TY - JOUR
T1 - Machine learning reveals bilateral distribution of somatic L1 insertions in human neurons and glia
AU - Brain Somatic Mosaicism Network
AU - Zhu, Xiaowei
AU - Zhou, Bo
AU - Pattni, Reenal
AU - Gleason, Kelly
AU - Tan, Chunfeng
AU - Kalinowski, Agnieszka
AU - Sloan, Steven
AU - Fiston-Lavier, Anna Sophie
AU - Mariani, Jessica
AU - Petrov, Dmitri
AU - Barres, Ben A.
AU - Duncan, Laramie
AU - Abyzov, Alexej
AU - Vogel, Hannes
AU - Zhou, Bo
AU - Urban, Alexander
AU - Walsh, Christopher
AU - Ganz, Javier
AU - Woodworth, Mollie
AU - Li, Pengpeng
AU - Rodin, Rachel
AU - Hill, Robert
AU - Bizzotto, Sara
AU - Zhou, Zinan
AU - Lee, Alice
AU - D’Gama, Alissa
AU - Galor, Alon
AU - Bohrson, Craig
AU - Kwon, Daniel
AU - Gulhan, Doga
AU - Lim, Elaine
AU - Cortes, Isidro
AU - Luquette, Joe
AU - Sherman, Maxwell
AU - Coulter, Michael
AU - Lodato, Michael
AU - Park, Peter
AU - Monroy, Rebeca
AU - Kim, Sonia
AU - Dou, Yanmei
AU - Chess, Andrew
AU - Jones, Attila
AU - Rosenbluh, Chaggai
AU - Akbarian, Schahram
AU - Langmead, Ben
AU - Thorpe, Jeremy
AU - Pevsner, Jonathan
AU - Scharpf, Rob
AU - Cho, Sean
AU - Abyzov, Alexej
N1 - Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2021/2/1
Y1 - 2021/2/1
N2 - Retrotransposons can cause somatic genome variation in the human nervous system, which is hypothesized to have relevance to brain development and neuropsychiatric disease. However, the detection of individual somatic mobile element insertions presents a difficult signal-to-noise problem. Using a machine-learning method (RetroSom) and deep whole-genome sequencing, we analyzed L1 and Alu retrotransposition in sorted neurons and glia from human brains. We characterized two brain-specific L1 insertions in neurons and glia from a donor with schizophrenia. There was anatomical distribution of the L1 insertions in neurons and glia across both hemispheres, indicating retrotransposition occurred during early embryogenesis. Both insertions were within the introns of genes (CNNM2 and FRMD4A) inside genomic loci associated with neuropsychiatric disorders. Proof-of-principle experiments revealed these L1 insertions significantly reduced gene expression. These results demonstrate that RetroSom has broad applications for studies of brain development and may provide insight into the possible pathological effects of somatic retrotransposition.
AB - Retrotransposons can cause somatic genome variation in the human nervous system, which is hypothesized to have relevance to brain development and neuropsychiatric disease. However, the detection of individual somatic mobile element insertions presents a difficult signal-to-noise problem. Using a machine-learning method (RetroSom) and deep whole-genome sequencing, we analyzed L1 and Alu retrotransposition in sorted neurons and glia from human brains. We characterized two brain-specific L1 insertions in neurons and glia from a donor with schizophrenia. There was anatomical distribution of the L1 insertions in neurons and glia across both hemispheres, indicating retrotransposition occurred during early embryogenesis. Both insertions were within the introns of genes (CNNM2 and FRMD4A) inside genomic loci associated with neuropsychiatric disorders. Proof-of-principle experiments revealed these L1 insertions significantly reduced gene expression. These results demonstrate that RetroSom has broad applications for studies of brain development and may provide insight into the possible pathological effects of somatic retrotransposition.
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U2 - 10.1038/s41593-020-00767-4
DO - 10.1038/s41593-020-00767-4
M3 - Article
C2 - 33432196
AN - SCOPUS:85100116976
SN - 1097-6256
VL - 24
SP - 186
EP - 196
JO - Nature Neuroscience
JF - Nature Neuroscience
IS - 2
ER -