Mayo Clinic researchers discover genetic variations that might sway course of COVID-19

(Source: MGN)
(Source: MGN)(MGN)
Published: Jul. 25, 2022 at 8:54 AM CDT
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ROCHESTER, Minn. (KTTC) – Researchers at Mayo Clinic’s Center for Individualized Medicine have discovered key human genomic signatures that could help explain why COVID-19 is severe in some people and mild in others.

According to Mayo Clinic, researchers analyzed volumes of diverse worldwide DNA sequence data and identified mutations in two human proteins that might sway the course of SARS-CoV-2, the virus responsible for COVID-19.

The study reveals that variants in the genes for ACE2 and TMPRESS2 can lead to an increase or decrease in protein expression.

An increase in protein expression might result in elevated COVID-19 susceptibility and severity, while a decrease might have a protective effect against the virus.

Mayo Clinic said proteins play many critical roles in the body. In this case, ACE2 and TMPRESS2 provide critical entry points for SARS-CoV-2 to invade and infect human cells.

The findings suggest a potential new diagnostic approach that is based on variation in the host cells rather than the constantly evolving virus itself.

“COVID-19 is a master of frequency in changing the sequences of its genes, but that only tells half of the story. Our findings suggest that the virus’s interaction with proteins encoded by the human genome may also be a contributor to a person’s disease outcome,” Lingxin Zhang, Ph.D., the lead author of the study and a researcher in the Pharmacogenomics Program of the Center for Individualized Medicine said.

“These results can now be applied to DNA sequence data for patients infected with SARS-CoV-2 to potentially determine the degree of susceptibility to the disease,” Dr. Zhang said. “I hope this methodology can be expanded for other genes involved in COVID-19, and that scientists and clinicians across the world can use this information to help their patients.”

For the study, Dr. Zhang and her team looked at the DNA sequencing data of nearly 71,000 people worldwide, including nearly 30,000 racial and ethnic minorities, to identify sequence variants in the ACE2 and TMPRESS2 genes.

Then they analyzed hundreds of protein variants encoded by those genes and identified variant genes that generated high and low expression levels. To do that, Dr. Zhang engineered cells capable of expressing the protein variants, and then, using color-coding, she and her team analyzed the variants to see which were more or less stable.

The study used nearly a million generated cells and produced billions of data points, which the team analyzed using a series of technologies, including cell sorting, modern genomics, high throughput DNA sequencing and a computer algorithm.

“To our knowledge, it’s the first time anyone has applied this approach to COVID-19,” Richard Weinshilboum, M.D., co-author of the study and a pharmacologist in the Center for Individualized Medicine, and Department of Molecular Pharmacology and Experimental Therapeutics said.

As of July 11, 2022, more than 6.3 million people worldwide have died from COVID-19 since the start of the pandemic.

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