期刊
NATURE NEUROSCIENCE
卷 19, 期 12, 页码 1583-1591出版社
NATURE PORTFOLIO
DOI: 10.1038/nn.4388
关键词
-
资金
- George E. Hewitt Foundation for Medical Research
- California Institute for Regenerative Medicine
- NIH [MH095741, MH088485]
- G. Harold & Leila Y. Mathers Foundation
- Engman Foundation
- Leona M. and Harry B. Helmsley Charitable Trust
- Paul G. Allen Family Foundation
- Glenn Center for Aging Research at the Salk Institute
- JPB Foundation
- Flow Cytometry Core Facility of the Salk Institute
- NIH-NCI [CCSG: P30 014195]
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 microhomologymediated 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据