Bionano Data Provides Understanding of Repeat Expansion Disorders Causing Muscular Dystrophy and ALS

SAN DIEGO, Sept. 17, 2020 (GLOBE NEWSWIRE) -- Bionano Genomics, Inc. (Nasdaq: BNGO) announced today that teams from the Mayo Clinic and from the University of Florida have separately released results generated with Saphyr relating to Amyotrophic Lateral Sclerosis (ALS) and Myotonic Dystrophy (DM), respectively, two severe genetic disorders caused by the expansion of repetitive sequences in the genome. Saphyr identified repeat expansions in patients with ALS and DM that were so large that only Saphyr is capable of sizing them correctly. These findings help increase understanding of the disease-causing mechanisms and may lead to better diagnostic tests, support direct drug development and facilitate better identification of patients who are likely to respond to treatment.

In a study published in bioRxiv, a team led by Dr. Eric Wang from the University of Florida used Saphyr to identify genomic variants that determine the severity of neurological symptoms caused by DM. These symptoms, caused by an abnormal processing of a number of brain-expressed genes, correlate with the length of a repeat expansion. The study helped demonstrate that ultra-long DNA analysis technology, such as Bionano’s Saphyr, is crucial to enabling the accurate measurement of these repeat expansions.

Separately, in an online presentation by Dr. Mark Ebbert from the Mayo Clinic, Saphyr data was used to measure the repeat expansion in the C9ORF72 gene that causes ALS. A large number of repeat sizes were detected in the brains of individual ALS patients, demonstrating how the expanded repeat is unstable and leads to increasingly large expansions. The amount of variation within individuals was previously underestimated due to the lack of accurate measurement techniques.

In both cases, the disease-causing repeats were found to be tens of thousands of basepairs in length, too long to be accurately measured by currently available short-read and even long-read sequencing technologies. Additionally, the amount of variation within individual brain samples requires a single-molecule analysis method, like Bionano’s genome imaging. The studies provide additional support for the utility of Bionano’s single molecule, ultra-long DNA analysis technology in advanced disease research. In contrast, current diagnostic tests for large repeat expansions like the ones typically involved in DM and ALS are imprecise, lack the resolution and sensitivity to determine the size of the expansion and typically require confirmation with outdated methods like Southern Blot.