Nucleome Therapeutics, a biotechnology company that is decoding the dark matter of the human genome to uncover novel ways to treat disease, is pleased to note that the company’s academic founders from the University of Oxford have published a paper in 'Nature Genetics' identifying a gene that potentially doubles the risk of death from COVID-19.
Since the start of the pandemic, research teams around the world have been searching for genetic signals in our genome that contribute to the susceptibility and severity of individuals’ responses to COVID-19. Previous work already identified a stretch of DNA on chromosome 3 which doubled the risk of adults under 65 dying from COVID-19. However, scientists did not know how this genetic signal worked to increase the risk, nor the exact genetic change that was responsible. Sixty percent of people with South Asian ancestry carry this high-risk genetic signal, compared with one in six people of European ancestry, partly explaining the excess deaths seen in some UK communities and the impact of COVID-19 in the Indian subcontinent.
The researchers used Nucleome’s platform, which combines machine learning and novel ultra-resolution 3D genome analysis method to identify the causative genetic variant, the cell types involved and the effector gene, leading them to identify the probable gene responsible, called LZTFL1.
The full paper ‘Identification of LZTFL1 as a candidate effector gene at a COVID-19 risk locus’ can be found here.
The genetic signal conferring increased risk was located within what we call the dark matter of the genome. This dark genome regulates cell type-specific gene expression and is still largely uncharted. Using Nucleome’s Micro-Capture-C technique we were able to pinpoint the gene. A higher level of LZTFL1 likely prevents the cells lining the airways and the lungs from fighting the virus properly, but importantly it doesn’t affect the immune system, so people carrying this version are likely to particularly benefit from vaccination.
- Prof James Davies, Academic Founder of Nucleome Therapeutics and co-lead of the study
In addition to shedding light on the biological mechanism of COVID-19, which is of the highest importance in the current pandemic, this study also represents a significant validation of Nucleome’s platform in identifying disease drivers by decoding the genetic variants located in the dark genome. This publication demonstrates that our platform can be applied to cell types and therapeutic areas beyond Nucleome’s focus on autoimmune diseases and lymphocytes, opening the door to potential discovery partnerships consistent with our mission of unlocking the dark genome to transform the lives of patients through precision medicine. - Dr Danuta Jeziorska, Chief Executive Officer & Founder of Nucleome