Researchers from the Wellcome Sanger Institute, the University of Cambridge and AstraZeneca have revealed new insights into widespread ‘gene misbehaviour’ in healthy populations.
The study published in the American Journal of Human Genetics reveals how the human genetic code operates, which could support investigations into various complex diseases.
Gene misbehaviour occurs when genes are active when they were expected to be switched off, which has been previously linked to several rare diseases, including congenital limb syndromes.
Around 19,900 genes make up the human genome and form part of the instruction manual for our bodies, which encode proteins needed to carry out cell functions.
Proper gene regulation occurs when these gene instructions are turned on and off as needed, depending on a cell’s specific role or environmental factors. When it fails, it can disrupt normal cell function.
Using advanced RNA sequencing techniques, researchers analysed blood samples from 4,568 healthy individuals as part of the INTERVAL study to measure gene activity as well as whole genome sequencing to identify genetic changes behind irregular gene activity.
They found that 96% of samples had some misexpression, with over half of the normally inactive genes showing misexpression.
“This suggests that when these essential genes do misexpress, the consequences for health and disease are likely to be more severe,” explained Wellcome Sanger’s Dr Katie Burnham, author of the study.
In addition, the team identified several mechanisms behind these gene activity errors, including rare structural changes in DNA, which could help inform precision medicine approaches and enable the development of targeted therapies to correct expression.
The findings from the study provide a valuable tool for further investigation into the complexities of human genetics and disease, which could help in diagnosing and developing treatments for conditions caused by misexpression.
First author of the study, Thomas Vanderstichele, Wellcome Sanger, commented: “Our study reveals ‘unusual’ gene activity is far more usual than previously thought… This is a big step towards more personalised healthcare, enabling a more comprehensive understanding of all the ways our genes impact our health.”
