4 pictures 1 word!

Learning Outcomes

• Examine how future medicine may take into account an individuals genome for personalised medicine

• Distinguish between neutral and harmful mutations (SNPs)

• Explain pharmacogenetics

Personal Genome Sequence

• Complete sequencing of person’s DNA bases – called personal geonomics

• Why has this become more and more possibly?

• Faster and cheaper due to techniques like PCR (next lesson!!)

• Analysis of an individual’s genome may lead to personalised medicine through understanding the genetic component of risk of disease eg. BRCA 1 and 2 genes for breast cancer means 45 to 65% chance of developing breast cancer by the age of 70!

Mutations – neutral vs. harmful

• What is a mutation? Genetic disorder?• What do you think the difference between

harmful and neutral?

• Genetic disorder – result of variation in genomic DNA sequence (mutation)

• Harmful – fail to code for an essential protein• Neutral – have no negative effect• Analysis of an individual’s genome may lead

to personalised medicine through understanding the genetic component of risk of disease eg. BRCA 1 and 2 genes for breast cancer means 45 to 65% chance of developing breast cancer by the age of 70!

Mutations – neutral vs. harmful

• Establish a casual link between mutation and disease

• However link DOES not mean CAUSE!• Disease is complex nature between

environment and genetics factors.

So we used breast cancer and BRAC1 and 2 genes, other genes . TC53, PTEN genes, CASP8, FGFR2, TNRCP, MAP3K1, rs4973768

and LSP1 – so complex interactions!

• However breast cancer increases over 50, so age a factor!

• Parabens (deodrant chemical) link to breast cancer

• Obseity linked to breast cancer!

• Many links!

Drug Problems?

• What are the potential problems when you take a drug?

• What are the potential problems/ effects when you take a drug?

You get better! Doesn’t seem to work

Side effects of the drug

Creates another

problem elsewhere in

the body Long term effects of the drug only later seen Die of complications

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Heart attacks/Strokes/Blood Clots

• Drug of choice is warfarin (previous rat poison!)

• Thins the blood, however people are resistant or sensitive to the drug.

• 5 gene SNP were investigated - VKORC1, CYP2C9, CALU, EPHX and GGCX

• VKORC1 and CYP2C9 SNPs – indicated sensitivity

• Resistance associated with p.Asp36Tyr in VKORC1 in their population base.

• Pharmacogenetic screening for initial warfarin dosing in clinic populations in Canada.

Pharmacogenetics

• Defined as the study of the effects of drugs (whether therapeutic, neutral or adverse) on genetically diverse members of the human population.

• In future able to tailor your drugs, dosage/type depending on your genome

• Also help in rational drug design (smart design)

Pharmaceutical drugs On genetics

Drug Design

• If DNA sequenced, the protein expressed – pharmacogenetics design a drug targeted to that molecule by computer modelling.

• eg/ Chronic myeloid leukaemia (CML) treated with tyrosine kinase inhibitor (imatinib) against the enzyme.

Genes Links ......

Genetic Profiling Risk and Ethics

• Genes are being linked to various conditions almost daily!

• Future will be able to scan for predisposition to a particular disease/condition

• Allow early prediction for earlier action/ treatment –

drugs or

lifestyle

Genetic Profiling Risk and Ethics

• If this becomes routine who should have access to the information?

• Persons family/offspring?• Persons employer/life insurer?

• People believe a law to prevent genetic discrimination needs to be introduced before this technology becomes cheap enough for everyone.

• What do you think?

Homework