Thursday 6 December 2012

In the Genes

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. 

This stuff - Image courtesy of

 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. 

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. 

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.


  1. This is one of the best break downs about DNA I've read. Easy to understand for even us lay people. Well done.

  2. Wow! Thank you for breaking this down for me, a poor endo sufferer! Although I now understand how far research has to go it still gives me hope for future endo sufferers.


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