Genotyping and its use for brain diseases

• Project/Area Number: 17020004
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Niigata University
• Principal Investigator: KUWANO Ryozo Niigata University, 脳研究所, 教授 (20111734)
• Co-Investigator(Kenkyū-buntansha): MIYASHITA Akinori 新潟大学, 脳研究所, 助教 (60323995)
• Project Period (FY): 2005 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥181,300,000 (Direct Cost: ¥181,300,000); Fiscal Year 2009: ¥37,800,000 (Direct Cost: ¥37,800,000); Fiscal Year 2008: ¥37,400,000 (Direct Cost: ¥37,400,000); Fiscal Year 2007: ¥37,400,000 (Direct Cost: ¥37,400,000); Fiscal Year 2006: ¥37,400,000 (Direct Cost: ¥37,400,000); Fiscal Year 2005: ¥31,300,000 (Direct Cost: ¥31,300,000)
• Keywords: タイピング支援 / アルツハイマー病 / 遺伝子多型解析 / ゲノムワイド相関解析 / 脳神経疾患 / 感受性遺伝子 / SNP / 原因遺伝子 / 認知症 / 相関解析 / ゲノムワイド / リスク遺伝子 / 疾患感受性遺伝子 / マイクロサテライト

Research Abstract

The goal of this project is to establish the genotyping system and its use for brain diseases. We supported microsatellite and SNP typing for sib pair analysis and linkage studies on familiar brain diseases such as Alzheimer disease and related neurodegenerative disorders. We identified susceptibility loci associated with late-onset Alzheimer disease by a large-scale genome-wide association study.

Research Products

• [Journal Article] Genetic association study on in and around the APOE in late-onset Alzheimer disease in Japanese (2009)
  • Author(s): Takei N, Miyashita A, Tsukie T, Arai H, Asada T, Imagawa M, Shoji M, Higuchi S, Urakami K, Kimura H, Kakita A, Takahashi H, Tsuji S, Kanazawa I, Ihara Y, Odani S, Kuwano R, the Japanese Genetic Study Consortium for Alzheimer Disease
  • Journal Title: Genomics 93 Pages: 441-448
  • Peer Reviewed
• [Journal Article] Depression and psychiatric symptoms preceding onset of dementia in a family with early-onset Alzheimer disease with a novel PSEN1 mutation (2009)
  • Author(s): Kasuga K, Ohno T, Ishihara T, Miyashita A, Kuwano R, Onodera O, Nishizawa M, Ikeuchi T.
  • Journal Title: J Neurol 256 Pages: 1351-1353
  • Peer Reviewed
• [Journal Article] Association of HTRA1 mutations and familial ischemic cerebral small-vessel disease (2009)
  • Author(s): Hara K, Shiga A, Fukutake T, Nozaki H, Miyashita A, Yokoseki A, Kawata H, Koyama A, Arima K, Takahashi T, Ikeda M, Shiota H, Tamura M, Shimoe Y, Hirayama M, Arisato T, Yanagawa S, Tanaka A, Nakano I, Ikeda S, Yoshida Y, Yamamoto T, Ikeuchi T, Kuwano R, Nishizawa M, Tsuji S, Onodera O.
  • Journal Title: N Engl J Med 360 Pages: 1729-1739
  • Peer Reviewed
• [Journal Article] Hoque MA: Programs for calculating the statistical powers of detecting susceptibility genes in case-control studies based on multistage designs (2009)
  • Author(s): Kitamura N, Akazawa K, Miyashita A, Kuwano R, Toyabe SI, Nakamura J, Nakamura N, Sato T
  • Journal Title: Bioinformatics 25 Pages: 272-273
  • Peer Reviewed
• [Journal Article] GAB2 is not associated with late-onset Alzheimer's disease in Japanese (2009)
  • Author(s): Miyashita A, Arai H, Asada T, Imagawa M, Shoji M, Higuchi S, Urakami K, Toyabe S, Akazawa K, Kanazawa I, Ihara Y, Kuwano R.
  • Journal Title: Eur J Hum Genet 17 Pages: 682-686
  • 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] Association of HTRA1 mutations and familial ischemic cerebral small-vessel disease. (2009)
  • Author(s): Hara K.
  • Journal Title: N Engl J Med 360 Pages: 1729-1739
  • Peer Reviewed
• [Journal Article] SNP HiTLink : a high-throughput linkage analysis system employing dense SNP data. (2009)
  • Author(s): Fukuda Y.
  • Journal Title: BMC Bioinformatics 10 Pages: 121-121
  • Peer Reviewed
• [Journal Article] TRPM7 Is Not Associated With Amyotrophic Lateral Sclerosis-Parkinsonism Dementia Complex in the Kii Peninsula of Japan. (2009)
  • Author(s): Hara K.
  • Journal Title: Am J Med Genet Part B. 153 Pages: 310-313
  • Peer Reviewed
• [Journal Article] The 28-amino acid form of an APLP1-derived Ab-like peptide is a surro gate marker for Ab42 production in the central nervous system. (2009)
  • Author(s): Yanagida K.
  • Journal Title: EMBO Mol Med 1 Pages: 1-13
  • Peer Reviewed
• [Journal Article] Identification of independent APP locus duplication in Japanese patients with early-onset Alzheimer's disease. (2009)
  • Author(s): Kasuga K
  • Journal Title: J Neurol Neurosurg Psychiatry. 80 Pages: 1050-1052
  • Peer Reviewed
• [Journal Article] A novel presenilin 1 mutation (L282F) in familial Alzheimer's disease. (2009)
  • Author(s): Hamaguchi T
  • Journal Title: J Neurol. 256 Pages: 1575-1577
  • Peer Reviewed
• [Journal Article] Depression and psychiatric symptoms preceding onset of dementia in a family with early-onset Alzheimer disease with a novel PSEN1 mutation (2009)
  • Author(s): Kasuga K.
  • Journal Title: J Neurol (In press)
  • Peer Reviewed
• [Journal Article] Genetic association study on in and around the APOE in late-onset Alzheimer disease in Japanese (2009)
  • Author(s): Takei N.
  • Journal Title: Genomics 25(In press)
  • Peer Reviewed
• [Journal Article] GAB2 is not associated with late-onset Alzheimer's disease in Japanese (2009)
  • Author(s): Miyashita A.
  • Journal Title: Eur J Hum Genet (In press)
  • Peer Reviewed
• [Journal Article] Programs for calculating the statistical powers of detecting susceptibility genes in case-control studies based on multistage designs (2009)
  • Author(s): Kitamura N.
  • Journal Title: Bioinformatics 25 Pages: 272-273
  • Peer Reviewed
• [Journal Article] Prediction of Disease-associated Single Nucleotide Polymorphisms Using Virtual Genomes Constructed from a Public Haplotype Database (2008)
  • Author(s): Toyabe S, Miyashita A, Kitamura N, Kuwano R, Akazawa K
  • Journal Title: Methods Inf Med 47(6) Pages: 522-528
  • Peer Reviewed
• [Journal Article] A new amyloidβvariant favoring oligomerization in Alzheimer-type dementia (2008)
  • Author(s): Tomiyama, T., Nagata, T., Shimada H., Teraoka, R., Fukushima, A., Kanemitsu, H., Takuma, H., Kuwano, R., Imagawa, M., Suzuka Ataka, S., et. Al
  • Journal Title: Ann Neurol 63(3) Pages: 377-387
  • Peer Reviewed
• [Journal Article] Mutational analysis in early-onset familial dementia in the Japanese population. The role of PSEN1 and MAPT R406W mutations (2008)
  • Author(s): Ikeuchi T, Kaneko H, Miyashita A, Nozaki H, Kasuga K, Tsukie T, Tsuchiya M, Imamura T, Ishizu H, Aoki K, Ishikawa A, Onodera O, Kuwano R, Nishizawa M
  • Journal Title: ement Geriatr Cogn Disord 26(1) Pages: 43-49
  • Peer Reviewed
• [Journal Article] Prediction of disease-associated single nucleotide polymorphisms using virtual genomes constructed from a public haplotype database (2008)
  • Author(s): Toyabe S.
  • Journal Title: Methods Inf Med 47 Pages: 522-528
  • Peer Reviewed
• [Journal Article] Mutational analysis in early-onset familial dementia in the Japanese population. The role of PSEN1 and MAPT R406W mutations (2008)
  • Author(s): Ikeuchi T.
  • Journal Title: Dement Geriatr Cogn Disord 26 Pages: 43-49
  • Peer Reviewed
• [Journal Article] A new amyloid β variant favoring oligomerization in Alzheimer-type dementia (2008)
  • Author(s): Tomiyama T
  • Journal Title: Ann Neurol 63 Pages: 377-387
  • Peer Reviewed
• [Journal Article] Sample-size properties of a case-control association analysis of multistage SNP studies for identifying disease susceptibility genes (2008)
  • Author(s): Kitamura N
  • Journal Title: J Hum Genet (In press)
  • Peer Reviewed
• [Journal Article] Genetic association of CTNNA3 with late-onset Alzheimer‘s disease in females (2007)
  • Author(s): Miyashita A, Arai H, Asada T, Imagawa M, Matsubara E, Shoji M, Higuchi S, Urakami K, Kakita A, Takahashi H, Toyabe S, Akazawa K, Kanazawa I, Ihara Y, Kuwano R
  • Journal Title: Hum Mol Genet 16(23) Pages: 2854-2869
  • Peer Reviewed
• [Journal Article] Genetic association of CTNNA3 with late-onset Alzheimer's disease in females (2007)
  • Author(s): Miyashita A
  • Journal Title: Hum Mol Genet 16 Pages: 2854-2869
  • Peer Reviewed
• [Journal Article] Clinical, molecular and histopathological features of short stature syndrome with novel CUL7 mutation in Yakuts: new population isolate in Asia (2007)
  • Author(s): Maksimova N
  • Journal Title: J Med Gene 44 Pages: 772-778
  • Peer Reviewed
• [Journal Article] Enhanced Accumulation of Phosphorylated a synuclein and Elevated Ab42/40 Ratio Caused by Expression of the Presenilin-1 DT440 Mutant Associated with Familial Lewy Body Disease and Variant Alzheimer Disease (2007)
  • Author(s): Kaneko H
  • Journal Title: J Neurosci. 27 Pages: 13092-13097
  • Peer Reviewed
• [Journal Article] Novel locus for benign hereditary chorea with adult-onset maps to chromosome 8q22.2-q23.3 (2007)
  • Author(s): Shimohata, T.
  • Journal Title: Brain (In press)
• [Journal Article] Japanese Genetic Study Consortium for Alzeheimer's Disease. Dynamin-binding protein gene on chromosome 10q is associated with late-onset Alzheimer's disease (2006)
  • Author(s): Kuwano R, Miyashita A, Arai H, Asada T, Imagawa M, Shoji M, Higuchi S, Urakami K, Kakita A, Takahashi H, Tsukie T, Toyabe S, Akazawa K, Kanazawa I, Ihara Y
  • Journal Title: Hum Mol Genet. 15 Pages: 2170-2182
• [Journal Article] Dynamin-binding protein gene on chromosome 10q is associated with late-onset Alzheimer's disease (2006)
  • Author(s): Kuwano R.
  • Journal Title: Hum Mol Genet 15 Pages: 2170-2182
  • NAID: 40015443849
• [Presentation] JGSCAD): Fine SNP mapping in and around the APOE in late-onset Alzheimer disease (2009)
  • Author(s): Kuwano R, Takei N, Miyashita A, Ihara Y
  • Organizer: The 12th International Conference on Alzheimer's Disease
  • Place of Presentation: Vienna, Austria
  • Year and Date: 2009-07-15
• [Presentation] Fine SNP mapping in and around the APOE in late-onset Alzheimei disease. (2009)
  • Author(s): Kuwano R.
  • Organizer: ICAD
  • Place of Presentation: オイーン(オーストリア)
  • Year and Date: 2009-07-15
• [Presentation] 死後脳を用いた晩期発症型アルツハイマー病の網羅的遺伝子発現解析 (2008)
  • Author(s): 宮下哲典
  • Organizer: 第27回日本認知症学会
  • Place of Presentation: 前橋市
  • Year and Date: 2008-10-11
• [Presentation] ヒト血漿中のアミロイドβ40および42定量法の確立 (2008)
  • Author(s): 月江玉緒
  • Organizer: 第27回日本認知症学会
  • Place of Presentation: 前橋市
  • Year and Date: 2008-10-10
• [Presentation] Gene Expression Profiling of Postmortem Brain Tissues Affected by Alzheimer's Disease (2008)
  • Author(s): Miyashita A, Saitoh Y, Kakita A, Ogishima S, Tanaka H, Takahashi H, Murayama S, Ihara Y, Kuwano R
  • Organizer: The 11th International Conference on Alzheimer ' s Disease and Related Disorders
  • Place of Presentation: Chicago, USA
  • Year and Date: 2008-07-29
• [Presentation] Identification and characterization of a novel APP mutation (E693Δ) in familiar Alzheimer' disease (2008)
  • Author(s): Tomiyama T.
  • Organizer: The 11th International Conference on Alzheimer's Disease and Related Disorder
  • Place of Presentation: シカゴ
  • Year and Date: 2008-06-30
• [Presentation] Gene expression profiling of postmortem brain tissues affected by Alzheimer7s disease (2008)
  • Author(s): Miyashita A.
  • Organizer: The 11th International Conference on Alzheimer's Disease and Related Disorder
  • Place of Presentation: シカゴ
  • Year and Date: 2008-06-29
• [Presentation] Gender-related genetic lociassociated with late-onset Alzheimer's disease on chromosome 10q. (2007)
  • Author(s): 宮下哲典
  • Organizer: 第26回日本認知症学会
  • Place of Presentation: 大阪
  • Year and Date: 2007-10-17
• [Presentation] 染色体10番長腕におけるアルツハイマー病のリスク遺伝子 (2007)
  • Author(s): 宮下哲典
  • Organizer: 第52回日本人類遺伝学会
  • Place of Presentation: 東京
  • Year and Date: 2007-09-14
• [Presentation] Genetic Association Study for late-onset Alzheimer's Disease in Japan (2007)
  • Author(s): Kuwano R
  • Organizer: The 2nd Alzheimer's Association International Conference on Prevention of Dementia
  • Place of Presentation: Washington, DC, USA
  • Year and Date: 2007-06-11
• [Presentation] Identification of new genetic risk factors (2007)
  • Author(s): Kuwano R.
  • Organizer: Alzheimer's Association International Conference on Prevention of Dementia
  • Place of Presentation: Washington D.C
  • Year and Date: 2007-06-11
• [Presentation] リスクファクターとしての遺伝子 (2007)
  • Author(s): 桑野良三
  • Organizer: 第48回日本神経学総会
  • Place of Presentation: 名古屋
  • Year and Date: 2007-05-15
• [Remarks] (1)ホームページ等
• [Remarks] 目的とするマイクロサテライト公開データを使いやすく一覧できる手順を開発した。情報支援班の支援を受けて公開した
• [Remarks] (1)pub markerソフトウエア
• [Remarks] NCBI公開データに登録のマイクロサテライトを染色体毎にリストを作成する。各マーカーのUniSTS No、position、PCRプライマーの配列、Tm値、PCR産物とその5'及び3'隣接領域のシークエンスが一覧できる。
  • URL: http://ocean.cb.k.u-tokyo.ac.jp/homocontig1/test.cgi
• [Remarks] (2)STR検索ソフトウエア
• [Remarks] 公開シークエンス配列から、2、3、4、5塩基繰り返し配列の回数を指定して検索する。繰り返し配列及び5'隣接領域3'隣接領域それぞれ400塩基のシークエンスを表示する。PCRのプライマーのTm値やPCR長を自在に設計し、独自のプライマーリストを作成し保存できる。それら新規の繰り返し配列のposition並びに既知のマーカーと同じ画面に図示する。
  • URL: http://ocean.cb.k.u-tokyo.ac.jp/str21/index.cgi
• [Remarks] (2)報道関連情報
• [Remarks] (1) [朝日新聞]:「アルツハイマー病関連遺伝子を特定(新潟大など共同研究)」2007年1月24日
• [Remarks] (2) [新潟日報]:「アルツハイマー病発症関連 遺伝子を特定 治療法開発へ光明(新大脳 研究所 桑野教授ら)」2007年1月30日
• [Remarks] (3) [朝日新聞]:「アルツハイマー病日本人女性にリスク遺伝子(新潟大など発見)」 2007年9月2日
• [Remarks] (4) [新潟日報]:「脳を究める」2007年10月24日
• [Remarks] (5) [日経産業新聞]:「アルツハイマー病関連遺伝子患者の4割保持」2010年1月13日
• [Remarks] (3)アウトリーチ活動
• [Remarks] (1)市民公開[ゲノム研究勢ぞろい2008 in 名古屋]:「ゲノム解析でアルツハイマー病予備軍を探す」2008年10月25-26日
• [Remarks]
  • URL: http://www.bri.niigata-u.acjp/~idenshi/
• [Remarks]
  • URL: http://www.bri.niigata-u.ac.jp/~idenshi/