Katrina Stone: What happens when I go for whole genome sequencing?

In this explainer episode, we’ve asked Katrina Stone, Clinical
Genetics Doctor, and Clinical Fellow at Genomics England, to
explain what happens when you go for whole genome sequencing for
a rare condition.


You can also find a series of short videos explaining some of the
common terms you might encounter about genomics on our YouTube
channel.


If you’ve got any questions, or have any other topics you’d like
us to explain, feel free to contact us on
info@genomicsengland.co.uk.


You can download the transcript or read it below.


Florence: What happens when I go for whole genome sequencing? I'm
joined by Katrina Stone, Clinical Genetics Doctor, to find out
more. So, Katrina, first things first. What is the purpose of
whole genome sequencing?  


Katrina: The purpose of whole genome sequencing is to try to make
a precise genetic diagnosis for someone with a suspected or
confirmed genetic condition. 


Florence: And why might someone get whole genome
sequencing?  


Katrina: They might get whole genome sequencing because they are
known to have a condition which is likely to be genetic, but the
medical team wants to find out what the exact genetic cause is.
In other cases, the diagnosis might not be known, and the reason
for doing whole genome sequencing is to find out whether there is
a genetic condition present. 


Some of the benefits of having the test is that. If a condition
is identified, this can provide an explanation for the family
about what's been going on, and it can also bring to an end
further unnecessary investigations. Also, if a genetic diagnosis
is confirmed, this can sometimes point towards other things which
might need to be kept an eye on for the individual. 


In addition, once a diagnosis is confirmed, a doctor can advise
the family on the likelihood of other members of the family or
future children being affected with the same condition, and they
can use this information to help with future family
planning. 


Florence: So, then what happens when a person physically goes to
get the test?  


Katrina: In most cases, an individual will see a specialist
doctor. This might be a genetics doctor, but it could be a doctor
specialising in another body system. They'll do a full assessment
of the individual, including finding out lots of information
about them and their family, and also examining them to look for
any clues that might point towards a specific genetic
diagnosis. 


Once the family have decided to go ahead with the test, their
consent will be taken, where the test will be explained in more
detail, including the pros and cons of going ahead with the test
and after that samples can be taken. Usually this is a blood
sample, but occasionally a saliva sample or cheek swab could be
taken. 


The best way to perform whole genome sequencing is with a sample
from the person being tested along with both of their parents.
And the reason for this is that it makes it easier to separate
out genetic changes that are more likely to be significant from
those that just represent harmless genetic variation what makes
us all unique. 


Florence: What happens to this sample after the test has taken
place?  


Katrina: So, the blood samples will go to a genetics lab where
the genetic material known as DNA is extracted. The DNA is then
sequenced, so we get an electronic file of all their genetic
information. This is then analysed firstly by a computer which
picks out changes or variants in their DNA, which are more likely
to be significant. 


After this, a trained clinical scientist analyses the data in
detail. Sometimes there isn't a clear-cut result, and the
scientists might need help from others and interpreting the
result, but if there is, they can create a report which details
the likely diagnosis. 


Florence: And finally, how will the patient get the result from
their whole genome sequencing test? 


Katrina: Usually, the result is fed back to the patient and their
family by the clinician who arranged their testing or one of
their close colleagues. It's important to note that not everyone
will get a genetic diagnosis from the test. This doesn't
necessarily mean there isn't a genetic diagnosis present. 


There are several reasons why tests might be negative. One is
that no test is perfect and something important might have been
missed because of the way the test works. Or it may be that the
person being tested has a change in a gene that hasn't been
described as causing a disease before, so we wouldn't even know
to look for it. 


There's also a possibility that there isn't a single genetic
cause for their symptoms. Rather, lots of minor genetic factors
are causing their condition. We're not very good at testing for
these yet. Finally, there could be a non-genetic cause that just
hasn't been identified yet. 


One of the benefits of having a whole genome sequencing test is
that the data can be stored and looked at again in the future,
either in light of new evidence or once our knowledge of genetics
has improved. 


Florence: That was Katrina Stone explaining what happens when you
get whole genome sequencing. If you'd like to hear more explainer
episodes like this, you can find them on our website at
www.genomicsengland.co.uk. 


Thank you for listening.