, in collaboration with scientists across Saudi Arabia, have unveiled NanoRanger, a new method that significantly speeds up the genetic diagnosis of Mendelian disorders.){kind=link}
Researchers at King Abdullah University of Science and Technology (KAUST), in collaboration with scientists across Saudi Arabia, have unveiled NanoRanger, a new method that significantly speeds up the genetic diagnosis of Mendelian disorders.
Mendelian genetic disorders affect millions worldwide, often requiring years of testing for an accurate diagnosis. With NanoRanger, the process now takes just a few hours, offering a precise and efficient solution for genetic screening.
“Precise, efficient genomic diagnosis is urgently needed to improve patient outcomes and facilitate carrier screening,” says Yingzi Zhang, a Ph.D. candidate at KAUST, supervised by Mo Li. “This study aligns with Saudi Arabia’s Vision 2030 — advancing healthcare through innovation to improve the quality of life for all citizens.”
Mendelian disorders, including nervous system and intellectual developmental conditions, are caused by alterations in specific genes or abnormal rearrangements in genome segments. Traditional screening techniques often miss these complex variants, especially in regions where consanguineous marriages are common.
“NanoRanger uses simple molecular biology strategies to ‘fish out’ genomic regions that are suspected of harboring complex mutations, deletions, or rearrangements,” explains Li.
The NanoRanger method is cost-effective and requires only a small DNA sample. Using molecular scissors called restriction enzymes, the DNA is fragmented, self-joined into circles, and amplified. This process targets and sequences the genomic regions of interest with Oxford Nanopore Technologies’ long-read sequencing technology.
“Using our custom-developed data analysis tool, NanoRanger accurately maps breakpoints at single base-pair resolution, providing a detailed picture that helps diagnose the genetic disorder,” says Zhang. “Diagnosis can be as fast as 12 minutes after initial sequencing, which is a game-changer.”
In trials conducted in collaboration with a group of Saudi clinicians led by Fowzan Alkuraya at King Faisal Specialist Hospital & Research Center, NanoRanger identified precise breakpoints in 13 familial cases of genomic disorders that were previously undetected by conventional genetic tests. These breakpoints were then used to screen the carrier status of related family members and 1,000 healthy Saudi individuals.
One Saudi couple participating in the trial chose in vitro fertilization after discovering they both carried a genomic deletion for an inherited Mendelian disease, highlighting the practical impact of this technology.
“We have filed for a patent and plan to integrate NanoRanger into standard diagnostic routines to provide a comprehensive toolkit for clinical settings, both here in Saudi Arabia and across the world,” concludes Li.