ArticlemedRxiv : the preprint server for health sciences2025
Patterns and drivers of 43,617 mosaic chromosomal alterations in blood.
Article in medRxiv : the preprint server for health sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Clonal expansions of hematopoietic cells carrying mosaic chromosomal alterations (mCAs) are commonly detectable in elderly individuals. Here, we studied 43,617 autosomal mCAs that we ascertained in 484,081 UK Biobank participants using new, high-resolution computational methods to analyze blood-derived whole-genome sequencing data. Shorter mCAs (≤1 Mb) clustered at 53 genomic hotspots (34 previously undetected), several of which implicated chromosomal fragile sites as a recurrent source of somatic deletions. Chronic lymphocytic leukemia (CLL)-associated deletions at 13q14 were detectable in 1% of 65- to 70-year-old individuals-a five-fold higher rate than previously observed-suggesting opportunities for incorporating this mosaic mutation in clinical screening and in genetic association studies. Rare protein-coding variants in 38 genes associated (
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