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25 November 2019

X chromosome differences in women could affect accuracy of genetic tests for health risk

Researchers have found that the X chromosome in women shows up differently in different parts of the body as they age, meaning that technologies that predict health risks based on genes on the X chromosome may not be as accurate in older women.

DNA helix in blue

In findings published today in Nature Communications, researchers found a skewed pattern of X chromosomes that are switched off in different areas of the body, through a process called X inactivation. X inactivation occurs in females (who have two X chromosomes) where one of the X chromosomes in each cell is switched off leading to roughly equal levels of each in the body.

The team, led by Antonino Zito and Dr Kerrin Small, Department of Twin Research & Genetic Epidemiology, studied blood, fat and skin samples from almost 800 twins, including 8 pairs where one twin had rheumatoid arthritis, and the other twin did not.

They found that blood, fat and skin have different X chromosome inactivation patterns. These patterns become more skewed with age and smoking. This means that genetic tests that use blood samples might be less reliable in older women due to the differences in which X chromosome is switched off in blood compared to other parts of the body.

They also found that twins who have autoimmune conditions have more skewed patterns of X chromosome inactivation in the blood than their co-twins without the condition.

These findings suggest that researchers will need to consider the differences in X inactivation throughout the body in females.

It’s important to note that X inactivation patterns in the blood are not a reliable indicator of X inactivation in other parts of the body. We need to take this into account when designing genetic tools to predict health risks, which often rely on specialised blood tests. Otherwise, it may be that future genetic health tests are less reliable for older women, as the dose of X chromosome genes in the blood sample is different from that found elsewhere in the body.

First author Antonino Zito

Senior author Dr Kerrin Small added: “Our results indicate an association between X inactivation patterns and genetics, age, smoking and autoimmune conditions. We will need to carry out further research to understand the relationship between these features, and the implications of skewed X inactivation for healthy ageing in women.”

In this story

Kerrin Small

Professor in Genomics