Study uncovers why some females may be more susceptible to disease


FINDINGS from a study claim to help explain why some females may be more predisposed to disease, suffer worse outcomes of virus infections or respond differently to drug therapies.

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

The findings from the study are said to allow for a better understanding of mechanisms that can cause disease and may point to new drug development.

Alejandro Brenes Murillo - Research News Scotland
Alejandro Brenes Murillo, Analytics Developer Gene Regulation and Expression, School of Life Sciences

Female mammals, including humans, have two X chromosomes (XX), while males have only one, plus a Y chromosome (XY).

The X chromosome contains over 1,000 genes which are vital for cell development.

However, two X chromosome gene products can be lethal to balance this, one of the X chromosomes in females is shut down.

This process, known as X chromosome inactivation (XCI), ensures that females have the correct levels of gene activity in cells.

In the study, published in Cell Reports, Analytics Developer Alejandro Brenes and colleagues show that issues with the XCI process in female cells can cause major changes in protein levels.

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

University of Dundee School of Life Sciences -Research News Scotland
The University of Dundee’s School of life Sciences is where the research will take place.

Mr Brenes 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.”