Publication Date:
2015-10-03
Description:
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 ongoing record of neuronal life history, from development through postmitotic function.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4664477/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4664477/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lodato, Michael A -- Woodworth, Mollie B -- Lee, Semin -- Evrony, Gilad D -- Mehta, Bhaven K -- Karger, Amir -- Lee, Soohyun -- Chittenden, Thomas W -- D'Gama, Alissa M -- Cai, Xuyu -- Luquette, Lovelace J -- Lee, Eunjung -- Park, Peter J -- Walsh, Christopher A -- 1S10RR028832-01/RR/NCRR NIH HHS/ -- P50 MH106933/MH/NIMH NIH HHS/ -- R01 NS032457/NS/NINDS NIH HHS/ -- R01 NS079277/NS/NINDS NIH HHS/ -- T32 AG000222/AG/NIA NIH HHS/ -- T32 GM007226/GM/NIGMS NIH HHS/ -- T32 GM007753/GM/NIGMS NIH HHS/ -- U01 MH106883/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Oct 2;350(6256):94-8. doi: 10.1126/science.aab1785.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Genetics and Genomics, Manton Center for Orphan Disease, and Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA, USA; Departments of Neurology and Pediatrics, Harvard Medical School, Boston, MA, USA; and Broad Institute of MIT and Harvard, Cambridge, MA, USA. ; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA. ; Research Computing, Harvard Medical School, Boston, MA, USA. ; Research Computing, Harvard Medical School, Boston, MA, USA. Complex Biological Systems Alliance, North Andover, MA, USA. ; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA. Division of Genetics, Brigham and Women's Hospital, Boston, MA, USA. ; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA. Division of Genetics, Brigham and Women's Hospital, Boston, MA, USA. peter_park@harvard.edu christopher.walsh@childrens.harvard.edu. ; Division of Genetics and Genomics, Manton Center for Orphan Disease, and Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA, USA; Departments of Neurology and Pediatrics, Harvard Medical School, Boston, MA, USA; and Broad Institute of MIT and Harvard, Cambridge, MA, USA. peter_park@harvard.edu christopher.walsh@childrens.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26430121" target="_blank"〉PubMed〈/a〉
Keywords:
Adolescent
;
Cell Lineage
;
Cerebral Cortex/*cytology/*growth & development
;
DNA Mutational Analysis
;
DNA Replication/genetics
;
Female
;
Genetic Loci
;
Humans
;
Male
;
Mitosis/genetics
;
*Mutation
;
Neurons/*cytology/*physiology
;
*Polymorphism, Single Nucleotide
;
Single-Cell Analysis
;
*Transcription, Genetic
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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