‘Changing the face of genetic diagnostics’

Study shows Bionano’s Saphyr system accurately detects genetic disorder FSHD

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SAN DIEGO—Bionano Genomics Inc., a life-sciences company that develops and markets Saphyr, a platform for ultra-sensitive detection in genome analysis, has released a journal article by scientists at China’s Wenzhou Medical University, Wenzhou Central Hospital, the First Hospital of Kunming and Berry Genomics that it thinks could “change the face of genetic diagnostics” in the future—even in the womb.
Using the Bionano Saphyr system to analyze patient samples, the researchers, writing in the journal Molecular Genetics and Genomic Medicine, obtained highly accurate molecular diagnoses of facioscapulohumeral muscular dystrophy (FSHD) in a multi-generation pedigree going back five generations in one family.
“This study is one of the most extensive in FSHD since we first began work in this disease with Johns Hopkins in 2017,” says Erik Holmlin, CEO of Bionano Genomics. “The comparison of Bionano genome mapping to existing methods such as Southern blot illustrates how Bionano Saphyr offers an improvement in workflow, while providing highly accurate results with the potential to increase clinical performance and utility by readily adding new clinical markers, such as the structural variation tied to a potentially milder form of FSHD described in this study, without modifying the assay or workflow.”
Although “DNA from amniocentesis has not been used on Saphyr, it is expected to be of sufficient quality for Bionano mapping—and could be used for a diagnosis of FSHD prior to birth,” Holmlin adds.
In the journal article entitled “Clinical application of single‐molecule optical mapping to a multigeneration FSHD1 pedigree,” lead author Qian Zhang found that Saphyr was superior compared to the slow and cumbersome Southern blot current standard of testing. Plus, Saphyr has the potential to increase clinical performance by adding new clinical markers.
This enabled the team to identify the founder of the disease within the pedigree, as well as a variant of the FSHD1 region involving a duplication of one allele, Zhang says. Known as one of the most prevalent hereditary muscle diseases, FSHD is tied to variation in the size of D4Z4 arrays, in which a 3.3 kilo base pair unit on chromosome 4 is repeated multiple times. Southern blot is used to characterize array sizes above and below a threshold level today, but these workflows are slow and cumbersome and can generate results that are difficult to interpret.
Scientists at leading academic medical centers in China, together with commercial diagnostic laboratory Berry Genomics, used Bionano genome mapping to correctly characterize the molecular structure of the FSHD locus in the affected individuals of a five-generation pedigree.
The study determined that Bionano’s Saphyr system’s “moderate sample requirements and short time frame compared to Southern hybridization”—which, together with its “potential to identify structural variants such as deletions, duplications or rearrangements,” has shown it to be a better diagnostic tool, according to the researchers.
FSHD is a highly complex, progressive muscle-wasting disease commonly associated with weakening of facial, shoulder and upper arm muscles, sometimes robbing people of their ability to walk, talk, smile or even eat. The progression often comes in bursts, with sudden deterioration followed by periods of no change. Despite being considered one of the most common forms of muscular dystrophy in adults and children, there are no treatments and no cure.
“FSHD is an autosomal dominant genetic disorder,” Holmlin explains. “It can develop spontaneously in an individual by deletion of part of the D4Z4 repeat array, such that the number of repeats is less than 10 copies on a 4qA ‘permissive’ allele.”
The estimated prevalence of FSHD is approximately one in 20,000 people, and is estimated to affect about 870,000 individuals worldwide, he says.
“The goal of the studies that we are initiating involve the comparison of Bionano Saphyr data to current cytogenetic methods like FISH (fluorsecent in-situ hybridization), karyotpying and aCGH,” Holmlin adds. “There is great interest by the cytogenetics community to explore use of the Saphyr platform to modernize and potentially collapse the number of assays needed to interrogate samples received for testing. Furthermore, the combination of Bionano Saphyr and WGS (whole-genome sequencing) is being pursued as a discovery tool for identifying novel disease-associated structural variants in both oncology and genetic diseases—given that Bionano detects the structural variants missed by short-read NGS platforms.
“The next step for Bionano Saphyr is to continue to streamline the workflow, improve sample throughput and further develop software analysis tools to enable rare variant detection in heterogenous samples (e.g. cancer), and integrate our data with other ‘omics’ data sets through both internal R&D efforts and through external collaborations and partnerships.”
“The long-term goal for the Bionano Saphyr platform is to grow our global footprint of instrument placements in translational and clinical research, as well as cytogenetics and molecular pathology labs,” he concludes.

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