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A2 Science In Society 3.2
Teacher Notes
Introduction
In this activity students find out more about a particular type of case control study known as a GenomeWide Association Study, GWAS, and then discuss the value of the information gained. Students will
read information and media accounts and answer questions. Then they discuss two controversial issues
in small groups.
How Science Works
Bd To investigate the relationship between a factor and an outcome, it is important to control all other
factors that might affect the outcome. Then changes in the outcome can be attributed to the factor that
is being changed.
Be In some situations, a causal factor can increase the probability of an outcome but not invariably
cause it. This is also called a correlation. It can occur when a combination of factors is needed for the
outcome to happen.
Bf Claims about large groups are usually based on measurements on a sample of the population (all
the individuals in the group). The sample should be selected randomly, or carefully chosen to represent
the population accurately. Failure to do this will introduce bias. The larger the sample, the more
confidence we can have in any claim about the population.
Bh Correlation between a factor and an outcome can be investigated using a case-control study. A
sample of cases of the outcome is compared with a matched sample where the outcome is not present.
A case-control study may be used when the outcome being studied happens only infrequently, so that
the number of cases we would observe in a cohort study is very small. It provides weaker evidence than
a cohort study, partly because data on possible factors has to be collected retrospectively and often
relies on recall.
Fc Media reports of scientific developments are always simplified, and sometimes inaccurate. A
newspaper report of a new development has not been through the stringent peer review process that
articles in scientific journals must undergo (though it may be reporting on work that has).
Fd In assessing how much trust to place in a reported scientific claim, it is important to assess the
extent to which it has been subjected to peer review. It may also be reasonable to take account of the
seniority, reputation, and place of work of the principal scientists involved.
Gc We can assess the size of a risk by counting the number of instances of harm in a representative
sample of cases. This estimate will be more accurate if the sample size is large, and if instances of
harm can be easily and accurately detected. If the probability is very low, it can be very difficult to get an
accurate estimate.
Science explanations
Cd Although each cell contains two genes with the same function both alleles are not always
expressed. One allele is expressed to determine the characteristics of the individual. This allele is
known as dominant. A recessive allele is only expressed if both chromosomes carry the recessive
allele.
Ce Most characteristics are determined by an interaction between several genes as well as by the effect
of the environment. The environment can influence gene expression.
La Every living thing has a specific genetic make up (genotype) dependent on the precise form of the
DNA present. The characteristics (phenotype) of a living organism are partly, determined by its genes.
Page 1
©The Nuffield Foundation, 2010
Copies may be made for UK in schools and colleges
A2 Science In Society 3.2
Teacher Notes
Suggested answers to questions
Part A Background information
These questions are intended for discussion, to ensure that students are familiar with the background
science
1 For most diseases the inheritance of genetic factors alone is unlikely to be the full story when it
comes to identifying the cause of the disease. Explain this with reference to skin cancers.
Our knowledge of the role of genes in disease since the sequencing of the human genome has
demonstrated that common and complex disease such as cardiovascular disease and cancers occur
as a result of complex interactions between the genes we inherit and the experiences we have. A
person whose genetic makeup puts them at a greater risk of developing a type of skin cancer may
increase their likelihood of developing the condition from 1 in 100 (which might be the average across
a population) to 2 in 100. The effects of exposure to strong sunlight or spending time on a UV tanning
bed may be far more likely to increase risk.
2 When a gene is identified as having a role in the risk of a disease this sometimes helps us
understand which proteins in the cell may contribute to the onset of the disease. Explain why.
Genes code for proteins, so knowing the gene identifies the proteins that are actually involved in the
metabolic pathways that lead to disease. The discovery of the role of immune system genes in agerelated blindness, mentioned by Steve Jones in the article later in this activity, is a good example of
this.
3 The identification of combinations of alleles implicated in disease could help an individual in
identifying the ‘risk’ of developing a disease later in life
(a) How might such a predictive test be helpful to an individual?
They could change their behaviour or habits, to compensate for the disadvantageous genotype or be
more vigilant about early signs of disease
(b)How might such a predictive test be distressing to an individual?
If no treatment or prevention is available, the person may be distressed to discover the additional risk
that their genes have given them, without being able to do anything about it.
Part B Genes for testicular cancer
1 Even before this case control study, researchers were fairly certain that there was a genetic
component to testicular cancer. With reference to the articles, suggest why they expected this.
Men with a family history of the disease were known to be more likely to develop it.
2 What did the Daily Mail article suggest would be the major outcome of this research?
Identifying men at risk of developing the disease leading to early detection and treatment
3 The initial two stage UK research was carried out using DNA from 1300 men with testicular cancer,
suggest why the team now wish to recruit a further 3000.
Larger sample size would provide a more statistically valid set of results
Some of the genes identified in the first phase were not confirmed in the second. The correlation
must been due to chance. A further larger study would identify false positives or confirm associations.
4 (a) How many genes were found to carry alleles that correlated with the disease in the first phase of
the UK study?
Five genes, 1, 4, 5, 6, 12
(b) How many of these turned out to be false positives in the second phase of the study?
Two, only 5, 6 and 12 were confirmed
Page 2
©The Nuffield Foundation, 2010
Copies may be made for UK in schools and colleges
A2 Science In Society 3.2
Teacher Notes
5 How might this research “open the door to the development of new drugs”?
Identification of the genes, such as the KITLG gene helps us understand the mechanism which leads
to the cancer. It may then be possible to develop drugs to target this metabolic pathway.
6 Suggest why race was one of the criteria used to select men for the US study.
It is important that the control group matches the case group in as many important characteristics as
possible. There are significant differences between different racial groups, in susceptibility to disease
as well as in other characteristics. If case and control groups are not matched then any correlation
found may be because both disease and allele are independently associated with the racial group
even though there is no causal connection. The easiest way to match is to ensure that all members
of both groups are from the same ethnic background as in this US research.
7 The NHS Knowledge Service report states that the average figure for the worldwide incidence of
testicular cancer is 7.5 per 100,000. :
(a) Using this value calculate the probability that an individual man will develop testicular cancer (i.e.
his chances are one in how many?)
1 in 13,333 (approx 1 in 13000)
(b) The research suggests that a man who carries two copies of all four ‘high-risk’ variants of the
genes implicated in testicular cancer has a four-fold increase in risk, compared to the average. What
is the probability of him developing the disease?
1 in 3333 (approx 1 in 3000)
(c) According to the researchers 0.7% of the UK population carry two copies of all four ‘high-risk
alleles’. In a random group of 1000 000 men how many will carry two copies of all four ‘high-risk
alleles’? Using the risk you calculated in (b) work out how many of these will actually develop
testicular cancer.
7000 carry high risk. At a risk of 1 in 3333 only 2 will develop the cancer.
(d) Discuss the significance of these figures for the prediction of risk and for overall understanding.
Having two copies of all four high-risk alleles would only increase the likelihood of developing
testicular cancer from 1 in 13000 to 1 in 3000. Since only 0.7% of the population posses this
combination of alleles most men who develop testicular cancer do not have all four high alleles. In
group of 1 million 75 men overall will develop disease. The predictive power of these genes is very
limited at the moment. The knowledge gained may well, however, increase understanding of the
disease
8 If you saw a popular news article on a health issue relevant to yourself or your family would you look
up the NHS Behind the Headlines site again to find out more? Explain your answer.
It would be a good idea to do so. The language is accessible and the comments by experts very
helpful in evaluating claims which may be made more to gain publicity than because they are yet
clearly established science.
Part C How useful are results from GWAS? Your opinions
1 Read the two articles in the Daily Telegraph expressing different opinions on the value of GWAS.
http://www.telegraph.co.uk/science/steve-jones/5189941/One-gene-will-not-reveal-all-lifessecrets.html
http://www.telegraph.co.uk/science/science-news/5195945/Genetic-research-has-led-to-anextraordinary-flowering-of-knowledge-claims-criticised-charity.html
Page 3
©The Nuffield Foundation, 2010
Copies may be made for UK in schools and colleges
A2 Science In Society 3.2
Teacher Notes
Which side are you on? Do you think research studies using GWAS are the best use of available
research funds?
Discuss your opinion with others. Remember the structure of a good argument. Use evidence to
back up your opinion.
A good argument might be expected to include acknowledgement that the case is not clear cut,
neither ‘head in the clouds’ nor ‘head in the sand’ would seem quite right. .
Possible points:
Even if personalised risk information is of very limited value the scientific understanding may be very
significant for some diseases, as Steve Jones admits. The Wellcome Trust is a highly respected
organisation and has funded some very good science. Their judgement is probably good. The cost
will come down as the technology advances. We can never know in advance how useful any
scientific knowledge will turn out to be. For a few individuals the risk is significant. They should not
be denied the information if they want it.
When scanning so many SNPs, each with a very small effect, the sample size has to be very large to
avoid false positives and also to avoid missing a gene with a small effect. Some published results
are not later confirmed. Doing case control studies on very large groups is extremely expensive. The
idea that genes are all important in understanding disease is a feature of the reductionist approach to
science. As knowledge advances the role of the environment, including the fetal environment, is
often seen to be much more important. The association is only meaningful if a precise diagnosis of
the disease is possible, not always the case with mental illness in particular. Even where genes are
involved the information may be of very limited value because each gene has such a small effect.
2 Imagine that a friend of yours is considering paying about £600 to have a complete scan of 1 million
SNPs in their genome, which it is claimed will give information on their genetic risk factors for about
40 traits and conditions. One of their close relatives has just developed Type2, Adult onset diabetes.
Not everyone thinks this they will get enough information to make any difference to their health but
the private companies that provide the tests are very persuasive. The information that companies
supply will be based on research such as that reported for testicular cancer.
Would you support them or tell them it is a waste of money? Discuss what you think in a small group
and then report back to the class.
You can find more information on two companies that supply such tests, although you do not need to
read it to answer the question.
http://www.decodeme.com/complete-genetic-scan
https://www.23andme.com/health/
In the discussion it is important that students recognise the very limited value of such information at
present. It is believed likely that several hundred genes may be involved in diabetes. Each would
contribute a very tiny increase in risk. Even if the information were significant in terms of risk it is
probable that there is little that can be done to change this. The benefit of such work at present is to
our understanding of disease, not to individuals.
One might say that the companies have a ‘head in the clouds’ approach, at least in their marketing.
December 2010
Page 4
©The Nuffield Foundation, 2010
Copies may be made for UK in schools and colleges
A2 Science In Society 3.2
Student sheets
Introduction
In this activity you are going to find out more about a particular type of case control study known as a
Genome-Wide Association Study, GWAS. GWA studies look for the genetic differences between cases
and controls, using information from the Human Genome project and the new technology of DNA chips.
Most of the news stories about discovery of a new gene linked to a disease are based on these types of
study.
Part A Background information
The term nature and nurture implies that both our genes and our environment act together when it
comes to determining certain features in the development of disease. For example, certain types of lung
cancer are more likely to occur if we have a particular genetic makeup, but only if we allow our lungs to
be exposed to cigarette smoke. Equally cannabis usage has been shown to increase the incidence of
schizophrenia in young people with a particular gene variant (or allele), whereas having another version
of the gene has no such effect.
Scientists are keen to discover to what extent gene variation contributes to common diseases. For
example, cancer, cardiovascular disease and rheumatoid arthritis are all major causes of lost years of
quality of life and in some cases, early death. These common and complex diseases are seldom caused
by single genes or even combinations of a few genes, but most often are the result of many genes acting
together. The more complicated the genetic relationship, the greater is the role of the environment and
our development in determining whether we will develop a disease at some point in our life.
Since the Human Genome Project published the DNA sequence of a human the scientific and medical
community have been keen to apply this knowledge in an attempt to discover the role of genes in
disease. One method currently applied to find the genetic needles in a haystack is that of a ‘case control
study’. In the simplest form this means comparing the genetic data from people with a specific condition
(case) with those who do not (control). About 99.5% of the human genetic code is identical in everyone.
However there are thought to be about 11 million specific sites where the DNA differs by a single base,
these are known as Single Nucleotide Polymorphisms, SNPs. Genome wide association studies use
automated equipment to scan up to 1 million of these SNPs, spread over the whole genome, to identify
differences and then to find correlations with disease. More detailed work is then needed to identify the
guilty gene itself.
If all other factors are controlled or matched in the two groups, people with the condition and those
without, then statistically significant differences in the frequency of alleles suggest that those alleles are
contributors to the onset of the conditions.
Once established, there are a few things that can (theoretically) be done to make use of the information:

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
Page 1
Understand the chemical metabolic pathway that may contribute to the onset of common
diseases and use this information to develop drugs or other treatments
Develop predictive tests through the use of knowledge about the likelihood that a certain
combinations of alleles will lead to the development of a disease
Help individuals at risk to be more vigilant and, for example, be tested more frequently using
conventional scanning or other clinical tests.
©The Nuffield Foundation, 2010
Copies may be made for UK in schools and colleges
A2 Science In Society 3.2
Student sheets
1 For most diseases the inheritance of genetic factors alone is unlikely to be the full story when it
comes to identifying the cause of the disease. Explain this with reference to skin cancers.
2 When a gene is identified as having a role in the risk of a disease, this sometimes helps us
understand which proteins in the cell may contribute to the onset of the disease. Explain why.
3 The identification of combinations of alleles implicated in disease could help an individual in
identifying the ‘risk’ of developing a disease later in life
(a) How might such a predictive test be helpful to an individual?
(b)How might such a predictive test be distressing to an individual?
Part B Genes for testicular cancer
Genome-wide association studies have been used to look for the genes associated with testicular
cancer. Read the two articles and then answer the questions.
Scientists pinpoint faulty genes in new hope for testicular cancer test
Fiona Macrae, the Daily Mail, 1st June 2009
http://www.dailymail.co.uk/health/article-1189896/Testicular-cancer-test-horizon-scientists-pinpointfaulty-genes.html
Genes for testicular cancer found
Behind the Headlines NHS Knowledge Service Monday June 1 2009
http://www.nhs.uk/news/2009/06June/Pages/TesticularCancerGeneTest.aspx
Questions
1 Even before this case control study, researchers were fairly certain that there was a genetic
component to testicular cancer. With reference to the articles, suggest why they expected this.
2 What did the Daily Mail article suggest would be the major outcome of this research?
3 The initial two-stage UK research was carried out using DNA from 1300 men with testicular cancer,
suggest why the team now wish to recruit a further 3000.
4 (a) How many genes were found to carry alleles that correlated with the disease in the first phase of
the UK study?
(b) How many of these turned out to be false positives in the second phase of the study?
5 How might this research “open the door to the development of new drugs”?
6 Why was race one of the criteria used to select men for the US study?
7 The NHS Knowledge Service report states that the average figure for the worldwide incidence of
testicular cancer is 7.5 per 100,000.
(a) Using this value calculate the probability that an individual man will develop testicular cancer (i.e.
his chances are one in how many?)
(b) The research suggests that a man with two copies of all four ‘high-risk’ variants of the genes
implicated in testicular cancer has a four-fold increase in his risk, compared to the average. What is
the probability of him developing the disease?
Page 2
©The Nuffield Foundation, 2010
Copies may be made for UK in schools and colleges
A2 Science In Society 3.2
Student sheets
(c) According to the researchers, 0.7% of the UK population carry two copies of all four ‘high-risk
alleles’. In a random group of 1000 000 men how many will carry two copies of all four ‘high-risk
alleles’? Using the risk you calculated in (b) work out how many of these will actually develop
testicular cancer.
(d) Discuss the significance of these figures for the prediction of risk and for overall understanding.
8 If you saw a popular news article on a health issue relevant to yourself or your family would you look
up the NHS Behind the Headlines site again to find out more? Explain your answer.
Part C How useful are results from GWAS?
Science is largely a reductionist activity, which means that it is based on a belief that all complexity can
be reduced to simple processes. Genomics and genetics are good examples of reductionism, in that
they simplify life and living process to a chemical code. It is tempting for scientists and non-scientists
alike to want to see a simple solution to the cause of disease, since it could lead to a cure. But our lives
are complicated and during the course of our time on earth, we are exposed to climatic factors, different
foods, infectious diseases, chemical substances and so on. Even before we are born, the environment in
the womb is known to have an effect on some aspects of our later lives including our health.
The scientific and medical world is divided over the potential for genetic association studies to be able to
change the ways in which we find out about disease and treat it. The cartoon illustrates the different
perspectives of head in the clouds and head in the sand.
Cartoon: Maya Evans
The head in the clouds perspective is the belief that knowing which genes are associated with specific
diseases will change medical practice significantly. Whereas the head in the sand approach is based on
the fact that in most cases the contribution of each identified allele to a disease, is small - and that even
when you add all of the identifiable alleles together, their impact has not yet been shown to be enough to
change the way diseases are diagnosed or treated.
Your Opinions
Two of the issues arising from GWAS are considered in the two questions below.
1 Read the two articles in the Daily Telegraph expressing different opinions on the value of GWAS.
http://www.telegraph.co.uk/science/steve-jones/5189941/One-gene-will-not-reveal-all-lifessecrets.html
http://www.telegraph.co.uk/science/science-news/5195945/Genetic-research-has-led-to-anextraordinary-flowering-of-knowledge-claims-criticised-charity.html
Page 3
©The Nuffield Foundation, 2010
Copies may be made for UK in schools and colleges
A2 Science In Society 3.2
Student sheets
Which side are you on? Do you think research studies using GWAS are the best use of available
research funds?
Discuss your opinion with others. Remember the structure of a good argument. Use evidence to
back up your opinion.
2 Imagine that a friend of yours is considering paying about £600 to have a complete scan of 1 million
SNPs in their genome, which it is claimed will give information on their genetic risk factors for about
40 traits and conditions. One of their close relatives has just developed Type2, Adult onset diabetes.
Not everyone thinks they will get enough information to make any difference to their health but the
private companies that provide the tests are very persuasive. The information that companies supply
will be based on research such as that reported for testicular cancer.
Would you support them or tell them it is a waste of money? Discuss what you think in a small group
and then report back to the class.
You can find more information on two companies that supply such tests, although you do not need to
read it to answer the question.
http://www.decodeme.com/complete-genetic-scan
https://www.23andme.com/health/
Page 4
©The Nuffield Foundation, 2010
Copies may be made for UK in schools and colleges