Queen Mary research recognised in top 10 advances in genomic medicine in 2022

Since 2019, the Genomic Medicine Working Group of the National Advisory Council for Human Genome Research of the National Human Genome Research Institute (NHGRI) in the US selects the ten most significant advances in genomic medicine to have occurred in the year. Summaries of the ten papers are published in an annual feature in the American Journal of Human Genetics.   

In this year's Genomic Medicine Year in Review, Queen Mary research was responsible for two of the ten most significant advances in genomic medicine. Both of the studies relate to the work of the 100,000 Genomes Project, a ground-breaking initiative led by Professor Sir Mark Caulfield, Vice Principal for Health at Queen Mary. The 100,000 Genomes Project, launched by the UK Government in 2013, aimed to apply whole genome sequencing to better understand rare diseases, cancers, and infections in a national care setting. Queen Mary continues to lead advances in precision/genomic medicine through our Barts Life Sciences precision medicine programme, the new Precision Health University Research Institute (PHURI) and the NIHR Barts Biomedical Research Centre.

Here are summaries of the two featured advances:

Genome sequencing may be the method of choice for detecting repeat expansion disorders

Much of the human genome is made up of repeating sequences of DNA. Often, these repetitive regions are harmless, but sometimes when there is a high number of certain repeats, they can cause neurological disorders known as repeat expansion disorders.

The majority of patients with rare genetic neurological disorders caused by repeat expansions go undiagnosed. This is partly because the technical difficulties of testing for complex and repetitive variants, many genetic tests used in diagnosis focus on specific areas in the genome that are commonly associated with these disorders. These disorders also produce a diverse range of symptoms, which can make it difficult for clinicians to choose the correct test.

In a paper published in Lancet Neurology, Ibañez and colleagues retrospectively evaluated the diagnostic accuracy of whole genome sequencing for the diagnosis of repeat expansion disorders. The authors applied an algorithm used to identify repeat expansions to whole genome sequences from participants in the 100,000 Genomes Project with a suspected, but undiagnosed neurogenetic condition. They found that it accurately detected these repeat expansions, offering support that whole genome sequencing could be used to diagnose these rare conditions in a clinical setting.

The 100,000 Genomes Project led to an increase in diagnoses for a range of rare diseases

Rare diseases affect around 6% of the population in Western societies. Many of these conditions are life-threatening, as well as difficult and expensive to diagnose and manage. The majority of rare diseases are genetic.

The 100,000 Genomes Project Pilot Investigators conducted a pilot study to investigate the impact of whole genome sequencing on the diagnoses of rare diseases. They recruited 4,600 participants who had been identified by healthcare professionals as having a rare disease or who were suspected of having one, but remained undiagnosed.

Their findings, published in the New England Journal of Medicine, showed that whole genome sequencing led to a substantial increase in diagnoses across a broad range of genetic disorders. This study had major implications for the use of whole genome sequencing in the diagnosis of rare diseases – both in the long and short term. In 25% of participants who received a diagnosis, there was immediate actionability.