Pacific Biosciences’ Single Molecule, Real-Time Sequencing technology has been selected by the European research program SOLVE-RD to help reveal the genetic mechanisms responsible for rare genetic diseases. As part of this work, scientists will sequence more than 500 whole human genomes with the PacBio Sequel II System to pinpoint disease-causing variants.
The SOLVE-RD research program, a consortium of >20 institutions funded with a five-year, €15 million award from the European Union’s Horizon 2020 initiative, aims to improve the diagnosis and treatment of rare diseases by applying novel tools to cases that were not solved with short-read exome sequencing, said Pacific Biosciences in a press release Thursday.
“Even with exome sequencing, as many as 50% of rare disease cases remain unsolved,” said Alexander Hoischen, Associate Professor for Genomic Technologies and Immuno-Genomics and a member of the SOLVE-RD team, at Radboud University Medical Center. “The SOLVE-RD team believes that long-read SMRT Sequencing will be essential for discovering the causal elements that have proven elusive with previous approaches, and we anticipate that this research will ultimately make it easier for doctors to diagnose other patients with these rare diseases in the future.”
Marcel Nelen, Laboratory Specialist in Genome Diagnostics at Radboud University Medical Center, said: “Our team is eager to deploy PacBio’s Sequel II System to generate hundreds of high-quality human genomes for phenotypes very likely to be associated with challenging genomic regions or structural variants including repeat expansions. In our experience, SMRT Sequencing reliably detects far more structural variants — including pathogenic variants — than any other sequencing technology.”
Structural variants are increasingly being recognized as the cause of many rare diseases, but these large genomic elements are often undetectable with short-read sequencing tools due to their length and repetitive content. Structural variation affects more base pairs of the human genome than single nucleotide variants and small insertions and deletions combined. With its extraordinarily long reads, SMRT Sequencing detects structural variants with high precision and recall, even at low coverage.
“SMRT Sequencing has already helped scientists untangle previously unsolvable cases of rare disease, and we believe it will provide exciting new answers for many of the medical mysteries targeted by this program,” said Jonas Korlach, PhD, Chief Scientific Officer at PacBio.