Identification of genes for hereditary neurological diseases by the high throughput SNP chip linkage system

• Project/Area Number: 20590989
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: The University of Tokyo
• Principal Investigator: GOTO Jun The University of Tokyo, 医学部附属病院, 講師 (10211252)
• Co-Investigator(Renkei-kenkyūsha): TAKAHASHI Yuji 東京大学, 医学部附属病院, 助教 (00372392) ; ICHIKAWA Yaeko 東京大学, 医学部附属病院, 助教 (90341081) ; FUKUDA Yoko 東京大学, 医学部附属病院, 特任助教 (60396744)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2008: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 連鎖解析 / 一塩基多型(SNP) / 遺伝性疾患 / 遺伝子同定 / SNP

Research Abstract

We have developed SNP HiTLink which can directly import SNP chip data to linkage analysis programs including MLINK, Superlink, Merlin and Allegro. SNP genotyping and linkage analysis can be completed minimally 4 days. Results of SNP linkage mapping are similar to those obtained by microsatellites markers and to those of radiation RH mapping. A novel mutation of FLVCR1 was identified in a Japanese family accompanying with posterior column ataxia with retinitis pigmentosa. Clinical implementation is also useful to improve genetic diagnosis.

Research Products

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