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Genetic Disease
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The Bionano Saphyr^® System detects structural variations in an unbiased manner at much higher sensitivities than sequencing-based technologies, and routinely at 5% variant allele fraction. Discover the variants missed by short- and long-read sequencing with one powerful workflow.

See Genetic Disease Research Case Studies

OGM finds the variants NGS can’t see

Structural variants (SVs) make up the majority of human genomic variation, driving genetic diversity but contributing to genetic diseases. SVs are frequently flanked by repetitive sequences which are challenging or impossible for current sequencing technologies to decipher. OGM reveals SVs with up to 99% sensitivity and detects mosaic variants down to as little as 5% variant allele fraction.

Find the Right Solution for Optical Genome Mapping

Our tools and platforms provide unparalleled structural variation detection for genetic disease research.

Data Examples

Explore how optical genome technology works

See camouflaged deletions other technologies miss

Find new candidate genes

Discover repeat expansions

Detect new variants in known genes

Uncover novel insertions

The OGM 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 automated manner by the Saphyr 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.

Many protein-coding exons are ‘camouflaged’ in NGS datasets because of variably-repeated binding domains—the exons occur in more than one gene or in tandem within the same gene, making correct alignment of short reads impossible. OGM allows for the direct measurement of the number of C3b/C4b binding domains for each haplotype in CR1, an Alzheimer-associated gene, in this subject with Alzheimer’s disease.

Ebbert MTW. Resolving complex genomic haplotypes in neurodegenerative disorders using Bionano Genomics Saphyr System. ASHG Bionano Symposium. 2019.

In a newborn with congenital diaphragmatic hernia (CDH), a severe developmental disorder affecting the diaphragm, lungs and sometimes heart, OGM detected two adjacent duplications, one direct and one inverted. OGM revealed a much more complex architecture than could be inferred from microarray data and identified several additional candidate genes for CDH.

High S. Advanced analysis of risk loci in congenital disorders using Bionano optical genome mapping. ASHG Bionano Symposium. 2019. https://bionanogenomics.com/videos/ashg-2019-series-dr-frances-high/

In a single postmortem brain sample from an ALS patient, OGM detected a highly mosaic range of expansions of the C9orf72 GGGGCC repeat, ranging from the reference allele (not shown) to a 32 kbp expansion. No modern technology has been capable of spanning and measuring these large C9orf72 repeat expansions, but OGM can.

In a subject with Duchenne Muscular Dystrophy (DMD), a 420 kbp segment from chromosome 15 was duplicated in an inverted orientation in intron 44 of the Dystrophin gene. This insertion was not detected by NGS, and while chromosomal microarray can detect the duplication, its location and therefore implication in DMD could not be determined.

Barseghyan H. Bionano mapping for evaluation of structural variants in genetic diseases. ASHG Bionano Symposium. 2019. https://bionanogenomics.com/videos/bionano-ashg-symposium-at-ashg-2019-hayk-barseghyan/

Unlike deletions, insertions are rarely picked up from NGS data. In a genetic male subject with gonadal dysgenesis, OGM identified a 6 kbp insertion in the WDR11 gene, associated with abnormal testes development and cryptorchidism.