Post on 15-Jan-2016
CloningCattle
A. (Sandy) E. McClintock
Embryo Multiplication and Transfer“Cloning”
• 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
2. Fertilises the egg in an elite
donor cow
3. Remove the fertilised egg from the cow
Potentially a Cheapand efficient process
Embryo Multiplication & Transfer (EMT)
-No selection.
5. Use the genes from this elite embryo to reprogram
eggs salvaged from an abattoir from “any old cow”
4. Check that the embryo is male.
1. Semen from an elite bull
6. Transfer copied embryos to
recipient cows
Cheap Identical
bulls
IRD / Genetics Australia System
… but not necessarily
highly valuable
Cloning with Testing and
Selection
0%
Reliability of a Bull’s Test
50%
100%
0 100 200 300
Number of progeny Records
Reliability
The more recorded progeny,
the more reliable the bull’s assessment.
(Progeny Testing)
0%
10%
20%
25% Heritability
30%
40%
50%
60%
70%
80%
90%
100%
0 50 100 150 200 250 300 350
Clones
Bulls progeny test
Reliability
Records
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
0 200 400 600 800 1000 1200 1400 1600
Clones
Bulls progeny test
Reliability
Records
Low (5%) Heritability
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”
2. Select the male embryos
Possible Selection Scheme - Terminal Beef Sires
EMT with FamilyTesting and Selection
IRD / Genetics Australia System
4a. Test fertility traits of the entire calves. Also
test the carcass traits of the steers
1. Make perhaps 200 embryos using a variety of breeds and crosses
6. Make thousands of bulls from the top few lines
Super Quality
Identical bulls
3. Make a limited number
(?50) bull calves from these
4b. Freeze some embryos for later
use5. Discard 95%
of the frozen embryos on the basis of fertility,
growth & carcase
2. Select the male embryos
Possible Selection Scheme - Straightbred Beef Sires
EMT with FamilyTesting and Selection
IRD / Genetics Australia System
4a. Test fertility and growth potential of these
bulls (and steers)
1. Make perhaps 200 embryos using a variety of breeds and crosses
7. Make thousands of bulls from the top lines
Super Quality
Identical Bulls
3. Make a limited
number (?50) bull
calves from these 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
4b. Freeze some embryos for later use
1. Collect a cell from the donor bull
2. Use the ‘Adult’ genes to reprogram an embryo
from “any old cow”
Expensive &Inefficient Process
Adult Cloning
Scottish System
3. Transfer reprogrammed embryo to a recipient cow
Expensive but High Quality Identical bull
Potential system to copy top beef bulls
Adult Cloningfollowed by EMT
Scottish System plus
Monash System
3. Make thousands of copies of this embryo using
EMT
4. Transfer copies of the reprogrammed
embryo to recipient cows
Cheap Identical copies of a High Quality beef bull
1. Collect a cell from a mature top bull
2. Use the ‘Adult’ genes to reprogram an embryo
from “any old cow”
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
Grow embryo in
the lab
Break embryo into 20-30 identical cell.
Salvage eggs from
abattoir cows
Remove genes
Transfer to recipients when enough have been made. Some can be frozen for
later use.
5 to 10 times more
embryos each 4 days.
Some embryos start to develop
Get embryo from elite parents
Electric pulse
merges the two parts
+ -
Monash IRD / Genetics Australia EMT System
Salvage eggs from
abattoir cows
Remove genes
Transfer to recipients
Some embryos ready for freezing
Some embryos start to develop
Alternative Monash / Genetics Australia EMT System
Take a cell from a culture with a million identical cells.
Direct Injection
merges the two parts
Grow cells in the lab
Get tissue sample from an elite animal. Eg
skin
Tissue culture
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 successin the next 5 years - 10%
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?
• Benefit:Cost 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)
Costs and benefits
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.
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 B:C ratios
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
Monash University Genetics Australia Alan TrounsonKym Boekel Kim GiliamTiki GougoulidisMark LaneIan LewisTeija PeuraDavid PushettSteven WildCollaborating scientist Orly Lacham-Kaplan
Bernie HarfordPeter ColemanChris ClosterAndrew HarfordIan LewisGlenn LyonsSandy McClintockJohn OwensMichael Ryan
Visiting Scientist Gabor Vajta - Embryo Technology Center, Foulum, Denmark
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
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?