Whole Genome Sequencing Improves Diagnosis of Rare Diseases

Whole genome sequencing can uncover new diagnoses for people across the broadest range of rare diseases investigated to date and could deliver enormous benefits across the U.K.’s National Health Service, a new study finds.

Photo: Mark Caulfield, lead author of the study and former chief scientist at Genomics England.

The study, published in the New England Journal of Medicine, analyzed the genes of 4,660 people from 2,183 families—all of whom were early participants in the 100,000 Genomes Project to see if it could diagnose people with rare undiagnosed diseases. The project, led by Genomics England and NHS England, was established in 2013 to sequence 100,000 whole genomes from NHS patients and their families.

The pilot study, led by Genomics England and Queen Mary University of London and undertaken in partnership with the National Institute for Health Research BioResource, found that using whole genome sequencing led to a new diagnosis for 25 percent of the participants.

Of these new diagnoses, 14 percent were found in regions of the genome that would be missed by other conventional methods, including other types of non-whole genomic tests.

Many of the participants had gone through years of appointments without getting any answers. By having their whole genome sequenced, diagnoses were uncovered that would not have previously been detectable. The pilot study shows that WGS can effectively secure a diagnosis for patients, save the NHS vital resources and pave the way for other interventions, the researchers said.

“We hope this major advance will enable rare disease patients worldwide to start receiving diagnostic whole genome sequencing where appropriate,” said Mark Caulfield, lead author of the study and former chief scientist at Genomics England. “Our findings show that deployment of this comprehensive and efficient genomic test at the first signs of symptoms can improve diagnostic rates. This study has paved the way for clinical implementation of whole genome sequencing as part of the NHS Genomic Medicine Service.”