Somatic mutation in single human neurons tracks developmental and transcriptional history

Lodato, Michael A.; Woodworth, Mollie B.; Lee, Semin; Lee, Semin; Evrony, Gilad D.; Mehta, Bhaven K.; Karger, Amir; Lee, Soohyun; Lee, Soohyun; Chittenden, Thomas W.; D’Gama, Alissa M.; Cai, Xuyu; Luquette, Lovelace J.; Lee, Eunjung; Park, Peter J.; Walsh, Christopher A.

doi:10.1126/science.aab1785

articleScienceOct 1, 2015Closed access

Somatic mutation in single human neurons tracks developmental and transcriptional history

MAMichael A. Lodato MBMollie B. Woodworth SLSemin LeeSLSemin LeeGDGilad D. Evrony

Broad Institute · Harvard University · +1 more institution

PubMed

Indexed incrossrefpubmed

Abstract

Neurons live for decades in a postmitotic state, their genomes susceptible to DNA damage. Here we survey the landscape of somatic single-nucleotide variants (SNVs) in the human brain. We identified thousands of somatic SNVs by single-cell sequencing of 36 neurons from the cerebral cortex of three normal individuals. Unlike germline and cancer SNVs, which are often caused by errors in DNA replication, neuronal mutations appear to reflect damage during active transcription. Somatic mutations create nested lineage trees, allowing them to be dated relative to developmental landmarks and revealing a polyclonal architecture of the human cerebral cortex. Thus, somatic mutations in the brain represent a durable and…

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Authors

16

MA
Michael A. LodatoCorresponding
Broad Institute, Harvard University
MB
Mollie B. WoodworthCorresponding
Broad Institute, Harvard University
SL
Semin Lee
Harvard University
SL
Semin LeeCorresponding
Broad Institute, Harvard University
GD
Gilad D. Evrony
Broad Institute, Harvard University

Topics & keywords

Topics

Keywords

Somatic cell
Biology
Germline
Germline mutation
Mutation
Genetics
Cerebral cortex
Gene

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