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. Saphyr allows for the direct measurement of the number of C3b/C4b binding domains for each haplotype in CR1, an Alzheimer associated gene, in this patient with Alzheimer’s Disease.

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

In a single postmortem brain sample from an ALS patient, Bionano Saphyr detected a highly mosaic range of expansions of the C9orf72 GGGGCC repeat, ranging from the reference allele to a 32 kbp expansion. No modern technology has been capable of spanning and measuring these large C9orf72 repeat expansions, but Bionano can.

In a patient 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.

While deletions are somewhat easier to detect by NGS, insertions are rarely picked up from NGS data. In a genetic male patient with gonadal dysgenesis, Bionano identified a 6 kbp insertion in the WDR11 gene, associated with abnormal testes development and cryptorchidism.