Increased L1 retrotransposition in the neuronal genome in schizophrenia

Miki Bundo; Manabu Toyoshima; Yohei Okada; Wado Akamatsu; Junko Ueda; Taeko Nemoto-Miyauchi; Fumiko Sunaga; Michihiro Toritsuka; Daisuke Ikawa; Akiyoshi Kakita; Motoichiro Kato; Kiyoto Kasai; Toshifumi Kishimoto; Hiroyuki Nawa; Hideyuki Okano; Takeo Yoshikawa; Tadafumi Kato; Kazuya Iwamoto

doi:10.1016/j.neuron.2013.10.053

Increased L1 retrotransposition in the neuronal genome in schizophrenia

Miki Bundo, Manabu Toyoshima, Yohei Okada, Wado Akamatsu, Junko Ueda, Taeko Nemoto-Miyauchi, Fumiko Sunaga, Michihiro Toritsuka, Daisuke Ikawa, Akiyoshi Kakita, Motoichiro Kato, Kiyoto Kasai, Toshifumi Kishimoto, Hiroyuki Nawa, Hideyuki Okano, Takeo Yoshikawa, Tadafumi Kato, Kazuya Iwamoto

Research output: Contribution to journal › Article › peer-review

250 Citations (Scopus)

Abstract

Recent studies indicate that long interspersed nuclear element-1 (L1) are mobilized in the genome of human neural progenitor cells and enhanced in Rett syndrome and ataxia telangiectasia. However, whether aberrant L1 retrotransposition occurs in mental disorders is unknown. Here, we report high L1 copy number in schizophrenia. Increased L1 was demonstrated in neurons from prefrontal cortex of patients and in induced pluripotent stem (iPS) cell-derived neurons containing 22q11 deletions. Whole-genome sequencing revealed brain-specific L1 insertion in patients localized preferentially to synapse- and schizophrenia-related genes. To study the mechanism of L1 transposition, we examined perinatal environmental risk factors for schizophrenia in animal models and observed an increased L1 copy number after immune activation by poly-I:C or epidermal growth factor. These findings suggest that hyperactive retrotransposition of L1 in neurons triggered by environmental and/or genetic risk factors may contribute to the susceptibility and pathophysiology of schizophrenia.

Original language	English
Pages (from-to)	306-313
Number of pages	8
Journal	Neuron
Volume	81
Issue number	2
DOIs	https://doi.org/10.1016/j.neuron.2013.10.053
Publication status	Published - 22-01-2014
Externally published	Yes

All Science Journal Classification (ASJC) codes

General Neuroscience

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Bundo, M., Toyoshima, M., Okada, Y., Akamatsu, W., Ueda, J., Nemoto-Miyauchi, T., Sunaga, F., Toritsuka, M., Ikawa, D., Kakita, A., Kato, M., Kasai, K., Kishimoto, T., Nawa, H., Okano, H., Yoshikawa, T., Kato, T., & Iwamoto, K. (2014). Increased L1 retrotransposition in the neuronal genome in schizophrenia. Neuron, 81(2), 306-313. https://doi.org/10.1016/j.neuron.2013.10.053

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title = "Increased L1 retrotransposition in the neuronal genome in schizophrenia",

abstract = "Recent studies indicate that long interspersed nuclear element-1 (L1) are mobilized in the genome of human neural progenitor cells and enhanced in Rett syndrome and ataxia telangiectasia. However, whether aberrant L1 retrotransposition occurs in mental disorders is unknown. Here, we report high L1 copy number in schizophrenia. Increased L1 was demonstrated in neurons from prefrontal cortex of patients and in induced pluripotent stem (iPS) cell-derived neurons containing 22q11 deletions. Whole-genome sequencing revealed brain-specific L1 insertion in patients localized preferentially to synapse- and schizophrenia-related genes. To study the mechanism of L1 transposition, we examined perinatal environmental risk factors for schizophrenia in animal models and observed an increased L1 copy number after immune activation by poly-I:C or epidermal growth factor. These findings suggest that hyperactive retrotransposition of L1 in neurons triggered by environmental and/or genetic risk factors may contribute to the susceptibility and pathophysiology of schizophrenia.",

author = "Miki Bundo and Manabu Toyoshima and Yohei Okada and Wado Akamatsu and Junko Ueda and Taeko Nemoto-Miyauchi and Fumiko Sunaga and Michihiro Toritsuka and Daisuke Ikawa and Akiyoshi Kakita and Motoichiro Kato and Kiyoto Kasai and Toshifumi Kishimoto and Hiroyuki Nawa and Hideyuki Okano and Takeo Yoshikawa and Tadafumi Kato and Kazuya Iwamoto",

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doi = "10.1016/j.neuron.2013.10.053",

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Bundo, M, Toyoshima, M, Okada, Y, Akamatsu, W, Ueda, J, Nemoto-Miyauchi, T, Sunaga, F, Toritsuka, M, Ikawa, D, Kakita, A, Kato, M, Kasai, K, Kishimoto, T, Nawa, H, Okano, H, Yoshikawa, T, Kato, T & Iwamoto, K 2014, 'Increased L1 retrotransposition in the neuronal genome in schizophrenia', Neuron, vol. 81, no. 2, pp. 306-313. https://doi.org/10.1016/j.neuron.2013.10.053

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T1 - Increased L1 retrotransposition in the neuronal genome in schizophrenia

AU - Bundo, Miki

AU - Toyoshima, Manabu

AU - Okada, Yohei

AU - Akamatsu, Wado

AU - Ueda, Junko

AU - Nemoto-Miyauchi, Taeko

AU - Sunaga, Fumiko

AU - Toritsuka, Michihiro

AU - Ikawa, Daisuke

AU - Kakita, Akiyoshi

AU - Kato, Motoichiro

AU - Kasai, Kiyoto

AU - Kishimoto, Toshifumi

AU - Nawa, Hiroyuki

AU - Okano, Hideyuki

AU - Yoshikawa, Takeo

AU - Kato, Tadafumi

AU - Iwamoto, Kazuya

PY - 2014/1/22

Y1 - 2014/1/22

N2 - Recent studies indicate that long interspersed nuclear element-1 (L1) are mobilized in the genome of human neural progenitor cells and enhanced in Rett syndrome and ataxia telangiectasia. However, whether aberrant L1 retrotransposition occurs in mental disorders is unknown. Here, we report high L1 copy number in schizophrenia. Increased L1 was demonstrated in neurons from prefrontal cortex of patients and in induced pluripotent stem (iPS) cell-derived neurons containing 22q11 deletions. Whole-genome sequencing revealed brain-specific L1 insertion in patients localized preferentially to synapse- and schizophrenia-related genes. To study the mechanism of L1 transposition, we examined perinatal environmental risk factors for schizophrenia in animal models and observed an increased L1 copy number after immune activation by poly-I:C or epidermal growth factor. These findings suggest that hyperactive retrotransposition of L1 in neurons triggered by environmental and/or genetic risk factors may contribute to the susceptibility and pathophysiology of schizophrenia.

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Increased L1 retrotransposition in the neuronal genome in schizophrenia

Abstract

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