Identification of causative genes and development of a new analytical method for familial neurological diseases

• Project/Area Number: 25670420
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: Kobe University
• Principal Investigator: SATAKE WATARU 神戸大学, 医学(系)研究科(研究院), 助教 (50467594)
• Co-Investigator(Renkei-kenkyūsha): TODA Tatsushi 神戸大学, 大学院医学研究科, 教授 (30262025)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2014: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2013: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: 神経遺伝 / エクソーム / ゲノム / 遺伝性神経疾患 / 神経内科学 / 人類遺伝学 / ゲノム医科学

Outline of Final Research Achievements

We performed exome sequencing for families with two genetic diseases; one is caused by a known gene-mutation and the other is caused by unknown gene. We used Hiseq2500 for high throughput sequencing, mapped sequence data to human reference genome sequence by BWA software, and called SNVs (Single nucleotide variation) by GATK software. The average depth of exome sequence data was x108-121. We searched for unknown causative genes for genetic diseases by using information of genomic position at the known gene-mutations. We extracted 2-3 candidate mutations for unknown genetic diseases.

Research Products

• [Journal Article] CHCHD2 mutations in autosomal dominant late-onset Parkinson’s disease: a genome-wide linkage and sequencing study. (2015)
  • Author(s): Funayama M, Ohe K, Amo T, Furuya N, Yamaguchi J, Saiki S, Yuanzhe L, Ogaki K, Ando M, Yoshinon H, Tomiyama H, Nishioka K, Hasegawa K, Saiki H, Satake W, Mogushi K, Sasaki R, Kokubo Y, Kuzuhara S, Toda T, Mizuno Y, Uchiyama Y, Ohno K, Hattori N.
  • Journal Title: Lancet Neurol Volume: 14 Issue: 3 Pages: 274-282
  • DOI: 10.1016/s1474-4422(14)70266-2
  • Peer Reviewed / Open Access
• [Journal Article] ABCG2 variant has opposing effects on onset ages of Parkinson's disease and gout. (2015)
  • Author(s): Matsuo H, Tomiyama H, Satake W, Chiba T, Onoue H, Kawamura Y, Nakayama A, ShimizuS, Sakiyama M, Funayama M, Nishioka K, Shimizu T, Kaida K, Kamakura K, Toda T, Hattori N, ShinomiyaN.
  • Journal Title: Ann Clin Transl Neurol Volume: 2 Issue: 3 Pages: 302-306
  • DOI: 10.1002/acn3.167
  • Peer Reviewed / Open Access
• [Journal Article] Variants associated with Gaucher disease in multiple system atrophy. (2015)
  • Author(s): Mitsui J, Matsukawa T, Sasaki H, Yabe I, Nakahara Y, Momose Y, Takahashi Y, Hara K, Kakita A, Yamada M, Takahashi H, Onodera O, Nishizawa M, Watanabe H, Nakashima K, Ito H, Izumi Y, Kaji R, Kato T, Tsuji S, et al.
  • Journal Title: Ann Clin Transl Neurol. Volume: 2 Issue: 4 Pages: 417-426
  • DOI: 10.1002/acn3.185
  • Peer Reviewed / Open Access
• [Journal Article] Novel calmodulin mutations associated with congenital arrhythmia susceptibility. (2014)
  • Author(s): Makita N, Tsuji Y（39人中21番目）et al
  • Journal Title: Circ Cardiovasc Genet. Volume: 7 Issue: 4 Pages: 466-474
  • DOI: 10.1161/circgenetics.113.000459
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A case of Bardet-Biedl syndrome complicated with intracranial hypertension in a Japanese child. (2014)
  • Author(s): Saida K, Inaba Y, Hirano M, Satake W, Toda T, Suzuki Y, Sudo A, Noda S, Hidaka Y, Hirabayashi K, Imai H, Kurokawa T, Koike K.
  • Journal Title: Brain Dev Volume: 印刷中 Issue: 8 Pages: 721-724
  • DOI: 10.1016/j.braindev.2013.10.013
  • Peer Reviewed / Open Access
• [Journal Article] YY1 binds to α-synuclein 3'-flanking region SNP and stimulates antisense noncoding RNA expression. (2013)
  • Author(s): Mizuta I, Takafuji K, Ando Y, Satake W, Kanagawa M, Kobayashi K, Nagamori S, Shinohara T, Ito C, Yamamoto M, Hattori N, Murata M, Kanai Y, Murayama S, Nakagawa M, Toda T.
  • Journal Title: J Hum Genet Volume: 58 Issue: 11 Pages: 711-719
  • DOI: 10.1038/jhg.2013.90
  • Peer Reviewed
• [Journal Article] Mutations in COQ2 in familial and sporadic multiple-system atrophy. (2013)
  • Author(s): Mitsui J, et. al.
  • Journal Title: N Engl J Med Volume: 369 Issue: 3 Pages: 233-244
  • DOI: 10.1056/nejmoa1212115
  • Peer Reviewed
• [Journal Article] 神経・精神疾患の動向 神経疾患と遺伝子 (2013)
  • Author(s): 佐竹 渉ら
  • Journal Title: 日本医師会雑誌神経・精神疾患診療マニュアル Volume: 142
• [Journal Article] 遺伝性疾患の遺伝子検査 (2013)
  • Author(s): 佐竹 渉
  • Journal Title: Modern Physician Volume: 33 Pages: 625-628
• [Journal Article] ゲノム多様性と神経変性疾患 (2013)
  • Author(s): 佐竹 渉ら
  • Journal Title: 細胞 Volume: 45 Pages: 120-123
• [Journal Article] ゲノムワイド関連解析からの知見とさらなる孤発性パーキンソン病遺伝子の発見へ向けて PARK16、BST1、α-synuclein、LRRK2、Tau (2013)
  • Author(s): 佐竹 渉ら
  • Journal Title: 医学のあゆみ Volume: 247 Pages: 1075-1078
• [Presentation] 孤発性パーキンソン病のエクソーム関連解析と第2期SNP-GWAS (2014)
  • Author(s): 佐竹渉、重水大智、鈴木穣 、山本健、富山弘幸、高橋篤、村田美穂、服部信孝、田中敏博 、角田達彦 、久保充明、辻省次、松本直通 、菅野純夫、戸田 達史
  • Organizer: 日本人類伝学会第59回大会
  • Place of Presentation: 東京
  • Year and Date: 2014-11-20 – 2014-11-22
• [Presentation] Risk genes and genome research of sporadic Parkinson’s disease (2014)
  • Author(s): Satake W, Toda T
  • Organizer: The 20th International Congress of Personalized Medicine
  • Place of Presentation: Tokyo
  • Year and Date: 2014-11-15
  • Invited
• [Presentation] Exome Association Study and 2nd SNP-GWAS of Japanese Parkinson’s disease (2014)
  • Author(s): Satake W, Shigemizu D, Suzuki Y, Yamamoto K, Tomiyama H, Yamamoto M, Murata M, Hattori N, Tsunoda T, Kubo M, Tsuji S, Nakamura Y, Sugano S, Toda T.
  • Organizer: American Society of Human Genetics Annual meeting
  • Place of Presentation: San Diego
  • Year and Date: 2014-10-18 – 2014-10-22
• [Presentation] Exome Association Study and 2nd SNP-GWAS of Japanese Parkinson’s disease (2014)
  • Author(s): Satake W, Hasegawa K, Murata M, Hattori N, Toda T.
  • Organizer: Genetic Epidemiology of Parkinson's disease Annual meeting
  • Place of Presentation: Vancouver
  • Year and Date: 2014-09-10 – 2014-09-12
• [Presentation] Exome sequencing of Parkinson's disease in order to identify genetic variants with high disease-risk (2014)
  • Author(s): Satake W, Ando Y, Tomiyama H, Kashihara K, Mochizuki H, Murayama S, Takeda A, Hasegawa K, Tsuji S, Yamamoto M, Murata M, Hattori N, Toda T.
  • Organizer: The MDS 18th International Congress of Parkinson's Disease and Movement Disorders
  • Place of Presentation: Stockholm
  • Year and Date: 2014-06-08 – 2014-06-12
• [Presentation] パーキンソン病感受性遺伝子α-synuiclein SNPとnoncoding RNA (2014)
  • Author(s): 水田依久子、佐竹渉、村山繁雄、金川基、小林千浩、高藤和輝、永森収志、山本光利、服部信孝、村田美穂、金井好克、水野敏樹、中川正法、戸田達史
  • Organizer: 第55回日本神経学会学術大会
  • Place of Presentation: 福岡
  • Year and Date: 2014-05-21 – 2014-05-24
• [Presentation] Exome sequencing of Parkinson's disease in order to identify genetic variants with high disease-risk (2014)
  • Author(s): Satake W et al
  • Organizer: New Frontier of Molecular Neuropathology
  • Place of Presentation: Tokyo, Japan
• [Presentation] Search for rare-variant risks of Parkinson’s disease by sequencing of candidate genes and exome sequencing (2013)
  • Author(s): Satake W et al
  • Organizer: The MDS 17th International Congress of Parkinson's Disease and Movement Disorders
  • Place of Presentation: Sydney, Australia
• [Presentation] Exome sequencing of Parkinson's disease in order to identify genetic variants with high disease-risk (2013)
  • Author(s): Satake W et al
  • Organizer: American Society of Human Genetics Annual meeting
  • Place of Presentation: Boston, USA
• [Presentation] エクソーム解読・一塩基多型解析によるパーキンソン病の遺伝背景の解明 (2013)
  • Author(s): 佐竹渉ら
  • Organizer: 2013年度包括脳ネットワーク夏のワークショップ
  • Place of Presentation: 名古屋
• [Presentation] 剖検脳を用いた孤発性パーキンソン病感受性遺伝子の解析 (2013)
  • Author(s): 上田健博ら
  • Organizer: 第54回日本神経学会学術大会
  • Place of Presentation: 東京
• [Remarks] 神戸大学神経内科
  • URL: http://www.med.kobe-u.ac.jp/im3/rinsyo/shinkei/index.html
• [Remarks] 神戸大学分子脳科学
  • URL: http://www.med.kobe-u.ac.jp/clgene/
• [Remarks] 神戸大学遺伝子診療部
  • URL: http://www.hosp.kobe-u.ac.jp/consultation/guide/department/idenshi.html