crc for discovery of genes for common human diseases (the gene crc) the human genome project? in...

CRC for Discovery of Genes for Common Human Diseases (the gene CRC)

The Human Genome Project?

in your classroom

The Human Genome Project?

in your classroom

Fiona Cunningham

Education Officer

the gene CRC


The Human Genome ProjectThe Human Genome Project

• Established 1988

• Initiated 1990

• Predicted to revolutionise human medicine:investigating molecular basis of

genetic disease

testing

prevention

new therapies


DNA 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 proteinGOOD, BAD or INDIFFERENT


First Draft completed

June 2000

First Draft published

Feb 2001


The Map…..The Map…..


Francis Collins, NIH

The playersThe players

Craig Venter, Celera Genomics

?


Whose genome was sequenced?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 individualsall sequenced, aligned

identified polymorphisms, SNPs, where differences occurred


Sequencing every base…..Sequencing every base…..


Why sequence every base pair?Why sequence every base pair?

• Maps of the genome are important

• Why?localisation of genes

homologies between species

why else?


Chicken Genome Project?Chicken Genome Project?

Baker’s Yeast

Drosophila

Arabidopsis


Has every base pair been sequenced?Has every base pair been sequenced?

• No

• 3.2Gb estimated size

• 84% of the genome

• ~30,000 genes

• What does it mean?


~30 000 genes ….~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?


Human complexity?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


The future…..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


Why genetics for my students?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


Genes, disease & testingGenes, disease & testing

• Over 6000 single gene disorders identified

• Many diseases are multifactorialmany 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)


Genetics in the 21st century (1)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?


Screening programs in VictoriaScreening programs in Victoria

• Newborn screeningPKU, Congenital Hypothyroidism, Cystic fibrosis, (other metabolic conditions?)

• Tay Sachs diseaseNeurodegenerative disorder, Jewish schools

• HAEMscreen (pilot study)Iron overload disorder - affects adults

Common and preventable

Pilot screening program in workplace



• Gene & related therapiesbetter drug therapies

better environmental modification strategies

cell & cloning technologies

gene therapy

therapeutic

enhancement



• pharmacogenomics



• Forensic science: genetics is used in • identifying suspects in criminal cases

• food contamination testing

• paternity testing



• Not just medical applications:

• GMO’sfood

agriculture

environment

industry

• Cloning nothing really to do with HGP


Cloning in the 21st centuryCloning in the 21st century

• Reproductive vs therapeutic

• Sevorino Antinori et al.

• Raelian cult & ClonaidCan personality be cloned?

Can we live for ever?


Therapeutic cloningTherapeutic 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 (!!!!!)


Stem cell uses?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 tissuesstill problem with rejection from patient


ETHICAL?

Human cloning may be ethical?Human cloning may be ethical?

ES cell lines: tissue for

transplantationunethical


Why the controversy?Why the controversy?

Deriving stem cells from embryos destroys them!


ELSI: Ethical, legal & social issuesELSI: Ethical, legal & social issues

• Privacy

• Confidentiality

• Discrimination

• Right to know

• Right not to know

• Family issues

• Social issues


Insurance & PatentingInsurance & 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


Gbenetics in your school?Gbenetics in your school?

•How can we ensure responsible & ethical use of genetic knowledge & technology? b


Strategies for the classroomStrategies 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


Equipping your students:Equipping your students:

• An understanding of genetics

• Skills toethically analyse genetic technologies

critically read and evaluate media reports

actively seek out appropriate information -

www, institutes, medical & research institutes


Biomedical ethics: a simple frameworkBiomedical ethics: a simple framework

• Maximising benefits (beneficence)

• Minimising harm (non-maleficence)

• Autonomyincludes individual rights and freedom of

choice

• Justicefairness, equality, non-discrimination


Equipping you:Equipping you:

• Be informed

• Professional development

• Critically read newspaper articles

• Actively seek out appropriate news and documentaries

• Participate in debate


Equipping you:Equipping you:

• Integration into other areas of the curriculumBiology/science

English, philosophy, religion & society, physical education, legal studies etc

• Resources: www, geneTHINK, geneTALK etc


Figure 5. An example of a worksheet and teacher notes.


GENE Think 2000GENE Think 2000


GENETalk 1General Genetics

November 2000

GENETalk 1General Genetics

November 2000

MCRI Education UnitMaryAnne Aitken

Fiona Cunningham

Eilís Hughes

Sylvia Metcalfe

MCRI Education UnitMaryAnne Aitken

Fiona Cunningham

Eilís Hughes

Sylvia Metcalfe


Every somatic cell in body has

the same 46 chromosomes

SPERM23 chromosomes

in nucleus

EGG23 chromosomes

in nucleus

fertilised egg (ZYGOTE) 46 chromosomes in nucleus

MITOSIS

MEIOSIShalves

chromosomenumber

Where do our chromosomes come from?Where do our chromosomes come from?


Autosomal recessive pedigree (cont.) Autosomal recessive pedigree (cont.)

Probability of CF = (Prob of c allele from mother) x (Prob of c allele from father)

C c

Mother’s Genotype

Cc

C C

C c

C c C c c c

Father’s GenotypeCc

Possible Offspring

Probability of CF = 1/2 x 1/2 = 1/4


The Genethics ChallengeThe 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

The Eutopian TimesThe Eutopian TimesGENEdreams, 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 ChipsDNA Chips


Genethics 2001Genethics 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


Genethics 2001Genethics 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

APC protein

(protease - anticoagulant

function)

Blood clotting factors

VIII V

Clotting factors cleaved/inactivated


Factor V Leiden screeningFactor 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?


Some questions to ask: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) the human genome project? in...

Documents

playerswhose genome

multifactorialmany genes

chicken genome project

base pair

human complexity

knowledge of genes role

human medicine

functionalter base sequence