Day Five of Bionano’s Next-Generation Cytogenomics Symposium

Saphyr Identifies Structural Variants that May Predispose to Severe COVID-19 Illness - Seite 2

Dr. Erich Jarvis, Howard Hughes Medical Institute investigator, professor at The Rockefeller University and head of the Vertebrate Genome Project (VGP), discussed an interesting difference between hospitalized patients and controls where the severely ill show more variation in a part of the Interferon Alpha and Beta Receptor Subunit 1 gene, a key part of the interferon pathway that regulates immune response. Dr. Jarvis is using Saphyr and the pipeline he developed for the VGP to build reference-quality genomes of patients and controls and will compare them with each other and with animal species that are sensitive to infection with SARS-CoV-2 or not, as previously reported.

Dr. Ravindra Kolhe, Vice-Chairman of Pathology at the Medical College of Georgia at Augusta University and founder of the COVID-19 Host Genome SV Consortium explained that he founded the consortium because COVID-19 shows a split mortality where a very large number of people get infected, but only a small percentage of those get sick or die. Mortalities are associated with diabetes, hypertension and a history of heart failure, yet independent of that a seemingly random group of patients get extremely ill. Since other studies looking at host genetics use NGS or single nucleotide polymorphism (SNP) arrays that are ill suited to analyze SVs, the consortium focuses on the use of OGM to detect the larger genomic variants most likely to make the largest impact.

Dr. Kolhe presented the previously announced finding from the consortium on 37 ICU-admitted, severely ill COVID-19 patients whose genomes were analyzed using Saphyr. In several severely ill patients Saphyr detected structural variants affecting important immune genes. In another patient Saphyr found a duplication of the STK26 gene, which reduces the production of interferon likely leading to reduced viral clearance and increasing the disease severity. When other severely ill patients were compared with asymptomatic COVID-19 patients, the same STK26 gene was found to be significantly more active in all the sick patients, making it a possible biomarker for disease severity. OGM identified many more variants in the severely ill patients affecting genes controlling immunity, airway mucous, and viral replication. Dr. Kolhe stated that his team wants to use structural variants identified with Saphyr to design preventative measures for those people whose genomes show them to be the most vulnerable and develop a biomarker panel that can be run at the time of patient admission, to make sure that appropriate measures are taken based on the genetic makeup and patients get the treatment they need as early as possible. In order to do so, the consortium has announced plans to analyze 1000 genomes with Saphyr allowing them to determine with high confidence which SV are involved in disease susceptibility and severity.