| Project/Area Number |
14570955
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Psychiatric science
|
|---|
| Research Institution | RIKEN (The Institute of Physical and Chemical Research) |
|---|
Principal Investigator |
YAMADA Kazuo RIKEN (The Institute of Physical and Chemical Research) Brain Science Institute, Lab. for Molecular Psychiatry, Research Scientist, 分子精神科学研究チーム, 研究員 (10322695)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
YOSHIKAWA Takeo RIKEN (The Institute of Physical and Chemical Research) Brain Science Institute, Lab. for Molecular Psychiatry, Laboratory Head, 分子精神科学研究チーム, チームリーダー (30249958)
|
|---|
| Project Period (FY) |
2002 – 2003
|
| Project Status |
Completed (Fiscal Year 2003)
|
| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2002: ¥2,200,000 (Direct Cost: ¥2,200,000)
|
|---|
| Keywords | Endogenous psychosis / Chromosome 18 / Mood disorder / Schizophrenia / Linkage disequilibrium mapping / Transmission disequilibrium test / IMPA2 gene / C18orf gene / C18orfl遺伝子 / 関連研究 |
|---|
| Research Abstract |
The pericentromeric region of chromosome 18,especially 18p11.2,is described as a schizophrenia susceptibility locus. We had previously cloned two novel brain-derived transcripts from this region : the gene for a second human myo-inosititol monophosphatase (IMPA2) and a gene of unknown function, C18orf1.
We performed a family-based LD study as the first step towards identifying relevant genetic loci around 18p11.2,and then followed up using a case-control approach. These markers covered 18p11.2 at an average density of 1/280 kb. A follow-up study of independent schizophrenics (n=214) and controls (n=313), revealed a significant association between the haplotype constructed by the D18S852 and 6409T>C and schizophrenia (P=0.00001).
In addition, we have performed a genome-wide LD survey of susceptibility loci for schizophrenia. We first typed 119 schizophrenic pedigrees (357 individuals) using 444 microsatellite markers. This analysis revealed 14 markers demonstrating significant transmissio
… More
n distortion. We scrutinized the most significant genomic locus on 11q11-13 by adding 26 new markers for analysis. Three-marker haplotype analysis in the region showed evidence of association with schizophrenia (most significant haplotype P=0.00005,global P=0.022). However, further support for chromosome 18 was not obtained by transmission distortion analysis.
Besides, we have genotyped 496 Japanese bipolar patients and 543 control subjects, using 17 SNPs on and around the IMPA2 gene. The distributions of haplotypes defined by -1051G>T,-708G>A,-461C>T and IVS1+1801C>T were different between control and schizophrenia groups (P=0.007). These findings suggest that the IMPA2 gene or a gene nearby may contribute to the overall genetic risk for bipolar disorder. Recently, we set out an in-vitro assay of the gene to reveal an influence of the SNPs on transcriptional activity. The present study should be expanded upon at increased marker resolution, followed by replication and confirmation tests in different sets of larger samples. Less
|
