I recently read,
with great interest, several stories
(also here)
about a new study into the genetics of endometriosis published by an
international research effort based in Australia (better summary here).
Most of the news items centred around a headline involving an announcement like
‘new genes linked to endometriosis’,
or something along those lines. As my background is in human genetics I was
keen on looking up the study at the centre of these reports. This particular
study (link to abstract here)
was looking at what gene/s may be related to endometriosis in women of Japanese
and European ancestry. This was quite a large study as well, including 4,604
women with endometriosis and 9,393 controls, a far greater number of any other
such investigation.
Lots of
studies on the genetics of endometriosis have been done in the past, mostly
with slightly disappointing results. This is mainly because we haven’t yet been
able to find a genetic link to endometriosis that is common amongst all women
of all races.
But before
we go any further into that study, or its results, I think I should go over
some of the basics about why genetics is important and why we should bother
looking for endometriosis related genes.
Let me ask
you something, when an item in your house (Like a fridge, cooker or energy
dispersive x-ray diffracter, for example) malfunctions what is the first thing
you do? If your answer is “buy a new one” congratulations, you have more money
than me. But we less monetarily endowed people tend to look at the instruction
manual to try and figure out what’s gone wrong. The human body is similar in
that way, because we too, have an instruction manual and that manual is called
our DNA.
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| This stuff - Image courtesy of Freedigitalphotos.net |
DNA is a
long, twirly, helix like substance found in nearly every cell in your entire body,
it’s the set of instruction that made you. But DNA isn’t written in any normal
alphabet, no the DNA alphabet is written in an alphabet consisting of only four
letters (A,T,G and C) which make up words, some thousands of letters long, which we refer to as ‘genes’. Each gene codes
for making a certain protein and there are tens of thousands of genes in your
DNA instruction manual making almost one hundred thousand proteins.
That’s all
fine and dandy, but when a cell divides it has to copy every single letter of
the DNA manual, all 3 billion letters, and your cells have divided many, many
times before you are even born. So, despite some astonishing cellular
proofreading, errors start to creep into your DNA; most are harmless, rarely
they are beneficial, sometimes they are harmful (we call these errors
‘mutations’). If these mutations occur in a gene (or number of genes), it can
corrupt the way the protein product of that gene functions, hence causing cells
to behave in odd/dangerous ways leading to, what we know as, a disease. So when
a disease occurs in a group of people, we can look at their collective DNA to
see if they share any common mutations.
This is what
the aforementioned study was looking at: common mutations in DNA amongst women
with endometriosis of European and Japanese descent; this would hopefully allow
us to begin picking apart how and why endometriosis arises in some women and
how it is passed on through generations. Mutation comes in different types
though and the particular mutations this latest study was looking for were
called SNPs (which stands for Single Nucleotide Polymorphism, not Scottish
Nationalist Party, for all our Caledonian readers). This type of mutation is
when only a single letter of your DNA is changed and, though you wouldn’t think
changing one letter out of 3 billion would make a difference, it can have wide
reaching implications.
Anyway this
latest study found several of these ‘SNPs’ that were common amongst women with
endometriosis. Unfortunately they all have terribly unmemorable names, such as ‘rs12700667’,
‘rs7521902’, ‘rs13394619’ and ‘rs10859871’, but who cares because now they’ve
found these mutations, we can start getting a better understanding of endo
leading to better diagnostics and treatments right? Well, yes and no.
One of the
troubles is that, unlike some diseases which are caused by a mutation in a
single gene, endometriosis is related to mutations in lots of different genes
(what we call, polygenic). Now the
more genes you add to the picture the more complicated it becomes because you
have to take into account the function of each gene in the wider context of the
disease. This information will eventually offer us some great insights into how
endometriosis works, but figuring out all the connections may take some time.
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| This, for example, is the interaction network for just ONE gene: Source - Wikipedia |
There’s
another issue as well, genes aren’t the only thing DNA is made of - far from it.
You see, genes make up only around 2% of
your DNA, so what is the rest of it there for? For a long time it was thought the
DNA that didn’t have genes was just ‘junk’, it had not function, a remnant of
our evolutionary past and graveyard of ‘dead’ genes. However, recently we have come to understand
that this ‘junk’ DNA has a lot of other, very important, things lurking in it.
Some of these things act as ‘switches’ for genes, basically controlling whether
a gene is on or off inside a certain cell. So it’s not just about the function
of a gene, but the regulation of it as well.
In this
latest study, several of the mutations they identified weren’t in genes at all,
but were instead found in DNA around them, which unfortunately complicates the
matter further because now we have to figure out what implications this has on
gene regulation as well as function.
So, where
are we at the moment? The diagram below shows where we are and how far we have
to go before we have a complete understanding of endometriosis.
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| Simple as that! |
Although we
are far from understanding endometriosis in its entirety, studies such as this
latest one have opened the door and pointed the way forward for us. It’s going
to take more time and a lot more effort, but then, nothing worth doing was ever
easy.
