Your Best Gene
n
i
k
r
s
Wo
F E ATURE S
n
Contains 128 DNA markers
where each marker is highly
associated with expression of
marbling score
n
Measures the cumulative effects
of all 128 markers associated
with marbling
n
Results are expressed as
the Molecular Genetic Value
(MGV) which can be utilized
to rank animals by their
genetic potential
n
Animals can be tested at
any age
n
Validated in Angus (validation
in other breeds is underway)
B ENEFITS
n
The most powerful and comprehensive DNA selection tool
currently available for marbling
n
Accounts for a significant
proportion of total observed
genetic variation for marbling
n
Results are easy to utilize and
incorporate into any existing
breeding program
n
Can be used to make early
selection and breeding
decisions
n
Provides accurate and reliable
results for ranking and/or
selection of animals
TRU-MARBLING ™
One in a series of break-through products that will advance breeding
practices in the cattle industry, Tru-Marbling™ is a powerful and comprehensive DNA selection tool that can determine the genetic potential of animals
to express marbling. In a collaborative research program between Cargill
and MMI Genomics, an innovative scientific approach was used on over
4000 feedlot animals to identify the majority of regions throughout the
bovine genome that have an effect on this economically important trait.
Tru-Marbling™ is a DNA-based genetic test that contains a panel of 128 unique DNA markers,
each one highly associated with the expression for marbling score and quality grade. By
measuring the cumulative effects for each of these 128 markers, Tru-Marbling™ accounts for a
significant proportion of the total genetic variation for this complex metabolic trait—the first
DNA-based product to do so!
Tru-Marbling™ is an advanced and revolutionary tool that will allow cattle producers to make
early breeding decisions that increase the accuracy of selection and decrease the age at
which animals can be selected.
The results? Rapid improvement of marbling within herds and the ability to determine
the “Tru” genetic potential of animals.
P R O V E N R E S U LT S
Tru-Marbling™ has been validated in both commercial cross-bred feeder cattle populations
and in Angus cattle.
The validation in Angus was conducted using samples from the National Carcass Merit Project,
representing Angus sires bred to Angus-based commercial cows. While this is a small population of animals, the data indicate that Tru-MarblingTM accounts for 70% of the genetic variation observed in this population.
No. of samples:
Heritability*:
No. of markers:
Phenotypic variation explained (R2)**:
As a percent of Heritability
414
0.36
128
0.25
70%
* Angus National Cattle Evaluation, Spring 2007
** estimated from a model that included contemporary group and MGV
Tru-Marbling™ has also been validated against commercial cross-bred feeder cattle populations.
This study utilized 89 marbling markers that are a subset of the 128 markers used in the
purebred Angus population. The data clearly demonstrates the relationship between quality
grade and average Molecular Genetic Value (MGV).
Quality Grade
PROVEN TECHNO LOGY
PROVEN RESU LTS
PROVEN PROFITS
1756 Picasso Avenue
Davis, CA 95618
1.800.311.8808
www.breedtru.com
MMI Genomics, Inc. is a wholly-owned
subsidiary of MetaMorphix, Inc.
Prime
High Choice
Medium Choice
Low Choice
High Select
Low Select
No Roll
Totals
Number
STEERS
% of total
9
93
475
2008
3989
1344
337
8255
0.1%
1.1%
5.8%
24.3%
48.3%
16.3%
4.1%
100.0%
Avg. MGV
14
20
14
7
-6
-14
-20
HEIFERS
Number
% of total
5
78
423
1526
2835
915
268
6050
0.1%
1.3%
7.0%
25.2%
46.9%
15.1%
4.4%
100.0%
Avg. MGV
14
12
9
0
-9
-20
-23
14,305 head tested from 6 commercial feedlots
Unlike other products, Tru-MarblingTM MGVs account for a highly significant amount of variation for marbling
score.
FE ATURE S
n
Contains 11 DNA markers
where each marker is highly
associated with expression of
tenderness in meat products
n
Measures the cumulative effects
of all 11 markers associated
with meat tenderness
n
Results are expressed as
the Molecular Genetic Value
(MGV) which can be utilized
to rank animals by their
genetic potential
n
Animals can be tested at
any age
n
Validated in Angus (validation
in other breeds is underway)
BENEFITS
n
The most powerful and comprehensive DNA selection
tool currently available for
tenderness
n
Accounts for a significant
proportion of total observed
genetic variation for tenderness
n
Results are easy to utilize and
incorporate into any existing
breeding program
n
Can be used to make early
and accurate selection and
breeding decisions
n
Provides accurate and reliable
results for ranking and/or
selection of animals
k in Your Best Genes
r
o
W
TRU-TENDERNESS ™
One in a series of break-through products that will advance breeding
practices in the cattle industry, Tru-Tenderness™ is a powerful and comprehensive DNA selection tool that can determine the genetic potential of
animals to produce tender meat. In a collaborative research program
between Cargill and MMI Genomics, an innovative scientific approach was
used on over 4000 feedlot animals to identify the majority of regions
throughout the bovine genome that have an effect on this valuable consumer trait.
Tru-Tenderness™ is a DNA-based genetic test that contains a panel of 11 unique DNA markers,
each one highly associated with expression for tender meat. By measuring the cumulative
effects for each of these 11 markers, Tru-Tenderness™ accounts for a substantial proportion of
the total genetic variation for this complex metabolic trait.
Since tenderness can only be measured in harvested cattle it is difficult, time consuming and
expensive to make genetic progress for this trait using traditional genetic improvement tools.
Tru-Tenderness™ changes this paradigm by allowing producers to accurately assess the genetic
potential of their breeding stock to produce tender meat. In addition, Tru-Tenderness™ also
shortens the interval for making genetic progress because it can be used to test animals of any age.
Tru-Tenderness™ is an advanced and revolutionary tool that will allow cattle producers to make
early breeding decisions that increase the accuracy of selection and decrease the age at
which animals can be selected.
The results? Rapid improvement of tenderness within herds and the ability to determine the
“Tru” genetic potential of animals.
P R O V E N R E S U LT S
PROVEN TECHNO LOGY
PROVEN RESU LTS
PROVEN PROFITS
1756 Picasso Avenue
Davis, CA 95618
1.800.311.8808
www.breedtru.com
MMI Genomics, Inc. is a wholly-owned
subsidiary of MetaMorphix, Inc.
Tru-Tenderness™ has been validated in Angus using samples from the National Carcass Merit
Project, representing Angus sires bred to Angus-based commercial cows. While this is a small
population of animals, the data indicate that Tru-Tenderness™ accounts for 100% of the genetic
variation observed in this population as measured by Warner-Bratzler shear force.
No. of samples:
Heritability*:
No. of markers:
Phenotypic variation explained (R2)**:
As a percent of Heritability
407
0.35
11
0.38
100%
* as estimated in Minick et al, 2004, Can. J. Anim. Sci. 84:599
** estimated from a model that included contemporary group and MGV
The Cargill - MetaMorphix Partnership
The Cargill-MetaMorphix relationship was formed, in part, to address some of the most pressing challenges facing
the beef cattle industry today. Over the last several decades, as the cattle industry found ways to enhance growth
rates through new production practices, it also saw a substantial reduction in meat quality. With overall consumer
demand for beef declining over the past thirty years due to quality issues, many in the industry sought ways to
address the problem. In May of 2002, the two companies entered into a Joint Development and Joint Marketing
Agreement which utilized the strengths of each, to develop and commercialize genomics-based products aimed at
creating significant value across all segments of the beef cattle production and processing industries. The partnership between Cargill and MMI Genomics, MetaMorphix’s wholly-owned subsidiary, was based on the premise that
each company could make a significant contribution to the development of a new class of DNA-based tools that
would create significantly better quality beef and substantially improve the economics of cattle production.
Both parties knew, however, that the development of extremely accurate and highly predictive DNA tests for
carcass and production traits would require a very innovative scientific approach and a great deal of resources.
With a combined investment of over $25 million, the team embarked on a major research and development
program to develop DNA-based diagnostic tests that focused on targeted traits with significant economic value
such as marbling and tenderness. MMI Genomics’ discovery assets, research capabilities and genotyping
resources were paired with Cargill’s animal resources, customer base and cattle industry leadership position to
develop genomics-based products for a number of important traits. To complete such an ambitious research
project, both genotypic and phenotypic data from thousands of animals would be required.
The magnitude of the effort was substantial with:
• Over 4,000 research animals used
• Over 6,000 DNA markers analyzed per animal
• Over 20,000,000 genotypes generated
• Over 200,000 phenotypic observations and carcass measurements
• Validation of over 5,000,000 genotypes in over 28,000 animals.
To date, this Cargill-MMI discovery program remains unmatched in scope.
The discovery strategy was based on a unique whole genome approach that utilized a high density DNA marker
map to identify all genomic regions and associated markers around a targeted trait (see Breed-Tru® Technical
Bulletin #1, Doc #B0701.01). The result of this experimental design was the discovery of DNA markers that
account for a majority of the observed genetic variation for a given trait. Tru-Gain™, Tru-Marbling™ and TruTenderness™ are diagnostic tests developed with this strategy. These and other products in the pipeline, including feedlot management tools, will be widely available so that all industry segments will have the opportunity to
make dramatic strides in the efficient production of better beef.
Trait specific diagnostic products can be utilized, as tools, to determine the genetic
potential of individual animals to express the trait as well as to rank animals. In order
for the cattle industry to take advantage of this breakthrough technology, the CargillMMI team developed a method for reporting the combined effects from multiple DNA
markers into a single expression that is easy to interpret and utilize for enhancing
breeding and selection decisions. It is called the Molecular Genetic Value or MGV
(see Breed-Tru® Technical Bulletin #2, Doc #B0702.01). The ability to determine the
MGV for individual animals or groups of animals gives cattle breeders, producers
and feedlot managers the unprecedented ability to selectively breed, sort and
manage cattle to optimize returns within their operations.
PROVEN TECHNOLOGY
PROVEN RESU LTS
PROVEN PROFITS
Upon commercialization, these trait specific diagnostic assays are developed
into a high-throughput genotyping system and run against customer samples.
Diagnostic results are reported to customers from various segments of the beef
cattle industry in a form that allows each segment to utilize the MGV for each
animal tested. The diagnostic results create substantial value for customers by
allowing them to identify, sort and selectively breed those animals with the most
desirable genetics. The Cargill-MMI team looks forward to developing an entire
line of products that provide value-added solutions for the beef cattle industry.
1756 Picasso Avenue • Davis, CA 95618 • 1.800.311.8808 • www.breedtru.com
MMI Genomics, Inc. is a wholly-owned subsidiary of MetaMorphix, Inc.
TECHNICAL BULLETIN #1
JANUARY 31,2007
DOC#B0701.01
1756 Picasso Avenue • Davis, CA 95618 • 1.800.311.8808 • www.breedtru.com
MMI Genomics, Inc. is a wholly-owned subsidiary of Metamorphix, Inc.
A P P L I C ATION OF GENIUS -WHOLE GENOME SYSTEM™ IN BEEF C AT T L E
In 2002, an historic agreement between Cargill and MMI Genomics, a wholly-owned subsidiary of MetaMorphix Inc, laid the
groundwork for the creation of advanced tools for the cattle industry. The partnership is structured to take advantage of MMI
Genomics’ discovery assets, research capabilities and genotyping resources and Cargill’s leadership position in the beef industry,
animal resources and customer base. The combination of these resources has provided a unique opportunity to develop and commercialize innovative genomics-based products that provide value-added solutions across all segments of the beef cattle industry.
Introduction:
In 2001, both Celera Genomics (Venter et al., 2001) and the International Human Genome Sequencing Consortium (IHGSC,
2001) published the draft sequence of the human genome. The two entities had different approaches to accomplish the
same goal. IHGSC relied on a more intensive approach which involved taking large DNA fragments from a single source
and of known position, cloning them into small fragments, sequencing them and then reassembling on the basis of short
sequence overlaps. Celera, on the other hand, relied on enormous computer power to take a shotgun approach: assemble
all fragments sequenced by using overlapping fragments and sized selected libraries to determine the distance between
fragment reads. These genetic libraries were developed from multiple individuals. Thus, Celera’s strategy had an additional
advantage that as sequences were aligned, single base pair changes were identified that uncovered naturally occurring
genetic variation called single nucleotide polymorphisms (SNPs).
The strategy employed by Celera to unravel the human genome and the knowledge gained provided an opportunity to
create genomic tools in livestock. Celera discovered that its sequencing approach could be used to generate hundreds of
thousands of SNP markers with minimal sequencing. Thus, tools could be developed to allow Celera to mine the genomes of
livestock and uncover the regions of the genome influencing economically important traits.
In 2001, shortly after the publication of the working draft of the human genome, where over two million SNPs were identified, similar genomic tools were developed for cattle, swine and chicken. The cattle sequencing resulted in 787,000 SNP markers, the swine sequencing resulted in 631,000 SNP markers and the chicken sequencing resulted in 96,000 SNP markers. Four
individuals representing four different breeds were sequenced in cattle: Angus, Limousin, Brahman and Simmental.
MMI Genomics and Cargill Joint Development Agreement:
In 2002, Celera Genomics sold their Celera AgGen assets, which included the facility in California and the cattle, swine and
poultry sequences and SNPs to MetaMorphix to create MMI Genomics. A short time later MMI and Cargill struck an agreement that would utilize the talents and resources of both companies. This research agreement proposed to genotype over
4000 head of cattle grown in Caprock Feedlots with 6000 SNP markers and to use significant associations among traits and
markers to develop highly accurate diagnostic tests. This strategy is known as a whole-genome association study and measures not only additive effects of genes, but non-additive effects (dominance and epistasis) as well.
The cattle utilized were typical feedlot cattle, without parentage or breed information. This approach was unprecedented and
was based on the premise that the research should be performed in the type of cattle on which the technology was expected
to be utilized. The only a priori information obtained from the cattle was a visual assessment of the biological type: English
crosses, Exotic crosses and Brahman crosses.
The association study resulted in hundreds of markers identified that influence marbling, ADG, retail yield, backfat and tenderness. Once the markers were discovered, the companies then sought to validate the predictive capability of the diagnostic
tests using over 25,000 feedlot cattle from eight commercial feedlots.
The first feedlot products to emerge from this unprecedented partnership are Tru-Marbling™ which has 89 SNP markers and
Tru-Gain™ which has 92 SNP markers. The effects of these markers are combined to create one value: Molecular Genetic Value
(MGV) which sums all the effects from all markers into a succinct unit. Average animals have an MGV of 0, those above the average value have positive MGVs and those below have negative MGVs. Results from the commercial feedlot trials have found
that the markers account for a substantial amount of the genetic variation.
The first seedstock products to emerge are Tru-Marbling™ which has 128 SNP markers and Tru-Tenderness™ which has 11 markers. These products have been tested in purebred Angus and Limousin cattle. The seedstock Tru-Marbling™ product contains the
base markers found in the feedlot product, but adds extra markers identified in the research segregating in English cross cattle.
Literature Cited
International Human Genome Sequencing Consortium. 2001. Initial sequencing and analysis of the human genome. Nature
409:860-921.
Venter, J.C., M.D. Adams, E.W. Myers, P. W. Li, R.J. Mural, G.G. Sutton, H.O. Smith, M. Yandell, et al. 2001. The sequence of the
human genome. Science 291:1304-1351.
TECHNICAL BULLETIN #2
JANUARY 31, 2007
DOC#B0702.01
1756 Picasso Avenue • Davis, CA 95618 • 1.800.311.8808 • www.breedtru.com
MMI Genomics, Inc. is a wholly-owned subsidiary of Metamorphix, Inc.
M O L E CUL AR GENETIC VALUE (MGV ) DEFINITION AND UTILIZ ATIO N
Introduction:
Molecular Genetic Value, or MGV, is a mathematical expression developed by MMI Genomics to help explain and utilize
the results from our Breed-Tru® products, such as Tru-Marbling™ and Tru-Tenderness™. Traits such as marbling, tenderness,
growth and many others are classified as “quantitative” traits because their expression is controlled by a large number of
genes rather than single genes. Cargill and MMI Genomics developed DNA-based diagnostic tests using our GENIUS-Whole
Genome System™ which identified and validated a substantial number of the genes and DNA markers that influence certain
traits. The result of this strategy was the development of our Breed-Tru® diagnostic assays that explain a substantial proportion of the total genetic variation observed for the trait. MGV is the method for reporting the combined effects from multiple
DNA markers into a single expression that is easy to interpret and utilize for enhancing breeding and selection decisions.
Definition of Molecular Genetic Value:
Technically, the Molecular Genetic Value is defined as an estimate of the genetic potential of an individual animal calculated
from the sum of all genetic effects at specific genome locations including additive and non-additive effects. Therefore, the
MGV calculates the effect that each DNA marker contributes to the result by assessing both the size of the effect (small or
large) and the direction of the effect (positive or negative) and combining the information for all markers into a single value
that can be utilized as an overall indicator of genetic potential.
Applications of MGVs:
Molecular Genetic Values can be utilized to enhance animal breeding and selection decisions in a number of important ways.
• MGVs can be used to rank animals based on their genetic potential to express the trait. These rankings can then be utilized
in comparing one animal against any other animal, within or across breed, so that decisions can be made on whether to
keep, breed, flush, cull or sell specific animals.
• MGVs can be used to enhance mating decisions. MMI Genomics is in the process of developing software tools that will provide probability outcomes for MGVs of progeny produced from specific matings to previously tested sires and dams. These
breeding tools can be used to optimize the MGVs from progeny produced in defined matings.
• Since the MGV for an animal is based on the animal’s actual DNA genotype, the MGV can be used to make early and accurate breeding decisions. The ability to rank and breed animals at an early age results in both increasing the accuracy of
selection and decreasing the age at which animals can be selected.
MGVs and EPDs:
Molecular Genetic Values (MGVs) are created from the actual genetic makeup of an individual animal as measured by the
genotypes for markers at each location. Expected Progeny Differences (EPDs) are estimated from phenotypes of animals
that have a genetic relationship: offspring, progeny, and collateral relatives. While the MGV will remain constant throughout
the animal’s life, the EPD changes according to the number of relatives an animal has with phenotypes. EPD accuracy can
improve even after the animal is deceased. An animal can have a reported EPD based only from the average EPDs of the
parents, for example, which could change substantially as additional information is obtained. While MGVs are substantially
different from EPDs, there are similarities between the two with regard to the way data is reported and how they are utilized
to enhance breeding and selection decisions.
MGVs are similar to EPDs in that:
• MGVs can be utilized similar to EPDs in ranking animals based on their potential to express the trait; the higher the MGV
the greater the potential expression of the trait.
• MGVs and EPDs are both reported as a deviation from a predetermined overall mean such as the base year mean used
for calculating EPDs. For example, a positive MGV value indicates the genetic potential of an animal is higher than the
mean; a negative value indicates it is lower. The overall mean currently established for reporting MGVs for any trait is
set to zero and is based on more than 4,000 cross-bred feeder calves representing English, Continental and Brahman
biological types.
(Continued)
TECHNICAL BULLETIN #2
MGVs are dissimilar to EPDs in that:
• The MGV does not utilize phenotypic information. The MGV defines the genetic potential of an animal to express the
trait based on that animal’s specific DNA content.
• Since DNA does not change from conception to death, the genotype of the animals remains constant and never needs
to be repeated. Consequently, the MGV remains unvarying regardless of the age the sample is taken.
• Genetic Prediction with EPDs requires that progeny and mates are not preferentially managed or selected. MGVs have
no such constraints because they are a direct measure of an animal’s genotype,
• MGVs do not utilize an associated “accuracy” value to determine the reliability of the genetic value that is reported. EPDs
are reported with an accuracy value that is a measure of the reliability of the EPD which can range from 0.0 to 1.0. Both
the EPD and the accuracy of an EPD will change throughout the animal’s life because phenotypic data is continually
added to the database. The MGV is a measure of an animal’s genetic potential to express the trait based on its DNA
genotype and will not change.
Sample Submission, Data Results, and Example Breed-Tru® Report:
Breeders submit a single drop of blood collected on an MMI Genomics MicroCard to the laboratory. Each sample is individually logged into the laboratory system and DNA extracted from the card is genotyped for all markers based on the test
requested. After genotyping, the data is uploaded into the database and calculations are performed to estimate the MGV for
each trait. An example of results is presented below.
All four animals represented in the above test result have Tru-MarblingTM and Tru-TendernessTM MGVs. All MGVs within a trait
have the same accuracy because every animal has the same number of markers in the prediction of genetic potential.
Paul Bunyan and Casey Jones are predicted to grade in the low Select and No Roll USDA grades because of their large
negative marbling MGVs. Alamo Rising and Geronimo are predicted to grade in the USDA grades of high Choice and Prime
because of their high MGVs for marbling. MGVs near 0 are expected to grade in the high Select USDA grading category.
Paul Bunyan is predicted to produce tough meat with the larger MGV for Tru-TendernessTM. Casey Jones and Geronimo are predicted to produce very tender meat. Alamo Rising is predicted to produce acceptable tenderness, bordering on slightly tough.
These results can be used to rank bulls for their genetic potential for marbling and tenderness.
Glossary:
Additive Genetic Effects: The portion of the genotype that is transmitted from parent to progeny.
Genotypes: The genetic makeup of an animal.
Non-additive Genetic Effects: Dominance and epistatic effects. Dominance is the interaction among alleles at a locus. Epistasis is the interaction among different loci.
Phenotypes: Any measurable characteristic of an animal.
Single Nucleotide Polymorphisms (SNPs): Pronounced “snips”; a single base-pair change in the DNA that marks a location on
a chromosome. A SNP can be a marker for a gene that influences a phenotype or can be the cause of the change.
Allele: Alternative forms of a SNP marker at a specific location.
Locus: Location of a specific SNP marker.