Mamoru TOCHIGI (栃木 衛)

Offer Organization: Japan Society for the Promotion of Science, System Name: Grants-in-Aid for Scientific Research, Category: Grant-in-Aid for Scientific Research (C), Fund Type: competitive_research_funding, Overall Grant Amount: - (direct: 3600000, indirect: 1080000)
We collected the DNA samples of the family, sporadic, and discordant twin patients of mental and developmental disorders, including schizophrenia, bipolar disorder, panic disorder, autism, and Tourette disorder. Through analyzing exome sequencing by using next-generation sequencer and microarray, the several candidate genes were collected for schizophrenia and Tourette disorder.

Offer Organization: Japan Society for the Promotion of Science, System Name: Grants-in-Aid for Scientific Research, Category: Grant-in-Aid for Scientific Research (C), Fund Type: -, Overall Grant Amount: - (direct: 4100000, indirect: 1230000)
Dendritic filopodia are most abundant during early phase of synaptogenesis, but the number of filopodia declines thereafter. When filopodia contact presynaptic sites and form synapses, filopodia convert into dendritic spines. Normal dendritic spinogenesis may be related to learning and memory function, and abnormal spine formation may cause the autistic spectrum disorder (ASD).TAO2b is a p38 MAP kinase kinase kinase, which binds to a protocadherin arcadlin at its cytoplasmic region. The gene encoding TAO2b is known to be located on chromosome 16p11.2, a region has been shown to carry substantial susceptibility to ASD. To address if TAO2b variants are associated with ASD, we sequenced TAO2b in patients and unaffected individuals. We identified two rare TAO2b variants in ASD individuals. Overexpression of each variant caused dendritic spine abnormality in cultured hippocampal neurons. We generated TAO2b knock mice. Tao2b knockout induced aberrant spine morphology and ASD-like behavior.

Offer Organization: Japan Society for the Promotion of Science, System Name: Grants-in-Aid for Scientific Research, Category: Grant-in-Aid for Young Scientists (B), Fund Type: competitive_research_funding, Overall Grant Amount: - (direct: 3200000, indirect: 960000)
The utility of sperm cells in the epgenetic studies of autism was reviewed. It was concluded that sperm cells from the patients' fathers may be helpful for identifying the candidate genes for autism. It was also tried to establish the method of evaluating the genome-wide DNA methylation status by using microarrays, and investigate the DNA methylation status by using blood cells as a pilot study. As a result, the reproducibility of the method was not enough, and further improvement of the assessment procedure was recommended.

Offer Organization: Ministry of Education, Culture, Sports, Science and Technology, System Name: Grants-in-Aid for Scientific Research(若手研究(B)), Category: 若手研究(B), Fund Type: competitive_research_funding, Overall Grant Amount: - (direct: 3000000, indirect: 900000)
As a result of the exome sequencing of a four-generation-extending autism spectrum disorder(ASD) family, several candidate genes, which completely co-segregate with the disease, were found and may lead to a new finding. In the copy number variation(CNV) analysis of 163 trios of ASD, eight de novo CNVs(> 500kb) were found in seven trios, one of which was duplication in 15q11. 2.

Offer Organization: Japan Society for the Promotion of Science, System Name: Grants-in-Aid for Scientific Research, Category: Grant-in-Aid for Scientific Research on Priority Areas, Fund Type: -, Overall Grant Amount: - (direct: 122600000, indirect: -)
Panic disorder (PD) is characterized by the recurrence of anxiety attacks and anticipatory anxiety that causes extensive restriction in daily activities. It is known that 2% of general population suffers from the disorder and genetic factor plays a role in the causation. We have established the largest DNA sample in the world, and searched risk SNPs, CNVs and micro chromosomal abnormalities for PD using 900k SNPs chip and CGH arrays. Common CNVs on chromosome 11, 14, 19 were found to be associated with PD and further analysis is in progress. We also found hypo-activation of prefrontal cortex is a trait and intermediate phenotype of PD, through NIRS measurements comparing between twins from identical twin pairs discordant for PD and between PD patients with and without family history.