Senior computational biologist and co-first author, Giulio Genovese, recently published “Genetic drivers and cellular selection of female mosaic X chromosome loss” in Nature. In this study, we explored the genetic causes and health implications of mosaic loss of the X chromosome (mLOX) in females. We analyzed data from over 880,000 females from eight biobanks and found that 12% of females had detectable levels of mLOX in their white blood cells. To overcome the challenging problem of analyzing data from multiple biobanks each siloed in different computational frameworks we developed MoChA WDL, a minimalist and scalable set of pipelines to detect mosaic chromosomal alterations and run genome-wide association studies. We identified 56 common germline variants associated with mLOX, implicating genes related to chromosomal missegregation, cancer predisposition, and autoimmune diseases. Females with mLOX had an elevated risk of myeloid and lymphoid leukemias. This research highlights the importance of understanding mLOX to better understand the genetic factors that influence female health.

This work was featured in Nature Genetics Research Highlights.

Image credit: National Cancer Institute