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• Generation of four iPSC lines from a family harboring a 1p36-35 haplotype linked with bipolar disorder and recurrent depressive disorder: Three-generation patients and a healthy sibling.

  Takamatsu G, Manome Y, Lee JS, Toyama K, Hayakawa T, Hara-Miyauchi C, Hasegawa-Ogawa M, Katagiri C, Kondo T, James Okano H, Matsushita M

  Stem cell research ( Elsevier BV )  64   102915 - 102915   2022.10 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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• Haplotype phasing of a bipolar disorder pedigree revealed rare multiple mutations of SPOCD1 gene in the 1p36-35 susceptibility locus.

  Takamatsu G, Yanagi K, Koganebuchi K, Yoshida F, Lee JS, Toyama K, Hattori K, Katagiri C, Kondo T, Kunugi H, Kimura R, Kaname T, Matsushita M

  Journal of affective disorders ( Journal of Affective Disorders )  310   96 - 105   2022.08 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  BACKGROUND: The etiology of bipolar disorder (BD) is poorly understood. Considering the complexity of BD, pedigree-based sequencing studies focusing on haplotypes at specific loci may be practical to discover high-impact risk variants. This study comprehensively examined the haplotype sequence at 1p36-35 BD and recurrent depressive disorder (RDD) susceptibility loci. METHODS: We surveyed BD families in Okinawa, Japan. We performed linkage analysis and determined the phased sequence of the affected haplotype using whole genome sequencing. We filtered rare missense variants on the haplotype. For validation, we conducted a case-control genetic association study on approximately 3000 Japanese subjects. RESULTS: We identified a three-generation multiplex pedigree with BD and RDD. Strikingly, we identified a significant linkage with mood disorders (logarithm of odds [LOD] = 3.61) at 1p36-35, supported in other ancestry studies. Finally, we determined the entire sequence of the 6.4-Mb haplotype shared by all affected subjects. Moreover, we found a rare triplet of missense variants in the SPOCD1 gene on the haplotype. Notably, despite the rare frequency, one heterozygote with multiple SPOCD1 variants was identified in an independent set of 88 BD type I genotyping samples. LIMITATIONS: The 1p36-35 sequence was obtained from only a single pedigree. The replicate sample was small. Short-read sequencing might miss structural variants. A polygenic risk score was not analyzed. CONCLUSION: The 1p36-35 haplotype sequence may be valuable for future BD variant studies. In particular, SPOCD1 is a promising candidate gene and should be validated.

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• Tescalcin is a potential target of class I histone deacetylase inhibitors in neurons.

  Takamatsu G, Katagiri C, Tomoyuki T, Shimizu-Okabe C, Nakamura W, Nakamura-Higa M, Hayakawa T, Wakabayashi S, Kondo T, Takayama C, Matsushita M

  Biochemical and biophysical research communications ( ACADEMIC PRESS INC ELSEVIER SCIENCE )  482 ( 4 ) 1327 - 1333   2017.01 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  Class I histone deacetylase (HDAC) inhibitors are believed to have positive effects on neurite outgrowth, synaptic plasticity, and neurogenesis in adult brain. However, the downstream molecular targets of class I HDAC inhibitors in neurons are not clear. Although class I HDAC inhibitors are thought to broadly promote transcription of many neuronal genes through enhancement of histone acetylation, the affected gene set may include unidentified genes that are essential for neuronal survival and function. To identify novel genes that are targets of class I HDAC inhibitors, we used a microarray to screen transcripts from neuronal cultures and evaluated changes in protein and mRNA expression following treatment with four HDAC inhibitors. We identified tescalcin (Tesc) as the most strongly up-regulated gene following treatment with class I HDAC inhibitors in neurons. Moreover, hippocampal neurons overexpressing TESC showed a greater than 5-fold increase in the total length of neurites and number of branch points compared with controls. These findings highlight a potentially important role for TESC in mediating the neuroprotective effect of class I HDAC inhibitors. TESC may also be involved in the development of brain and neurodegenerative diseases through epigenetic mechanisms. (C) 2016 The Authors. Published by Elsevier Inc.

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Grant-in-Aid for Scientific Research 【 display / non-display 】

Grant-in-Aid for Scientific Research 【 display / non-display 】

• Development of biological regulation system with artificial peptide

  Challenging research (development)

  Project Year: 2017.06  -  2020.03 

  Direct: 20,000,000 (YEN)  Overheads: 26,000,000 (YEN)  Total: 6,000,000 (YEN)