NanoRanger Offers Rapid, Precise Diagnosis for Genetic Diseases

An effective long-read sequencing method that looks for intricate genomic variations can quickly and accurately diagnose genetic disorders molecularly.

Even though genetic testing has advanced quickly in recent years, over half of all individuals with suspected Mendelian genetic disorders lack a precise molecular diagnosis. Others undergo testing for over six years before receiving a diagnosis.

Researchers at KAUST and other Saudi Arabian universities have now created NanoRanger, a quick and precise genetic disease diagnosis tool that can be used in a matter of hours.

Precise, efficient genomic diagnosis is urgently needed to improve patient outcomes and facilitate carrier screening. This study aligns with Saudi Arabia’s Vision 2030 - advancing healthcare through innovation to improve quality of life for all citizens.”

Yingzi Zhang, Ph.D. Candidate, King Abdullah University of Science and Technology

Yingzi Zhang was supervised by Mo Li.

Mendelian disorders are caused by abnormal rearrangements in a single genome segment or changes to a single gene, affecting the nervous system and intellectual development. Every illness has a unique "breakpoint," which is the genomic position of a structural variant where DNA is changed, flipped, or removed.

Although these variants can be found using conventional screening methods, they are frequently overlooked due to the intricacy of the rearrangements. Mendelian diseases are heritable, especially in cases where the same defective segment is carried by both parents. These illnesses are more common in areas where marriages between relatives are customary (consanguinity).

NanoRanger uses simple molecular biology strategies to ‘fish out’ genomic regions that are suspected of harboring complex mutations, deletions or rearrangements.”

Mo Li, Corresponding Author, King Abdullah University of Science and Technology

The procedure only requires a small amount of DNA from a patient or possible carrier and is very affordable. Using molecular scissors known as restriction enzymes, NanoRanger divides a sample of genomic DNA into fragments with identical end sequences.

After that, these fragments self-join into circles and are amplified, which facilitates the use of Oxford Nanopore Technologies' long-read sequencing technology to target and sequence the genomic regions of interest.

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. Diagnosis can be as fast as 12 minutes after initial sequencing, which is a game-changer.”

Yingzi Zhang, Ph.D. Candidate, King Abdullah University of Science and Technology

In studies conducted at King Faisal Specialist Hospital & Research Center in cooperation with a team of Saudi physicians under Fowzan Alkuraya's direction, NanoRanger could pinpoint exact breakpoints in 13 familial cases of genomic disorders that traditional genetic testing had overlooked.

The researchers then used these breakpoints to screen 1,000 Saudi individuals who were in good health and related family members for carrier status.

One Saudi couple in the trial was found to carry the genomic deletion for an inherited Mendelian disease, which led them to choose in vitro fertilization as a result of the testing method.

“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,” concluded Li.