PRIMER: GENETIC TESTING
What can it tell us about our future health risks, and should we all be getting tested?
Actor Chris Hemsworth, who you might know as Thor in the Marvel Cinematic Universe, recently announced that he was taking a break from the limelight after carrying out a genetic test that highlighted he had a heightened risk of developing Alzheimer’s disease. To find out whether we all ought to be considering testing ourselves, we spoke to Sir Peter Donnelly, CEO and co-founder of Genomics PLC, and emeritus professor of statistical science at the University of Oxford, about what genetic screening can tell us about our health.
WHAT HAPPENS WHEN SOMEONE TAKES A GENETIC TEST?
Usually, the test would involve taking a biological sample from the individual. Typically, that’s either a blood sample, or a saliva sample. Then the sample would be sent to a laboratory, which would extract the DNA and then analyse it for the piece of genetic information that the test is trying to find.
WHAT IS DNA?
DNA is the chemical material that contains all of the information our cells use to do their stuff – to make the proteins that allow them to function, and to build up tissues and organs. We get one copy of our DNA from our mother and one from our father. The totality of the DNA is called our genome – that’s just a word for all of the DNA.
DNA itself is a long chemical made up of different components. You can think of it as a long list and at each position there’s one of four possibilities that happen to start with letters A, G, C or T. In total we get three billion letters of DNA from our mother and three billion letters of DNA from our father. In every cell in our bodies, each of us has six billion letters.
WHAT IS A GENE?
A gene is a piece of our DNA where the letters contain explicit instructions that help our cells make a protein. They can differ in length.
A gene might be just a few hundred or thousand DNA letters long, but some genes are much longer. If we look at the totality of our DNA, only about 1 per cent of it is the genes. The rest used to be called ‘junk DNA’ before we understood what it was doing.
We now understand that it contains other information. For example, information that tells a particular gene when it should be making a protein. All of our cells have all of our genes. There might be a gene that makes a protein that’s really important in the retina, but you absolutely don’t need that protein in your tongue. And so there’s instructions in the DNA that will be able to tell that gene, ‘I want you to make this protein if you’re sitting in a retina, but not if you’re sitting in the tongue.’
HOW BIG AN INFLUENCE CAN A SINGLE GENE HAVE ON OUR BODIES?
We’ve got about 20,000 genes in total. In Chris Hemsworth’s case, he’s been talking about one particular gene. We know some things about what that gene does, but there are many mysteries – as there are with lots of human biology. We all have two copies of that gene, one from our mother and one from our father. The issue is that there can be slight differences between the copies. Lots of these differences don’t have any effect at all, but some of them can have consequences and sometimes those consequences can be really severe. In conditions like cystic fibrosis, for example, where if you inherit a mutated copy of a gene that doesn’t work the way it’s meant to, you can end up getting really sick. Sometimes, if you have one copy of a gene that doesn’t work, you’re fine. For example, if the one from your mother doesn’t work, but the one from your father is fine.
HEMSWORTH HAS BEEN TOLD HE’S AROUND 10 TIMES MORE LIKELY TO DEVELOP ALZHEIMER’S DUE TO THIS GENETIC FACTOR. HOW SIGNIFICANT IS THAT?
There are some diseases where if you inherit the genetic change, you will get sick. There are other examples, and this is one of those, where if you inherit a particular genetic change, you can be more likely – sometimes quite a bit more likely – to develop the disease.
“In Hemsworth’s case, we’re talking about one particular gene. We know some things about what that gene does, but there are many mysteries”
For most of the common conditions, such as heart disease, diabetes and many of the common cancers, genetics is a big part of the risk. But it’s not just one change or two changes; it’s millions of positions that each contribute a tiny bit to that risk. So Hemsworth’s example is in the middle, where he’s probably about 10 times more likely to develop disease. And although we’re all very aware of diseases like Alzheimer’s, it’s quite rare. So there’s a big difference between relative risk, which is how much more likely you are to get the disease than someone else, and absolute risk, which is about whether you’ll actually get it. So the important point is it doesn’t determine that he will or won’t get the disease. It just increases the risk for him.
WHAT WOULD YOU SAY TO PEOPLE WHO WOULD RATHER NOT KNOW ABOUT THEIR POTENTIAL GENETIC RISK FACTORS?
It depends on the disease and on how big the impact is. In the case of Alzheimer’s disease, the gene that was checked for Hemsworth is called APOE and it has quite a big impact on his risk of getting the disease. At the moment, there’s not much you can do about it, so I think different people will take different views. Some would rather know and some would rather not know, and that’s absolutely up to the individual. But I think Alzheimer’s research is progressing really quickly. So it might well be the case that, before too long, there might be things you could do and drugs you could take to help reduce the risk or slow its progression. I think that it’s a slightly different question for different diseases.
WILL WE EVER SEE A DAY WHERE WE HAVE ENTIRE POPULATIONS ROUTINELY HAVING GENETIC TESTS LIKE THESE?
I think that will happen. First of all, it should be up to the individual. No one should be forcing people to have tests like this. But for most common diseases, genetics is a risk factor and if we knew about it, instead of just saying: ‘here are the 10 or 20 diseases you should be most worried about and here’s some generic advice’, we could be saying: ‘in your case, you’re at particularly high risk of heart disease’. We can actually tell you this when you’re in your 20s, so you should work even harder on diet and lifestyle, or maybe it would be appropriate to go on drugs to reduce your cholesterol a bit earlier in life. We could do that because we have that special information about you.
SIR PETER DONNELLY Peter is an emeritus professor of statistical science and director of the Wellcome Trust Centre for Human Genetics at the University of Oxford. He is also the CEO of Genomics PLC.