Control of genes could explain why females suffer worse virus infection – study

A university study could explain why females may suffer worse outcomes of virus infection such as Covid-19.

Researchers from the University of Dundee’s School of Life Sciences found the control of genes on X chromosomes in females can cause much wider effects on cells than previously realised.

The X chromosome – of which females have two and men have only one – contains more than 1,000 genes that are vital for cell development.

However, a double dose of such gene products can be lethal, meaning one of the two chromosomes in female cells shuts down in a process known as X chromosome inactivation (XCI).

The team found that issues with the XCI process in female cells can cause major changes in protein levels.

Proteins are the main targets of almost every drug and differences in the levels of a cell are frequently responsible for many different types of disease, including cancer.

Alejandro Brenes, an analytics developer at the university school, said: “This study has revealed major consequences for the female cells if the XCI mechanism is defective.

“By analysing a collection of human stem cells from both healthy male and female donors, we found that a defective XCI increased the levels of thousands of proteins from all chromosomes, many of which are known markers of disease.

“The data can help to explain why some people may be more likely to develop specific types of disease, suffer worse outcomes of virus infection, such as Covid-19, or vary in how they respond to treatments and therapy.

“The results could also be important for the safe development of stem cell therapies.

“It also highlights the importance of sex-specific studies, as there are still many uncharacterised differences between females and males that need to be better understood in order to advance precision medicine.”

The study, Erosion of human X chromosome inactivation causes major remodeling of the iPSC proteome, is published in Cell Reports and can be found online.

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