‘Hope is not lost for people with undiagnosed rare diseases’ was the key message of the presentation given by Neil Ward, Vice President and General Manager EMEA for PacBio, at the Genomics England Research Summit. Around 3.5 million people (1 in 17) in the UK have or are affected by a rare disease, but finding the underlying causes of rare disease is a significant challenge, with people left waiting an average of 4-5 years for answers. As well as great personal cost, research has found the complex diagnostic process has cost NHS England more than £3.4 billion over the past ten years. While 80% of rare diseases have genetic origins, Ward pointed out that less than 50% of rare disease patients have received a diagnosis even with short-read whole genome sequencing. He argued the current testing techniques used in the UK are outdated, and that alternative technologies could provide more answers faster.

“The UK has invested significantly into genomics research to tackle rare diseases. Initiatives such as the 100,000 Genomes Project have certainly contributed to significant breakthroughs in human health. But we must now shift focus to getting answers for those people that are still in the dark,” comments Ward. “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.”

“less than 50% of rare disease patients have received a diagnosis even with short-read whole genome sequencing“

The current standard pathway for rare diseases varies across the UK; In England and Wales, short-read whole genome sequencing is the current standard of care. This process involves DNA being broken down into small fragments which are then aligned to a reference genome hoping to identify variants that are potentially causative of disease. According to data presented by Ward at the Summit, these tests fail to yield answers in more than 50% of cases. Meanwhile, Scotland uses a multi-stage ‘process of elimination’ technique called exome sequencing which looks for small genetic changes associated with specific rare diseases. Yet, these tests are limited to only 50 million base pairs, out of 3 billion in the human genome, so the test cannot pick up some of the longer, more complex variations linked to rare diseases.

Ward discussed how an alternative sequencing technology called HiFi long read sequencing could play a key role to improve understanding of rare diseases for researchers in the UK. This technology uses much longer stretches of DNA, and when combined with new, cutting-edge computational data analysis tools, provides deeper, more accurate insights into the genome than conventional genetic tests. According to Ward, the use of long read sequencing earlier in the process may ultimately reduce costs and provide better insights for families wanting to understand the genetic underpinning of certain rare diseases.

“There is hope for those still waiting for answers. The cost of long reads has significantly decreased over the past year, making it more feasible to implement them at scale,” continued Ward. “The NHS was the first healthcare service in the world to offer short-read whole genome sequencing as part of routine care. We must now prioritize how long read technology might afford our scientists even deeper insights into the genome and deliver better outcomes for families.”