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
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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AB
Indirect genetic markers
A Ram:
His semen:A
B
A
A A
A
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B
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BB
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Indirect genetic markers
‘recombinants’
B
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Indirect genetic markers
‘recombinants’
B
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Indirect genetic markers
‘recombinants’
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Indirect genetic markers
B
A B A
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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
G G gggggg
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/