Bionano Genomics, Inc. (NASDAQ:BNGO) today announced the publication of a study from researchers at Radboud University Medical Center showing the use of optical genome mapping (OGM) to identify gene disruptive structural variants (SVs) that might contribute to inherited retinal diseases (IRDs). OGM detected a large inversion (173 megabases) impacting the USH2A gene that was initially ignored as a false positive in short-read next-generation sequencing (NGS) data. The authors sought to determine whether OGM could improve SV detection in genetically unexplained IRD cases. Their results identified several pathogenic SVs had been overlooked in their initial genome analyses by NGS. The publication illustrates the potential impact of combining NGS and OGM for more comprehensive variant analysis.
Inherited retinal diseases (IRDs) are a clinically and genetically heterogeneous group of disorders that can cause severe vision loss or even blindness and are often degenerative. Genetic research in this area may help to improve the accuracy of diagnosis, prognostication, and treatment prospects of targeted therapeutics. Approximately 30% of individuals suspected of IRD lack a conclusive genetic diagnosis after genome sequencing has been performed.
Study authors used OGM to search for pathogenic SVs in an IRD sample and resolved a subject that had been genetically unexplained for decades.
- Researchers used OGM to analyze Usher syndrome type-II (OMIM 276901), a recessively inherited disorder characterized by retinitis pigmentosa and congenital hearing loss and associated with variants in several genes, an important one being USH2A
- OGM detected a 173 megabase USH2A-disruptive pericentric inversion on chromosome 1 that had been overlooked and misinterpreted during previous analysis by NGS. The finding by OGM provided a genetic explanation for this subject after decades of research. Reanalysis of NGS data for 427 IRD cases subsequently yielded 30 likely pathogenic SVs in 29 IRD probands. Notably, 8 of the identified pathogenic variants (>25%) were overlooked during the initial analysis
“We are pleased to see the study authors note OGM’s utility for the detection of structural variants that may be relevant to the understanding of IRD. With new gene therapy and clinical trials related to IRD, research into the underlying genetic cause of IRDs is critical. We believe this study underscores the importance of OGM as an integral part of genome analysis, especially in complex disorders where it can aid in discovering new variants and validating the findings of other methods,” commented Erik Holmlin, PhD, president and chief executive officer of Bionano.
This publication can be found here.
