Researchers at Mayo Clinic’s Center for Individualized Medicine have discovered key human genomic signatures that may help explain why COVID-19 is severe in some people and mild in others. After analyzing the amount of diverse DNA sequence data around the world, scientists identified mutations in two human proteins that may affect the course of SARS-CoV-2 – the virus responsible for COVID-19.
Their study shows that variation in genes ACE2 And TMPRESS2 Protein expression may be increased or decreased. An increase in protein expression may increase the susceptibility and severity of COVID-19, while a decrease may have a protective effect against the virus. Proteins play many important roles in the body. in this matterACE2 And TMPRESS2 They provide important entry points for SARS-CoV-2 to invade and infect human cells.
Study findings, published in human molecular geneticssuggest a possible new diagnostic approach based on variation in host cells rather than on a constantly evolving virus.
“COVID-19 is a master of frequency in changing the sequence of its genes, but that only tells half of the story. Our findings suggest that the virus’s interactions with proteins encoded by the human genome can also contribute to a person’s disease. may be a contributor to the results,” says Lingxin Zhang, PhD, lead author of the study and a researcher in the Center for Individualized Medicine’s Pharmacogenomics Program.
“These results can now be applied to DNA sequence data from patients infected with SARS-CoV-2 to potentially determine the degree of susceptibility to the disease,” says Dr. Zhang. “I hope that this method can be expanded to other genes involved in COVID-19, and that scientists and clinicians around the world can use this information to help their patients.”
For the study, Dr. Zhang and his team delved deeply into DNA sequencing data from approximately 71,000 people worldwide, including about 30,000 racial and ethnic minorities, to identify sequence variants in the world. ACE2 And TMPRESS2 Jean. The team then analyzed hundreds of protein types encoded by those genes and identified the different genes causing the high and low expression levels. To do this, Dr. Zhang engineered cells capable of expressing protein variants, and then, using color-coding, he and his team analyzed the variants to see which were more or less stable.
The study used nearly one million generated cells and produced billions of data points, which the team analyzed using a range of technologies, including cell sorting, modern genomics, high throughput DNA sequencing and a computer algorithm.
“To our knowledge, this is the first time anyone has applied this approach to COVID-19,” said Richard Wenshielbaum, MD, study co-author and director of the Center for Individualized Medicine, and in the Department of Molecular Pharmacology and Experimental Medicine. Says a pharmacologist. , “This work would not have been possible without the dramatic advances that have occurred in DNA sequencing, coupled with parallel advances in our ability to test the functional and medical effects of individual variations in DNA sequence—and, consequently—of the proteins encoded by our genes. in individual variation.”
Dr. Wenshielbaum says this study was also made possible by the large amount of human DNA sequence information that is now publicly available – with the provision that those data must be carefully protected and their use reviewed. and must be approved to avoid any possible infringement. Privacy.
As of July 11, 2022, more than 6.3 million people worldwide have died from COVID-19 since the start of the pandemic.
approvals
This study was funded by NIH grants U19 GM61388 (The Pharmacogenomics Research Network), R01 GM028157, R01 GM125633, R01 AA027486, K01 AA28050 and the Mayo Clinic Center for Individualized Medicine.
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material provided by Mayo Clinic, Original written by Colette Gallagher. Note: Content can be edited for style and length.
