Scientists at the HudsonAlpha Institute for Biotechnology have received a five-year, $2.9 million grant from the National Institutes of Health (NIH) to explore how long-read genome sequencing could help diagnose rare genetic diseases. This effort focuses on individuals who remain undiagnosed, even after undergoing state-of-the-art genetic testing.
Long-read sequencing is a newer technology that provides a more detailed view of the genome, potentially revealing genetic variants that traditional methods might miss. The team, led by Dr. Greg Cooper, plans to re-sequence hundreds of genomes from patients who previously underwent testing but didn’t receive a diagnosis. Initial studies suggest that long-read sequencing could uncover genetic causes in 5-10 percent of these cases.
Since 2013, Dr. Cooper’s team has been working to improve genetic diagnoses, particularly in children. So far, they’ve sequenced the genomes of nearly 2,000 children, finding potential links between genetic variations and symptoms in more than 40 percent of those cases. Now, they hope that long-read sequencing will increase that success rate.
“Long-read sequencing offers a new way to look for the genetic causes of diseases,” said Dr. Cooper. “We’re hoping to uncover variations that were missed before and, in doing so, provide more accurate and timely diagnoses for families.”
The project will focus on re-analyzing the genomes of over 500 individuals whose previous short-read sequencing didn’t yield results. In some cases, researchers will also sequence the genomes of the patients’ parents, which could help identify shared or new genetic variations that explain the patient’s condition.
One of the key advantages of long-read sequencing is its ability to detect structural variants—large-scale genetic changes like deletions or duplications—that short-read sequencing often misses. These types of variants can disrupt how genes function and may be linked to certain rare diseases.
Dr. Cooper’s team will collaborate with HudsonAlpha researchers Dr. Jane Grimwood and Dr. Jeremy Schmutz, who co-direct the Genome Sequencing Center. Their lab will handle the sequencing, while Dr. Cooper’s team will focus on analyzing the data to identify any relevant genetic findings.