Format

Send to

Choose Destination
Science. 2018 Feb 2;359(6375):550-555. doi: 10.1126/science.aan8690. Epub 2017 Dec 7.

Different mutational rates and mechanisms in human cells at pregastrulation and neurogenesis.

Author information

1
Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA.
2
Child Study Center, Yale University, New Haven, CT 06520, USA.
3
Departments of Psychiatry and Genetics, Stanford University, Palo Alto, CA 94305, USA.
4
Department of Neuroscience, Yale University, New Haven, CT 06520, USA.
5
New York Genome Center, New York, NY 10013, USA.
6
Yale Kavli Institute for Neuroscience, New Haven, CT 06520, USA.
7
Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA. abyzov.alexej@mayo.edu flora.vaccarino@yale.edu.
8
Child Study Center, Yale University, New Haven, CT 06520, USA. abyzov.alexej@mayo.edu flora.vaccarino@yale.edu.

Abstract

Somatic mosaicism in the human brain may alter function of individual neurons. We analyzed genomes of single cells from the forebrains of three human fetuses (15 to 21 weeks postconception) using clonal cell populations. We detected 200 to 400 single-nucleotide variations (SNVs) per cell. SNV patterns resembled those found in cancer cell genomes, indicating a role of background mutagenesis in cancer. SNVs with a frequency of >2% in brain were also present in the spleen, revealing a pregastrulation origin. We reconstructed cell lineages for the first five postzygotic cleavages and calculated a mutation rate of ~1.3 mutations per division per cell. Later in development, during neurogenesis, the mutation spectrum shifted toward oxidative damage, and the mutation rate increased. Both neurogenesis and early embryogenesis exhibit substantially more mutagenesis than adulthood.

Comment in

PMID:
29217587
DOI:
10.1126/science.aan8690
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center