Sun, ChenKathuria, KunalEmery, Sarah E.Kim, ByungJunBurbulis, Ian E.Shin, Joo HeonBrain Somatic Mosaicism NetworkWeinberger, Daniel R.Moran, John V.Kidd, Jeffrey M.McConnell, Michael J.2025-04-042025-04-042024Sun C, Kathuria K, Emery SB, Kim B, Burbulis IE, Shin JH, et al. Mapping recurrent mosaic copy number variation in human neurons. Nat Commun. 2024 May 17;15(1):4220. DOI: 10.1038/s41467-024-48392-02041-1723http://hdl.handle.net/10230/70090When somatic cells acquire complex karyotypes, they often are removed by the immune system. Mutant somatic cells that evade immune surveillance can lead to cancer. Neurons with complex karyotypes arise during neurotypical brain development, but neurons are almost never the origin of brain cancers. Instead, somatic mutations in neurons can bring about neurodevelopmental disorders, and contribute to the polygenic landscape of neuropsychiatric and neurodegenerative disease. A subset of human neurons harbors idiosyncratic copy number variants (CNVs, "CNV neurons"), but previous analyses of CNV neurons are limited by relatively small sample sizes. Here, we develop an allele-based validation approach, SCOVAL, to corroborate or reject read-depth based CNV calls in single human neurons. We apply this approach to 2,125 frontal cortical neurons from a neurotypical human brain. SCOVAL identifies 226 CNV neurons, which include a subclass of 65 CNV neurons with highly aberrant karyotypes containing whole or substantial losses on multiple chromosomes. Moreover, we find that CNV location appears to be nonrandom. Recurrent regions of neuronal genome rearrangement contain fewer, but longer, genes.application/pdfeng© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41467-024-48392-0Genetics of the nervous systemMolecular neuroscienceinfo:eu-repo/semantics/openAccess