Aging and neurodegeneration are associated with increased mutations in single human neurons-Reference-Cited by-同舟云学术

Aging and neurodegeneration are associated with increased mutations in single human neurons

Published:2018-02-02 Issue:6375 Volume:359 Page:555-559
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Lodato Michael A.¹²³^ORCID,Rodin Rachel E.¹²³⁴^ORCID,Bohrson Craig L.⁵^ORCID,Coulter Michael E.¹²³⁴^ORCID,Barton Alison R.⁵^ORCID,Kwon Minseok⁵^ORCID,Sherman Maxwell A.⁵^ORCID,Vitzthum Carl M.⁵^ORCID,Luquette Lovelace J.⁵,Yandava Chandri N.⁶,Yang Pengwei⁶^ORCID,Chittenden Thomas W.⁶⁷⁸^ORCID,Hatem Nicole E.¹²³^ORCID,Ryu Steven C.¹²³^ORCID,Woodworth Mollie B.¹²³^ORCID,Park Peter J.⁵⁹^ORCID,Walsh Christopher A.¹²³^ORCID

Affiliation:

1. Division of Genetics and Genomics, Manton Center for Orphan Disease, and Howard Hughes Medical Institute, Boston Children’s Hospital, Boston, MA, USA.

2. Departments of Neurology and Pediatrics, Harvard Medical School, Boston, MA, USA.

3. Broad Institute of MIT and Harvard, Cambridge, MA, USA.

4. Program in Neuroscience and Harvard/MIT MD-PHD Program, Harvard Medical School, Boston, MA, USA.

5. Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.

6. Computational Statistics and Bioinformatics Group, Advanced Artificial Intelligence Research Laboratory, WuXi NextCODE, Cambridge, MA, USA.

7. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.

8. Division of Genetics and Genomics, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA.

9. Division of Genetics, Brigham and Women’s Hospital, Boston, MA, USA.

Abstract

Brain mutations, young and old Most neurons that make up the human brain are postmitotic, living and functioning for a very long time without renewal (see the Perspective by Lee). Bae et al. examined the genomes of single neurons from the prenatal developing human brain. Both the type of mutation and the rates of accumulation changed between gastrulation and neurogenesis. These early mutations could be generating useful neuronal diversity or could predispose individuals to later dysfunction. Lodato et al. also found that neurons take on somatic mutations as they age by sequencing single neurons from subjects aged 4 months to 82 years. Somatic mutations accumulated with increasing age and accumulated faster in individuals affected by inborn errors in DNA repair. Postmitotic mutations might only affect one neuron, but the accumulated divergence of genomes across the brain could affect function. Science , this issue p. 550 , p. 555 ; see also p. 521

Funder

Howard Hughes Medical Institute

National Institute of Mental Health

National Institute on Aging

National Human Genome Research Institute

National Center for Research Resources

Harvard Ludwig Center

Paul G. Allen Family Foundation

National Institute of Neurological Disorders and Stroke

Manton Center for Orphan Disease Research

National Institute of General Medical Sciences

Stuart H.Q. and Victoria Quan Foundation