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

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100%

0 100 200 300

Number of progeny Records

Reliability

The more recorded progeny,

the more reliable the bull’s assessment.

(Progeny Testing)

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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?