| Project/Area Number |
23659531
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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 |
Pediatrics
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| Research Institution | National Center of Neurology and Psychiatry |
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Principal Investigator |
INOUE Ken 独立行政法人国立精神・神経医療研究センター, 神経研究所 疾病研究第二部, 室長 (30392418)
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| Project Period (FY) |
2011 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 小児神経学 / 神経遺伝学 / ゲノム病 / 脳神経疾患 / アレイCGH / ペリツェウス・メルツバッ ハ病 / 国際情報交流 / ペリツェウス・メルツバッハ病 |
|---|
| Research Abstract |
Pelizaeus-Merzbacher disease (PMD) is inherited intractable disorder characterized by hypomyelination of central nervous system. Genomic duplication containing PLP1 gene is the most common cause of PMD. However, it is unknown as to why duplication is the most common cause of PMD. We hypothesized that there may be a genomic structural feature that predispose this genomic region for susceptibility of genomic rearrangement. We tested this hypothesis by applying numerous DNA samples from PLP1 duplication patients for high-resolution genomic analysis to delineate molecular mechanism underlying the abnormal genomic rearrangement resulting in PLP1 duplication. We designed a high-resolution custom CGH array specific to the PLP1 genomic region and analyzed 70 PMD cases with duplication. We confirmed genomic duplications involving PLP1 in all cases. Duplicated segments vary in length and region. No common breakpoint was found in either proximal or distal breakpoints, although distal breakpoints tend to cluster within a few thousands kb region enriched with segmental duplication. We also found interruption of duplication by single copy or triplicated copy segments in some cases, indicating a complex mechanism underlying genomic rearrangement. We are examining the recombination junction fragments in these cases at the nucleotide level.
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