2012 Fiscal Year Final Research Report
Study on molecular mechanism underlying genomic susceptibility to congenital hypomyelinating leukodystrophy
| 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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| Keywords | 小児神経学 |
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| 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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[Journal Article] Genome-wide association study identifies HLA-DP as a susceptibility gene for pediatric asthma in Asian populations2011
Author(s)
Noguchi E, Sakamoto H, Hirota T, Ochiai K, Imoto Y, Sakashita M, Kurosaka F, Akasawa A, Yoshihara S, Kanno N, Yamada Y, Shimojo N, Kohno Y, Suzuki Y, Kang MJ, Kwon JW, Hong SJ, Inoue K, Goto Y, Yamashita F, Asada T, Hirose H, Saito I, Fujieda S, Hizawa N, Sakamoto T, Masuko H, Nakamura Y, Nomura I, Tamari M, Arinami T, Yoshida T, Saito H, Matsumoto K
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Journal Title
DOI
Peer Reviewed
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[Journal Article] Mutations in POLR3A and POLR3B encoding RNA polymerase III subunits cause an autosomal-recessive hypomyelinating leukoencephalopathy2011
Author(s)
Saitsu H, Osaka H, Sasaki M, Takanashi JI, Hamada K, Yamashita A, Shibayama H, Shiina M, Kondo Y, Nishiyama K, Tsurusaki Y, Miyake N, Doi H, Ogata K, Inoue K, Matsumoto N
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Journal Title
Am J Hum Genet
Volume: 89(5)
Pages: 644-51
DOI
Peer Reviewed
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[Presentation] Treating Pelizaeus-Merzbacher disease with clinically applicable compounds, curumin and chloroquine: preclinical studies2012
Author(s)
Ken Inoue, Toshifumi Morimura, Yurika Numata, Li-Hua Yu, Leo Gotoh, Ryoko Yamamoto, Naoko Inoue, Barbara Antalfy, Kimiko Deguchi, Hitoshi Osaka, Yu-ichi Goto
Organizer
62^nd Annual meeting of the American Society of Human Genetics
Place of Presentation
San Francisco, USA
Year and Date
2012-11-08
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[Presentation] A comprehensive nation-wide epidemiological survey for Pelizaeus- Merzbacher disease and associated disorders in Japan2011
Author(s)
Inoue K, Numata Y, Ohkubo T, Arima E, Iwaki A, Kurosawa K, Takanashi J, Deguchi K, Yamamoto T, Osaka H
Organizer
12th International Congress of Human Genetics
Place of Presentation
Montreal, Canada
Year and Date
2011-10-13
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