Identification of somatic mutations in postmortem human brains by whole genome sequencing and their implications for psychiatric disorders

Masaki Nishioka, Miki Bundo, Junko Ueda, Fumiki Katsuoka, Yukuto Sato, Yoko Kuroki, Takao Ishii, Wataru Ukai, Shigeo Murayama, Eri Hashimoto, Masao Nagasaki, Jun Yasuda, Kiyoto Kasai, Tadafumi Kato, Kazuya Iwamoto

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Aim: Somatic mutations in the human brain are hypothesized to contribute to the functional diversity of brain cells as well as the pathophysiology of neuropsychiatric diseases. However, there are still few reports on somatic mutations in non-neoplastic human brain tissues. This study attempted to unveil the landscape of somatic mutations in the human brain. Methods: We explored the landscape of somatic mutations in human brain tissues derived from three individuals with no neuropsychiatric diseases by whole-genome deep sequencing at a depth of around 100. The candidate mutations underwent multi-layered filtering, and were validated by ultra-deep target amplicon sequencing at a depth of around 200 000. Results: Thirty-one somatic mutations were identified in the human brain, demonstrating the utility of whole-genome sequencing of bulk brain tissue. The mutations were enriched in neuron-expressed genes, and two-thirds of the identified somatic single nucleotide variants in the brain tissues were cytosine-to-thymine transitions, half of which were in CpG dinucleotides. Conclusion: Our developed filtering and validation approaches will be useful to identify somatic mutations in the human brain. The vulnerability of neuron-expressed genes to mutational events suggests their potential relevance to neuropsychiatric diseases.

Original languageEnglish
Pages (from-to)280-294
Number of pages15
JournalPsychiatry and Clinical Neurosciences
Volume72
Issue number4
DOIs
Publication statusPublished - 2018 Apr

Keywords

  • human brain
  • neuron
  • psychiatric disorder
  • somatic mutation
  • whole genome sequencing

ASJC Scopus subject areas

  • Neuroscience(all)
  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health

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    Nishioka, M., Bundo, M., Ueda, J., Katsuoka, F., Sato, Y., Kuroki, Y., Ishii, T., Ukai, W., Murayama, S., Hashimoto, E., Nagasaki, M., Yasuda, J., Kasai, K., Kato, T., & Iwamoto, K. (2018). Identification of somatic mutations in postmortem human brains by whole genome sequencing and their implications for psychiatric disorders. Psychiatry and Clinical Neurosciences, 72(4), 280-294. https://doi.org/10.1111/pcn.12632