clinical focus
How might this approach work in practice? Would it be something that someone requested or do you think it could become standard one day? I imagine it will always be something that is requested. A doctor might see a patient and find particular indications that [ gene sequencing ] might be useful. I’ m an immunologist and there are some rare immunological disorders that we know are caused by genetic defects, but in many cases it’ s hard to predict which particular gene will harbour that defect just from routine blood tests and clinical assessment. Up until quite recently, the only way to proceed beyond that was to go gene by gene, performing slow and laborious sequencing to try to track down the variation in the gene sequence that was responsible for causing the disease. What will be possible now is to sequence all the genes and then use sophisticated analysis tools to sort out which of the variations are most likely to account for the patient’ s disease.
It’ s now possible to do that for disorders that are caused by a single gene defect, and there are many of those sorts of diseases. Each of them is rare but collectively they amount to a significant burden of disease.
In the routine clinical setting, we’ ll be concentrating on those sorts of disorders, and then as time goes on and we understand more about how genetic variation leads to disease, we’ ll be able to tackle some of the more common diseases as well. about 2 per cent of our total genetic makeup. All of that is made up of a sequence of Gs, Cs, Ts and As, so when we genotype someone, we simply determine that sequence – the arrangement of Gs, Ts, Cs and As in a particular segment of the genome.
What specifically will your team explore through the new centre? Our group, and many other groups around the world, to be honest, have been working hard to try to understand how we can harness all the information that is available now from variation across the human genome, to better understand mechanisms of disease. There’ s still a long way to go. There’ s still a lot to be discovered, but we’ re now getting to the point where we can use the information we do have to make diagnoses, in some cases, in patients that were previously undiagnosed. This is based on information that we, collectively, around the world, have generated, about variations in the human gene sequence, and it’ s also become possible because of technical developments that [ give us the ability ] to sequence individuals’ genes in a rapid, efficient and relatively cost-effective manner.
So, first, what we’ re seeking to do is start to make the transition from work that’ s going on in discovery research labs to having this same process as more of a routine diagnostic service. To begin with, it will probably have relatively specific and special applications, but it may become more broadly applicable as time goes on.
What impact could that have on people who are falling ill or those who are already taking medicines or undergoing treatments? If you have a rare disease and there’ s an element of uncertainty about the diagnosis and the mechanism of the disease, it poses constant anxiety. It also often leads to many tests being performed, and many of those don’ t lead to an answer. This is often a difficult situation for patients and their families to be in.
Simply having the tools to make an accurate diagnosis is a significant advance. Beyond that, once we understand which particular gene is responsible for causing a disease, that gives us an avenue for understanding the mechanism of disease, and ultimately that’ s the best pathway to arriving at a precise therapy.
There’ s a close connection between understanding how variation across the genome causes disease, and arriving at precision medicines, which are administered according to a particular genetic abnormality that might be present in a patient to cause their disease.
How far are we from being able to use this method of personalising medications in Australian health services? It’ s far from routine, and our group in our centre, which has recently been funded, is one effort in this direction. There are other efforts taking place simultaneously in other states and territories around the country, and collectively we’ re working together to come up with the best possible approach for patients across Australia so that we can, first of all, expedite access to what is a revolution in healthcare, but also do it in a way that ensures correct quality controls and considers the ethical implications of doing these sorts of tests. [ We also have to ] make sure the people who might use this information are sufficiently informed about what it means to be able to use it in the most effective way.
Things are moving relatively quickly. We’ d like to see them move as fast as possible, but we have to do it within those constraints as well. Collectively, there is an effective move underway towards personalised medicine in Australia. ■
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