2016 Fiscal Year Final Research Report
RAN translation and repeat instabilty mechanism in non-coding repeat expansion disorders
| Project/Area Number |
26670170
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Human genetics
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| Research Institution | Jichi Medical University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
Ishii Kazuhiro 筑波大学, 医学医療系, 准教授 (70323293)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Keywords | 脆弱X随伴振戦/失調症候群 / FMR1遺伝子 / CGGリピート / 体細胞モザイク / mismatach repair遺伝子 / リピート不安定性 |
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| Outline of Final Research Achievements |
Fragile X-associated tremor and ataxia syndrome (FXTAS) is a heritable neurological disorder caused by premutation (55-200 CGG repeats) of the Fragile-X-mental retardation 1 (FMR1) gene. The mechanism of fragile X repeat expansion is not well understood, including the somatic repeat number heterogeneity evident in distinct tissues from the same individual. Using multiple tissues from the autopsied FXTAS patient, we have analyzed the association between the degree of somatic mosacism and the expression level of mismatach repair (MMR) genes. The CGG repeat sizes ranged from 86～93 with one AGG interruption in multiple tissues. The difference of the repeat size was determined by the number of 3’CGG repeat. The repeat size correlated with the expression level of MMR genes in each tissue. However, cancerous tissues exhibited a bimodal repeat distribution despite extremely low expression of MMR genes.
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| Free Research Field |
遺伝性神経筋疾患の分子病態
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