Genomes and Genetics

Dr Janet Allen, Director of Research & Care, explains why the launch of the 100,000 genome project and the move towards personalised medicine are so exciting.

This morning the 100,000 genome project was launched. This is an exciting and ambitious programme that will put the UK at the forefront of applying genomics to develop personalised or stratified medicines. Personalised medicine is also now called ‘precision medicine’ and this is a term that you will probably increasingly hear about. 

So what does this mean? For many diseases, genetics is known to play an important role. If we understand the genetics better, we may be able to design treatments for individuals in a more targeted way. This is what is known as ’personalised medicine’. So, the classic example is cancer.  In the past, a cancer was defined by the place it was found, so breast cancer, colon cancer, lung cancer. In the last decade or so, we have realised that not all cancers are the same and so a lot of work has been done to classify each cancer more specifically and this classification would then define the nature of the treatment. The 100,000 genome project for cancer is taking this approach to another level and will provide a detailed fingerprint of an individual’s cancer. If we understand the genetic make-up, we may begin to understand why some cancers grow slowly or fast, or respond to treatment or some people are more vulnerable than others. The 100,000 genome project is hunting for those genes.

Cystic fibrosis is different. We already know which gene causes the condition. The gene for CFTR was found in 1989. We also know the majority of the mutations that result in cystic fibrosis; the common mutation in the UK is F508del. In fact, in the area of cystic fibrosis, we are way ahead of everyone else as we have personalised medicines already. Kalydeco (ivacaftor) is a perfect example. It can only be prescribed to people with a particular mutation, G551D. The recent combination trial was only run in people with two copies of F508del; people with only one copy do not respond to the combination treatment. There are other drugs in development that may benefit people with an ’X’ in their genotype. This is personalised medicine in action. 

So what of the 100,000 genome project? As this is aimed at identifying disease-causing genes, the immediate value to cystic fibrosis is harder to understand as we know the gene that causes it. However, we have started a dialogue with academic scientists to explore. For instance, it is clear that the nature of cystic fibrosis and the way it affects individuals is not totally dictated by the nature of the mutation. People with the same mutation can have differing severity of the condition. To some academics, this implies there may be other genes in the genome that modify the condition to cause milder or more severe cystic fibrosis. There are also some individuals where the mutation in CFTR has not been found despite using the most recent tests. Again the 100,000 genome project could help unravel this.

Just to be clear, this is a massive and exciting project but the scientific challenge really should not be underestimated.  The human genome is enormous – it consists of 3.3 billion separate data points for any one person.That is 3,300,000,000. Each one has to be ’read‘ correctly and recorded. That is the first step; only then is it possible to start to explore how this information informs any clinical condition. Just to put this in perspective, the CFTR gene is 1,988,702 data points long, and of this the bit that matters and is currently tested is 6,129 data points.