The Bionano Genome Imaging workflow starts with mega-base size DNA isolation. A single enzymatic reaction labels the genome at a specific sequence motif occurring approximately 15 times per 100 kbp in the human genome. The long, labeled DNA molecules are linearized in nanochannel arrays on a Saphyr chip® and imaged in an extremely high throughput, automated manner by the Saphyr® Genome Imaging Instrument. Using pairwise alignments, the molecules are assembled into local maps or whole genome de novo assemblies. Changes in patterning or spacing of the labels are detected automatically, genome wide, to call all structural variants.

Facioscapulohumeral Muscular Dystrophy (FSHD) is a common form of muscular dystrophy with an extremely complex genotype. A molecular detection requires the accurate sizing of a very large repeat region in the subtelomeric region of chr 4, a correct determining of the pathogenic vs non-pathogenic allele, and the distinction between the chromosome 4 repeat and an almost identical repeat on chr 10 not related to the disease. Molecular methods fail to do so, and hence a cumbersome, imprecise Southern Blot is currently used to molecularly diagnose this disease. The Bionano EnFocus FSHD Analysis performs the entire detection automatically, and validation studies have shown perfect concordance with the gold standard method.