A team of researchers from Children’s National Health System and the University of California, Los Angeles, led by Eric Vilain, MD, PhD, have reported the first molecular diagnoses of patients with genetic disease using systems from Bionano Genomics, San Diego, to perform genome mapping.

The Saphyr system from Bionano Genomics

The Saphyr system from Bionano Genomics

In a series of patients diagnosed with Duchenne muscular dystrophy (DMD), the scientists used Irys and Saphyr systems from Bionano Genomics to identify pathogenic structural variants caused by large deletions, insertions, and inversions disrupting the X-linked dystrophin gene. DMD is a severe degenerative muscle disorder mostly affecting boys, for which there is currently no cure.

In the study, Vilain’s team identified both single- and multiple-exon deletions up to 250 Kbp in size, a 13 Kbp duplication, and a 5.1 Mbp inversion—all disrupting the dystrophin gene of study patients.1 Large structural variants of this size are typically detected with poor sensitivity using next-generation sequencing (NGS) or long-read sequencing. The researchers also successfully identified the carrier status in mothers of the patients.

The patient with the large inversion had been diagnosed with DMD through an invasive muscle biopsy after other methods—chromosomal microarray, multiplex ligation-dependent probe amplification (MLPA), polymerase chain reaction sequencing of all 79 exons, and exome sequencing—had all previously failed to detect the pathogenic inversion.

According to the study authors, the genome mapping technique “has the capacity to replace both MLPA and chromosomal microarrays in the clinical setting.” MLPA is a probe-based assay to detect the deletion or duplication of specific loci in the genome.

For the study, the authors cite the ability of next-generation genome mapping to provide order and orientation of structural variants, and to detect these variants genomewide. Compared to chromosomal microarray, Vilain’s team discusses the capability to detect balanced events such as inversions and balanced translocations, as well as much smaller variations completely missed by microarray. Relative to NGS, the authors state that genome mapping provides higher sensitivity for large structural variants, with better false-positive and false-negative rates. Turnaround time and cost are comparable to the aforementioned tests.

The study concludes that next-generation genome mapping “is poised to become a new tool in the clinical genetic diagnostic strategy and research due to its ability to sensitively identify large genomic variations.”

Erik Holmlin, PhD, MBA, Bionano Genomics.

Erik Holmlin, PhD, MBA, Bionano Genomics.

“We are excited by Dr. Vilain’s team demonstrating Bionano’s ability to correctly identify structural variants in patients with genetic disease,” says Erik Holmlin, PhD, MBA, CEO of Bionano Genomics. “The current diagnostic process proves to be a true odyssey for many of the children and parents hoping to find answers or treatment. Dr. Vilain shows that in some cases a single Bionano test could replace or outperform up to four different tests, which would not only simplify testing, but would also dramatically shorten the search for answers.”


  1. Lipson A, Douine ED, Délot EC, et al. Next-generation mapping: a novel approach for detection of pathogenic structural variants with a potential utility in clinical diagnosis. Genome Med. 2017;9(1):90; doi: 1186/s13073-017-0479-0.