Yesterday I attended a talk at the Royal College of Physicians exploring the exciting area of human genome sequencing and how it can inevitably save lives in the NHS. It was given by Dr. Richard Scott, a consultant in Child Genetics at Great Ormond Street Hospital (GOSH) – his specialisms are in understanding complex childhood disorders and how genetic technologies can be incorporated into clinical practice.

Our ability to pry into the human genome, and look at the DNA bases that make us who we are, has improved exponentially over the last century. In 1952, Rosalind Franklin’s work introduced us to the helical structure of DNA, further looked into by the research of Watson and Crick in 1953. In 1977, Sanger pioneered a rapid DNA sequencing technique still used today as a gold standard for clinical research sequencing.

However, Next Generation Sequencing allows us to work on a much bigger scale, analysing millions of fragments in parallel – it is therefore faster and more cost-effective. Amongst many situations, this would be useful during a critical outbreak, where you need to quickly classify a pathogen according to its genome and possibly trace its roots. Another example would be sequencing the many genes (around 30,000) in the human body drastically quicker. This accelerated the Human Genome Project, which witnessed the benefits of this technology evolution after being completed in 2003. In the modern day, newer technologies have allowed us to complete this analysis in a matter of hours and has translated into measurable clinical benefit. Doing genome-wide association studies, we can see patterns and abnormalities which present in certain diseases when compared to the reference healthy population. With a patient, we can screen for these abnormalities if the superficial features are not conclusive.

Before looking at some instances of where it has helped patients, it’s important to clarify what a rare disease is: a disease/disorder which affects less than 1 in 2000 (in the UK). Collectively, there is a 1 in 17 chance of finding a rare disease in the general population. It doesn’t necessarily have to be genetic, but most cases are. The mutations that give rise to these diseases can be as small as the loss of 3 nucleotides – as in the common form of cystic fibrosis – so it’s a bit like finding a needle in a haystack for less documented rare diseases. Considering that there are 5 million common variants, with 500k not seen before, much of the challenge is shear computing and data analysis.

However, working in the field can be incredibly rewarding when a diagnosis is reached, as often occurs at great hospitals like GOSH. For example, after traditional approaches couldn’t identify the cause of epilepsy in a child, a mutation was found that pointed to epileptic encephalopathy type 9: a very rare condition caused by the lack of a glucose transporter and which disrupts cognitive development. As a result they were able to find ways of treating the condition.

Through sequencing, we can also work backwards with an initial condition and find the patterns that point to it. In patients which high blood cholesterol levels, they found a gene called PCSK9 which was crucial for regulating cholesterol – through inhibitors of the protein coded for by PCSK9, they are able to significantly lower LDL levels. This is a novel approach to looking at gene functions that were unknown before.

A natural progression from genome sequencing would be genome editting, a particularly hot topic in the world of medicine with the advent of CRISPR-Cas9. We are not at the stage of mainstream embryonic experimentation yet, and this would come with all sorts of ethical debates. However, gene editing is being looked at for specific cases like engineering T-cells to fight cancer (as it did successfully in a little girl with leukemia). Gene therapy is also another avenue, and the focus is very much on realising the potential of working with somatic cells (which would be all the cells in an adult rather than in early embryonic stages).

Overall, the lecture was a good overview into the world of genomics research and was very accessible. It will be interesting to see how these technologies develop (see: 3rd generation sequencing) and the new applications, especially in childhood genetic disorders.