Download Computer modelling as an aid in making breeding decisions

Siemens Science Experience
January 14-16th 2003.
Where are we going with our genes?
Do we need GMO's?
Brian Kinghorn
Sygen Chair of Genetic Information Systems
http://metz.une.edu.au/~bkinghor/
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:
 Agriculture
 Health (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
Gene expression programming
Candida Ferreira
http://www.gene-expression-programming.com
“Organism”
“DNA”
+
Q
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+/Q*c-abde
a
-
c
*
b
d
a *b
 d e
c
e
Gene expression programming ?
“DNA”
Toolbox
???????????
“Organism”
Sources of information for inferring biological activity
Agriculture: why seek genetic change?
IN
OUT
Grass
Meat
Fences
Fibre
Labour
Milk
Climate
Bread
 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.
Active and passive approaches to
bringing about genetic change.
Active
Passive
 Gene detection
 Gene detection
 Gene location
 Gene location
 Gene cloning
 Indirect marker
 Gene construct
 Direct marker
 Gene transfer
 Marker-assisted
breeding
Gene Transfer
http://www.criver.com/techdocs/transgen.html
Genetically Modified Organisms
Prospects
 Increased production efficiency
 Disease resistance
 Herbicide resistance
 Labour savings
 Increased production function
 Daffodil beta-carotene into rice
 Fat profiles in milk and meat
 Control of ripening
 Production in more marginal environments
 Caffeine-free coffee
 Allergen-free peanuts
Genetically Modified Organisms
Prospects
Increased safety in agriculture
Reduced application of pesticides and herbicides
Eg. secretion of chitinase from sweat glands in sheep.
(Immunological or structural change is better)
Production of pharmaceuticals & neutraceuticals
Human proteins etc. in milk from transgenic sheep
Genetically Modified Organisms
Prospects
Artificially generated DNA sequences
In-vitro optimisation of isozyme sequences
Designer fibres
Novel pharmaceuticals & neutraceuticals
Gene therapy
Somatic modifications
Screening of gametes (non-GMO)  IVF
Gene 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)
Multiple transgene copies.
Loss of proper feedback
control.
Bad expression:
Possible
outcome(s)
Risk
minimization
Organism ‘out of harmony’
Low viability or death.
Use progressive methods
Should be detectable during
development.
Level, tissue, time.
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)
Changes in immunological
profile.
Possible
outcome(s)
GMO susceptible to other
pathogens, possibly rare and
previously harmless.
Resulting organism competes Physically dominant but
inappropriately with normal
reproductively deficient
individuals.
GMOs can threaten the
normal population.
Risk
minimization
Understand the biology of
changes generated.
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.
Hormones, pesticides,
Resulting organism generates
residues, allergens etc. in
inappropriate food product.
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 failure
Generate arguably safe
GMOs and educate public –
maybe difficult.
Other unknown causes
Other unknown outcomes
Keep 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
Major gene
Chromosomes from Mum
Genetic markers
Q
q
q
q

×
q
q
q
q
q
q
Q
q
Q
×
×
q
Q
q
×
q
q

q

q

Q
q
q
q
×
×
×

Indirect genetic markers
A
B
A Ram:
His semen:
A
B
B
B
B
A
B
A
A
B
B
A
A
B
A
B
A
Indirect genetic markers
A
B
A
A
A
A
A
A
B
B
B
B
B
B
B
B
A
B
A
‘recombinants’
Indirect genetic markers
A
B
A
A
A
B
B
B
B
A
B
A
A
B
B
B
A
B
A
‘recombinants’
Indirect genetic markers
A
B
A
A
A
B
B
B
B
A
B
A
B
A
A
A
B
B
B
‘recombinants’
Indirect genetic markers
In reality,
we are colorblind ...
A
A
A
A
B
B
B
B
B
A
B
A
B
A
A
A
B
B
B
‘recombinants’
Simple QTL detection with markers
g
G
Gene location
Parents:
g
g
m
m
X
m
M
Marker location
Cows
Bull
G
g
g
g
g
g
G
g
M
m
m
m
M
m
m
m
Progeny:
Probabilities:
90%
10%
QTL detection with markers
Logarithm of the ODds
Log(prob result with QTL)
Log(prob result without QTL)
Lod score
Likely location
of major gene
Location of
markers
Position on chromosome
Direct genetic markers
A
B
- always circle, always good
- 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/