Research reveals misbehaving genes in healthy humans
29 Jul 2024
So-called ‘gene misbehaviour’ within the bodies of healthy human beings is far more widespread than previously supposed, suggests findings from a new study.
Teams from the Wellcome Sanger Institute, University of Cambridge and AstraZeneca analysed inactive genes in a large, healthy population for the first time, in a paper published in the American Journal of Human Genetics.
The human genome contains an estimated 19,900 genes that encode information required for cell function. Normal regulation turns gene instructions on and off as required. However, says the researchers, failures that result in an inactive gene being activated could disrupt normal cell function, with such ‘misexpressions’ linked to certain rare diseases.
Studying more than 4,500 healthy individuals’ blood samples, the study employed both RNA sequencing to measure gene activity and whole genome sequencing to pinpoint genetic changes behind irregular gene activity.
This confirmed that misexpression events were very rare within individual genes, affecting a mere 0.07 per cent overall. Yet, almost every human sample examined (96%) demonstrated some evidence of misexpression, which affected more than half of the normally inactive genes. They also found these events can be caused by rare structural changes in the DNA.
First author of the study Thomas Vanderstichele of the Wellcome Sanger Institute said:
“Until now, we have been looking at disease risk through the lens of highly active genes. Our study reveals ‘unusual’ gene activity is far more usual than previously thought and we need to consider the full picture, including genes that shouldn't be active but sometimes are.”
His colleague and study author Dr Katie Burnham pointed out that certain critical genes, particularly those governing development, rarely made such mistakes.
“This suggests that when these essential genes do misexpress, the consequences for health and disease are likely to be more severe,” she emphasised.
