BETHESDA, Md., June 12, 2024 ~ A team of researchers, led by Mitchell Machiela from the National Cancer Institute, has made a groundbreaking discovery in the field of genetics. They have identified inherited genetic variants that may predict the loss of one copy of a woman's two X chromosomes as she ages, a phenomenon known as mosaic loss of chromosome X (mLOX). This finding could have significant implications for understanding and potentially preventing various health conditions, including cancer.

The study, published in Nature on June 12, 2024, involved analyzing circulating white blood cells from nearly 900,000 women across eight biobanks. Of these women, 12% were found to have mLOX. Through their analysis, the researchers identified 56 common genetic variants that were associated with the development of mLOX. These variants were located near genes linked to autoimmune diseases and cancer susceptibility.

In addition to these common variants, rare variants in a gene called FBXO10 were also found to be associated with a doubling in the risk of mLOX. This highlights the potential role this gene plays in promoting abnormal blood cells with only one copy of chromosome X.

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Furthermore, the team discovered a set of inherited genetic variants on the X chromosome that were more frequently observed on the retained copy than on the lost one in women with mLOX. This could potentially be used to predict which copy of the X chromosome is retained when mLOX occurs. It is important because this retained copy may have a growth advantage that could increase a woman's risk for blood cancer.

The researchers also investigated associations between mLOX and over 1,200 diseases and confirmed previous findings linking it to an increased risk of leukemia and susceptibility to infections such as pneumonia.

According to Machiela, future research should focus on understanding how mLOX interacts with other types of genetic variation and age-related changes to potentially alter disease risk. This could lead to new strategies for preventing and treating various health conditions.

The study, titled "Population analyses of mosaic X chromosome loss identify genetic drivers and widespread signatures of cellular selection," was published in Nature on June 12, 2024. The team's findings have shed new light on the role of inherited genetic variants in mLOX and could pave the way for further advancements in the field of genetics.

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