Unleashing the power of the genome to help children with rare diseases

With 80% of rare diseases having a genetic component, understanding a person’s genome – their unique sequence of DNA and complete genetic code  – has a huge part to play in both diagnosis and care for patients and their families. Dr Daniel Gale, Rare Disease Lead for the North Thames Genomics Laboratory Hub, which is led by Great Ormond Street Hospital (GOSH), provides an update on where genomics is now in relation to rare disease, and the exciting developments ahead in this field.

Patients with a rare disease can experience years of uncertainty, often referred to as the ‘diagnostic odyssey’. Gaps in our knowledge of patients’ genetic make-up makes it challenging to match people to the most effective medications and interventions.

In about 80% of rare diseases, changes to a person’s DNA are involved in the cause. While as doctors we may know there is a genetic element from clues such as family history and symptoms, it is only when we have the full picture of a person's genes  – the genome  – that we can identify the exact cause of the disease or condition. Finding the genetic cause of disease can be enormously helpful because it sometimes tells us which treatments will (or won’t) be effective; can allow us to better predict prognosis; and allows predictive testing for at-risk family members, which can facilitate kidney donation (for instance by showing a relative who would like to donate their kidney is not at risk of the same disease in the future) or help people make informed decisions around having children.

Genomics is the study of the genome, including interactions of genes with each other and with the person's environment, and is a step-change from more traditional genetic testing, which tends to focus on finding changes in specific genes.

Whole genome sequencing (WGS) gives us the opportunity to “read” almost every letter of DNA in a person’s genome. This gives us more chance of finding the change that is responsible for causing a disease.

Many patients and families have already benefited from Whole Genome Sequencing through the 100,000 Genomes Project. The project successfully sequenced 100,000 whole human genomes to help researchers and clinicians better understand, and ultimately treat, rare and inherited diseases and common cancers and has delivered a precise genetic diagnosis to many hundreds of participating patients in the North Thames region.

The NHS is creating a genomic medicine service (GMS), building on the success of 100,000 Genomes consisting of;

• A national genomic laboratory service through a network of 7 Genomic Laboratory Hubs including North Thames GLH hosted by GOSH
• A new National Genomic Test Directory to underpin the genomic laboratory network
• A national Whole Genomic Sequencing provision and supporting informatics infrastructure developed in partnership with Genomics England

The future for genomic medicine is an exciting one for patients and professionals, with nearly all medical specialties impacted by genetic disease. We’re working towards 'mainstreaming' of genomics into routine practice and embedding whole genome sequencing in the NHS.

As well as advances benefiting patients there are lots of exciting opportunities for health professionals to develop new skills, and pursue a career in genomic medicine.

North Thames Genomic Laboratory Hub will be visiting Trusts to provide genomic medicine training and support for NHS staff – to find out more contact Education and Training Lead Corinne Trim Corinne.Trim@gosh.nhs.uk

Dr Gale is a clinician scientist, honorary consultant nephrologist and Rare Disease Lead for the North Thames Genomics Laboratory Hub, which is led by GOSH. The hub provides genomic testing for NHS Trusts and Clinical Commissioning Groups across North Thames and parts of Hertfordshire and Essex.