Genomics summit speaker calls for radical thinking to aid millions of rare disease patients

In his presentation to the event, Ward outlined the scale of the issue, saying that undiagnosed rare diseases affected approximately 3.5 million individuals in the UK, equivalent to one in 17 people. The diagnostic process has cost NHS England more than £3.4 billion over the last decade.

And though some 80% of rare diseases had genetic origins, less than 50% of rare disease patients have received a conclusive diagnosis even with the application of short-read whole genome sequencing.

"The UK has made significant investments in genomics research to combat rare diseases. Initiatives like the 100,000 Genomes Project have contributed to substantial breakthroughs in human health. However, our primary focus now must be on delivering answers to those who still remain in the dark," insisted Ward.

He claimed that existing testing methods were outdated, while alternative technologies offer the potential to expedite the diagnostic process and provide more answers.

“More advanced genomic technologies are now available and can shed light on some of the more challenging variants that may have been missed during initial analysis. If the UK wants to maintain its position as a science superpower – and get families the answers they deserve – we must invest in the latest sequencing methods.”

He pointed out that he current diagnostic pathway for rare diseases in the UK is not standardised across the four nations, with England and Wales focused on short-read whole genome sequencing, where DNA is fragmented into small pieces and aligned with a reference genome to identify potential disease-causing variants. However, data presented at the Summit suggested theses fail to provide answers in over 50% of cases, stated Ward.

In contrast, Scotland employs an exome sequencing approach, a multi-stage ‘process of elimination’ technique, targeting small genetic changes associated with specific rare diseases. However, this method can analyse only 50 million out of some 3 billion base pairs in the human genome, meaning it may be unable to detect longer, more complex variations linked to rare diseases.

Ward highlighted the potential of  HiFi long read sequencing technology; this uses significantly longer stretches of DNA and, when coupled with cutting-edge computational data analysis tools, yields deeper and more precise insights into the genome compared to traditional genetic tests, advocated Ward.

Early integration of long read sequencing had the potential to reduce costs and improve insights sufferers of rare diseases he added.

"There is hope for those who have been waiting for answers. The cost of long read sequencing has markedly decreased over the past year, making it a more feasible option for large-scale implementation.

"The NHS was the pioneer in offering short-read whole genome sequencing as a part of routine care worldwide. Now, we must prioritise long read technology to provide our scientists with even deeper insights into the genome and offer better outcomes for families."

Pic: Cottonbro