A world-first scientific study has shown that a technique called whole genome sequencing can uncover new diagnoses for rare diseases.

The pilot study involved analysing the genes of 4,660 people from 2,183 families. All of these were early participants in the 100,000 Genomes Project. The Project is led by Genomics England and NHS England. Guy’s and St Thomas’ is one of the sites which has recruited patients.

A person’s genome is all the DNA in their genes, which programme how their body works. Each person’s genome is unique. Genetic diseases are caused by variations in a gene that affects how it works.

Traditionally, it has taken a long time to understand whether a genetic disease might be causing a person’s symptoms. Clinicians have had to identify diseases that might cause those symptoms. They then run tests looking for the gene variants that causes that condition. They then keep doing this, until they find the genetic variant for a particular disease in someone’s genome.

Whole genome sequencing involves using computers to read a person’s entire genome. The computer looks through and identifies all the gene variants in a person’s genome which are known to cause disease. This means that in one test, clinicians can find out if a person has a genetic disease.

This has been made possible by advances in the technology used to read a person’s DNA and in the computer power required to search a whole genome.

The pilot study of the technique was led by Genomics England and Queen Mary University of London and undertaken in partnership with the National Institute for Health Research (NIHR) BioResource.

It found that using whole genome sequencing led to a new diagnosis for 25% of the participants. Of these new diagnoses, 14% were found in regions of the genome that would be missed by other conventional methods.

Many of the participants had gone through years of appointments, without getting any answers. By having their whole genome sequenced, patients received diagnoses that would not have previously been detectable. The pilot study shows that whole genome sequencing can diagnose conditions, save the NHS vital resources and pave the way for other interventions.

For around a quarter of participants, their diagnosis meant they were able to receive more focused clinical care. This included further family screening, changes in diet and other therapies.

The study is the first to analyse the impact of whole genome sequencing for a range of rare diseases in a national healthcare system. The findings support its use in health systems worldwide.

Richard Scott, Chief Medical Officer at Genomics England, said: “Until now, diagnosis of rare diseases has been achieved via trial and error – an approach that’s both costly to the NHS and frustrating for the patient. Improved knowledge of genomics now offers us the ability to radically transform the process. As well as speeding up diagnosis, genomics can be used to predict how well a person will respond to a particular treatment so it can be tailored accordingly. This proof of concept is a significant step towards the goal of precision medicine – a transition that will have a huge impact across the NHS.”

Dr Louise Wood CBE, Director of Science, Research and Evidence at the Department of Health and Social Care and Deputy CEO of the NIHR, said: “This study underpinned the UK’s 100,000 genomes project which went on to provide the evidence base for integration of whole genome sequencing into routine clinical care in the NHS. Rare diseases patients and their carers tell us one of their top priorities is getting a diagnosis. This research showed significant progress can be made in addressing this ask and, in about a quarter of cases, in enabling clinical action to be taken on the basis of the diagnosis.”

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