Q&A: How DNA detective work is helping crack complex diseases

Recent breakthroughs in genetics have transformed our understanding of many complex diseases. Image / 123RF

The human genetic code is mind-bogglingly complex - but it's a field of science Professor Justin O'Sullivan feels at home in. The deputy director of the University of Auckland's Liggins Institute, and a fellow of the Office of the Prime Minister's Chief Science Advisor, will be giving his inaugural professorial lecture tomorrow afternoon about genetics, complex diseases and the microbiome. Science reporter Jamie Morton chatted with him ahead of his talk.

First off, what exactly is the genetic code? How has our knowledge of it evolved over the years, and why has it become so important to unravelling complex diseases today?

The genetic code is the set of three letter words, made up of different combinations of A, T, C and G, that are used to access the information that is inherited in DNA.

When the code was first cracked we thought it was the same in all organisms, since then it has been shown that despite the structure being the same, the code is not always read the same way.

For example, the nuclei of our cells that hold our DNA use a different code to that found in the power houses of the cell - the mitochondria.

We have to understand the code when we look for mutations that are associated with complex diseases because some changes in the three letter word won't actually have any impact at all – this is because the code has redundancy between words.

Much of your recent work has effectively reassessed the importance of non-coding DNA. Can you elaborate what its role is in our bodies, and why we're now thinking differently about it?

The non-coding DNA does not contain genes, as we classically recognise them.

So for a long time it was thought of as "junk". But it isn't junk and is actually really important.

Some features of the non-coding DNA clearly have functions and are under evolutionary pressure – just much of the non-coding DNA is under selection is quite hotly debated.

But it is clear that some of these non-coding DNA regions act as switches that turn genes on and off.

Interestingly, these switches are often identified by studies that are linking changes in our DNA sequence to the risk of developing a disease.

So, at least for this subset, it is really important to try and understand which genes they are actually turning on or off and how this impacts on the risk of developing disease.

There's similarly been great leaps in understanding the microbiome, and the influence it has on us. What is this, and what are some of the biggest insights we've made about the microbes within us in the last decade or so?

I think the biggest change has been the recognition that it is not an us versus them situation.

Microbes don't just contribute to making us sick, they are a part of us, they help nurture us, affect our mood, health and wellbeing.

For some people this will have always been obvious, but for a large number of us this was a shift in thinking.

This change was helped largely by technological changes that have really enabled us to start to study the microbiome without having to grow the organisms that form the community.

A lot more work is now moving our understanding from simple associations to really understand the causative nature of the interactions between ourselves, our microbiomes and our environments.

Over recent times, you've been involved in research, supported by Hollywood star Michael J Fox's world-renowned charity, to reveal one gene's critical role in the development of Parkinson's disease. Can you tell me about this work?

I was lucky enough to lead a small collaboration that was funded by the Michael J Fox Foundation for Parkinson's research and the Silverstein Foundation for Parkinson's with GBA.

This project has been amazing and I think it is really opening up some amazing possibilities.

It's very early stage of course, but I think it is very exciting.

University of Auckland geneticist Professor Justin O'Sullivan. Photo / Supplied

The thing that most stands out to me now is the fact that we have shown there are three changes in the non-coding DNA of the GBA gene that are associated with the age of onset of Parkinson's disease.

We think that the three non-coding DNA regions marked by these changes act as switches for other genes.

We have to prove it yet, but the result validates in at least one other international cohort.

There is much more coming but it is currently in review, so I can't talk about it here.

What other complex diseases might we soon be able to tackle more effectively, with a greater understanding of genetics?

Genetics is fundamental to the variation we see in ourselves and the organisms around us.

So as a friend of mine once asked me – "why do we ignore a person's DNA when that must be half of the story?"

I have a pretty simple view on this, basically I think the more we understand about genetics, the more we will be able to understand about the features that increase our risk of developing different diseases.

However, just because you have a risk for developing a disease doesn't mean you will.

Rather it is like having a weighted coin – more likely to land on heads than tails.

A complex mix of environmental factors affects the final outcome and triggers the actual development of the disease.

So it is important to not just study the genetics but also to connect the genes to the environments a person is exposed to over their life-time.

That is tricky – because we don't tend to collect information without a reason.

Nonetheless, are there any that are likely to remain to complex, or difficult, to fully unravel?

Huge advances are being made on different diseases now. Absolutely some diseases are more difficult to unravel.

Sometimes we are not asking the right questions.

But I like to think that we will eventually understand most complex diseases.

Back to the microbiome: there's been plenty of debate around how we can maintain a healthy one - and we've also seen the advent of transplants. Are there any science-backed ways that people can maintain better gut health?

The simplest way seems to be eat a variety of fresh foods, exercise and drink in moderation.

That's familiar advice, I think.

• Details about O'Sullivan's lecture can be found here.