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2021-03-29

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cc-by (c) Wang, Yifan et al., 2021
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/185960

Comprehensive identification of somatic nucleotide variants in human brain tissue

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https://doi.org/10.1186/s13059-021-02285-3

Resum

Background: Post-zygotic mutations incurred during DNA replication, DNA repair, and other cellular processes lead to somatic mosaicism. Somatic mosaicism is an established cause of various diseases, including cancers. However, detecting mosaic variants in DNA from non-cancerous somatic tissues poses significant challenges, particularly if the variants only are present in a small fraction of cells. Results: Here, the Brain Somatic Mosaicism Network conducts a coordinated, multi-institutional study to examine the ability of existing methods to detect simulated somatic single-nucleotide variants (SNVs) in DNA mixing experiments, generate multiple replicates of whole-genome sequencing data from the dorsolateral prefrontal cortex, other brain regions, dura mater, and dural fibroblasts of a single neurotypical individual, devise strategies to discover somatic SNVs, and apply various approaches to validate somatic SNVs. These efforts lead to the identification of 43 bona fide somatic SNVs that range in variant allele fractions from ~ 0.005 to ~ 0.28. Guided by these results, we devise best practices for calling mosaic SNVs from 250× whole-genome sequencing data in the accessible portion of the human genome that achieve 90% specificity and sensitivity. Finally, we demonstrate that analysis of multiple bulk DNA samples from a single individual allows the reconstruction of early developmental cell lineage trees. Conclusions: This study provides a unified set of best practices to detect somatic SNVs in non-cancerous tissues. The data and methods are freely available to the scientific community and should serve as a guide to assess the contributions of somatic SNVs to neuropsychiatric diseases.

Matèries

Malalties, Neuropsiquiatria, Reparació de l'ADN, Duplicació de l'ADN

Matèries (anglès)

Diseases, Neuropsychiatry, DNA repair, DNA replication

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Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)

Citació

WANG, Yifan, BAE, Taejeong, THORPE, Jeremy, SHERMAN, Maxwell a., JONES, Attila g., CHO, Sean, DAILY, Kenneth, DOU, Yanmei, GANZ, Javier, GALOR, Alon, LOBON, Irene, PATTNI, Reenal, ROSENBLUH, Chaggai, TOMASI, Simone, TOMASINI, Livia, YANG, Xiaoxu, ZHOU, Bo, AKBARIAN, Schahram, BALL, Laurel l., BIZZOTTO, Sara, EMERY, Sarah b., DOAN, Ryan, FASCHING, Liana, JANG, Yeongjun, JUAN, David, LIZANO, Esther, LUQUETTE, Lovelace j., MOLDOVAN, John b., NARURKAR, Rujuta, OETJENS, Matthew t., RODIN, Rachel e., SEKAR, Shobana., SHIN, Joo heon, SORIANO GARCÍA, Eduardo, STRAUB, Richard e., ZHOU, Weichen, CHESS, Andrew, GLEESON, Joseph g., MARQUÈS I BONET, Tomàs, PARK, Peter j., PETERS, Mette a., PEVSNER, Jonathan, WALSH, Christopher a., WEINBERGER, Daniel r., Brain Somatic Mosaicism Network, MORAN, John v., URBAN, Alexander e., KIDD, Jeffrey m., MILLS, Ryan e., ABYZOV, Alexej. Comprehensive identification of somatic nucleotide variants in human brain tissue. _Genome Biology_. 2021. Vol. 22, núm. 92, pàgs. 1-32. [consulta: 24 de gener de 2026]. ISSN: 1474-7596. [Disponible a: https://hdl.handle.net/2445/185960]

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