@article{55ca67df783a4635bc1731d4b7e5526a,
title = "Machine learning reveals bilateral distribution of somatic L1 insertions in human neurons and glia",
abstract = "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.",
keywords = "machine learning, L1 insertions, glia, Retrotransposons, human nervous system, neurons",
author = "Xiaowei Zhu and Bo Zhou and Reenal Pattni and Kelly Gleason and Chunfeng Tan and Agnieszka Kalinowski and Steven Sloan and Anna-Sophie Fiston-Lavier and Jessica Mariani and Dmitri Petrov and Barres, {Ben A.} and Laramie Duncan and Alexej Abyzov and Hannes Vogel and {Brain Somatic Mosaicism Network} and Alexander Urban and Christopher Walsh and Javier Ganz and Mollie Woodworth and Pengpeng Li and Rachel Rodin and Robert Hill and Sara Bizzotto and Zinan Zhou and Alice Lee and Alissa D{\textquoteright}Gama and Alon Galor and Craig Bohrson and Daniel Kwon and Doga Gulhan and Elaine Lim and Isidro Cortes and Joe Luquette and Maxwell Sherman and Michael Coulter and Michael Lodato and Peter Park and Rebeca Monroy and Sonia Kim and Yanmei Dou and Andrew Chess and Attila Jones and Chaggai Rosenbluh and Schahram Akbarian and Ben Langmead and Jeremy Thorpe and Jonathan Pevsner and Rob Scharpf and Sean Cho and Flora Vaccarino and Liana Fasching and Simone Tomasi and Nenad Sestan and Sirisha Pochareddy and Andrew Jaffe and Apua Paquola and Daniel Weinberger and Jennifer Erwin and Jooheon Shin and Richard Straub and Rujuta Narurkar and Anjene Addington and David Panchision and Doug Meinecke and Geetha Senthil and Lora Bingaman and Tara Dutka and Thomas Lehner and Alexej Abyzov and Taejeong Bae and Laura Saucedo-Cuevas and Tara Conniff and Flasch, {Diane A.} and Frisbie, {Trenton J.} and Kidd, {Jeffrey M.} and Lam, {Mandy M.} and Moldovan, {John B.} and Moran, {John V.} and Kwan, {Kenneth Y.} and Mills, {Ryan E.} and Sarah Emery and Weichen Zhou and Yifan Wang and Kenneth Daily and Mette Peters and Fred Gage and Meiyan Wang and Patrick Reed and Sara Linker and Ani Sarkar and Aitor Serres and David Juan and Inna Povolotskaya and Irene Lobon and Manuel Solis and Raquel Garcia and Tomas Marques-Bonet and Gary Mathern and Jing Gu and Joseph Gleeson and Laurel Ball and Renee George and Tiziano Pramparo and Aakrosh Ratan and McConnell, {Mike J.} and Moran, {John V.} and Vaccarino, {Flora M.} and Tamminga, {Carol A.} and Levinson, {Douglas F.} and Urban, {Alexander E.}",
year = "2021",
month = feb,
doi = "10.1038/s41593-020-00767-4",
language = "English",
volume = "24",
pages = "186--196",
journal = "NATURE NEUROSCIENCE",
issn = "1097-6256",
publisher = "Nature Research",
number = "2",
}