Increased l1 retrotransposition in the neuronal genome in schizophrenia - PubMed (original) (raw)

. 2014 Jan 22;81(2):306-13.

doi: 10.1016/j.neuron.2013.10.053. Epub 2014 Jan 2.

Manabu Toyoshima 2, Yohei Okada 3, Wado Akamatsu 3, Junko Ueda 4, Taeko Nemoto-Miyauchi 4, Fumiko Sunaga 5, Michihiro Toritsuka 6, Daisuke Ikawa 6, Akiyoshi Kakita 7, Motoichiro Kato 8, Kiyoto Kasai 9, Toshifumi Kishimoto 6, Hiroyuki Nawa 10, Hideyuki Okano 3, Takeo Yoshikawa 2, Tadafumi Kato 11, Kazuya Iwamoto 12

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• PMID: 24389010
• DOI: 10.1016/j.neuron.2013.10.053

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Increased l1 retrotransposition in the neuronal genome in schizophrenia

Miki Bundo et al. Neuron. 2014.

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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.

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Comment in

• Long interspersed retrotransposable elements and susceptibility to schizophrenia.
  Lozano R, Marin R, Santacruz MJ, Pascual A. Lozano R, et al. Acta Neuropsychiatr. 2015 Jun;27(3):195-6. doi: 10.1017/neu.2015.2. Epub 2015 Mar 20. Acta Neuropsychiatr. 2015. PMID: 25793943 No abstract available.

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