ゲノム情報学、プロテオミクス、システム生物学的手法 Genome Informatics, Proteomics, and Systems Biology

P2-2-238 ヒト死後脳を用いた脳特異的な体細胞変異の探索 In search of brain-specific somatic mutation in human postmortem brain genome ○西岡将基1,2, 文東美紀1, 上田順子3, 村山繁雄4, 笠井清登2, 加藤忠史3, 岩本和也1 ○Masaki Nishioka1,2, Miki Bundo1, Junko Ueda3, Shigeo Murayama4, Kiyoto Kasai2, Tadafumi Kato3, Kazuya Iwamoto1 東京大院・医・分子精神1, 東京大院・医・精神2, 理化研・BSI・精神疾患動態3, 都健康長寿研・老年病理4 Dept Mol Psy, Univ of Tokyo, Tokyo, Japan1, Dept Neuropsy, Univ of Tokyo, Tokyo, Japan2, Lab Mol Dynamics of Mental Dis, RIKEN BSI, Saitama, Japan3, Brain Bank for Aging Res, Tokyo Metro Inst of Gerontology, Tokyo, Japan4 Accumulating evidences have revealed that normal somatic human cells other than cancer cells have somatic mutations. One recent study reported the existence of microDNA, small extrachromosomal circular DNA, in somatic cells including brain cells, which was thought to be derived from somatic microdeletion. Among somatic cells, brain cells particularly experience frequent somatic mutation events such as retrotransposition and chromosomal aneuploidy during neural stem /neuroprogenitor cell stages. We hypothesized that neuropsychiatric disorders are partly caused by somatic mutations, including somatic single nucleotide variations (SNVs) and somatic structural variations (SVs), in brain cell genome. As a preliminary study, we are searching for the brain-specific somatic mutations in a healthy elderly female.We separated neuronal nuclei from the fresh-frozen postmortem brain of the subject by NeuN-based cell-sorting. We then extracted genomic DNA from the neuronal nuclei as well as from the liver of the same subject. Pair-end exome sequencing with Illumina platform was performed on each tissue sample. The total reads/ each tissue counted around one hundred million with the average length of 75 nucleotides/ one read. We are analyzing brain-specific somatic SNVs and SVs (e.g., retrotransposon insertion polymorphisms, microdeletion, insertion, and translocation), by comparing the sequencing data from the neuronal nuclei with those from the liver. We detected strong enrichment of retrotransposon insertions in neuronal nuclei and identified the genomic regions of brain-specific retrotransposon insertions in sequencing data analysis, which are going on validation. In this conference, we report the results of our analysis on somatic SNVs and SVs, focusing on retrotransposon insertions, and discuss the physiological and pathophysiological meanings of somatic mutations in the brain tissue.

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