Where are we going with our genes?

Do we need GMO's?

Sygen Chair of Genetic Information Systems

http://metz.une.edu.au/~bkinghor/

Siemens Science Experience

January 14-16th 2003.

Brian Kinghorn

New Genetic Technologies …

Give us knowledge on structure and function of genetic material and its downstream products.

Let us manipulate that material directly or indirectly to target improved and novel function:AgricultureHealth (especially diagnostics)Forensics (who done it?)Manufacturing (including Farmaceuticals)

http://www.expasy.ch/cgi-bin/show_thumbnails.pl

“DNA Chips”

Affymetrix GeneChip®

“DNA chips” to “Lab-on-a-chip” Nanoinstrumentation ...

Fluid channels

Pumps

Electrophoresis

Lasers

Polymerase Chain Reaction

Mixing things

power supplies

Heating

and lots of other exciting things on a somewhat small scale …

“DNA Chips”Masks of oligonucleoides etc. on silicon.

www.affymetrix.com

Microarrays for detecting gene and protein expression[www.accessexcellence.org/AB/GG/microArray.html]

Microarrays for detecting gene and protein expression

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Gene expression programmingCandida Ferreira http://www.gene-expression-programming.com

“DNA” “Organism”

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Gene expression programming ?

“DNA” “Organism”

Toolbox

Sources of information for inferring biological activity

Eg. a disease cycle

Agriculture: why seek genetic change?

Animals and plants convert inputs to outputs. 

Better animals and plants do the job more efficiently.

We can improve animals and plants by changing them genetically.

INGrass

Fences

Labour

Climate

OUTMeat

Milk

Fibre

Bread

Active and passive approaches to bringing about genetic change.

Passive

Gene detection

Gene location

Indirect marker

Direct marker

Marker-assisted breeding

Active

Gene detection

Gene location

Gene cloning

Gene construct

Gene transfer

Gene Transfer

http://www.criver.com/techdocs/transgen.html

Genetically Modified Organisms

Prospects

Increased production efficiencyDisease resistanceHerbicide resistanceLabour savings

Increased production functionDaffodil beta-carotene into riceFat profiles in milk and meatControl of ripeningProduction in more marginal environmentsCaffeine-free coffeeAllergen-free peanuts

Genetically Modified Organisms

Prospects

Increased safety in agricultureReduced application of pesticides and herbicides

Eg. secretion of chitinase from sweat glands in sheep.

(Immunological or structural change is better)

Production of pharmaceuticals & neutraceuticalsHuman proteins etc. in milk from transgenic sheep

Genetically Modified Organisms

Prospects

Artificially generated DNA sequencesIn-vitro optimisation of isozyme sequencesDesigner fibresNovel pharmaceuticals & neutraceuticals

Gene therapySomatic modifications

Screening of gametes (non-GMO) IVFGene therapy of gametes (GMO) IVF

Genetically Modified Organisms

Prospects

Pure research Leading to understanding of life processes. Eg. Use of ‘knockout’ mice.

Genetically Modified Organisms

Pitfalls

Possible cause(s)

Possible outcome(s)

Risk minimization

Multiple transgene copies.

Loss of proper feedback control.

Bad expression:Level, tissue, time.

Organism ‘out of harmony’

Low viability or death.

Should be detectable during development.

Use progressive methods

Disturbance at insertion site

Danger is with occasional need for normal function, such as resistance to a rare pathogen.

Insertion in appropriately “benign” region.

Genetically Modified Organisms

Pitfalls

Possible cause(s)

Possible outcome(s)

Risk minimization

Changes in immunological profile.

GMO susceptible to other pathogens, possibly rare and previously harmless.

Understand the biology of changes generated.

Resulting organism competes inappropriately with normal individuals.

Physically dominant but reproductively deficient GMOs can threaten the normal population.

Test GMO in competition studies.

Genetically Modified Organisms

Pitfalls

Possible cause(s)

Possible outcome(s)

Risk minimization

Resulting organism conflicts with environment and/or interacting organisms.

Threatened insect populations. Resistant pests. GMOs could spread out of control, either directly or via their gametes.

Understand the species, its modes of propagation, and its interactions with other species and the environment.

Resulting organism generates inappropriate food product.

Hormones, pesticides, residues, allergens etc. in product.

Understand risks and test widely for safety.

Genetically Modified Organisms

Pitfalls

Possible cause(s)

Possible outcome(s)

Risk minimization

Public perception on safety, ethics, welfare.

Market failureGenerate arguably safe GMOs and educate public –maybe difficult.

Other unknown causes Other unknown outcomesKeep an open and critical mind.

That was the active approach to genetic change.

Now the passive approach …

Genetic markers and a major gene.

Chromosomes from Dad

Chromosomes from Mum

Major gene

Genetic markers

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Indirect genetic markers

A Ram:

His semen:A

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Indirect genetic markers

‘recombinants’

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Indirect genetic markers

‘recombinants’

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Indirect genetic markers

‘recombinants’

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Indirect genetic markers

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‘recombinants’

In reality,we are colorblind ...

Simple QTL detection with markers

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Parents:

Progeny:

Probabilities: 90% 10%

Bull Cows

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Gene location

Marker location

QTL detection with markers

Likely locationof major gene

Location ofmarkersL

od s

core

Position on chromosome

Logarithm of the ODds

Log(prob result with QTL)Log(prob result without QTL)

Direct genetic markers

A - always circle, always good

B - always triangle, always bad

“Marker Assisted Selection”(The Passive approach)

• Gather information about the genes carried by each individual

• Use this information to help select parents and allocate mates

• Just do what could have happened ‘naturally’ anyway.

No recombinant DNA

No funny test-tube business

Conclusions

New genetic technologies are causing a revolution

GMOs give:Biggest prospects, biggest pitfalls

Philosophy on evaluating GMOs:Actively seek potential problems

Scientists must not adopt a defensive attitude

Using just information from DNA work provides a slower but safe route

GMOs will ultimately be used widely, and for more innovative purposes.

http://metz.une.edu.au/~bkinghor/