WHOLE-GENOME SEQUENCING

HEALTH EDUCATION ENGLAND

WEEK 2 SEQUENCING THE GENOME

POSSIBILITIES FOR WHOLE GENOME SEQUENCING

00:00:12
Steve Scott: The human genome is really large so it’s almost 3.2 billion letters long. So if
you were to read that out one letter at a time, one every second, then that would take you
about a century to read it all out. But there’s lots of information in there.

00:00:27
Michelle Bishop: One of the problems that we do have is that we don’t know what all of
this information means yet. So in a lot of cases we will get this string of letters – the As,
Ts, Cs and Gs – but we don’t actually know what the function is of this information that
we’re getting out. One of the important things about WGS is that while we get this
information we don’t have to use all of it right now, we can select which bits we want to
look at. And at the moment we’re selecting the bits that we understand. But that
information is still there. We can look at it later when we start to understand a little bit
more about the different aspects of the genome. We can then go back and interrogate the
data again. So I suppose we can think about it as you sequence once and you interrogate
often.

00:01:12
Steve: Although the first human genome took a long time to sequence, we’re now
sequencing genomes much quicker because of changes in the technology. Now that we can
compare lots and lots of genomes we can get a better understanding of the differences
between them, and those differences are important because they’re the ones that tell us why
someone might have a particular disease or what risk they might have of certain disease.

00:01:32
Michelle: The more people’s genomes we sequence, the more that we’re understanding
about the different changes and that means that we’re learning more about all the different
changes, which means that we can then go back and ask the same questions again of the
data. So it’s not just the one-stop shop, we don’t just do this once. You may do the
sequencing once but the interrogation will happen, possibly multiple times over a person’s
lifetime.

[a lab member operates a sequencer]

What’s been used in quite a lot of clinical settings is what we call whole exome
sequencing. So about 2% of our genome has what we call protein-coding genes and these

FutureLearn 1
are the genes that contain the instructions for our cells to develop proteins, which is
essentially what allows our cells to function and ensure that it does the job is supposed to
be doing.

It’s believed that quite a lot of the variations that can cause human disease, or at least these
rare genetic conditions, will be located in these exomes. So initially it was felt that if we
just sequenced these exomes we’re going to be able to find out quite a lot of this
information and it means you’re only sequencing 2% of the human genome – it’s a much
shorter job. The more we learn about this, the more we’re finding that people can use the
technique of WGS, sequencing all aspects of the genome, but then when you’re analysing
you’re just pulling out the exomes to analyse. A lot of researchers are finding that they’re
getting much better results, or they’re picking up a lot more variant,s by using that
technique, rather than just sequencing the exomes.

00:03:04
Steve: We’ve come a long way in our understanding of genomes over the last 10-15 years.
With the changes in technology, we’re now able to compare lots and lots of genomes and
generate lots and lots of data. All of that data collectively, will help us to get a much better
understanding of the role of genetics and genomics in health and disease. And that will
lead to much better treatments, much better diagnostic methods to be able to understand
how we can improve health.

FutureLearn 2