Erin Shields Current Applications of Genomics in the Beef Cattle Industry April 2012

The beef and dairy industries contribute more than $40 billion to the Canadian economy every year. Global
demand for animal protein is expected to double by 2050 and genetic improvement will be key to enabling cattle
producers to meet that demand in a cost-effective and efficient manner.

A genome is the total of all genetic material in an organism. Genomics is a branch of science concerned with
development and utilization of DNA sequences and genetic maps that represent the architecture of the genome.
The first genetic sequence of a cow was published in 2009. This milestone was achieved through an international
collaboration with 300 scientists in 25 countries and took six years to complete. The cow sequenced was a
Hereford, but additional breeds have also been sequenced now including Holstein, Angus, Jersey, Limousin,
Norwegian Red and Brahman. This sequence information can be analyzed directly, used for comparing animals
within a breed, or for comparing animals across breeds. As one tries to get up to speed on this ever increasingly-
popular topic, one is quickly faced with a plethora of terms and wishing they had a genetics degree! The
importance of this technology will certainly only grow in terms of its applications and relevance, and thus it
behoves one to make efforts to gain an understanding of this field.

Traditional animal breeding relies on scoring animals based on their observed physical characteristics, or
phenotype, to determine their breeding value (BV). This BV is often recorded in terms of Expected Progeny
Differences (EPDs). EPDs are common measures of genetic merit used in evaluations performed for North
American breeds. They are typically expressed in units of the underlying trait; EPDs represent the expected
difference in the performance of future progeny relative to the breed base for that trait. For example, a bull with a
birth weight EPD of 4.5 would be expected to sire calves that weighed, on average, 4.5 lbs more than the average
for the breed. EPDs are derived from pedigree records and progeny performance data. This process is often
inexact, inefficient, and time consuming, with most traits (e.g. meat quality) hard to assess and evident only after
the animal reaches maturity, resulting in a delay verifying breeding results. The traditional method is limited by
many variables including: limitations in understanding of most traits at the biological level due to complex
inheritance (rather than simple Mendelian inheritance); limitations in the number of traits that are difficult to
measure (e.g. meat quality) or have low heritability (e.g. reproduction); restriction to traits that can be
reproducibly and inexpensively measured in a large number of animals; and the slow rate of genetic progress with
this method that puts a high selection pressure on key production traits that may have deleterious effect on other
important traits that are not readily scored.

DNA information has proven very beneficial in both the seedstock and commercial beef sectors for
identifying carriers of genetic defects and other simple recessive alleles (i.e. red color, horns) and for resolving
uncertain paternity. Another core application of genetic testing is to dependably predict genetic merit and rank
animals for the economically important performance traits of interest. This ranking is the basis for making more
profitable selection, mating and marketing decisions. Dependable ranking of animals early in life, for the traits
that are most important to the breeding objectives and profitability of the operations and its customers, enables
producers to achieve their goals. Identifying the elite individuals in the herd is important, but identifying animals
with lower genetic potential is equally important. The removal of animals with lesser genetic merit from the
breeding population increases the herds cumulative long-term potential for efficient and profitable production.

One category of genetic difference now frequently used for comparison is Single Nucleotide Polymorphisms
(SNPs). SNPs are used as genetic markers to track the ancestral heritage of regions of DNA or of individual
animals. SNPs can also be used to predict the likelihood that a given animal will possess an individual or a series
Erin Shields Current Applications of Genomics in the Beef Cattle Industry April 2012

of desirable trait(s). The latter can only occur once a SNP or a collection of SNPs has been determined through
research to be linked to a particular trait. Many traits of interest are Complex Traits which are genetic traits that
are controlled by a number of genes as opposed to a single gene. Traits such as reproduction characteristics,
growth, and carcass quality are controlled by numerous genes.

Currently on the market through companies such as Illumina and Pfizer Animal Health Animal Genetics are
various genetic tests that utilize genomic technology. The number of genetic markers (SNPs) that are included in
each test have increased from, initially in the year 2000, one single marker associated with beef marbling to today
where there is a test that has 54 000 markers correlated to the assessment of 14 economically important traits.

Figure
Figure:Percentage of genetic
1: Percentage variation
of genetic (r2) (rassociated
variation 2 withwith
) associated commercial DNA
commercial teststests
DNA for for
targeted traits.
targeted Bold
traits.
currently
2 being incorporated
h : Estimate of heritability. into the Angus genomic-enhanced EPDs.
r : Genetic correlation between molecular value and trait of interest.
Bold traits are those that are currently being incorporated into the Angus genomic-enhanced EPDs.

In order to capitalize on how this information can be utilized by producers with varying goals, one must first
understand how this genomic information is derived and is used in the construction of a Genomic enhanced EPD
(GeEPD). This will give one the ability to critically evaluate the information at hand, integrate the genomic
information with already available expected breeding progeny (EPD) information, consider the economic merit of
the tests, and assess its applicability to ones specific herd operation.

During the discovery phase DNA from thousands of animals from various environments is collected using hair
and/or blood samples. Depending on the set of data one is looking at, the number of animals and breeds included
may vary and will have important implications on the applicability of resultant set of test markers. This training
data serves as the reference population in which the animals are scored for key production traits (phenotypic
traits) and genotypes are fully elucidated. The most predictive SNP for each trait is selected for the SNP Key (30-
Erin Shields Current Applications of Genomics in the Beef Cattle Industry April 2012

300 SNP/trait) which will be used in the creation of the final product panel. To verify the validity and genetic
correlation of the SNP selected, further analysis is conducted during the validation stage. Finally, in the
evaluation stage, a prediction equation is generated combining all the marker genotypes with their effects to
generate a Molecular Breeding Value (MBV) for each animal which can be integrated with pedigree and EPD
information to create a GeEPD and utilized in the selection process during breeding.

Figure2:
Figure 2:Genomic
GenomicSelection
Selectionin
inLivestock
LivestockBreeding
Breeding

Genomic information in the form of SNPs not only holds the promise to increase the accuracy of EPDs but also to
add novel traits to our suite of available EPDs. The deployment of Marker-Assisted EPDs (MA-EPDs);
however, is currently limited to the American Angus Association (AAA), although other breeds (such as
Simmental) are moving rapidly towards this goal. The development of selection tools for traits such as feed
efficiency, disease resistance, and other novel traits have been slow to develop. In order for these genomic tools
to develop and evolve, large resource populations that have these phenotypes collected are required both for
discovery and validation of SNP associations with these traits. Consequently, we have seen the development
and deployment of genomic tools for traits that we have phenotypes routinely recorded for (see Figure 1).

Without the seamless integration of this technology into EPD calculations, we find ourselves in the context of
being faced with two disjoined pieces of information: traditional EPD and marker panel results. In this scenario, it
is impossible to directly compare EPD (or Beef Improvement Federation [BIF] accuracy ratings) to marker
panel results. In contrast to the thought process of DNA marker panel results being a separate and disjoined piece
of information, these test results should be thought of as a potentially useful indicator that is correlated to the trait
of interest. Work has recently been done by numerous independent research groups to attempt to combine these
results into user-friendly, universally used values that can be utilized in production sectors. As such, the
Molecular Breeding Value can be included in National Cattle Evaluations as a correlated trait following
methods of Kachman (2008). This is what AAA currently does.

Numerous considerations must be taken into account when this genomic information is compiled; such as the
true accuracy (r) of the test panel to be correlated with a trait of interest, the proportion of genetic variation
explained (%GV) by the test, and the pedigree relationships between the training, validation, and evaluation
data sets. These measures must be assessed individually for each trait in order to obtain accurate estimates of the
 Erin Shields Current Applications of Genomics in the Beef Cattle Industry April 2012

true effectiveness of a generated Molecular Breeding Value, to give the proper weight to genomic information,
and to obtain accurate estimates of the accuracy of a GeEPD. Assigning the proper weight to genomic
information along with its effect on the estimated accuracy of a GeEPD depends on the animals in the test group
of interest (the evaluation data set) being closely related to those utilized in the formation of the genetic
marker tests. The further the pedigree relationships differ between the groups (i.e. different breeds, or in
admixed/crossbred population) the less accurate and applicable are the marker tests.

Other methods have been proposed including using SNP genotypes to form a genomic relationship matrix that
could allow for known relationships instead of those estimated by pedigree, or forming an index of MBV and
EPD in a blending approach. Combining these sources of information, molecular tools and traditional EPD, has
the potential to allow for the benefits of increased accuracy and increased rate of genetic change. The magnitude
of the benefits of Marker-Assisted Selection (MAS) will depend on the proportion of genetic variation explained
by a given marker panel.

Figure 3 below illustrate the benefits of including a MBV into EPD (or Estimated Breeding Value [EBV] which
is twice the value of an EPD) on accuracy (on the BIF scale) when the MBV explains 10 or 40% of the genetic
variation which is synonymous with R2 values of 0.1 and 0.4. The darker portion of the bars shows the EPD
accuracy before the inclusion of genomic information and the lighter colored portion shows the increase in
accuracy after the inclusion of the MBV into the EPD calculation. As the %GV increases, the increase in EPD
accuracy becomes larger. Lower accuracy animals (such as yearling unproven bulls) benefit more from the
inclusion of genomic information and the benefits decline as the EPD accuracy increases (such as in older bulls
with more accurate progeny records). Regardless of the %GV assumed here, the benefits of including genomic
information into EPD dissipate when EPD accuracy is between 0.6 and 0.7. On the other hand, when %GV is 40
an animal with 0 accuracy could go to over 0.2 accuracy with genomic information alone. This would be the
same as having approximately 4 progeny for a highly heritable trait or 7 progeny for a moderately heritable trait.
This example underscores that the degree of assistance genomics plays in the breeding selection process will vary
depending upon the population considered.

Figure: 3
R2 = 0.1 R2 = 0.4

Genomic
+ EBV
Accuracy

EBV Accuracy EBV Accuracy

Erin Shields Current Applications of Genomics in the Beef Cattle Industry April 2012

As mentioned previously, it is important to understand some limitations in the current application of Marker
Assisted Selection. Current marker panels are likely to work best in the populations where discovery occurred, in
other words where the producers cattle match as closely as possible the cattle in which the data was originally
derived to make the test. The tests currently available are most accurately and appropriately applied within the
Angus purebred population at this time. The available tests will potentially decrease in predictive power as the
target population becomes more genetically distant from the discovery population. The same erosion in accuracy
is likely to occur overtime as well (i.e. over generations if panels are not retrained).

The field of genomics is vast, exponentially growing, and has the potential to have a wide array of applications
and an incredible impact within the beef industry. Currently hundreds of millions of dollars internationally are
being dedicated to research in this field. Collaboration between industry, academia, government and producers
has been, and will continue to be required. Examples of such groups currently involved include: USDA-ARS,
UNCEIA-INRA, Pfizer Animal Genetics, Illumina, Igenity, National Beef Cattle Evaluation Consortium,
University of Missouri, University of Alberta, Genome Alberta, Livestock Gentec, The Bovine Genome
Sequencing Consortium, National Program for Genetic Improvement of Feed Efficiency in Beef Cattle through
the USDA, IdentiGen Canada Ltd., Alberta Agriculture and Rural Development, UC Davis, Colorado State,
University of Nebraska-Lincoln, Iowa State, Texas A&M, American Angus Association, Canadian Simmental
Association etc.

Future applications are almost infinite and current research efforts include topics such as building genotypic
databases for all breeds and stages of production, and novel trait development in the areas of reproduction, feed
efficiency, disease resistance, and healthfulness of beef products. With a feed efficiency improvement of 1%
having the same economic impact as a 3% improvement in rate of gain; with diseases like BRD causing annual
losses of more than 1 million animals and ~$700 million in the US; with increased public concern regarding
animal welfare and therapeutic treatment, as well as increased human nutritional concerns regarding beef
consumption, any improvements brought by the use of genomics will be welcomed. As the cattle genomic
database and tests available become even more efficacious and cost effective for a wider variety of traits
applicable to broader populations of interest, the use of genomics in all sectors of the cattle industry will
undoubtedly become commonplace. Stake holders at all levels should be encouraged to stay abreast of updates in
this area in order to reap the benefits of such advancing technologies.

References:
http://www.beefefficiency.org/marcmtgjune11.html
http://genomealberta.ca/livestock/applying-genomics-to-commercial-cattle-operations.aspx
http://www.bioinfo.in/uploadfiles/13255836891_1_2_IJGP.pdf
http://www.illumina.com/applications/sequencing.ilmn?utm_source=illumina.com/sequencing&utm_campaign=sequencing+
gene+expression
www.pfizer.ca/animalhealth/home/
Kachman S. D. (2008) The Impact of Pedigree Relationship on Molecular Breeding Value Accuracy