大量高速ゲノムSNPチップ連鎖解析システムによる遺伝性神経疾患の遺伝子同定

• 研究課題/領域番号: 20590989
• 研究種目: 基盤研究(C)
• 配分区分: 補助金
• 応募区分: 一般
• 研究分野: 神経内科学
• 研究機関: 東京大学
• 研究代表者: 後藤 順 東京大学, 医学部附属病院, 講師 (10211252)
• 連携研究者: 高橋 祐二 東京大学, 医学部附属病院, 助教 (00372392) ; 市川 弥生子 東京大学, 医学部附属病院, 助教 (90341081) ; 福田 陽子 東京大学, 医学部附属病院, 特任助教 (60396744)
• 研究期間 (年度): 2008 – 2010
• 研究課題ステータス: 完了 (2010年度)
• 配分額: 4,680千円 (直接経費: 3,600千円、間接経費: 1,080千円); 2010年度: 910千円 (直接経費: 700千円、間接経費: 210千円); 2009年度: 1,300千円 (直接経費: 1,000千円、間接経費: 300千円); 2008年度: 2,470千円 (直接経費: 1,900千円、間接経費: 570千円)
• キーワード: 連鎖解析 / 一塩基多型(SNP) / 遺伝性疾患 / 遺伝子同定 / SNP

研究概要

SNPチップ解析結果から直接連鎖解析を行えるパイプラインSNP HiTLinkを開発した。SNPチップによる家系のタイピングと連鎖解析を含め、最短4日間でマッピングを可能である。SNP連鎖解析はマイクロサテライトと同等である。放射線雑種細胞による物理的マッピングともよく一致していた。網膜色素変性症を伴う後索性失調症の原因遺伝子を同定した。また、臨床現場で、遺伝子診断の補助として応用できる。

研究成果

• [雑誌論文] Adult-onset leukoencephalopathies with vanishing white matter with novel missense mutations in EIF2B2, EIF2B3, and EIF2B5. (2011)
  • 著者名/発表者名: Matsukawa T, Wang X, Liu R, Wortham NC, Onuki Y, Kubota A, Hida A, Kowa H, Fukuda Y, Ishiura H, Mitsui J, Takahashi Y, Aoki S, Takizawa S, Shimizu J, Goto J, Proud CG, Tsuji S
  • 雑誌名: Neurogenetics. (Epub ahead of print)
  • 査読あり
• [雑誌論文] Posterior column ataxia with retinitis pigmentosa in a Japanese family with a novel mutation in FLVCR1. (2011)
  • 著者名/発表者名: Ishiura H, Fukuda Y, Mitsui J, Nakahara Y, Ahsan B, Takahashi Y, Ichikawa Y, Goto J, Sakai T, Tsuji S
  • 雑誌名: Neurogenetics. 12(2) ページ: 117-21
  • 査読あり
• [雑誌論文] Posterior column ataxia with retinitis pigmentosa in a Japanese family with a novel mutation in FLVCR1. (2011)
  • 著者名/発表者名: Ishiura H, (6名略), Goto J, Sakai T, Tsuji S.
  • 雑誌名: Neurogenetics 巻: (In press)
  • 査読あり
• [雑誌論文] Identification of novel SNPs of ABCD1, ABCD2, ABCD3, and ABCD4 genes in patients with X-linked adrenoleukodystrophy (ALD) based on comprehensive resequencing and association studies with ALD phenotypes. (2011)
  • 著者名/発表者名: Matsukawa T, Asheuer M, Takahashi Y, Goto J, et al.
  • 雑誌名: Neurogenetics 巻: 12 ページ: 41-50
  • 査読あり
• [雑誌論文] Mechanisms of genomic instabilities underlying two common fragile-site-associated loci, PARK2 and DMD, in germ cell and cancer cell lines. (2011)
  • 著者名/発表者名: Mitsui J, Takahashi Y, Goto J, et al.
  • 雑誌名: Am J Hum Genet 巻: 87 ページ: 75-89
  • 査読あり
• [雑誌論文] A mutation database for amyotrophic lateral sclerosis. (2010)
  • 著者名/発表者名: Yoshida M, (3名略), Goto J, Tsuji S
  • 雑誌名: Hum Mutat 巻: 31 ページ: 1003-1010
  • 査読あり
• [雑誌論文] A case of atypical amyloid polyneuropathy with predominant upper-limb involvement with the diagnosis unexpectedly found at lung operation. (2010)
  • 著者名/発表者名: Shirota Y, (3名略), Goto J, et al.
  • 雑誌名: Intern Med. 巻: 49 ページ: 1627-1631
  • NAID: 130000299592
  • 査読あり
• [雑誌論文] TDP-43 M337V mutation in familial amyotrophic lateral sclerosis in Japan. (2010)
  • 著者名/発表者名: Tamaoka A, 10名略, Goto J, Tsuji S, Akiyama H.
  • 雑誌名: Intern Med. 49 ページ: 331-334
  • NAID: 130000152618
  • 査読あり
• [雑誌論文] TRPM7 is not associated with amyotrophic lateral sclerosis-parkinsonism dementia complex in the Kii peninsula of Japan. (2010)
  • 著者名/発表者名: Hara K, 6名略, Goto J, Nishizawa M, Kuzuhara S, Tsuji S.
  • 雑誌名: Am J Med Genet B Neuropsychiatr Genet. 153B ページ: 310-313
  • 査読あり
• [雑誌論文] SNP haplotype mapping in a small ALS family. (2009)
  • 著者名/発表者名: Krueger KA, Tsuji S, Fukuda Y, Takahashi Y, Goto J, Mitsui J, Ishiura H, Dalton JC, Miller MB, Day JW, Ranum LP
  • 雑誌名: PLoS One. 4(5)
  • 査読あり
• [雑誌論文] SNP HiTLink : a high-throughput linkage analysis system employing dense SNP data. (2009)
  • 著者名/発表者名: Fukuda Y, Nakahara Y, Date H, Takahashi Y, Goto J, Miyashita A, Kuwano R, Adachi H, Nakamura E, Tsuji S
  • 雑誌名: BMC Bioinformatics. 10 ページ: 121-121
  • 査読あり
• [雑誌論文] SNP haplotype mapping in a small ALS family. (2009)
  • 著者名/発表者名: Krueger KA, 3名略, Goto J, 5名略, Ranum LP
  • 雑誌名: PLoS One. 4
  • 査読あり
• [雑誌論文] Mitochondrial ND3 as the novel causative gene for Leber hereditary optic neuropathy and dystonia. (2009)
  • 著者名/発表者名: Wang K, Takahashi Y, 3名略, Goto J, Lou JN, Tsuji S
  • 雑誌名: Neurogenetics 10 ページ: 337-345
  • 査読あり
• [雑誌論文] Mutations for Gaucher disease confer high susceptibility to Parkinson disease. (2009)
  • 著者名/発表者名: Mitsui J, 4名略, Goto J, 7名略, Tsuji S
  • 雑誌名: Arch Neurol 66 ページ: 571-576
  • 査読あり
• [雑誌論文] SNP HiTLink : a high-throughput linkage analysis system employing dense SNP data. (2009)
  • 著者名/発表者名: Fukuda Y, Nakahara Y, Date H, Takahashi Y, Goto J, 4名略, Tsuji S
  • 雑誌名: BMC Bioinformatics. 10 ページ: 121-121
  • 査読あり
• [雑誌論文] SNP HiTLink: a high-throughput likage analysis system employing dense SNP data. (2009)
  • 著者名/発表者名: Fukuda Y, Nakahara Y, Date H, Takahashi Y, Goto J, et al
  • 雑誌名: BMC Bioinformatics (In press)
  • 査読あり
• [雑誌論文] Devcelopment of a high-throughput microarray-based resequencing system for neurological disorders and its application to molecular genetics of amyotrophic lateral sclerosis. (2008)
  • 著者名/発表者名: Takahashi Y, (13名略), Goto J, Tsuji S
  • 雑誌名: Archives of Neurology 65 ページ: 1326-1332
  • 査読あり
• [雑誌論文] Total deletion and a missense mutation of ITPR1 in Japanese SCA15 families. (2008)
  • 著者名/発表者名: Hara K, (7名略), Goto J. Ikeuchi T, Tsuji S, Nishizawa M, Onodera O
  • 雑誌名: Neurology 71 ページ: 547-551
  • 査読あり
• [学会発表] A Japanese family ofnemaline myopathy which is caused by TPM2 mutation. (2010)
  • 著者名/発表者名: Goto J, Ishiura H, Fukuda Y, Nagashima Y, Shimizu J, Takahashi Y, Ichikawa Y, Tsuji S
  • 学会等名: 60^<th> Annual Meeting of the American Society of Human Genetics
  • 発表場所: Washington DC, USA
• [学会発表] Siblings of pathologically proven multiple system atrophy : an application of whole genome analysis toward finding strong genetic factors for sporadic diseases. (2010)
  • 著者名/発表者名: Ishiura H, Ahsan B, Mitsui J, Takahashi Y, Fukuda Y, Ichikawa Y, Nakahara Y, Kara K, Takahashi T, Kakita A, Onodera O, Nishizawa M, Goto J, Tsuji S
  • 学会等名: 60^<th> Annual Meeting of the American Society of Human Genetics
  • 発表場所: Washington DC, USA
• [学会発表] A Japanese family of nemaline myopathy which is caused by TPM2 mutation. (2010)
  • 著者名/発表者名: Goto J, (7名略)
  • 学会等名: 60^<th> Annual Meeting of the American Society of Human Genetics
  • 発表場所: Washington, DC USA
• [学会発表] Clinical features of spinocerebellar ataxia type 31 in Japanese population. (2010)
  • 著者名/発表者名: Ichikawa Y, (4名略), Goto J
  • 学会等名: 60^<th> Annual Meeting of the American Society of Human Genetics
  • 発表場所: Washington, DC USA
• [学会発表] Siblings of pathologically proven multiple system atrophy : an application of whole genome analysis toward finding strong genetic factors for sporadic diseases. (2010)
  • 著者名/発表者名: Ishiura H, (11名略), Goto J, Tsuji S
  • 学会等名: 60^<th> Annual Meeting of the American Society of Human Genetics
  • 発表場所: Washington, DC USA
• [学会発表] Case-control association study of PARK2 exon rearrangements in Parkinson disease using an array comparative genomoic hybridization analysis. (2010)
  • 著者名/発表者名: Mitsui J, Takahashi Y, Matsukawa T, Goto J.Saito Y, Murayama S, Tsuji S
  • 学会等名: 60^<th> Annual Meeting of the American Society of Human Genetics
  • 発表場所: Washington, DC USA
• [学会発表] A case-control study focusing on rare variants obtained by comprehensive resequencing of the causative genes for familial amyotrophic lateral sclerosis (ALS) to identify disease-relevant alleles for sporadic ALS. (2010)
  • 著者名/発表者名: Takahashi Y, Goto J, Toyoda A, Fujiyama A, Tsuji S
  • 学会等名: 60^<th> Annual Meeting of the American Society of Human Genetics
  • 発表場所: Washington, DC USA
• [学会発表] Mutational analysis of optineurin (OPTN) in familial amyotrophic lateral sclerosis in the Japanese population. (2010)
  • 著者名/発表者名: Naruse H, Takahashi Y, Goto J, Tsuji S
  • 学会等名: 60^<th> Annual Meeting of the American Society of Human Genetics
  • 発表場所: Washington, DC USA
• [学会発表] A variation database for amyotrophic lateral sclerosis. (2009)
  • 著者名/発表者名: Yoshida M, Takahashi Y, Koike A, Fukuda Y, Goto J, Tsuji S
  • 学会等名: 59th Annual Meeting of the American Society of Human Genetics
  • 発表場所: Honolulu, Hawaii, USA
  • 年月日: 2009-10-23
• [学会発表] Mutational analysis FUS/TLS in familial and sporadic amyotrophic lateral sclrerosis in the Japanese population. (2009)
  • 著者名/発表者名: Takahashi Y, Goto J, Tsuji S
  • 学会等名: 59th Annual Meeting of the American Society of Human Genetics
  • 発表場所: Honolulu, Hawaii, USA
  • 年月日: 2009-10-22
• [学会発表] Adult-onset leuloencephalopathies with vanishing white matter with novel missense mutations in EIF2B2 and EIF2B5 and decreased eIF2B activity (2009)
  • 著者名/発表者名: Matsukawa T, 9名略, Goto J, Proud CG, Tsuji S
  • 学会等名: 59th Annual Meeting of the American Society of Human Genetics
  • 発表場所: Honolulu, Hawaii, USA
  • 年月日: 2009-10-21
• [学会発表] Molecular epidemiology of spinocerebellar ataxias in Japanese population. (2009)
  • 著者名/発表者名: Ichikawa Y, Tsuji S, Goto J
  • 学会等名: 59th Annual Meeting of the American Society of Human Genetics
  • 発表場所: Honolulu, Hawaii, USA
  • 年月日: 2009-10-21
• [学会発表] A comprehensive diagnostic system for hereditary spastic paraplegia employing resequencing microarray, Snager sequencing and comparative genomic hybridization array allows efficient identification of various types of mutations in the causative genes. (2009)
  • 著者名/発表者名: Ishiura H, Takahashi Y, Goto J, Tsuji S
  • 学会等名: 59th Annual Meeting of the American Society of Human Genetics
  • 発表場所: Honolulu, Hawaii, USA
  • 年月日: 2009-10-21
• [学会発表] Multiplexed resequencing analysis to identify rare variants in pooled DNA of barcode-indexed DNAs (2009)
  • 著者名/発表者名: Mitsui J, 4名略, Goto J, Tsuji S
  • 学会等名: 59th Annual Meeting of the American Society of Human Genetics
  • 発表場所: Honolulu, Hawaii, USA
  • 年月日: 2009-10-21
• [学会発表] Adult-onset leukoencephalopathies with vanishing white matter with novel mussense mutations in EIF2B2 and EIF2B5, and decresed eIF2B activity. (2009)
  • 著者名/発表者名: Matsukawa T, Wang X, Liu R, Hida A, Kubota A, Fukuda Y, Kowa H, Takahashi Y, Aoki S, Shimizu J, Goto J, Proud CG, Tsuji S
  • 学会等名: 59^<th> Annual Meeting of the American Society of Human Genetics
  • 発表場所: Honolulu, Hawaii, USA
• [学会発表] Development of a high-throughput analysis system and application for the linkage analysis of familial multiple system atrophy (MSA). (2008)
  • 著者名/発表者名: Fukuda Y, Nakahara Y, Date H, Takahashi Y, Goto J, Hara K, Nishizawa M, Nakamura E, Adachi H, Tsuji S
  • 学会等名: 58^<th> Annual Meeting of the American Society of Human Genetics
  • 発表場所: Philadelphia, Pennsylvania, USA
• [学会発表] Development of high-throughput linkage analysis system and application for the linkage analysis of familial multiple system atrophy (MAS). (2008)
  • 著者名/発表者名: Fukuda Y, Nakahara Y, Date H, Takahashi Y, Goto J, et al
  • 学会等名: The American Society of Human Genetics, 58th Annual Meeting
  • 発表場所: Philadelphia
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