Details

Autor(en) / Beteiligte

• Erwin, Jennifer A
• Paquola, Apuã C M
• Singer, Tatjana
• Gallina, Iryna
• Novotny, Mark
• Quayle, Carolina
• Bedrosian, Tracy A
• Alves, Francisco I A
• Butcher, Cheyenne R
• Herdy, Joseph R
• Sarkar, Anindita
• Lasken, Roger S
• Muotri, Alysson R
• Gage, Fred H

Titel

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

Ist Teil von

• Nature neuroscience, 2016-12, Vol.19 (12), p.1583-1591

Ort / Verlag

United States

Erscheinungsjahr

2016

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.