ISSUE 11 JANUARY 2010

Big genes, genomes

and health

Picture
bringing CUTTING-EDGE SCIENCE INto THE CLASSROOM

The
wonder
of you
Exploring your
genetic identity

n Inside the human genome

or te ac h
c ef e n The genetic basis of
health and disease
rs
ur
A re s o

and

n Regulating the use of

REE genetic information

F
le ar n

n What DNA studies tell

us about the past
Corbis/Photolibrary

er

s
Big
Picture

Big Picture on genes,

E
GENOM lete
p
The com formation
e n e ti c in
g
anism,
of an org early

genomes and health

in n
found ll.
pe of ce
every ty

Beyond the human genome CELL

Nucleus
Where almost all
the DNA is found.
Our genes play a key part in making us who we are, but how can
science help us unpick and understand our genetic identity?
Since the working draft of the human genome was unveiled in
2000, mind-boggling progress has been made in our ability CHROMOSOME
both to sequence a genome accurately and quickly, and to A large package of
DNA found in cells.
process and understand the huge amount of data these It contains a set of
activities produce. What do these developments mean genes and other DNA
for each of us – our health, identity, and the world we elements. Humans
have 46 (23 pairs).
live in – now and in the future?
GENE unit
amental
The fund nce. Genes DNA
ta
GENETIC CODE of inheri s of DNA, Deo
KEY TERMS

x
th
are leng contain the yribonu
The order of the t c
gen hemica cleic ac
chemical units and mos n for e l
rm a ti o It is tic info that ca id,
of DNA (bases) in fo
p roteins. entw
mad rm r
e up ation. ries
order in g
determines the ma k
‘dou ined str of two
units
of the chemical chemble helix ings (th
ein s (am ino e
of pr ot
64 A, T, ical un ’) of fou
acids). There are G an its (b
d C. ases
r
ds’
three-letter ‘wor ):
in the code.

MUTATION BASE PAIR

A change in the Two DNA bases
DNA sequence TRANSCRIPTION paired up, like
of
an organism. Th rungs on a ladder,
e
simplest mutation which produces
is the double helix
the loss or alterati
on
of a single base structure.
pair.
Mutations can ha
ve
a positive, nega
tive
or neutral effect. PROTE
IN
A large
m
A quick specifie olecule,
d
whizz gene or by a
g
RNA
ic that pe enes,
around the Ribonucle TRANSLATION rf
speciali orms a
h
language acid, whic of s
in the c ed job
m a d e u p ell.
is
of the four chem ses:
ical
genes. o r b a
units,
d C.
A, U, G an

All in sequence
Why is determining an organism’s genome sequence important?

Most types of cell in an organism window on to evolution and recent human Others are important for maintaining
contain a complete copy of its genome. history – including the migration of people health, or have potential use in the
The organisation is quite complicated, around the world. DNA can also provide clues industrial production of biologically
but the simplest fact about any genome in police work, from crime scene samples, active chemicals and enzymes.
is that it is a collection of DNA sequences and can help to identify disaster victims. Genomic information is used to track
– long strings of the chemical ‘letters’ A, The genome sequences of other species harmful bacteria such as those that cause
T, G and C (adenine, thymine, guanine and have many other uses. The genomes infection in hospitals, as well as to aid
cytosine) in a particular order. of organisms used in farming, from rice the development of new drugs. New flu
Learn to read an organism’s genome and wheat to pigs and cattle, are being strains have their genomes read quickly
sequence, and compare it with that of sequenced to help to breed improved to understand how the virus spreads and
other organisms, and it can tell you lots strains. But the vast majority of the many to speed up vaccine production.
of different things. hundreds of genomes already completed Knowledge of genome sequences also
The human genome sequence contains a are from bacteria. Some are species that speeds up developments in biotechnology,
wealth of information about human biology, cause diseases in people, as well as in and is finding uses in tracking biodiversity
in both health and disease. Our DNA is a agriculturally important animals or plants. and policing trade in protected species.

2 Big Picture 11: Genes, genomes and health

 A brief history of DNA sequencing
1953 – James Watson and Francis Crick reveal the structure of
1950 DNA as a double-stranded helix. They acknowledge the importance
s of ideas and data from Rosalind Franklin and Maurice Wilkins.

1956 – Human chromosome number established at 46,

overturning the previously accepted figure of 48.

1961 – Marshall Nirenberg and Johann Matthaei read the first DNA
‘word’, three letters that code for a single amino acid in a protein.

1970
The rest of the genetic code is worked out within five years.

1990 – After some years of discussion, the Human

1960

s
s Genome Project – to map, then sequence the entire
complement of human DNA – gets underway.
1977 – Fred Sanger and
Walter Gilbert develop 1995 – Genome of the bacterium
efficient methods for DNA Haemophilus influenzae published, with
sequencing. Sanger’s 1.8 million base pairs (the first genome
team sequences the first of a non-viral organism to be sequenced).
DNA genome, that of the
bacterium-infecting virus 1996 – Yeast genome
phi X174. 199 published, containing 6000
0s genes (the first eukaryotic cell
1981 – Human mitochondrial genome to be sequenced).
genome sequence published by 198
Fred Sanger and colleagues. 0s 1999 – 1999 – First human
Fruit fly chromosome
2000 – UK Prime Minister Tony Blair and US genome sequence – number
President Bill Clinton announce a ‘working draft’ published. 22 – published.
of the human genome, produced by researchers
working in the public and private sectors.

2001 – The international Human Genome

Project and private company Celera Genomics
publish two independent drafts of the human
genome sequence.

2002 – Mouse 2002 – Plasmodium genome sequenced,

Genome Sequencing providing information that should be useful
Consortium completes for understanding malaria, developing a
first draft. vaccine and finding new drug targets.

2008 – Launch of the 1000

Genomes Project, aimed at
producing the best catalogue of
2009 – Researchers from
human genetic variation to date.
Germany announce that they have
sequenced the entire genome of a 200
38 000-year-old Neanderthal. 0s

$1000 genome
Alexander Kalina/iStockphoto

Could getting our genomes sequenced be an affordable option in the future?

Sequencing is still getting cheaper. In August to sequence a human genome in four weeks. than one error in every
2009, US engineer Stephen Quake announced The bill? Around $50 000. Illumina, a company 100 000 bases, for no
his company’s ‘Single Molecule Sequencer’, a that makes sequencing machines that are more than $10 000
million-dollar machine that allows three people used in many of the large genome-sequencing per genome.
centres, charges the same for a new
personal genome service. on the web
A $1000 genome analysis
would open the way to routine ch-ch-ch-changes
use in medicine, although it is Discover how gene sequencing
still probably some years away. technologies have developed since
To help speed things up, a US-based the 1980s.
foundation is offering a $10 million award.
The X Prize for Genomics will go to whoever www.wellcome.ac.uk/
builds a machine that can sequence 100
human genomes in ten days, with no more
bigpicture/genes

january 2010 3
Big
Picture

Introducing
the genome
Many of the scientists working to decode the human genome
were surprised to find far fewer genes than expected.
Subsequent work continues to uncover interesting features
of the human genome, which has proved to be so much more
than just a collection of genes. What makes up the human
genome? How does it compare with those of other organisms?

Adrian Brooks
Great expectations James Watson, co-discoverer of DNA’s double helical structure.

The draft human genome held many surprises for researchers.

Printing all 3 billion letters of the human DNA is achieved through ‘alternative splicing’, The versatility of genomes is still being
sequence would fill 200 telephone directories. which basically means taking genes, or their revealed. Recent findings indicate that some
When the ‘book of life’ was fully decoded, it messenger RNAs, in bits and reshuffling ‘jumping genes’, which can move around
turned out to be full of surprises. them. The result is rearranged proteins, with the genome, are especially active during
Most scientists had assumed that humans different structures. brain development, for example – which
had around 100 000 genes. Wrong: the true This makes it harder to define what a gene is. might allow the brain to generate new
number is nearer 25 000. So does this mean It is no longer a piece of DNA that always does types of neuron. Nor is the human genome
that we’re much simpler genetically than the same thing – ‘one gene, one enzyme’, as sequence quite complete. Certain regions of
rice, for example, which has around 50 000 biologists used to say. Many genes are shape- chromosomes, usually with highly repetitive
genes? Not necessarily – the human genome shifters, making one product then another. sequences, are hard to nail with current
harbours some organisational secrets. What’s more, many genes can ‘multitask’ – technologies. There are also still a few gaps
Human cells make perhaps three times playing different roles in different tissues, or at in the coverage of actual genes, though these
as many proteins as they have genes. This different life stages. amount to under one per cent of the total.

Bare essentials More than genes

The genome is far from just a collection of genes.
How few genes does
an organism need to live? Genes take up only complementary RNA
a small part of the or DNA. This seems to
Turn off the sat nav and you
genome: protein-coding make it ideal for lots of
can still drive a car. Remove
sequences account for the detailed regulation of
the fuel pump and
only around 1.5 per cent gene action. Small RNAs
you won’t be going out’
of human DNA. that bind to mRNA or
anywhere. Similarly, genes in
Biologists used to DNA can stop a protein
even simple mice or bacteria.
regard the other regions being made or tag the
organisms carry Often, single gene
(which don’t code for mRNA for disposal, for
genes they can knockouts have
proteins) as ‘junk’. Now example. The newfound
do without, at a no obvious effect,
though, these regions versatility of RNA is
pinch. Some genes, in the lab at least. You
are slowly yielding their giving it a starring role in
such as those that can define the ‘minimal
secrets. Some of the non- the workings of the cell
code for the cell’s protein genome’ by knocking out
coding DNA regions are – but every RNA is still
factories, are essential. But genes one at a time, and
probably parasitic bits produced from reading
how few genes can an organism checking whether the organism
and pieces that are along a stretch of code in
get away with? survives. The bacterium Bacillus
for the evolutionary ride. the genome.
Viruses don’t count here because subtilis is able, if supplied with good
But at least 10 per cent Just how many RNAs
they need – for example – a sneezing nutrients, to manage without all but
and perhaps a lot more there are will become
host’s cells to reproduce. But some 271 of its 4100 genes.
of the whole genome is clearer when the US-led
independently living bacteria are More ambitious is to make your
transcribed into RNA at Encyclopedia of DNA
pretty light on genes. One of the own genome from scratch, then stick
some time. The role these Elements (ENCODE)
simplest found so far is Mycoplasma it into an empty cell and see whether
‘extra’ RNAs play is still project is complete.
genitalium, which – as its name it works. Craig Venter is trying
being teased out. They Researchers are looking
suggests – lives on the genitals this approach using Mycoplasma.
are often short-lived and at more than 40 different
of primates. Its tiny genome, If he succeeds, this ‘synthetic
some are much smaller kinds of human cell, to
sequenced in 1995, has around organism’ might then be developed
than mRNAs. make sure they catch all
500 genes. for industrial applications such as
RNA, because it the parts of the human
Genetic engineers can now ‘knock creating biofuels.
Big in Japan: has a single strand of genome that get read out
Luciano Pavarotti, bass. bases, can bind to a into RNA.

4 Big Picture 11: Genes, genomes and health

 Measuring up FAST FACT
It would take 9.5 years non-stop to read
How does the human genome compare with those aloud a person’s genome base by base.
of other organisms? Source: genomics.energy.gov

Adrian Brooks
Gene number Whose genes?
The reference human genome combines
the DNA of several people.
The original of ‘the’ human genome was a reference
sequence, compiled by analysing DNA from blood
samples donated by a handful of anonymous
volunteers. It stands as a comparison for genomes
analysed later on.
23 600 20 800 23 100 50900 14100 6700 4300 11
Human Chimp Mouse Rice Fruit fly Yeast E. coli Flu virus That sequence covers the nuclear DNA –
that contained in the cell’s nucleus – over 99
per cent of the total. The mitochondrion, the tiny
organelle that acts as the cell’s energy generator,
Genome size has its own separate genome, with 16 500 base
pairs and just 37 genes. Every cell has hundreds
of copies of this DNA, and many different samples
have been sequenced. For more on mitochondria,
see page 8.
Since the Human Genome Project was
completed, a few named individuals have had
their genomes analysed. The first two were Craig
Venter (the driving force behind the private genome
3.1bn 3.4bn 2.7bn 372m 169m 12m 4.6m 13 500
Human Chimp Mouse Rice Fruit fly Yeast E. coli Flu virus project) in 2007, and DNA pioneer James Watson
the following year. Genome analyses have since
Gene number refers to protein-coding genes. Genome size measured in base pairs. been published for individuals from three distinct
Rice: Japonica subspecies; yeast: Saccharomyces cerevisiae; E.coli: K-12. geographic regions: Korea, China and Nigeria
All figures from Ensembl (www.ensembl.org), except rice (rice.plantbiology.msu.edu), (in the latter case, one of the Yoruba people).
E. coli (Science 1997;277:1453–62) and flu virus (Nature 2005;437:1162–6).
Meanwhile, the 1000 Genomes Project,
launched in 2008, will refine the reference
Now we have whole genomes from a the other. This reveals simple differences sequence with information from a larger number
range of organisms, comparing them and allows us to calculate a percentage of anonymous samples. The project, involving
is a powerful way to investigate what similarity. Such a comparison becomes researchers in the UK, the USA and China, is
makes each creature distinctive. The less meaningful with organisms that are cataloguing variations between individuals
simplest measure is to count genes and less closely related, e.g. humans and that occur in at least 1 per cent of the
check which are there. Do that and you nematode worms, because less of population to pinpoint differences in DNA
find, for example, that the tiger puffer the two genome sequences can be relevant to health and disease.
fish (Fugu rubripes), the first backboned aligned together.
Clockwise from left: A Han Chinese man, a Korean
creature to have its genome sequenced So, even for our closest relative, woman, a Yoruba man from Nigeria. The genome analyses
after humans, has many genes in the crude measure of 98.8 per cent published so far include those for individuals from China,
common with us. On the other hand, similarity conceals important differences. Korea and Nigeria.
around a quarter of human genes have Apart from the precise sequence of
Amar Grover/Photolibrary, Gina Smith/iStockphoto, Ross & Weiss Photography/Photolibrary

no equivalents in the fish, and we have genes there are some differences in
almost ten times as much DNA. the overall set of genes. Also, the time
Animals without backbones, such as when particular genes switch on and
fruit flies and nematode worms, share off during development does not show
very many genes with humans too. up, and this is very different for some
Researchers are still poring over the genes – especially ones that affect
chimpanzee genome, first published the brain. These subtle differences in
in draft in 2005. This confirms that the gene regulation and expression are
chimp is our closest living relative, with a likely to underlie the
genome 98.8 per cent identical to ours. most important
But what does this figure mean? For differences
very closely related organisms, such as between
humans and chimps, we can align most closely related
of one organism’s genome with that of species.

on the slide
Try our interactive slider to explore how similar,
or not, we are to a number of organisms. on the web
www.wellcome.ac.uk/bigpicture/genes

january 2010 5
Big
Picture

In sickness and in health

Genetics plays a part in many diseases. In a few conditions, such as
cystic fibrosis, a particular mutation in a single gene is enough to
cause disease. In the majority of diseases, though – including common
disorders such as diabetes and asthma – the influence of our genes can
be much more subtle. What do we know now about the genetic basis
of disease? How has the progress in genome sequencing informed the
way we categorise, diagnose and treat conditions?

Can you resist?

Genetic variations play a part in disease resistance.
Stephen Fuller

Some gene variants are good news. If you are of northern

European descent, for instance, there is a 1 per cent chance that
you carry two mutated copies of the CCR5 gene, which means
that key cells in your immune system lack working copies of the
CCR5 receptor. This receptor is what HIV latches on to when
it attacks those cells, so a lack of working receptors provides
defence against HIV. About 10 per cent of the same population
AMI Images/SPL

lack one working copy, and have partial protection. Why did this
happen? One possibility is that the gene mutation arose when
smallpox was an everyday hazard, and persisted because it
helps to prevent that scourge as well.

Eye of Science/SPL
Top left: Internal structure of an HIV particle, including the RNA-containing core (red).
Bottom left: Smallpox virus particle, including its DNA genome (red).
Right: Smallpox viruses. Smallpox was eradicated in the 1970s by a global vaccination programme,
but is the virus’s once-widespread presence the reason some people are protected from HIV infection today?

Nature Seeing into the future

and Why finding a ‘disease gene’ is just the
beginning of finding a treatment or cure.

nurture
Bernard Maurin/iStockphoto

Once a gene is linked firmly to However, there are promising

a particular condition, it may results in trials of drugs that may
Most conditions lead to a genetic test, perhaps restore the function of some
involve an before birth, to assess disease altered forms of CFTR. There
interaction risks. Going beyond that can are also early trials underway
between prove a lengthy effort. with gene therapy, building on
genes and Cystic fibrosis is now one of earlier research in this area, to
environment. the better-understood genetic give people a dose of the normal
People in protective workwear removing asbestos.
diseases. We know the gene, all gene so they can make the right
Almost everything about health There are a number of known the ways it can be altered, the form of the protein. The cystic
is affected by genes. Most mutations in the gene for the protein that is affected and what fibrosis saga does not suggest
often, the effect of an individual blood’s oxygen-carrying protein job the protein does in cells. that unravelling disease genes is
genetic variation is small, haemoglobin. Carrying one There are tests available for not helpful, just that the benefits
and is usually influenced by altered copy of the gene can the condition, helping carriers of take time, and a lot more hard
additional external factors: diet help to protect against infection the mutation to make informed work from researchers.
or exercise, exposure to a virus, by the parasite that causes choices about having children,
Jennifer Grannell, who was dignosed
bacterium or radiation, or a malaria. However, carrying two for example (see page 13). with cystic fibrosis when she was
more general challenge such as altered copies (and hence no Yet 20 years after the gene was two, with some of the medications
heat stress or exhaustion. normal haemoglobin) can lead found, treatments that build on she uses.
For example, people to diseases including sickle-cell this remain elusive.
who develop the cancer anaemia or thalassaemia. Therapy has improved over
mesothelioma have almost Cancer cells have aberrant those decades, and people
always been exposed to genomes, usually as a result with the condition now typically
asbestos, the fibres of which of a series of genetic changes live a great deal longer. But
lodge in the lungs. Some that happen as the disease no treatments have yet come
people exposed will be at a develops. In the first step, through that are targeted at
higher risk because of minor normal cells may be exposed the protein – the cystic fibrosis
Cystic Fibrosis Trust

genetic differences. Which to chemicals that damage DNA transmembrane conductance

genes matter is still being or interfere with its repair. regulator (CFTR) – whose
investigated. For more on the influence defects cause lung congestion,
Some genetic differences of genes and environment on digestive problems and damage
have mixed costs and benefits. disease, see page 8. to the pancreas.

6 Big Picture 11: Genes, genomes and health

 BB boys
Beer gene gives the belly! and the Getting personal
Sun

Half of gay gene Is the future of pharmaceuticals really all

carry ‘ people
Sun
me, me, me?

fat gen Gene tests could help doctors to identify the

Experts
Daily T

e’
elegrap best treatment for each patient. This is important
h

issue 'fat gene'

because some gene variants affect how the body

ene
breaks down different drugs, for example. Giving the

i o n g right drug to the right patient at the right dose, when

warning Depre
ss
red e
there is a choice, should increase effectiveness and

v
Mail

o
Daily reduce adverse reactions.
Express

d i s c A more complete knowledge of how genetics

affects our responses to drugs – pharmacogenetics
– could eventually lead to an era of personalised
medicine.

What do we know now? Examples so far include identifying variants in a key

enzyme complex in the liver known as cytochrome
How is current research investigating the genetic basis of disease? P450, which metabolises drugs. Some types of P450
reduce the effectiveness of antidepressants, while
Access to data about the entire genome gene region does, so each one has to others diminish people’s responses to painkillers such
is increasing knowledge of many be looked at more closely for clues to as codeine. Another example is Herceptin, a drug
diseases, but also reinforcing awareness the underlying mechanisms of disease. given to women with breast tumours if they have
of how complex cells, tissues and Such studies can produce strong an overactive gene for a receptor known as HER2.
bodies are. Although the press may still findings. Several teams, including one They benefit from Herceptin, an antibody that blocks
report a ‘gene for’ things like arthritis or led by Professor Andrew Hattersley the receptors on the cancer cells, whereas women
depression, studies almost always show at the Peninsula Medical School in without the receptor do not.
that there are multiple factors involved. Plymouth, have identified genes that Personalised medicine has economic implications.
One powerful research approach affect the risk of developing type 2 (late- Drug companies spend heavily on research to find
is to use genome-wide association onset) diabetes. This disease is caused compounds that will be prescribed for thousands of
studies. These involve going through the by the body not responding properly people. Pharmacogenetics might mean each drug is
entire genome looking for statistically to the hormone insulin, and further used by a smaller number of patients, although each
significant links between genetic investigation is helping to tease out the of them would benefit more.
variation and a disorder. Usually, the complex regulation of responses.
larger the population studied, the more Some genome-wide association Women with breast cancer, their relatives and supporters
on a march in Cardiff to demand the end of a Herceptin
genetic links that appear. But each studies have proved less fruitful so far ‘postcode lottery’, where people in different areas have
link contributes only a tiny fraction – for example, those looking for genes different access to particular treatments.
of susceptibility to the disease. The linked to some psychiatric illnesses,
method does not tell you what each including schizophrenia and depression.

Single-gene larger group of genetic disorders that

Johnny Green/PA Archive/Press Association Images

occur only if you inherit two copies of

and
a mutated gene (i.e. one from each
parent).
There are also conditions due to
chromosome larger changes in the chromosomes.
Down’s syndrome, for instance,
disorders is caused by an extra copy of
chromosome 21.
These diseases can be more
Some conditions are caused
complicated than they may seem
by genetic ‘abnormalities’.
at first glance. The protein affected
Some conditions are so tightly tied to in cystic fibrosis can be altered by
DNA mutations that they can be called more than a thousand different
genetic diseases. In a few cases, mutations. Some have almost no
inheriting just one copy of a mutated effect, while others cause severe lung Got the bug?
gene (i.e. a ‘normal’ version from and stomach problems. The extent From protecting orange trees to
one parent and a ‘mutated’ version of symptoms can also be affected by fighting the plague, find out what we
from the other) can lead to disease. other genes, which modify the effect can learn from sequencing
These are known as dominant of the cystic fibrosis gene. People the genomes of all kinds of
conditions, and include with Down’s bacteria and viruses. on the web
Huntington’s disease, syndrome differ
an incurable condition on a whole range No more insulin
Wessex Regional Genetics Centre

that causes gradual of characteristics, Watch a video to find out how the discovery of a
deterioration of the which depend on genetic mutation that caused neonatal diabetes has
brain (for more on this factors including led to a new treatment that’s transformed the lives of
see page 15). how much of patients and their families.
Recessive chromosome 21
conditions, such as is present in three www.wellcome.ac.uk/
cystic fibrosis, are a copies. bigpicture/genes

january 2010 7
Big
Picture

Genes and the wider world

Just as researchers conduct studies to unpick the genetic
basis of disease, they must also consider how our lifestyle and
surroundings interact with our genome to shape our current
and long-term health. It’s not all about the DNA found in our
cells either – studies of the billions of microorganisms that
call our bodies home are yielding fascinating insights into
everything from the bacterial causes of medical conditions to
the history of human migration.

FAST FACT
Kelly Cline/iStockphoto

In an average meal you eat around

150 000 km of DNA.
Source: Iowa State University Office of Biotechnology

Understanding
the links
Dr David Furness/Keele University/SPL

How do researchers tease apart genetic and

environmental factors?
Before the genome era, twin studies helped researchers
to assess the relative influences of genes and environment
– without knowing details of particular genes. Researchers
can record what happens to lots of pairs of identical twins,
and similar numbers of non-identical, same-sex twins,
when each pair is raised together in a similar environment.
If some characteristic differs more in non-identical twins,

Beyond nuclear this is likely to be because of some genetic effect.

Better, but more difficult to arrange, is to look at
identical twins who have been raised in different
Mitochondria mean that there’s a bit more of mum in all of us. households (and, therefore, different environments). If
There’s another bacterial genome, mutations this causes can lead to they nevertheless turn out very alike, the likeness will be,
or some of one, in all of our cells – mitochondrial diseases, an often at least partly, due to genes shaping their development.
but it lies in the energy-generating perplexing set of conditions that Identifying the genes involved requires a different kind
organelles, the mitochondria can have widely varying symptoms. of study. For example, Professor Nick Wareham at the
(one shown above). These vital Not all mitochondria may be UK Medical Research Council’s Epidemiology Unit in
accessories are almost certainly affected, and the consequences Cambridge is leading a study to understand the complex
descendants of symbiotic bacteria can be different in different tissues. effects of diet, exercise and other behaviours on the
that colonised larger cells more When a sperm cell unites with an risk of developing type 2 diabetes, and how this risk is
than 2 billion years ago. Most egg, it brings some mitochondria modulated by genes.
of a mitochondrion’s essential from your dad. These are eliminated The researchers are using a mega-database of 350 000
functions depend on genes in the soon after fertilisation, however, so people across Europe, which was assembled for a
cell’s nucleus (which have been the hundreds of mitochondria study of diet and health originally designed to investigate
transferred there over millions of in each of your cells are causes of cancer. The records are so detailed that they
years), but mitochondria retain and descended from your mum. will allow the Cambridge team to pull out 10 000 people
use a separate genome. This unusual maternal pattern with diabetes and match them with 10 000 diabetes-free
Mistakes in copying the of inheritance for these controls. This will provide a large enough group to get
mitochondrial DNA seem more few mitochondrial good indications of which genes and lifestyle differences
common than mistakes made genes is important in are important contributors to diabetes risk. The results will
when copying nuclear DNA. The studies of evolution. feed into health policies to tackle what is becoming one
of the most common conditions of middle age.
Indeed, there could be scope to use genetic
teacherS’ pack information more widely to develop population-based
interventions and campaigns, where preventative
on the web
Check out free videos, animations and more.
strategies can be targeted at the subgroups most at
www.wellcome.ac.uk/bigpicture/genes risk of particular conditions.

8 Big Picture 11: Genes, genomes and health

 Future plans
Long-term population studies
help researchers plan for future
discoveries today.
The effects of the long-term interaction
between genes and environment weave
through a life story, and the medical
consequences often appear late in
life. That means waiting a long time for
research results, too. Nowadays, the
collection of DNA samples from people
who enrol in studies is done alongside
plans to keep the samples for many
decades, and to make sure that any
new tests that appear along the way can
still be applied to them.
One far-sighted study in the west
of England began in 1991. The Avon
Longitudinal Study of Parents and Children
(ALSPAC) signed up more than 14 000
mothers before their babies were born.

The genomes in us The children have been followed ever

since – and, as young adults, some are
on the advisory panel that oversees the
Like it or not, our bodies are teeming with billions of microorganisms.
project. The research explores a range of
We carry many more genomes than just meningitidis, which lives harmlessly in social and medical issues. Findings so far
our own. Thousands of different kinds the nose and throat of about four people include that eating oily fish in pregnancy
of bacterium live on and in humans, and in ten. But the bacterium, whose genome improves the child’s eyesight, and that
there are perhaps ten times as many was sequenced in 2000, also causes children growing up in very hygienic
bacterial cells present as there are cells around half a million cases of meningitis homes are more likely to get asthma.
in our bodies. The Human Microbiome every year worldwide. Larger still is UK Biobank, a national
Project is an international effort uniting Much current research focuses on study that is recruiting 500 000 people
the labs sequencing the genomes of the bacteria in our intestines, most aged 45–69. They will have a health
these passengers, both welcome and of which cannot live anywhere else. screening interview, donate blood
unwelcome. The total number of genes There is a whole ecosystem in there. samples and agree to allow their future
involved is probably more than a hundred Variations in this vast population – the medical records to be shared with the
times as big as in the actual human gut microbiota – seem to affect the risk researchers. The big numbers should
genome. of obesity, as well as subtler responses help to reveal the numerous factors, each
Meanwhile, there is a growing number to our diet. Other effects of microbial with small effects, that contribute to the
of studies of what these bacteria do for us, genomes include influence on allergies development of a disease – although
or to us. Some bacteria are essential, such and asthma. A growing number of serious there are already ideas in discussion to
as those needed for digestion. Some are medical conditions formerly thought to be combine the data with even larger studies
harmful. Some can be benign but turn nasty. microbe-free, from ulcers to heart disease, from, for example, China.
An example of the last kind is Neisseria turn out to have some bacterial culprits.

Epigenetics genetic switch or switches.

This means that there may be
probably, in humans. And some
of those changes will still be
Is it through epigenetics a cascade effect, where one there in the grandchildren. So
that environment affects small change leads to larger a famine, say, will leave traces
our DNA? adjustments in gene expression. down the generations in the way
Study of this kind of survivors’ children metabolise
The gene–environment story secondary modification of their food.
is complex enough, but has the genome is known as A group of researchers based
acquired a new twist in recent epigenetics, and the whole at the London School of Hygiene
years with growing evidence that set of tags is the epigenome. and Tropical Medicine is currently
environment can actually modify The epigenome is a bit like the looking more closely at these
genes – after a fashion. personal settings that gradually effects in mothers and children
The modification is indirect. customise the operating system in the Gambia. Those who live
DNA sequences stay the same, on a computer. Most, but not all on the land there have more
but there are changes in the set of it, is ‘reset’ in sperm and egg. and fresher food at harvest time
of chemical tags that the genes, But some epigenetic changes than during the rest of the year,
Anna Bryukhanova/iStockphoto

or the proteins bound to them, can pass down to the next so the researchers will monitor
carry. These tags, most often generation. the effects on babies born in
simple methyl (CH3) groups, There is good evidence that a different seasons. The study will
affect gene expression – usually mother’s diet during pregnancy look at the exact links between
by preventing transcription. and even just after birth can specific nutrients in the mothers’
Often, the gene affected is affect expression of some of blood samples and DNA
itself one that controls another a baby’s genes – in mice and, methylation in their offspring.

january 2010 9
Big
Picture

Identity: your genes and you

Genetically speaking, humans are all remarkably similar. But most of us,
including identical twins, see ourselves as highly individual people with
our own personality, appearance and sense of identity. How far do our
genes go in making each of us look and behave as an individual? What
can studies of our genes tell us about the history of humanity and –
more personally – how closely related we are to other people?

It’s all history now

How DNA studies help to trace the origins of modern humans.
Following individual genes down more than a there are two sets of genes that
few human generations is next to impossible. are normally passed cleanly from
Egg and sperm are each made in a specially one generation to the next.
orchestrated cell division, and their paired Analysis of both kinds has been
genes – one copy from each parent in the used to track the history of human One
previous generation – are thoroughly shuffled migration out of Africa. More recently, recent
before their single sets of chromosomes are it has been extended to more detailed study traced
assembled. These then combine to create tracking of who may have been where a lineage of
a new person’s genome. That happens in and when. Helicobacter pylori
every round of reproduction, so clear lines of More subtle traces of our past can (the bug that causes
descent get very blurred. also be found in the bacteria in our stomach ulcers) from
Both sexes, though, contribute portions guts, and sampling shows they differ populations scattered across
of DNA that escape this mixing-up. Males from place to place. Genome analysis the Polynesian islands of the Pacific
have a single copy of the genes on their of samples of a single species recovered from Ocean. The researchers compared this with
sex-determining Y chromosome. And, as two different human populations can indicate a similar mapping based on a close analysis
explained on page 8, everyone has lots of when the populations became separated, of the likely evolution of the more than 400
copies of the mitochondrial genes, which are assuming that the bacteria are undergoing a different languages spoken on the islands –
only passed on from the egg. That means roughly constant rate of mutation. which also change over time. The conclusions

Getting
physical FAST
Small genetic changes FACT
The tallest man
can mean big physical
differences. in history was
8' 11" (2.72 m).
We are fascinated by difference, The current
but humans are really world’s shortest
genetically rather similar. The man is 2' 5.37"
latest figures suggest that we (74.61 cm).
are all (identical twins excepted)
99.6 per cent similar.
Many human characteristics
vary continuously – there are
people at many different points
on the scale. Height is a typical
example, and recent analysis
suggests at least 50 different
genes (as well as environment)
affect how tall a person grows. gene is related to pain receptor been linked with increased risk makes a big contribution to
A few characteristics of genes in the brain. However, of breast cancer, so it could hair thickness in eastern Asian
appearance vary more simply. redheads’ reputation for ‘fiery’ turn out to be a medically populations. The gene EDAR
Red hair, for example, goes temperament probably has useful sign. comes in a thick-hair variant,
with having two altered copies more to do with the associations Meanwhile, genomics is which must have appeared after
of a gene known as MC1R, of the colour than with anything uncovering more details of the ancestral Asian and European
which is involved in making in the DNA. small differences in genes that populations divided. The gene
Image Source Pink/Alamy

the pigment melanin. There is Less obvious personal can make a big difference to appears to affect the activity of
some evidence for a number differences, such as having your appearance. For example, a transcription factor – one of
of the other characteristics softer earwax, have been tied the International HapMap the many ways one gene can
often said to be associated to a specific gene. Although Project helped to pin down alter the regulation of another.
with red hair, such as a lower softer earwax is harmless, the a single gene out of the 170 This factor is important in fixing
tolerance for pain. The MC1R same genetic variation has involved in hair growth that the final thickness of hair fibres.

10 Big Picture 11: Genes, genomes and health

 Putting the Y into you
What the Y chromosome tells us about our past.

The male Y chromosome contains more can be compared with old-fashioned

DNA than the mitochondrion – around genealogies and used to see whether
50 million base pairs compared with two people with the same surname are
16 000. That difference provides greater genetically related. More remarkably, DNA
scope for variation, allowing more detailed profiles from a crime scene might be useful
analysis of how DNA markers have been in predicting possible surnames of men
carried down the generations. who were there. A team led by Professor
Such analysis can even shed light on Mark Jobling at the University of Leicester
aspects of individual ancestry, as well as is testing out how useful this could be,
tracking population movements. As many and whether it might raise unjustified
countries share our custom of passing suspicions.
surnames from father to son, DNA results Other analysis of the Y chromosome can
tell men which one of several ‘clans’ – as
Professor Bryan Sykes of the University of
Oxford calls them – their Y chromosome
belongs to, from the analysis of just 15
Y-chromosome markers. So far, 18 clans
have been identified, varying in frequency
across different parts of the world.
This sort of work is drawing
new maps of countries, such
A modern skull (right) and a cast of a prehistoric skull
as the UK, which have
(left). Extracting DNA that is of sufficient quantity and
quality to be sequenced from ancient bones can be experienced repeated waves
difficult, because of decay and DNA contamination. of migration. It can show, for
However, researchers announced in 2009 that they example, how Viking place
have sequenced the entire genome of a Neanderthal.
names and the surnames

Jeanell Norvell/iStockphoto
derived from them in parts
were a close match, and indicate strongly that of northern England go along
the gradual colonising of the vast space of the with Viking-descended Y
Pacific spread out from what is now Taiwan, chromosomes.
starting around 5000 years ago.

optimistic trait, though, studies of the influence of a gene

continuing to work on the origins active in the brain that makes the
of a whole range of behaviours, protein monoamine oxidase A
including abilities such as (MAOA). The gene affects levels
reading and maths. of an important neurotransmitter,

In your
They continue to find new one of the chemicals that
twists in the connections transmits signals across the
between genetics and life gaps (synapses) between nerve
genes? histories. For example, there is
evidence from psychological
cells. One rare form of the MAOA
gene was implicated in the
studies that children’s school origins of antisocial behaviour in
Paul Kline/iStockphoto

performance is influenced by studies in the 1990s.

how smart they think they are Later work found that children
– their ‘self-perceived ability’ who had been ill-treated by their
(SPA). In 2009, Robert Plomin parents coped better if they had
and colleagues at King’s College the normal, more active form of
London, who work with a large the gene than children with the
How much of ‘me’ – such as optimism, aggression database of twins, reported variant form. Antisocial behaviour
is determined by or liking for novelty – can be that SPA is highly heritable. So was linked to both ill-treatment
my genome? hard to define. And, as with while there is still a self-fulfilling and the rarer variant gene.
complex physical traits, genomic prophecy involved, it may be So perhaps the genetic
Our personality and how analysis typically finds many at least partly due to some influence is more to
we behave are undoubtedly DNA variations that have weak genetic influence on self-belief, do with coping with
influenced by our genome. associations with the behaviour rather than solely the messages some kinds of stress,
But there are real difficulties in in question. children get from teachers or rather than any
researching the links. A lot of the Geneticists who work in the parents about their ability. more direct link
possible traits you might study area seem to have a persistently A different twist appears in with behaviour.

Seeing red
Is red hair dying out? Do your bit to save this characteristic in the Wellcome Trust-funded game Ginger Dawn.

www.wellcome.ac.uk/bigpicture/genes on the web

january 2010 11
Big
Picture

Your genome, your rights?

Genetic advances bring great potential for health, but they also raise questions around
privacy and who should have access to personal information such as genetic data. Take
a look at the made-up scenarios below to explore two issues that are far
Insurance
from black and white. Number
decision
of people

1. Insurance and genetic

Accepted at
2
Case study: ordinary rates
Huntington’s of insurance
information disease
In 2007, the
Accepted with
higher premiums
14
For some genetic conditions, there are predictive tests that can be used to show Association of British or revised terms
whether someone is likely to develop the disease. Potentially, whole-genome Insurers reported
testing could give you a much wider view of your possible future health. There is Declined
that 132 people 3
some way to go until these tests are widely available, affordable and applicable insurance
applying for insurance
to many common diseases, but imagine a future where this is the case, and disclosed results for
think about the questions below. We’ve used the insurance industry as an genetic tests for Huntington’s. Of these, 108
example, but concerns about misuse of genetic data apply to many groups, had negative (i.e. ‘normal’) results and 19 had positive
including employers, governments and journalists. results, meaning that they carry
the relevant mutation.
The table shows the outcomes for the 19 people
“In my family there’s a
whose tests showed that they carry the mutation
history of early-onset Alzheimer’s
for Huntington’s.
disease. My dad died from this disease
and my older sister already has symptoms.
I’d like to get my genome sequenced to see
if any of the known mutations for this
disease are present.” Sarah, 18. What regulation
is there?
In May 2008, the Genetic Information Non-
Do you think Sarah should be allo discrimination Act (GINA) was passed by the US
wed
to get her genome sequenced? Congress. Other countries have legislated against

?
this kind of discrimination, including France, Finland
and Sweden.
In the UK, there is a voluntary, rather than legislative,
“As an insurer I want system in place. In 1999, the Genetics and Insurance
to know if potential customers Committee (GAIC) was established by the government.
have had their genome sequenced This committee oversees insurance companies to
because this could affect the policies ensure that they comply with a code of conduct
I would offer them.” James, 35, published by the Association of British Insurers. This
insurance professional. code includes a moratorium on the use of genetic tests
for insurance purposes. The moratorium lasts until
2014, and a review is planned for 2011.
The GAIC asks insurers to show the clinical,

?
companies have
Do you think it’s right that insurance scientific and actuarial (relating to the statistics of risk)
ome sequences
access to potential customers’ gen relevance of using the results of predictive genetic
r them insurance?
before considering whether to offe
tests in working out insurance policy premiums. At the
moment, the only test insurers are allowed to use is
that for Huntington’s disease, for life insurance policies
over £500 000. Huntington’s is a rare and incurable
“Access to human genetic disease that causes gradual deterioration of
genome sequences, along the brain. It is caused by carrying a faulty copy of the
with anonymised data on the Huntingtin gene.
people’s medical histories and lifestyle More broadly, in the UK, issues surrounding
information, could make a great difference developments in human genetics are overseen by
to our understanding of the genetic the Human Genetics Commission, a government
basis of disease.” Mark, 27, advisory body. It includes a monitoring group for
researcher. genetic discrimination.

With this in mind, what do you think will

?
Would you have your genome seq happen with such regulation in the future?
uenced

?
and allow scientists to have access Will more genetic tests be approved
to the
information for the good of medica for use by insurers?
l science?

12 Big Picture 11: Genes, genomes and health

2. Genetic testing before birth
Prenatal genetic testing can be used to detect mutations in an embryo or fetus that are linked to particular conditions.
Read the text below and study our imaginary headlines to see what you think about the questions that follow.

Prenatal genetic testing Preimplantation genetic Preimplantation tissue typing

Parents at high risk of having a child diagnosis This allows parents to select an embryo
with a genetic condition will be given This is a particular kind of prenatal that could become a ‘saviour sibling’,
genetic counselling and will then be testing. Embryos are created by in vitro a brother or sister who can donate
offered prenatal genetic tests. A limited fertilisation, then one cell is taken from ‘matched’ stem cells to a sick sibling
number of diseases can be detected in each and tested for the presence of a affected by illnesses such as leukaemia.
this way, including sickle-cell disease, particular genetic mutation. Embryos Here, parents select an embryo for
muscular dystrophy and cystic fibrosis. are then selected accordingly. This implantation that has the same tissue
Prenatal genetic testing is also used to procedure can help couples of whom type (i.e. that is matched for human
detect chromosome disorders such as one or both carry disease-causing leukocyte antigen) as the sick child.
Down’s syndrome. mutations to have unaffected children. The Human Fertilisation and
Tests for a number of other Preimplantation genetic diagnosis can Embryology Authority (HFEA) licenses
conditions are in development, be used to test for over 50 conditions. preimplantation tissue typing (to
including for autism. Some people In 2008, preimplantation genetic produce ‘saviour siblings’) on a case-
argue that we should do all we can to diagnosis was used to help a woman by-case basis in the UK. The first such
rid society of any debilitating condition. with a family history of breast cancer licence was granted in 2002.
Others think that tests for something to conceive a baby free of a mutation Look at the headlines below to see
such as autism would discriminate that causes early-onset, hereditary how two papers tell the story in very
against ‘differently abled’ people, breast cancer. different ways: the first more positive,
producing a society that’s intolerant Look at the headlines below to see the second less so. With these in
of difference. how two papers tell the story in very mind, think about your own views and
Look at the headlines below to see different ways: the first more positive, answer the question that follows.
how two papers tell the story in very the second less so. With these in
different ways: the first more positive, mind, think about your own views and

My little brother was

the second less so. With these in answer the question that follows.
mind, think about your own views and

born to save my life

answer the question that follows.
Baby to be born free
of breast cancer after
Prenatal test for autism would
embryo screening
deprive world of geniuses
Concern over
for autism Genetic embryo ‘spare part’
Gene test hope
screening: where babies
Who do you think should be will it end?
offered prenatal genetic testing?

?
For what kinds of condition? Do you think that preimplantation Do you think it’s fair to
genetic diagnosis should be used select an embryo in this
to screen embryos in this way?

?
way to save a sibling?
?
What regulation is there?
Prenatal diagnosis has no special legislation apart from that covering termination of
pregnancy (abortion). The decision about whether to have a test during pregnancy is Law out of
made between the woman, her family and the doctors looking after her. order?
Genetic tests during pregnancy are available on the NHS if there is a family history of In 1995, the Police National
a condition, or if they are offered as part of a population screening programme. The UK DNA Database was launched
National Screening Committee decides which conditions are screened for. While some tests in England and Wales to allow
may be available through private clinics, there is no test to screen all of a baby’s genes. the police to store DNA
The Human Fertilisation and Embryology Authority oversees all in vitro fertilisation profiles. Do you think it on the web
procedures and research on embryos in the UK. should be compulsory
Sex selection is only allowed for medical reasons, for instance to avoid having a child for everyone’s DNA to be stored on the
affected by an X-linked disorder such as Duchenne muscular dystrophy. Such diseases, database? Take a look at our exclusive online
in which mutated genes are carried on the X chromosome, more often affect males (who lesson plan and video to explore the issues
have one X chromosome) than females (who have two). around this.

www.wellcome.ac.uk/
Question to discuss: Who should decide what

?
prenatal genetic tests and screening are carried out? bigpicture/genes

january 2010 13
Big
Picture

Real voices
Progress in genetic research affects all of our lives, but what’s it like to face these issues every day in your
work or personal life? We talk to a genetic counsellor, a research scientist and a man who carries the mutation
that causes Huntington’s disease to find out.

Anaar Sajoo Elizabeth Murchison

What do you do? What do you do?
I am a Principal Genetic Counsellor, and I’m a postdoctoral researcher at the
have been working in the field for 15 years. Wellcome Trust Sanger Institute,
Cambridge, working at the Cancer
Why did you become a genetic Genome Project.
counsellor?
Why did you become a scientist?
I did a science degree at university. I liked the science part but
I didn’t want to spend all my time in the lab, and wanted some I was really interested in biology as I was growing up. I became
human contact, so I trained as a genetic counsellor. aware of the Human Genome Project as I was finishing school
– I was quite disappointed as it was just ending and I thought
What does your job entail? there’d be nothing left to do. Then I discovered the world of
molecular biology and genetics and realised that the Human
Some genetic counsellors specialise, but I cover most areas, Genome Project was just the beginning. After completing a
including prenatal diagnosis, cancer genetics and neurological biology degree in Australia I got my PhD in the USA.
conditions. The diseases I counsel on include cystic fibrosis,
muscular dystrophy and Huntington’s disease. What does your job entail?
About half of what genetic counsellors do is to study families
with lots of cancer. We test for genetic mutations that could be Cancer is caused by genetic changes – mutations – in a person’s
increasing a family’s risk of linked cancers – we find these in DNA. For the Cancer Genome Project, we’re looking at genomes
around 20 per cent of the families. This can be heartening work taken from cancerous cells to try and work out how these genetic
as this kind of knowledge can help subsequent cancers be changes could contribute to cancer development and cancer
detected early, and there are often therapies available. evolution.
We take tumour tissue and normal tissue from the host and
How do you break bad news to patients? then sequence the genomes of both. We can’t use a standard
human genome to compare the cancer genome to, as every
People often think that giving bad news is the hardest part of my individual is much more different to each other than an individual
job, but it’s not something I do that often. Also, what we think of is to their cancer.
as ‘bad’ may not be so for the patient. When we do have ‘life-
and-death’ news to give we plan with the patient how they’d like What cancers do you study?
to hear it – we can phone them before we see them in person,
for example. At the Cancer Genome Project, some researchers focus on
specific kinds of cancer, others screen ‘their’ gene through lots of
How has genetic testing changed over your career? different cancers. Most research is on human cancers, but I’m the
exception: I study transmissible cancers in Tasmanian devils and
We don’t have cures for genetic conditions yet, but there’s been dogs. Transmissible cancers are spread by the physical transfer
a lot of progress – such as increased life expectancies, better of cancer cells. They are very unusual and, as I grew up in
treatments and new ways to test – so we have to stay up to Tasmania, I wanted to do something to help the Tasmanian devil.
date. We are guided by the family, who deal with the condition
first-hand, every day. Genetic counsellors translate complex How has sequencing changed over your career?
medical and genetic information. Our advantage lies in listening
to what they are going through, and offering a combination of The progress of sequencing technology is just incredible – it’s
support and genetic information. moving so quickly that we’re always fighting to stay on top of it.
My job is a lot of work and it can be hard to take holidays, but I’m
For information on a career in genetic counselling, see: so excited by the new discoveries I come across in the data we
www.agnc.org.uk/howtobecomeaGC.htm generate. It’s a huge thrill to be the first person to see something
biological, and there’s real excitement in the air where I work.
on the web
What it’s like for me For more information on the Cancer Genome Project, see:
Meet other young people living with genetic conditions and find out www.sanger.ac.uk/genetics/CGP/
more about the science involved, with our exclusive online interviews.

www.wellcome.ac.uk/bigpicture/genes

14 Big Picture 11: Genes, genomes and health

 Get online
Everything you need to take your
lessons to the next level at the
click of a mouse. on the web

Medicimage/Photolibrary
Although you’ve nearly reached the end of
the magazine, the Big Picture action doesn’t stop there. Go to
www.wellcome.ac.uk/bigpicture/genes to browse exclusive
online articles, videos and other content, which take you further
into the topics covered in this issue.
Find out what researchers can learn by sequencing the
genomes of pathogens, watch our video about how the
discovery of a genetic mutation has led to a treatment that’s
transformed the life of children with neonatal diabetes, and do
Matt Ellison your bit to save ginger-haired people in the game Ginger Dawn.
Also online is our exclusive curriculum-matched lesson plan and
What do you do? video to help you and your students discuss the issues around
the Police National DNA Database.
I’m 21 and a full-time carer for my dad,
who has Huntington’s disease.

What is Huntington’s disease?

Huntington’s is a genetic disease that
causes gradual deterioration of the brain. It can affect all ages; Opinions wanted!
there’s a juvenile form that occurs in children as young as five. Your chance to be on the
My dad first got symptoms when I was at primary school. They
Big Picture Teachers’
were very mild at first, and it seemed like a good thing to me
because he was home all the time and I saw a lot of him. When I
Advisory Board.
was 12 he started to get really bad. He’s 54 now and in the late Would you like to be involved in the
stages: he’s unable to talk, walk or eat. development of Big Picture and have your
say about future topics and content? If you’ve
How has Huntington’s disease affected your life? got ideas about what resources you’d like us
to produce, or thoughts about how we could
It is very difficult growing up in a family with Huntington’s disease. support science teachers better, then get in
My dad’s illness means that I found out about Huntington’s early touch and let us know.
in life, and my mum was very open about everything. I didn’t The Big Picture team is setting up a
really think about it in terms of my own risk until I was 18 – I don’t Teachers’ Advisory Board and we’re looking
know why, it just hit me then that I needed to face it. for science teachers from across the UK to
join us. The time commitment will be minimal,
How does the testing process work? and we’ll provide incentives.
For more information or to register your interest,
I asked my GP to refer me to a genetics team. They see you
please email bigpicture@wellcome.ac.uk, subject
every month for six months to check how you’re coping with
line ‘Teachers’ advisory board’.
the process, then you get tested. In June 2008 I found out I was

MBPHOTO/iStockphoto
positive for the mutation. It was a surreal day, really strange. I was
glad to find out, but at the same time it was terrible news that I
didn’t want to hear.

How has your diagnosis changed you?

After I was tested I starting fundraising for the Huntington’s

Disease Association. Running was completely new to me, Education editor: Stephanie Sinclair
Editor: Chrissie Giles
but since June 2008 I’ve run four marathons and have two Writers: Jon Turney, Chrissie Giles
more to do. Illustrator: Glen McBeth
Doctors can’t predict when the disease will start to affect me, Graphic designer: Paulo Estriga
Project manager: Jennifer Trent Staves
but it usually occurs earlier in the next generation if it’s passed Advisory board: Jess Buxton, Dave Carr, Nan Davies, Rachel Iredale, Jane Itzhaki,
down the male line – so I’ve probably got 10–15 good years left. Mark Jobling, Rhona Knight, Julian Parkhill, Michael Reiss, Bronwyn Terrill
With Huntington’s you either sit back and let it defeat you, or you All images, unless otherwise indicated, are from Wellcome Images.
stand up and fight back a bit. It took me a few months to get The Wellcome Trust is a charity whose mission is to foster and promote research
back on my feet, but once I did I realised that I can take a lot of with the aim of improving human and animal health (a charity registered in England,
no. 210183). Reflecting the profound impact today’s research will have on society,
strength from it. the Wellcome Trust also seeks to raise awareness of the medical, ethical and social
implications of research and promote dialogue between scientists, the public and
For Matt’s marathon progress, see: policy makers.

www.justgiving.com/mysorelegs ISSN 1745-7777

© The trustee of the Wellcome Trust 2010. 

This is an open access publication and, with the exception of images and illustrations,
the content may unless otherwise stated be reproduced free of charge in any
format or medium, subject to the following conditions: content must be reproduced
Sadly, Matt’s dad died three weeks after this interview. accurately; content must not be used in a misleading context; the Wellcome Trust
Matt and his family wanted this article to be published. must be attributed as the original author and the title of the document specified in
the attribution. 

PU-4638/14K/12–2009/PE

january 2010 15
Big genes, genomes
Picture and health
l What is genome sequencing, and
how and why is it done?
l How do our genes affect our personality,
appearance and health?
l What can studying DNA tell us about human history?
l How similar are we to other organisms?
l How should genetic information be used?

In 2000, the working draft of the human

genome was unveiled. Published a decade The Identity Project is a nine-month
later, Big Picture: Genes, genomes and health season of activity from the Wellcome
explores the developments in sequencing Trust, starting in November 2009,
and genetic research made since this including a major exhibition and
landmark event. Look inside to discover diverse events presented in Wellcome
how technological developments are raising Collection, plus exhibitions, live
new questions around the regulation of and events and films at other venues
access to genetic information. across the UK. The season explores
scientific and social perspectives of
Explore what we know now about the human identity – historical and contemporary
genome and how it compares with those – to encourage debate and discussion
from other living things. Find out how the and to ask how well we will ever be
genetic information we carry in nearly all of able to know ourselves.
our cells can not only give an insight into our
past, but is also beginning to reveal clues www.theidentityproject.org.uk
about our lives and health in the future.

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