Page 1 of EMT slide

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CloningCattle
A. (Sandy) E. McClintock
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Embryo Multiplication and TransferCloning

• Until recently - embryo cloning only
• Many labs are involved worldwide
• Institute for Reproduction and Development -IRD
• Now - Adult cloning too.
• The Scottish System
• ProBio
• ABS

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IRD / Genetics Australia System
Potentially a Cheap and efficient process
Embryo Multiplication Transfer (EMT) -No
selection.
1. Semen from an elite bull
3. Remove the fertilised egg from the cow
4. Check that the embryo is male.
2. Fertilises the egg in an elite donor cow
5. Use the genes from this elite embryo to
reprogram eggs salvaged from an abattoir from
any old cow
but not necessarily highly valuable
Cheap Identical bulls
6. Transfer copied embryos to recipient cows
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Cloning with Testing and Selection
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Reliability of a Bulls Test
100
Reliability
The more recorded progeny, the more reliable the
bulls assessment. (Progeny Testing)
50
Number of progeny Records
0
100
200
300
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25 Heritability
Reliability
100
Clones
90
80
Bulls progeny test
70
60
50
40
30
Records
0
50
100
150
200
250
300
350
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Low (5) Heritability
Reliability
100
Clones
90
Bulls progeny test
80
70
60
50
40
30
20
Records
10
0
0
200
400
600
800
1000
1200
1400
1600
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Cloning

• Roughly four to five times fewer clone records to
  obtain the same level of Reliability as a Progeny
  Test
• Initially farmers may want to sacrifice selection
  pressure so as to gain accuracy
• For traits with a heritability of 5 to 25, we
  can expect little change in the within herd
  variation.
• Clones will not be like peas in a pod

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IRD / Genetics Australia System
Possible Selection Scheme - Terminal Beef Sires
EMT with Family Testing and Selection
1. Make perhaps 200 embryos using a variety of
breeds and crosses
4a. Test fertility traits of the entire calves.
Also test the carcass traits of the steers
3. Make a limited number (?50) bull calves from
these
2. Select the male embryos
5. Discard 95 of the frozen embryos on the basis
of fertility, growth carcase
Super Quality Identical bulls
6. Make thousands of bulls from the top few lines
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IRD / Genetics Australia System
Possible Selection Scheme - Straightbred Beef
Sires
EMT with Family Testing and Selection
1. Make perhaps 200 embryos using a variety of
breeds and crosses
3. Make a limited number (?50) bull calves from
these
4a. Test fertility and growth potential of these
bulls (and steers)
2. Select the male embryos
5. Discard 50-80 of the frozen embryos on the
basis of fertility, growth carcase
6. Run Progeny Test. Discard those with poorer
daughter fertility and steer progeny performance
Super Quality Identical Bulls
7. Make thousands of bulls from the top lines
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Expensive Inefficient Process
Scottish System
Adult Cloning
1. Collect a cell from the donor bull
2. Use the Adult genes to reprogram an embryo
from any old cow
3. Transfer reprogrammed embryo to a recipient
cow
Expensive but High Quality Identical bull
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Potential system to copy top beef bulls
Scottish System plus Monash System
Adult Cloning followed by EMT
1. Collect a cell from a mature top bull
4. Transfer copies of the reprogrammed embryo to
recipient cows
3. Make thousands of copies of this embryo using
EMT
2. Use the Adult genes to reprogram an embryo
from any old cow
Cheap Identical copies of a High Quality beef bull
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Three Scenarios

• Scenario One
• Adult clones
• Too good to be true
• Scenario Two
• One generation Cloned Embryo Testing
• Terminal sires mainly
• Scenario Three
• Two generation Cloned Embryo Testing
• Straightbred sires and terminal sires

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Monash IRD / Genetics Australia EMT System
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Alternative Monash / Genetics Australia EMT
System
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Cloning Targets

• Price per embryo - 30?
• Transfers done by trained AI technicians
• Eggs consumed per embryo sold - Low!
• Calving rate - 50 (two embryos at a time?)
• Calf health - Good!
• Chance of becoming a commercial success in the
  next 5 years - 10

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Impact of Cloning

• Impact on genetic improvement programs.
• Demise of PT systems?
• MOET Nucleus Breeding Programs?
• Sale of Natural Service super bulls?
• Impact on production systems
• Beef from Dairy herds
• Terminal breed Males and F1 females
• Twins?

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Costs and benefits

• BenefitCost too small at present due to-
• Conception rates are far too low.
• Family sizes are too small.
• Cloned embryos are too expensive.
• 30 Cloned F1 embryos sold.
  (Mainly females - Dairy)
• 300 Cloned embryos sold as Elite Breeding
  stock (Males Females)
• 3000 Cloned embryos sold as Elite Breeding
  stock (Males mainly)

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Conclusion

• Calves born per spent is critical!
• Unless cloned embryos cost little more than 30
  the benefits will be too low except for cloned
  beef bulls.

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Overuse of Cattle Clones?

• Dangers of Monoculture
• Potato famine
• Several lines per herd recommended
• Some farmers will reject cloning
• Emergence of specialist genotypes for Niche
  Markets
• Optimisation rather than maximisation
• Initial rapid gain then lowered BC ratios

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Politics

• Impact Of Public Perception
• Transgenic pigs
• BST (Growth hormone)
• Soy meal for cows
• Gene Banks
• Which countries have a gamete museum?
• The cost of long term storage is minimal
• Now is the time to act

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Monash University Genetics Australia
Alan Trounson Kym Boekel Kim Giliam Tiki
Gougoulidis Mark Lane Ian Lewis Teija Peura David
Pushett Steven Wild Collaborating scientist
Orly Lacham-Kaplan
Bernie Harford Peter Coleman Chris
Closter Andrew Harford Ian Lewis Glenn
Lyons Sandy McClintock John Owens Michael Ryan
Visiting Scientist
Gabor Vajta - Embryo Technology Center, Foulum,
Denmark
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Summary

• Higher Accuracy with clones
• Mainly cloned BULLS for beef industry
• How to make clones
• How to test clones
• 90 certain - not possible in next 5 years
• Need to retain genetic diversity

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Other Aspects

• Impact on genetic improvement programs
• Dramatic if cloned embryos are cheap
• Cloning from Adult, rather than Foetal cells
• Nice, but not essential for genetic improvement
• Reproduction without the need for males
• Could we cross 2 female clone lines to create
  new genetic variation?