Animal Genomics and Biotechnology Education
Biotech Beef and Cloned Cows:
Progress in Translational
Genomics Alison Van Eenennaam, Ph.D. Cooperative Extension Specialist
Animal Biotechnology and Genomics Department of Animal Science
University of California, Davis
(530) 752-7942
Twitter: @biobeef
animalscience.ucdavis.edu/animalbiotech
Animal Biotechnology and Genomics Education
“Translational genomics” is defined as the
adaptation of information derived from
genome technologies for animal improvement
Van Eenennaam CalPoly 3/10/11
SNP (Single Nucleotide Polymorphism)
A DNA sequence variation that
varies sufficiently between
individuals that its inheritance can be tracked
through families
Animal Biotechnology and Genomics Education
Overview: A whirlwind tour of
translational genomics
1. Using DNA information to identify carriers of recessive traits (coat color, horns, disease)
2. Marker-assisted selection
3. Genome-enabled or genomic selection
4. Cloning
5. Genetic engineering
Animal Biotechnology and Genomics Education
This is a picture
of D _ A.
B N C L
0% 0%0%0%
1. B
2. N
3. C
4. L
Animal Biotechnology and Genomics Education
Given this information……
Animal Biotechnology and Genomics Education
1. 1
2. 2
3. 3
4. 4
Which do you think is my dog?
1 2 3 4
0% 0%0%0%
1 2
3 4
Animal Biotechnology and Genomics Education
1. Using DNA information to
identify carriers of recessive traits Images from an article by David S. Buchanan, NDSU http://www.ag.ndsu.edu/williamscountyextension/livestock/genetic-defects-in-cattle
Animal Biotechnology and Genomics Education
Both are important!!
The ‘homozygous’ bull is a source of favorable form of the genetic variant. Can eventually be used to create homozygous calves
The other bull contributes other favorable genes, which will improve the other genes affecting the trait.
Breeding the marker-associated form of the gene into the bull that has no copies should improve the trait by combining all of the good forms of the genes together in one animal Van Eenennaam CalPoly 3/10/11
Compare dwarfism response in the 50s to the response to curly calf (AM)
An early '50's
advertisement that
superimposed a
measuring stick in the
picture of this bull
who was nick-named
"Short Snorter."
Based upon his height
and age, he was less
than a frame score 1.
Image from https://www.msu.edu/~ritchieh/historical/shortsnorter.jpg
Curly calf – Arthrogryposis multiplex
From a scientific standpoint,
AM is the complete deletion
of a segment of DNA that
encompasses two different genes
One of these genes is expressed at a crucial time in the development of nerve and muscle tissue. The mutation results in no protein being produced from this gene and therefore it is unable to carry out its normal function so homozygotes show phenotype
Dr. David Stefan of the University of Nebraska and Dr. Jon Beever of the University of Illinois worked to develop a genetic test from September – October, 2008
Animal Genomics and Biotechnology Education
From September 8 – December, 2008 identified genetic problem, developed test, and released carrier status of 736 bulls!
From: Buchanan, D.S. Genetic Defects in Cattle. http://www.ag.ndsu.edu/williamscountyextension/livestock/genetic-defects-in-cattle
In the 10 months following the release of the test, the AAA posted the results of tests for AM on about 90,000 cattle.
These AM test costs less than $30 (~2.7 million).
Of these, almost 5,000 bulls and more than 13,000 heifers have tested as carriers of AM. That leaves more than 22,000 bulls and more than 50,000 heifers which tested as free of AM.
Early extension education about dwarfism
explaining carriers and inheritance
Image from Special CollectionsUniversity Libraries, Virginia Tech: http://spec.lib.vt.edu/imagebase/agextension/boxseven/screen/AGR3618.jpg
If you breed a curly calf carrier cow (AMC) to an curly calf free bull (AMF), what is the chance that the offspring will be stillborn
as a result of being curly calf?
0
¼ (2
5%)
½ (5
0%)
2/3
(66%)
¾ (
75%)
1 (
100%)
0% 0% 0%0%0%0%
1. 0
2. ¼ (25%)
3. ½ (50%)
4. 2/3 (66%)
5. ¾ (75%)
6. 1 (100%) Van Eenennaam CalPoly 3/10/11
Animal Biotechnology and Genomics Education
2. There are various companies offering DNA tests for marker-assisted selection in beef cattle
Van Eenennaam CalPoly 3/10/11
Animal Biotechnology and Genomics Education
Meat Tenderness
Quality Grade (Marbling)
Beef Cattle Feed Efficiency
Meat Yield
Disease Resistance
Dairy Form
Milk and Milk Component Yield
Tests for quantitative traits – before 2010 10-100 SNPs
Van Eenennaam CalPoly 3/10/11
Animal Biotechnology and Genomics Education
Which would you rather have???
1 2
0%0%**
1. A bull that is ‘homozygous’ or two stars for a trait who also has an EPD of +3, or
2. A bull carrying no copies of that genetic variant with an EPD of +3
Animal Biotechnology and Genomics Education
Both are important!!
The ‘homozygous’ bull is a source of favorable form of the genetic variant. Can eventually be used to create homozygous calves
The other bull contributes other favorable genes, which will improve the other genes affecting the trait.
Breeding the marker-associated form of the gene into the bull that has no copies should improve the trait by combining all of the good forms of the genes together in one animal Van Eenennaam CalPoly 3/10/11
Animal Biotechnology and Genomics Education
What is wrong with this model?
A few markers are not sufficient to account for much (>10%) of the additive genetic variation – so little obvious relationship between phenotype and DNA-test results and little genetic progress likely to result from MAS
Markers do not exist for many important traits
Early adopters of genotyping for MAS in livestock have not experienced sufficient value capture i.e. they are too expensive !
Van Eenennaam CalPoly 3/10/11
Challenge for breeders is to identify those individuals that have the best
true breeding values
ΔG (rate of genetic gain)
= intensity of selection X
accuracy of selection X
genetic standard deviation
generation interval
Animal Biotechnology and Genomics Education
3. Mooving onto Genomic Selection
Training 1: Old Progeny Tested Bulls
Validation: New Progeny Tested Bulls
Application: New Sire Candidates
r0
r1
Training 2: Old & New Progeny Tested Bulls
Slide courtesy of Marc Thallman, US MARC
Degree of genetic relationship between
populations (ideally similar)
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Animal Biotechnology and Genomics Education
Young sire Parent Average
x
AS AD
Mendelian Sampling ?
Accuracy 0.20
Breeding value prediction in Dairy Sires
5 years; >>>> cost
x
AS AD
Mendelian Sampling
Young sire Progeny Test
Accuracy 0.80
x
AS AD
Mendelian Sampling
Accuracy 0.65
Young sire Genomic Selection
?
Birth Birth; <<<< cost
Slide courtesy of Gonzalo Rincon, UC Davis
Genomic selection can help breeders identify animals with superior
breeding values at a young age
ΔG = intensity of selection X
accuracy of selection X
genetic variation in the population /
generation interval)
Van Eenennaam CalPoly 3/10/11 Animal Genomics and Biotechnology Education
Animal Biotechnology and Genomics Education
Dairy industry suited to WGS
• High use of AI
• Clear selection goal
• One breed used extensively
• Large number of high accuracy A.I. sires for training
• Extensive, uniform collection of data on traits
• Central evaluation (AIPL) receiving genotypes
• Obvious way to increase rate of genetic gain
• AI companies funding the genotyping because they
get a clear cost savings in terms of young sire
program
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Animal Biotechnology and Genomics Education
Genomic selection can double rate of genetic gain
Rate of genetic gain ΔG
ΔG = (im rm +if rf)/ (Lm + Lf) genetic standard deviation/year
= (2*0.8 + 0)/ (6+2) = 0.2 s.d./year (progeny test)
= (2*0.6 + 0.8*0.6)/ (2+2) = 0.42 (genomic selection)
i = intensity of selection
r = accuracy of selection
L = generation interval
Modified from Goddard. (2009) BIF Meeting
Velogenetics (Georges and Massey (1991) Theriogenology
35:151-159)
• Harvest oocytes from in-utero calves
• In-vitro
• maturation
• fertilization
• Selection based on genetic markers
• Implant in recipient cows
• L = 6 months (0.5 instead of 6 years)
Van Eenennaam CalPoly 3/10/11
Animal Biotechnology and Genomics Education
Velogenetics could increase rate of genetic gain 8X
Rate of genetic gain ΔG
ΔG = (im rm +if rf)/ (Lm + Lf) genetic standard deviation/year
= (2*0.8 + 0)/ (6+2) = 0.2 (progeny test)
= (2*0.6 + 0.8*0.6)/ (2+2) = 0.42 (genomic selection)
= (2*0.6 + 0.8*0.6)/ (.5+.5) = 1.68 (velogenetics) i.e. 8X
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Animal Biotechnology and Genomics Education
4. Onto cloning!!
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Animal Biotechnology and Genomics Education
Have you ever eaten a
clone?
Yes N
o
0%0%
1. Yes
2. No
0
30
Van Eenennaam CalPoly 3/10/11
Animal Biotechnology and Genomics Education
What is a clone ?
• Cloning, in horticulture and biology, any
organism whose genetic information is
identical to that of a "mother organism"
from which it was created.
• Food from clones has been a part of our
diet for years. Many common fruits (e.g.,
pears, apples, oranges and lemons) and
several vegetables (e.g., potatoes and
truffles) are clones. Van Eenennaam CalPoly 3/10/11
Animal Biotechnology and Genomics Education
Have you ever eaten milk or
meat from a cloned animal?
Yes N
o
0%0%
1. Yes
2. No
0
30
Van Eenennaam CalPoly 3/10/11
Animal Biotechnology and Genomics Education
Holstein Association USA (Brattleboro, VT)
first registered clones from embryo splitting
(ETS) in 1982 and clones from embryo
nuclear transfer (ETN) in 1989.
Most of us have probably ingested meat and
dairy products from livestock cloned by
natural reproduction (monozygotic siblings),
mechanical embryo-splitting, or even nuclear
transfer from an embryonic donor cell into an
enucleated oocyte.
Have I ever eaten products
from a cloned animal? YES!!
Animal Biotechnology and Genomics Education
Mechanical embryo splitting
The Holstein association of America has registered 2319 embryo split clones (ETS) through October 2002 – probably
the most widely recognized were DUPLICATE and DIVIDE.
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Animal Biotechnology and Genomics Education
Dolly (1996), the first
adult SCNT clone
Animal Biotechnology and Genomics Education
Dolly rapidly became entangled with the debate over human cloning
Ensuing discussion failed to elaborate on the reasons as to why cloning was developed
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Animal Biotechnology and Genomics Education
Animal Biotechnology and Genomics Education
Who’s Buying?
Animal Biotechnology and Genomics Education
On January 15th, 2008 the FDA published its final 968-page risk assessment on animal cloning. This report, which summarizes all available data on clones and their progeny are as safe to eat as food from conventionally bred animals
Are the milk and meat from SCNT clones safe for human
consumption?
Van Eenennaam CalPoly 3/10/11
Animal Biotechnology and Genomics Education Van Eenennaam CalPoly 3/10/11
Animal Biotechnology and Genomics Education
Animal cloning regulations in Denmark and Norway
prohibit cloning for food and agricultural purposes.
January 2007: The European Food Standards Agency is seeking urgent legal advice after farmers announced the birth of a calf whose genetic mother is the clone of an American prizewinning dairy cow.
Animal Biotechnology and Genomics Education
Do you oppose the genetic
modification of animals?
Yes N
o
0%0%
1. Yes
2. No
0
30
Van Eenennaam CalPoly 3/10/11
Animal Biotechnology and Genomics Education
56% of Americans oppose scientific research
into the genetic modification of animals http://pewagbiotech.org/research/2005update/2005summary.pdf
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Animal Biotechnology and Genomics Education
No one seem to get too upset about the
genetic modifications made by traditional
animal breeders ……….
Van Eenennaam CalPoly 3/10/11
Animal Biotechnology and Genomics Education
But they do get VERY upset about genetic
modifications made by the process of genetic
engineering…….
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Animal Biotechnology and Genomics Education
ESPECIALLY genetically-
engineered food animals
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Animal Biotechnology and Genomics Education
Aqua bounty growth-enhanced salmon
http://www.aquabounty.com/
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Product Definition for the
AquAdvantage Salmon
Product Identity
Triploid hemizygous, all-female Atlantic salmon (Salmo salar)
bearing a single copy of the α-form of the opAFP-GHc2 rDNA
construct at the α-locus in the EO-1α lineage.
Claim
Significantly more of these Atlantic salmon grow to at least 100 g
within 2700 deg C days than their comparators.
Limitations for Use
These Atlantic salmon are produced as eyed-eggs for grow-out only
in the FDA-approved physically-contained fresh water culture facility.
Van Eenennaam CalPoly 3/10/11 Alison Van Eenennaam , Ph.D., UC Davis
Animal Biotechnology and Genomics Education Van Eenennaam CalPoly 3/10/11
Animal Biotechnology and Genomics Education
Retrieved from “AquAdvantage” image search on web
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CASE STUDY: MASTITIS
inflammation of the mammary gland
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Animal Biotechnology and Genomics Education
1. Conventional: Antibiotic therapy
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2. Natural: alternative therapy
“An infected cow should be given an extra tablespoon of dolomite night and morning until the infection clears. Hydrogen peroxide; 10 ml squirted straight into the affected quarter has cured black mastitis in hours.”
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Animal Biotechnology and Genomics Education
The use of 50,000 or more SNP markers across the entire genome enables an estimation of genetic merit
3. Genomic Selection (DNA-informed
selective breeding on a grand scale)
Can be used to predict genetic merit for mastitis resistance
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Animal Biotechnology and Genomics Education
4. Genetic Engineering: Transgenic
cows show resistance to mastitis.
Wall,R.J. et al. Genetically enhanced cows resist intramammary Staphylococcus aureus infection. Nature Biotechnology 23, 445-451 (2005).
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5. Clone a bull whose daughters are very
mastitis resistant (ie high accuracy EPD for
disease resistance) and use these bulls as
sires for mastitis resistance.
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Animal Biotechnology and Genomics Education
Which Animal Biotechnology
would you use to combat mastitis?
Conve
ntiona
l Tre
atm
ent
Nat
ural T
hera
py
Gen
omic
Sel
ectio
n
Gen
etic
Engin
eerin
g
Clo
ne a
Res
ista
nt Bull
0% 0%0%0%0%
1. Conventional Treatment
2. Natural Therapy
3. Genomic Selection
4. Genetic Engineering
5. Clone a Resistant Bull
0
30
Van Eenennaam CalPoly 3/10/11
Animal Biotechnology and Genomics Education
“We have recently advanced our knowledge of genetics to the point where we can manipulate life in a way never intended by nature. We must proceed with the utmost caution in the application of this new found knowledge.”
LUTHER BURBANK, 1906 Creator of over 800 new plant varieties through plant breeding.
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Animal Biotechnology and Genomics Education
“to fail to apply the best available technologies to the
solution of contemporary and future food shortages
would be morally reprehensible.”
Fahrenkrug et al. 2010. Precision Genetics for Complex Objectives in Animal Agriculture. J. Anim Sci. 88 (7): 2530-2539.
Animal Biotechnology and Genomics Education Van Eenennaam CalPoly 3/10/11