Comprehensive genetic analysis by DNA Chip in inherited neuropathies
Project/Area Number |
18390262
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Neurology
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Research Institution | Kagoshima University |
Principal Investigator |
ARIMURA Kimiyoshi Kagoshima University, 大学院・医歯学総合研究科, Associate Professor (20159510)
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Co-Investigator(Kenkyū-buntansha) |
TAKASHIMA Hiroshi Kagoshima University, 大学院・医歯学総合研究科, Assistant Professor (80372803)
SOBUE Gen Nagoya University, 大学院・医学系研究科, Professor (20148315)
NAKAGAWA Masanori Kyoto prefectural University, 大学院・医学研究科, Professor (50198040)
HAYASAKA Kiyoshi Yamagata University, 医学部, Professor (20142961)
|
Project Period (FY) |
2006 – 2007
|
Project Status |
Completed (Fiscal Year 2007)
|
Budget Amount *help |
¥17,100,000 (Direct Cost: ¥15,600,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2007: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2006: ¥10,600,000 (Direct Cost: ¥10,600,000)
|
Keywords | Charcot-Marie-Tooth disease / CMT / DNA chip / reseguencing method / genetic diagnosis / molecular diagnosis / inherited neuropathy / mutation screening / resequencing array / multiple PCR / 遺伝子検査 |
Research Abstract |
Inherited neuropathies are clinically and genetically heterogeneous. At least 28 genes and 12 loci have been associated with Charcot-Marie-Tooth disease (CMT). Genotype-phenotype correlations of these genes are important for understanding the pathomechanisms of inherited neuropathy. Some clinical trials have been conducted for the treatment of CMT1A patients, and therefore, genetic diagnosis is becoming more important. However, concomitant with the increase in the number of genes to be screened for mutations, the labor and reagent costs for molecular genetic testing have also increased significantly. Direct sequence analysis is the standard method for mutation detection, but DNA sequencing costs are considerable. Therefore, sensitive, high-throughput, and cost-effective mutation screening methods are desired. Recent advances in microarray-based resequencing technology appear to provide accurate and economical mutation detection. We developed a microarray-based resequencing system to detect sequence alterations in multiple CMT genes on a single,high-throughput platform. We designed a microarray chip that includes both strands of the target exons and the splice sites. A total of 110,938 bp of sequences obtained from 27 disease causing and 10 disease candidate genes associated with peripheral nerves were tiled on a resequencing DNA chip. A total of 586 primer sets were amplified by multiplex PCR methods, and 69 kinds of alterations in 20 disease causing genes were identified. Some of the alterations are potentially pathogenic ; however, additional analysis is needed to determine whether these changes are responsible for CMT. Quality of resequencing is equivalent of direct sequencing, suggesting that our CMT diagnostic DNA chip is a useful technology for determining sequence alterations. Our microarray resequencing system is a sensitive,cost-effective, and high-throughput screening method for mutation detection in CMT patients.
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Report
(3 results)
Research Products
(54 results)
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[Journal Article] Prevalence and incidence rates of chronic inflammatory demyelinating polyneuropathy in the Japanese population2008
Author(s)
Iijima, M., Koike, H., Hattori, N., Tamakoshi, A., Katsuno, M., Tanaka, F., Yamamoto, M., Arimura, K., Sobue, G
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Journal Title
J Neurol Neurosurg Psychiatry (in press)
Description
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[Journal Article] Spinocerebellar ataxia with axonal neuropathy : consequence of a Tdp1 recessive neomorphic mutation?2007
Author(s)
Hirano, R., Interthal, H., Huang, C., Nakamura, T., Deguchi, K., Choi, K., Bhattacharjee, MB., Arimura, K., Umehara, F., Izumo, S., Northrop, JL., Salih, MA., Inoue, K., Armstrong, PL., Champoux, JJ., Takashima, H., Boerkoel, CF
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Journal Title
EMBO J. 26
Pages: 4732-43
Description
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[Journal Article] Refinement of a locus for autosomal dominant hereditary motor and sensory neuropathy with proximal dominancy(HMSN-P) and genetic heterogeneity2007
Author(s)
Maeda, K., Kaji, R., Yasuno, K., Jambaldorj, J., Nodera, H., Takashima, H., Nakaeawa, M., Makino, S., Tamiya, G
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Journal Title
J Hum Genet 52
Pages: 907-914
NAID
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[Journal Article] Serum VEGF as a prognostic factor of atherosclerosis2007
Author(s)
Kimura, K., Hashiguchi, T., Deguchi, T., Horinouchi, S., Uto, T., Oku, H., Setoyama, S., Maruyama, I., Osame, M., Arimura, K
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Journal Title
Atherosclerosis 194
Pages: 182-188
Description
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[Journal Article] Ataxic vs painful form of paraneoplastic neuropathy2007
Author(s)
Oki, Y., Koike, H., Iijima, M., Mori, K., Hatlori, N., Katsuno, M., Nakamura, T., Hirayama, M., Tanaka, F., Shiraishi, M., Yazaki, S., Nokura, K., Yamamoto, H., Sobue, G
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Journal Title
J Neurol Neurosurg Psychiatry 78
Pages: 899-901
Description
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[Journal Article] Nonmyelinating Schwann cell involvement with well-preserved unmyelinated axons in Charcot-Marie-Tooth disease type 1A2007
Author(s)
Koike, H., Iijima, M., Mori, K., Yamamoto, M., Hattoi-i, N., Katsuno, M., Tanaka, F., Watanabe, H., Doyu, M., Yoshikawa, H., Sobue, G
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Journal Title
J Neuropathol Exp Neurol 66
Pages: 1027-36
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[Journal Article] Association of AKT1 haplotype with the risk of schizophrenia in Iranian population2006
Author(s)
Bajestan, SN., Sabouri, AH., Nakamura, M., Takashima, H., Keikhaee MR., Behdani F., Fayyazi MR., Sargolzaee MR., Bajestan, MN., Sabouri, Z., Khayami, E., Haghighi, S., Hashemi, SB., Eiraku, N., Tufani, H., Najmabadi, H., Arimura, K., Sano, A., Osame, M
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Journal Title
Am J Med Genet B Neuropsychiatr Genet 141
Pages: 383-6
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[Journal Article] Early clinical signs and imaging findings in Gerstmann-Straussler-Scheinker syndrome(Pro102Leu)2006
Author(s)
Arata, H., Takashima, H., Hirano, R., Tomimitsu, H., Machigashira, K., Izumi, K., Kikuno, M., Ng, AR., Umehara, F., Arisato, T., Ohkubo, R., Nakabeppu, Y., Nakajo, M., Osame, M., Arimura, K
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Journal Title
Neurology 66
Pages: 1672-8
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[Presentation] 糖尿病性神経障害の最近の知見2007
Author(s)
有村 公良
Organizer
第45回日本糖尿病学会九州地方会
Place of Presentation
宮崎市
Year and Date
2007-10-12
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[Presentation] 糖尿病性神経障害の最近の知見2007
Author(s)
有村 公良
Organizer
日本神経学会第86回近畿地方会
Place of Presentation
大阪市
Year and Date
2007-06-23
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