, the chip products and 
companies selling genotyping services are competing; thus, genotyping costs per animal are 
becoming much cheaper. Typical costs of genotyping/animal are approximately $250, $100, 
and $45 for the HD, 50K and lower density chips. Competition in the genomics market is a 
beneficial to the beef industry. However, we all must realize that DNA technology, and the 
translation of these technologies, will continue to rapidly evolve.  
 
How do we keep up with advancing technology:  
The most prevalent challenge to the segments of the beef industry working with 
genotyping technology will be deciding the most cost effective genotyping platform (i.e., 
which chips and which genotypes to use with their EPD system?). In parallel, how will 
breeding organizations manage these BIG DATA, which quickly makes files terabytes in size 
(i.e., 1012 bytes). As in the history of developing EPD, breeders and breed improvement 
committees of breed associations must work hard to understand the technology and how to 
best use it for genetic improvement. This will be a challenge as everyone must realize that 
the federal funding for NBCEC has been eliminated and the base-funding for animal 
agriculture research at land grant universities has not kept pace with the value of the dollar 
for decades. Thus, new partnerships among the beef industry, USDA, and universities must 
be formed.  Please note that a cooperative relationship for management of big data was 
established in September of 2013 between the USDA-ARS and the Colorado State University 
Agricultural Experiment Station. The groups provided funding to start to construct a database 
to manage genomic data to parallel phenotypic information now stored in A-GRIN 
(http://nrrc.ars.usda.gov/A-GRIN/main_webpage/ars?record_source=US), which preserves 
germplasm for livestock. The partnership is reaching out to breed associations for 
participation and long-term sustainability and use of the database.  
  
	   102	  
 
Figure 1. Yearling weight genetic trend in Angus cattle 1972 to 2012. 
 
 
 
Figure 2. BovineSNP50 from Illumina, Inc. A genotyping chip with 24 wells that each 
contains DNA probes for 50,000 genotypes. 


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