Scientists have discovered that gene misbehavior, where genes are active when they should be inactive, is quite common in healthy individuals.
Researchers from the Wellcome Sanger Institute, the University of Cambridge, and AstraZeneca have identified various mechanisms that lead to gene activity errors. Understanding this could aid in personalized medicine and the development of targeted therapies.
The team studied the inactivity of genes in a large, healthy population for the first time and found that although rare on an individual gene basis, gene misexpression is widespread across samples, affecting more than half of the genes that should be inactive.
The findings, published in the American Journal of Human Genetics, provide new insights into the functioning of our genetic code and hold potential for investigating complex diseases.
Our genetic code comprises around 19,900 genes that encode proteins essential for cell functions. Proper gene regulation involves switching these genes on and off as required based on the cell’s function or environmental conditions. When a typically inactive gene becomes active, it can disrupt normal cell activities.
Although gene misexpression has been previously associated with rare diseases, its occurrence and reasons in the general population were unknown.
In this recent study, researchers analyzed blood samples from 4,568 healthy individuals from the INTERVAL study. They utilized advanced RNA sequencing techniques and whole-genome sequencing to identify genetic alterations underlying irregular gene activities.
The team observed that while misexpression events were infrequent at the individual gene level, occurring in only 0.07% of genes, nearly all samples (96%) displayed some misexpression, with over half of the usually inactive genes exhibiting misexpression. They also noted that rare structural DNA changes can cause these events.
Although gene misbehavior is common, it may not always result in health issues. This new understanding of the prevalence and mechanisms of gene misexpression can facilitate further exploration of human genetics and diseases, aiding in diagnosis and treatment development for conditions arising from misexpression.
The study’s first author, Thomas Vanderstichele from the Wellcome Sanger Institute, emphasized the importance of considering all gene activities for a comprehensive understanding of their impact on health, moving towards more personalized healthcare.
Dr. Katie Burnham highlighted that while most genes may misexpress at times, critical genes, especially those related to development, rarely exhibit such errors, indicating severe consequences for health and disease when they do.
Dr. Emma Davenport, the study’s senior author, praised the collaborative effort between experts from different institutions and emphasized the potential for future research into gene misexpression across various tissues to comprehend its role in diseases and potential therapies.
