PERSONAL GENOMICS
1.3 Genome: d (iii) Personal Genomics
From the Arrangements
Analysis of an individual’s genome may lead to personalised medicine
(pharmacogenetics) through knowledge of the genetic component of risk of
disease and likelihood of success of a particular tr eatment. The difficulties in
distinguishing between neutral and harmful mutations in both genes and
regulatory sequences, and in understanding the complex nature of many
diseases.
Teacher’s notes
There are two activities. The first is a straightforward read the information
card and answer questions. The second is a ‘diamond 9’ pairs activity.
1.
Summary questions
As an introduction you may wish to show this short 4-minute video clip,
which introduces the 1000 genome project.
http://genome.wellcome.ac.uk/doc_WTX063334.html
Point out the banks of computers, occupying whole floors of buildings,
which are needed to analyse sequence information.
There is an information card and a question sh eet. The questions are
based on the information card.
2.
Diamond 9 pairs game
Collect a set of nine cards for each discussion group. Arrange them into
a diamond shape.
To do this look at the information on them and arrange them in the
order that you think is most important.
UNIT 1, PART (III) GENOME (H, BIOLOGY)
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When you are finished the cards should look like this:
Most important
Least important
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UNIT 1, PART (III) GENOME (H, BIOLOGY)
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After each group has finished the
activity get a person from each pair
to explain why they chose that
particular order.
Highlight if there were any
differences in the layout of cards for
each group.
PERSONAL GENOMICS
Summary questions
Learning objectives
By completing these questions you will know what is meant by the term
pharmacogenetics.
You will realise that the action of drugs is complex and may be affected at
several levels.
You will know that different people respond to drugs differently and there is
an underlying genetic influence on the action of drugs.
You will know that variation within humans is significant but can be analysed
and personalised to specific treatments.
Use the information card to help you answer these questions.
1.
What is pharmacogenetics?
2.
So far, what has pharmacogenetics research largely focused on?
3.
What sort of genetic tests are now being developed?
4.
What are the pharmacological consequences of genetic variation?
5.
What is it about an enzyme that makes it fully functional?
6.
Where might mutations occur that would ultimately affect a protein’s
ability to do its job within the cell?
7.
What examples are given that may arise from sequencing an
individual’s genome?
8.
How many hospital patients in America are thought to die every year as
a result of adverse drug reactions?
9.
What is meant by a single nucleotide polymorphism (SNP) and how
might these affect gene expression (look closely at your answer to
question 6)?
10.
What percentage of the human genome is thought to have SNPs?
UNIT 1, PART (III) GENOME (H, BIOLOGY)
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If you have time look at the website
http://www.actionbioscience.org/genomic/barash.html to find out more about
some of the ethical issues.
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UNIT 1, PART (III) GENOME (H, BIOLOGY)
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PERSONAL GENOMICS
Information card
What is pharmacogenetics?
The following information was taken from the Wellcome Trust website.
http://genome.wellcome.ac.uk/doc_WTD020884.html
Genetic variability among humans has an obvious impact on features such as
height, hair colour and appearance, but also has an unseen role in our
susceptibility to disease and the way in which our bodies metabolise drugs.
This last area of study – termed pharmacogenetics – brings together the study
of how drugs work in the body (pharmacology) and genetics. Understanding
how genes can influence the response to drugs can help explain why some
patients respond well to drugs and others do not. It can also help doctors
understand why some patients require higher or lower doses of a particular
drug.
The goal of pharmacogenetics research is to provide information for
‘personalised medicine’, ie giving a patient the right medicine at the right
dose.
A great deal of pharmacogenetics research has focused on the mechanisms
that determine drug concentration within the body, looking at the end result
of the ingestion, absorption, metabolism, clearance and excretion of a drug.
Genetic tests are being developed to determine a patient ’s ability to
metabolise a particular drug, which will allow dosage to be determined with
greater certainty, and also to determine which patients may be susceptibl e to
adverse side effects as a result of being prescribed a drug.
The pharmacological consequences of genetic variation are highly diverse. In
some cases a patient may break down or convert a drug slightly more quickly,
or slightly slower, than another. But in other cases the absence of drugmetabolising enzymes can cause excessive, and fatal, drug action, or the
therapy may fail because the drug is not activated.
Remember, gene expression is the transcription of DNA, which will lead to
protein synthesis from a mRNA transcript. It is the functional protein within
the cell that leads to the correct physiological conditions being maintained.
The protein, usually an enzyme, will only be fully fun ctional if it has the
correct three-dimensional shape.
Mutations may occur in gene regulatory sequences, post -transcriptional RNA
processing sites, which may affect the removal of introns (RNA splicing), the
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open reading frame, which would affect the amino acid sequence, and posttranslational protein modification, such as protein folding or carbohydrate
conjugation (glycosylation). The scope for error is complex and it is hope d
that determining an individual’s genomic sequence may lead to advanced
screening for disease; better, safer medicines, more accurate methods of
prescribing drug doses, the discovery of new drugs, better vaccines and even
reduced overall costs.
In America adverse drug reactions are thought to kill up to 100 000 hospital
patients a year with over two million serious but non -fatal reactions
(http://www.actionbioscience.org/genomic/barash.html ). Many of these
problems are thought to be due to single nucleotide polymorphisms (single
base substitutions), so collecting and analysing individual sequence data will
become increasingly important.
An offshoot of the human genome project is the 1000 genome project , which
aims to sequence 2500 samples from 27 populations over the next two years.
The variation between individual humans is t hought to be about three million
bases (one in every thousand) out of the total of three billion bases.
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PERSONAL GENOMICS
What if I couldn’t get
insurance cover because of
my genetics? I may even lose
my job!
What if my DNA
sequence was different
but it turned out to be a
neutral mutation?
If I knew I had a genetic
problem it might put me
off having children.
I’d rather not know if I
have a genetic anomaly
or disease.
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PERSONAL GENOMICS
If I knew what the problem
was likely to be I could plan
ahead and make the most of
my time.
What if I was a
minority case and the
drug companies didn’t
think it worthwhile
investing in finetuning my treatment?
By knowing my exact
genetics they could
tailor-make drugs with
minimal side effects.
Just because my DNA
sequence may be slightly
different doesn’t mean I
will develop symptoms.
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UNIT 1, PART (III) GENOME (H, BIOLOGY)
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By getting the right
treatment I would be able
to lead a completely
normal life.