Send to

Choose Destination
Nat Neurosci. 2016 Dec;19(12):1583-1591. doi: 10.1038/nn.4388. Epub 2016 Sep 12.

L1-associated genomic regions are deleted in somatic cells of the healthy human brain.

Author information

The Salk Institute for Biological Studies, La Jolla, California, USA.
Department of Cellular &Molecular Medicine, University of California San Diego, School of Medicine, La Jolla, California, USA.
J. Craig Venter Institute, La Jolla, California, USA.
University of São Paulo, Departamento de Microbiologia, Instituto de Ciências Biomédicas, São Paulo, Brazil.
Department of Pediatrics, Rady Children's Hospital, San Diego, California, USA.


The healthy human brain is a mosaic of varied genomes. Long interspersed element-1 (LINE-1 or L1) retrotransposition is known to create mosaicism by inserting L1 sequences into new locations of somatic cell genomes. Using a machine learning-based, single-cell sequencing approach, we discovered that somatic L1-associated variants (SLAVs) are composed of two classes: L1 retrotransposition insertions and retrotransposition-independent L1-associated variants. We demonstrate that a subset of SLAVs comprises somatic deletions generated by L1 endonuclease cutting activity. Retrotransposition-independent rearrangements in inherited L1s resulted in the deletion of proximal genomic regions. These rearrangements were resolved by microhomology-mediated repair, which suggests that L1-associated genomic regions are hotspots for somatic copy number variants in the brain and therefore a heritable genetic contributor to somatic mosaicism. We demonstrate that SLAVs are present in crucial neural genes, such as DLG2 (also called PSD93), and affect 44-63% of cells of the cells in the healthy brain.

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center