Publications

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

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 post-conception) using clonal cell populations. We detected 200-400 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 shared with the spleen, revealing a pregastrulation origin. We reconstructed cell lineages for the first five post-zygotic cleavages and calculated a mutation rate of ~1.3 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 drastically more mutagenesis than adulthood.

 2017 Dec 7. pii: eaan8690. doi: 10.1126/science.aan8690. [Epub ahead of print]

Other Contributors

Bae T1, Tomasini L2, Mariani J2, Zhou B3, Roychowdhury T1, Franjic D4, Pletikos M4, Pattni R3, Chen BJ5, Venturini E5, Riley-Gillis B5, Sestan N4,6, Urban AE3, Abyzov A7, Vaccarino FM8,4,6.
1 Mayo Clinic, Department of Health Sciences Research, Rochester, MN 55905, USA.
2 Yale University, Child Study Center, Yale University, New Haven, CT 06520, USA.
3 Stanford University, Departments of Psychiatry and Genetics, Palo Alto, CA 94305, USA.
4 Yale University, Department of Neuroscience, 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 Mayo Clinic, Department of Health Sciences Research, Rochester, MN 55905, USA.
8 Yale University, Child Study Center, Yale University, New Haven, CT 06520, USA.

loading...