no way As women age, strange things sometimes happen to their blood cells. This is the loss of one copy of the X chromosome. This process, called mLOX (loss of X mosaicism), causes blood cells to divide abnormally and can contribute to health conditions such as cancer. now, nature, A global team of scientists revealed the following frequencies: mLOX of population and environmental and genetic forces associated with the process.1
“This study is very important because the X chromosome has been mostly excluded from genetic research in the past.” Amy RobertsThe molecular epidemiologist at King’s College London was not involved in the study. “It’s really exciting to see a study of this magnitude.”
During early female development, one of the two X chromosomes is transcriptionally silenced through X inactivation. This allows women to produce similar numbers of X chromosome gene products as XY men. However, mLOX is a harmful process. Scientists know that mLOX occurs primarily later in life, but it has been unclear how common this phenomenon is.
To explore the frequency of mLOX: Mitchell Maciellaa genetic epidemiologist at the National Cancer Institute, and his team analyzed genotype array data from nearly 900,000 participants born with two XX chromosomes drawn from eight biobanks from diverse regions including the United Kingdom, Estonia, and Japan. I did it.
Analysis of allelic imbalance and copy number variation on the X chromosome showed that 12% of women across studies had detectable levels of mLOX. “We didn’t realize how common it was,” Machiela said.
More than 35% of individuals over 80 years of age have experienced mLOX, compared with approximately 3% of individuals under 40 years of age. Researchers found that across all age groups, the proportion of blood cells in individuals expressing mLOX was small, about 2%. However, in some individuals, mLOX appeared in 5% of cells, which researchers linked to higher levels of smoking.
The team also studied whether mLOX was associated with an increased risk of certain diseases. They found that this phenomenon was linked to genes associated with cancer predisposition, including: TP53 The gene encoding the tumor suppressor protein p53. They also associated higher mLOX rates with a higher risk for certain blood cancers. In a recent preprint, Machiela’s group also found an association between mLOX frequency and risk of developing heart disease. atrial fibrillation.2
They also wanted to identify genetic and cellular factors associated with mLOX that may drive this process. Machiela and his team took a closer look at the data and identified 56 genetic variants associated with mLOX, many of which occurred in genes involved in cancer, immunity, and chromosome segregation. rare variants of genes FBXO10an abbreviation that codes for F-box protein 10, increased the risk of acquiring mLOX by 2-fold. The protein encoded by this gene regulates levels of anti-apoptotic molecules, but researchers do not yet know how this affects the development of mLOX.
“This is a genetic age-related trait on a huge scale that we haven’t been able to do before,” he said. Taru TukyainenGeneticist at the University of Helsinki and co-author of the study.
Since men also experience Y chromosome loss, researchers wondered how the two phenomena differed. The researchers identified some overlap in genetic variants, particularly those associated with genes important for cancer susceptibility and blood cell characteristics, but each process represented a unique set of genes. For example, variants in immune-related genes are more associated with mLOX than Y chromosome loss, indicating that X and Y chromosome loss likely occur through independent mechanisms.
The researchers’ findings suggest that genetic variants may help predict mLOX in women and assess their susceptibility to cancer. But Machiela said longitudinal studies need to be conducted first. “This is just a snapshot of that time,” he said. “We don’t know much about the trajectory of how these events occurred.”
There is a lot of interesting biology to unravel regarding the X chromosome, Roberts said. For example, she would like to see more studies examining the link between inactivation of the X during development and pathological loss of the X that occurs later in life. This study also supports previous studies suggesting that chromosomes lost via mLOX are: X has been deactivated. Early in life.3
“The X chromosome is very curious,” Tukiainen said. “There is a lot of interesting biology that has the potential to contribute to women’s health.”
