A2 Science In Society 3.2
Teacher Notes
Introduction
This activity introduces the concept of ‘epigenetics’
– generally defined as inheritable changes that do
not affect the coding sequence of DNA. Epigenetics
is an exciting area of research, and is having a
significant impact in many areas of biology.
Activity
The activity consists of text with questions. It is
suggested that the questions are discussed in small
groups with class discussion at the end of each
section. Some teachers have found it helpful to
begin with an explanation of epigenetics. You could
use the power point slides, Epigenetic modification
of DNA, a web site such as
http://learn.genetics.utah.edu/content/epigenetics/
which has both text and animations (try ‘lick your
rats’) or the textbook pages 60-63.
Science explanations
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.
Lb There are controlled processes by which the information
coded in a gene is converted into the chemicals in the cell.
This is gene expression. Expression of any particular gene
is controlled by other genes called gene regulators. Gene
regulators switch a gene on or off in response to specific
input from the internal or external environment.
Lc Genes can be switched on or off in a way that is passed
on to the next generation of cells (epigenetics). These
changes are reversible but can be are inherited from one
generation to the next.
Ld Many factors influence which particular genes are
expressed at any point in time. These include: stages in
development, where in the body the cell is, epigenetic
inheritance, the action of other genes and direct influences
from the intenal and external environment.
How Science Works
Statistical significance
Bg To investigate the hypothesis that a factor increases the probability of an outcome,
scientists compare a sample exposed to the factor with a control sample that is not. This is
called a cohort study. The two samples should be selected randomly from each population,
or carefully matched on all the other factors that might have an effect. To assess the
outcome of a cohort study, scientists compare the number of cases in the two groups after
a period of exposure. To judge that a factor does affect the outcome, the difference must
be big enough not to be attributable simply to normal variation.
Cc An event is often explained by relating it to a particular scientific theory (or theories). A
scientific theory proposes an underlying process that results in the observations we have
made. Many scientific theories involve objects or properties that cannot be directly
observed. Scientific theories do not ‘emerge’ from data by a process of logical deduction;
proposing an explanation always involves imagination and conjecture. An explanation is
not just a summary of the data, but is distinct from it.
Cd Scientists test an explanation by seeing if specific predictions based upon it are in
agreement with data from observation or from an experiment (a deliberate intervention to
generate data). If data agree with predictions that are very novel or unexpected, this is
particularly influential. The aim is to rule out alternative explanations, and so reach a single
explanation that most scientists can agree about.
Page 1
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A2 Science In Society 3.2
Teacher Notes
Part 1
1
We have data on six ancestors for each person involved in the study. The researchers suggest that
only the results in bold are statistically significant.
(i) Which p-value, 0.05 or 0.01, have the paper’s authors chosen as the threshold of significance?
Justify your answer.
p = 0.05
(p =0.04 significant, p = 0.06 not significant)
(ii) Express this p value as the percentage of times that such a result might be expected by chance.
5%
or 95% chance that there is a real difference in mortality risk ratio
For which combinations does a grandparent’s nutrition during their slow growth period have a
statistically significant (results in bold) effect on his or her grandchildren?
Paternal grandfather and grandson.
Paternal grandmother and granddaughter.
2
3
If a grandmother experienced good nutrition during her slow growth period, what effect did this have
on the survival of (a) her granddaughters and (b) her grandsons?
(a) Increased the risk of dying.
(b) No effect.
4
If a grandfather experienced good nutrition during his slow growth period, what effect did this have
on the survival of (a) his grandsons and (b) his granddaughters?
(a) Increased the risk of dying.
(b) No effect.
5
Think about the different ways in which people are influenced by their parents and grandparents,
directly or indirectly, biologically and socially. How many different influences can you think of? What
were the key stages in their lives that might affect their descendants?
This question gives students the opportunity to think about transgenerational nature and nurture
effects within the context of people’s lives. They should recognise that people share a genetic
linkage to their grandparents, but may also have a direct personal involvement. In addition, parents
are also likely to have been influenced by their own parents. A potentially important additional factor
that could be overlooked is the womb environment. There is considerable evidence that the
environment experienced by a fetus in the womb may have a long-term effect in later life.
6
An environmental impact affecting subsequent generations is known as a transgenerational effect.
Why is it difficult for traditional genetics-based explanations of inheritance to explain
transgenerational effects?
The fact that the effect is seen from one generation to the next. It seems to be an acquired
characteristic. The pattern of inheritance involving the paternal grandmother does not fit normal
inheritance patterns.
7
Transgenerational environmental effects across one generation are well known. Suggest why they
are generally seen in mothers and offspring rather than fathers and offspring?
What happens to the baby in the womb can influence long-term development and health. Possible
influences include nutrition, infections, alcohol use and maternal stress.
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A2 Science In Society 3.2
8
Teacher Notes
The Överkalix case in unusual because the effect is seen over two generations and it is sex-specific.
Why is this a challenge to traditional environmental explanations?
An environmental impact might affect someone’s physiology, potentially in a long-term way. Other
than via a direct impact of the mother on her fetus, it is difficult to think of a mechanism by which
someone could pass on a physiological change, nor why offspring of only one sex would be affected.
Part 2
1
It has been known for some time that the environment can influence the expression of DNA during an
individual’s lifetime. The fact that such epigenetic effects can be inherited is a relatively new area of
research.
Which particular cells would have to be altered by an environmental influence for it to affect subsequent
generations epigenetically?
An environmental impact would have to affect sex cells, which are the only cells that contribute to future
generations.
2
Transgenerational effects have been discovered closer to home, in a study of children and parents living
around Bristol. The Avon Longitudinal Study of Children and Parents (ALSPAC) has been following
14,000 children and parents since birth, providing a rich data resource on early development.
Researchers found that the body mass index of boys aged 9 (but not girls) was linked to early paternal
smoking in fathers. What epigenetic mechanism could explain this link to the male sex?
Boys must inherit a Y chromosome from their father, suggesting that the effect is mediated by
modification of the Y chromosome.
3
Explain the difference between an epigenetic change and a mutation in DNA.
an epigenetic change is often the attachment of methyl groups to DNA. These can be lost again,
restoring the normal function. A mutation is a permanent change.
4
Much of the increased death rate in the Överkalix grandchildren was due to diseases known to be partly
affected by diet such as diabetes and heart disease. Suggest a hypothesis that might explain the link
between over-eating in the grand children and grandparents deprived of enough food. See textbook
page 63.
An epigenetic change that encouraged over-eating would be an advantage in times of shortage or a
preparation for the next shortage. If this change was passed on it would explain the particular nutrition
linked diseases.
5
Transgenerational epigenetic inheritance seems to be a new scientific explanation. Some people are
always reluctant to change their views. How could you put the case for epigenetic inheritance to each of
the objectors below?
Lamarck
The epigenetic inheritance is certainly inheritance of acquired characteristics as Lamarck suggested. However
it is not a basis for evolution. The effect is temporary, it would not last through many generations. In the
examples here it was almost entirely harmful, not beneficial.
DNA
The basic code is still passed on unchanged. However the mechanism for switching a gene on or off according
to the internal or external environment is an important one in all living organisms. The effect is passed on to
daughter cells during growth and development of the organism. Epigenetic changes have contributed to their
specific function but all cells in our body carry the same basic genetic information. The epigenetic
transgenerational effect is an extension of this kind of control of DNA but does not alter the basic code.
Page 3
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A2 Science In Society 3.2
Teacher Notes
Environment
Of course it is true that cultural effects are passed down but it is hard to explain how these could be so sex
specific, why paternal grandparents are the ones with the influence and then only grandchildren of the same
sex. Epigenetic changes to the Y chromosome would explain some of these. The cultural explanation could be
tested if data on people who had moved away or lost contact with grandparents was available.
Nature and nurture activities developed and written by Nowgen as part of the Wellcome Trust funded Nowgen
School Genomics Project.
August 2009
Page 4
©The Nuffield Foundation, 2009
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A2 Science In Society 3.2
Student sheets
Introduction
Introduction
You are by now familiar with the idea that our genes determine our basic characteristics but that genetic
effects are also influenced by our environment, from conception onwards. Our height, for example, is
governed by our genes but nutrition will determine whether we reach our genetic potential. (See
textbook, pages 54 to 56 for a more complex example). In this activity you will looks at results that seem
to challenge this basic model and then learn more about the explanation for such results.
Part 1 Överkalix
Researchers have made a historical analysis of the excellent records kept for the remote population of
Överkalix in northern Sweden since the early nineteenth century. Much is known about the people who
lived in Överkalix, how long they survived and what happened to their children. Life was often tough;
some years the harvest was good and food was plentiful but in other years it was scarce and the
population suffered accordingly.
Överkalix
This remarkable set of data has allowed researchers to examine links between levels of nutrition (as
judged by crop success) and the health not just of people alive then, but also their children and
grandchildren. Remarkably, they discovered that the health of individuals could be affected by
environmental factors affecting their grandparents.
Figure 1 shows how the grandparent’s nutrition during the slow growth period of their development, (age
8-12 for girls and 9-12 for boys), affects the life expectancy of their grandchildren. This is expressed as a
mortality risk ratio. The mortality risk ratio shows their risk of dying compared with all their peers. A risk
of 1 implies that their risk of dying is the same as their peers; less than 1, they are less likely to die; more
than 1, they are more likely to die.
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Student sheets
The p-value is the measure of the probability that the increase or decrease from 1 in relative risk is due
merely to chance and therefore not statistically significant.
See separate note explaining significance.
The maximum value of p that allows the result to be considered significant is selected, depending on the
type of experiment and data being collected. The most widely accepted value for p is 0.05, but lower
values of 0.01 and 0.001 are frequently used, these lower values would give even greater confidence
that the result was not simply due to chance.
Figure 1 Mortality risk ratios of males and females in study depending on their ancestors’ food
availability in their slow growth period
Ancestors
exposed
Mother
Father
Maternal
grandmother
Maternal
grandfather
Paternal
grandmother
Paternal
grandfather
GOOD FOOD AVAILABILITY
Females in
study
Males in study
POOR FOOD AVAILABILITY
Females in study
Males in study
Risk
ratio
Risk
ratio
Risk
ratio
p-value
Risk
ratio
p-value
p-value
p-value
1.66
1.68
0.03
0.02
1.53
1.07
0.06
0.73
0.51
1.31
0.04
0.24
0.78
0.96
0.3
0.85
0.79
0.27
0.92
0.62
1.3
0.22
1.25
0.24
1.23
0.34
0.81
0.22
1.05
0.81
0.98
0.9
2.13
0.001
1.02
0.93
0.72
0.12
1.23
0.27
0.81
0.32
1.67
0.009
1.17
0.43
0.65
0.025
Data from
Marcus E Pembrey1,2, Lars Olov Bygren3,6, Gunnar Kaati4, Sören Edvinsson5, Kate Northstone2, Michael Sjöström6, Jean Golding2 and The
ALSPAC Study Team
Sex-specific, male-line transgenerational responses in humans European Journal of Human Genetics (2006) 14, 159–166. published
online 14 December 2005.
http://www.nature.com/ejhg/journal/v14/n2/abs/5201538a.html
Figure 2 The family
maternal
grandmother
mother
Page 2
maternal
grandfather
paternal
grandmother
paternal
grandfather
father
©The Nuffield Foundation, 2009
Copies may be made for UK in schools and colleges
A2 Science In Society 3.2
Student sheets
Questions to discuss
1
We have data on six ancestors for each person involved in the study. The researchers suggest that
only the results in bold are statistically significant.
(i) Which p-value, 0.05 or 0.01, have the paper’s authors chosen as the threshold of
significance?Justify your answer.
(ii) Express this p-value as the percentage of times that such a result might be expected by chance.
2
For which combinations does a grandparent’s nutrition during their slow growth period have a
statistically significant (results in bold) effect on his or her grandchildren?
3
If a grandmother experienced good nutrition during her slow growth period, what effect did this have
on the survival of
(a) her granddaughters and
(b) her grandsons?
4
If a grandfather experienced good nutrition during his slow growth period, what effect did this have
on the survival of
(a) his grandsons and
(b) his granddaughters?
5
Think about the different ways in which people are influenced by their parents and grandparents,
directly or indirectly, biologically and socially. How many different influences can you think of?
6
An environmental impact affecting subsequent generations is known as a transgenerational effect.
Why is it difficult to use a traditional genetics-based explanation of inheritance to explain
transgenerational effects such as those seen in Figure 1?
7
Transgenerational effects across one generation caused by environmental factors are well known.
Suggest why such effects are generally seen in mothers and offspring rather than fathers and
offspring?
8
The Overkalix case in unusual because the effect is seen over two generations and it is sex-specific.
Explain why this is a challenge to traditional environmental explanations.
Part 2 An explanation?
The Överkalix data are difficult to explain by either conventional genetic or environmental influences.
They seem to indicate a bit of both – an inherited effect, which suggests genetic factors, and also a
nutritional impact, which implies an environmental explanation. In fact, the two may indeed be acting
together, through an ‘epigenetic’ effect. See textbook pages 60-63.
There is growing interest in the field of epigenetics – modifications to a gene that do not affect its DNA
sequence but do alter its activity in cells and hence affect tissues, organs or whole organisms. Crucially,
it is not just which genes someone inherits that is important – it is how those genes are used; they need
to be turned on and off at the right time and the right place, and their activity finely tuned. While particular
sections of DNA regulate gene activity, so too can epigenetic modifications. These are typically chemical
modification either of DNA itself or of proteins associated with it. These changes can
make DNA more or less accessible to the enzymes that transcribe genes into RNA. In effect, epigenetic
changes can lock a gene away, rendering it inactive, or expose it so that it can be activated.
Page 3
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A2 Science In Society 3.2
Student sheets
Animal studies have shown that this is one of the ways in which the environment affects the
development of an individual. Now it seems that these epigenetic changes may be inheritable, though
less long-lasting than DNA mutations.
Epigenetic changes are a kind of ‘half-way house’ to evolutionary change. In classical Darwinian
evolution, the environment sculpts the genome by selecting the individuals with genes that promote
survival and reproduction. That process inevitably takes a long time, particularly for multicellular
organisms. An epigenetic change, on the other hand, can be introduced immediately and apparently
inherited through further generations.
Questions to discuss
It has been known for some time that the environment can influence the expression of DNA during an
individual’s lifetime. The fact that such epigenetic effects can be inherited is a relatively new area of
research.
1
Which particular cells would have to be altered by an environmental influence for it to influence
subsequent generations epigenetically?
2
Transgenerational effects have been discovered closer to home, in a recent study of children and
parents living around Bristol. The Avon Longitudinal Study of Children and Parents (ALSPAC) has
been following 14,000 children and parents since birth, providing a rich data resource on early
development, see textbook page 47.
Researchers found that the body mass index of boys aged 9 (but not girls) was linked to early
smoking in fathers. Where might this epigenetic change happen to explain this link to the male sex?
3
Explain the difference between an epigenetic change and a mutation in DNA.
4
Much of the increased death rate in the Överkalix grandchildren was due to diseases known to be
partly affected by diet such as diabetes and heart disease. Suggest a hypothesis that might explain
the link between over-eating in the grand children and grandparents deprived of enough food. See
textbook page 63.
5
Transgenerational epigenetic inheritance seems to be a new scientific explanation. Some people are
always reluctant to change their views. How could you put the case for epigenetic inheritance to
each of the objectors below?
The whole point of
DNA as the basis of
inheritance is that it is
passed on unchanged.
fromone generation to
the next
Page 4
This sounds like
Lamarck’s inheritance of
acquired characteristics.
Darwin proved that wrong
150 years ago.
Of course grandparents might
influence their grandchildren’s eating
habits and lifestyle. Why do you need
epigenetics to explain it?
©The Nuffield Foundation, 2009
Copies may be made for UK in schools and colleges