Transcript No Slide Title

The
Human Genome Project?
in your classroom
Fiona Cunningham
Education Officer
the gene CRC
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)
The Human Genome Project
• Established 1988
• Initiated 1990
• Predicted to revolutionise
human medicine:
investigating molecular basis of
genetic disease
testing
prevention
new therapies
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)
DNA
• Twisted ladder or DOUBLE HELIX
• Rungs of ladder - bases A G C T
• Sequence of AT & GC pairs determines
proteins structure and function
• Alter base sequence - MAY change protein
GOOD, BAD or INDIFFERENT
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)
First Draft
completed
June 2000
First Draft
published
Feb 2001
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)
The Map…..
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)
The players
?
Francis Collins, NIH
Craig Venter, Celera Genomics
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)
Whose genome was sequenced?
• How many individuals?
• Public effort (NIH, DOE etc)
1 (15%) + 1 (70%) + some (the rest)
Could they miss any genes?
• Celera’s 5 individuals
all sequenced, aligned
identified polymorphisms, SNPs, where differences
occurred
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)
Sequencing every base…..
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)
Why sequence every base pair?
• Maps of the genome are important
• Why?
localisation of genes
homologies between species
why else?
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)
Chicken Genome Project?
Arabidopsis
Baker’s Yeast
Drosophila
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)
Has every base pair been sequenced?
• No
• 3.2Gb estimated size
• 84% of the genome
• ~30,000 genes
• What does it mean?
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)
~30 000 genes ….
• NIH - 31 000, 22 000 listed
• Celera - ~26 000
• ~740 non-protein coding RNAs - cell
housekeeping (many more not IDd)
• Compared to:
yeast 6 000, fly 13 000, worm 18 000, plant 26 000
• Only 30 000 genes: are humans really
quite biologically simple?
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)
Human complexity?
• Most genes from our evolutionary past
• Only ~94 of 1278 protein families
specific to vertebrates
• Diff between us and worms is the
complexity of our proteins:
more domains per protein
greater regulation of transcription & translation
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)
The future…..
• First there was HUGO
• Now there is HUPO!
• Proteomics: the cash ‘crop’ of research in
the future?
• Functions and expression patterns of
proteins encoded by the genes
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)
Why genetics for my students?
• Will it change anything?
• Knowledge of genes role in diseases
• Immediately ~ still woke up and had
cornflakes the next day
• Short term
• Long term
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)
Genes, disease & testing
• Over 6000 single gene disorders identified
• Many diseases are multifactorial
many genes interact with each other
& with the environment
eg Alzheimer disease, diabetes, CHD, asthma
(many other common diseases may have a genetic
component: inherit predisposition or increased risk to
develop these)
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)
Genetics in the 21st century (1)
• Genetic testing:
• carrier, diagnostic, predictive, predisposition
• newborn
• prenatal
• Risk vs certainty
• Uses of this info?
• Non-disease traits?
IQ, aggression, height?
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)
Screening programs in Victoria
• Newborn screening
PKU, Congenital Hypothyroidism, Cystic fibrosis,
(other metabolic conditions?)
• Tay Sachs disease
Neurodegenerative disorder, Jewish schools
• HAEMscreen (pilot study)
Iron overload disorder - affects adults
Common and preventable
Pilot screening program in workplace
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)
Genetics in the 21st century (2)
• Gene & related therapies
better drug therapies
better environmental modification strategies
cell & cloning technologies
gene therapy
therapeutic
enhancement
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)
Genetics in the 21st century (3)
• pharmacogenomics
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)
Genetics in the 21st century (4)
• Forensic science: genetics is used in
• identifying suspects in criminal cases
• food contamination testing
• paternity testing
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)
Genetics in the 21st century (4)
• Not just medical applications:
• GMO’s
food
agriculture
environment
industry
• Cloning
nothing really to do with HGP
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)
Cloning in the 21st century
• Reproductive vs therapeutic
• Sevorino Antinori et al.
• Raelian cult & Clonaid
Can personality be cloned?
Can we live for ever?
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)
Therapeutic cloning
• Involves stem cell technology
• Stem cells are derived from the inner
cell mass of a 1-week-old embryo
(blastocyst)
• Unlimited, prolonged self-renewal
• Can divide and differentiate into any
type of body cell (!!!!!)
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)
Stem cell uses?
• Screening of drugs that may cause birth
defects
• Discovery & study of rare human proteins
• Study of early human development
• Gene therapy vector
• For transplantation of tissues
still problem with rejection from patient
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)
Human cloning may be ethical?
ES cell lines:
tissue for
transplantation
ETHICAL?
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)
Why the controversy?
Deriving stem cells from
embryos destroys them!
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)
ELSI: Ethical, legal & social issues
• Privacy
• Confidentiality
• Discrimination
• Right to know
• Right not to know
• Family issues
• Social issues
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)
Insurance & Patenting
• Health insurance in Aust
• Life insurance in Aust
• What can be patented?
Gene
gene product
specific drugs which target the gene or gene product
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)
Gbenetics in your school?
• How can we ensure responsible
& ethical use of genetic
knowledge & technology? b
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)
Strategies for the classroom
• Don’t start with peas, flies or worms
• Start with human stories
• Encourage students to express their views
(try not to be directive)
• But also to give solid argument & reasons for
these views
• Encourage them to think beyond their own
personal field:
legal, economic, social, religious views, family, community
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)
Equipping your students:
• An understanding of genetics
• Skills to
ethically analyse genetic technologies
critically read and evaluate media reports
actively seek out appropriate information www, institutes, medical & research institutes
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)
Biomedical ethics: a simple framework
• Maximising benefits
(beneficence)
• Minimising harm
(non-maleficence)
• Autonomy
includes individual rights and freedom of choice
• Justice
fairness, equality, non-discrimination
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)
Equipping you:
• Be informed
• Professional development
• Critically read newspaper articles
• Actively seek out appropriate news and
documentaries
• Participate in debate
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)
Equipping you:
• Integration into other areas of the
curriculum
Biology/science
English, philosophy, religion & society, physical
education, legal studies etc
• Resources:
www, geneTHINK, geneTALK etc
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)
Figure 5. An example of a worksheet and teacher notes.
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)
GENE Think 2000
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)
GENETalk 1
General Genetics
November 2000
MCRI Education Unit
MaryAnne Aitken
Fiona Cunningham
Eilís Hughes
Sylvia Metcalfe
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)
Where do our chromosomes
come from?
SPERM
23 chromosomes
in nucleus
EGG
23 chromosomes
in nucleus
fertilised egg (ZYGOTE) 46
chromosomes in nucleus
MEIOSIS
halves
chromosome
number
MITOSIS
Every somatic
cell in body has
the same 46
chromosomes
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)
Autosomal recessive pedigree (cont.)
Mother’s
Genotype
Cc
Possible
Offspring
C c
C C
Father’s Genotype
Cc
C c
C c
C c
c c
Probability of CF = (Prob
Probability
of c allele
offrom
CF =mother)
1/2 x 1/2
x (Prob
= 1/4 of c allele from father)
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)
The Genethics Challenge
“A controversial technology with enormous potential. And our
challenge? To fulfil this potential without compromising our ethical
ideals.”
Ling San Lau, Genethics 2000 winner
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)
The Eutopian Times
GENEdreams, a human biotechnology company in
Eutopia, has captured the attention of parents-to-be with
their offer of ‘Design your own healthy baby!’ after
launching a proposal to conduct genetic screening of
unborn babies to prospective mothers. This program
uses their patented “BABY BODY microchip” that uses
DNA microarray technology to screen foetuses between
the 10th & 12th week of pregnancy for gene alterations
that cause deafness, dwarfism & predisposition to breast
& colon cancer. All for a mere cost of Eut$10 000!
Civil rights & right-to-life activist groups have been
outraged by this proposal, along with disability groups
such as the Eutopian Cultural Deaf Foundation & SSPE
(Short Statured People of Eutopia).
A spokesman from the Eutopian Health Ministry ridiculed
the proposal, stating that “all babies are offered newborn
screening for treatable genetic conditions such as PKU &
cystic fibrosis free of charge. The GENEdreams service
preys on the fears of parents & and is unnecessary.”
GENEdreams commented “it is the right of every parent
to choose whether or not to have a baby with or without a
disability and to desire the best possible health outcomes
for their children. If most parents decide against having a
child with a disability, there will be more money available
to help those who are born with a disability.”
Is the “GENEdreams” genetic
screening proposal ethically
acceptable?
Do you think this proposal is
more or less acceptable if
parents have to pay for it?
DNA Chips
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)
Genethics 2001
• Gene Dreams Baby Body Microchip:
prenatal genetic testing for deafness, short stature,
predisposition to breast or colon cancer
• Gene Dreams Baby Body Fix:
germline gene therapy for these????
• Prizes
• Chair of judging panel: Sir Gus Nossal AO
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)
Genethics 2001
• GrandFinal:
Melbourne Museum
Monday, 3 September, 10.30 to 11.45
Followed by Genetic Testing in Australia discussion
featuring Bob Williamson, Tom Shakespeare
Contact Fiona Cunningham to reverse seats (limited,
up to 10 per school):
[email protected]
03 8341 6319
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)
APC protein
Clotting factors
cleaved/inactivated
(protease anticoagulant
function)
VIII
V
Blood clotting factors
Factor V Leiden screening
• Mutation in Factor V gene prevents
inactivation of the factor V clotting protein
• Predisposition to thrombosis (clots)
heterozygotes 7x greater risk
homozygotes 80 x greater risk
• COC pill is also risk factor for thrombosis
• COC pill + Factor V Leiden even greater risk
Should all year 11 girls be screened for the
Factor V Leiden mutation?
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)
Some questions to ask:
• What would be the benefits of this
screening program?
• Could anyone be harmed?
• What effects would this proposal have on
the girls’ autonomy (ability to make
choices about their lives)?
• What rules would you put in place about
who gets access to the test results and
under what conditions?
CRC for Discovery of Genes for Common Human Diseases (the gene CRC)