Zinan Zhou, Christopher A Walsh
The findings indicate that the UCAD method showed preliminary feasibility across the evaluated cancer types in this pilot cohort, and the TFx value serves as a quantitative indicator of tumor burden and treatment efficacy, warranting further prospective validation in larger cohorts.
Somatic mosaicism is increasingly recognized as a pervasive feature of the human brain and a potential contributor to neurological disease across the lifespan. Unlike germline variants, somatic variants arise post-zygotically and are unevenly distributed across regions, cell types and even individual neurons, enabling focal biological effects that can scale to network-level dysfunction. In this Review, we synthesize current evidence that developmental timing, clonal architecture and cell-type-specific selective pressures shape how somatic variants influence brain structure and function. Early embryonic variants can produce broad regional clones and severe phenotypes, whereas later events are usually more restricted; with ageing, ongoing DNA damage and imperfect repair generate private variants that might cumulatively reduce cellular resilience. We also summarize advances in detection approaches, including bulk, error-corrected and single-cell sequencing, and discuss their strengths and current limitations for clinical translation. Emerging data link brain somatic variants to neurodevelopmental and neurodegenerative phenotypes, supporting a unified framework in which mosaic genetics bridges focal lesions and distributed neurological syndromes. Integrating genomic, cellular and physiological analyses in longitudinal human studies will be essential to define causality, identify biomarkers and guide future targeted interventions.