Molecular pathogenesis study for migraine through integrated genomics based on exome analysis

• Project/Area Number: 25461270
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: National Center of Neurology and Psychiatry
• Principal Investigator: Takahashi Yuji 国立研究開発法人国立精神・神経医療研究センター, 病院, 医長 (00372392)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 片麻痺性片頭痛 / エクソーム / 網膜色素変性症 / 電位依存性カルシウムチャネル / イオントランスポーター / 変異解析

Outline of Final Research Achievements

The purpose of this study is to identify causative genes for familial hemiplegic migraine through exome analysis and bioinformatics. Affected individuals of a pedigree with severe attacks of hemiplegic migraine complicated with retinitis pigmentosa were subjected to whole exome analysis. Narrowing-down of variants shared among affected individuals through bioinformatic analysis integrating gene expression data has led to the successful identification of three variants considered as candidates for the pathogenic mutation. In addition, 29 exomes have been conducted in this project, which led to the identification of mutations in known causative genes in two pedigrees. In the remaining 27 pedigrees, 2473 novel non-synonymous variants have been identified in total, among which 188 variants were shared among multiple pedigrees. Further accumulation of exome data should be necessary to identify causative genes through leveraging the variation data obtained in this study.

Research Products

• [Journal Article] Rapid detection of expanded short tandem repeats in personal genomics using hybrid sequencing. (2014)
  • Author(s): Doi K, Monjo T, Hoang PH, Yoshimura J, Yurino H, Mitsui J, Ishiura H, Takahashi Y, Ichikawa Y, Goto J, Tsuji S, Morishita S.
  • Journal Title: Bioinformatics Volume: 30 Issue: 6 Pages: 815-822
  • DOI: 10.1093/bioinformatics/btt647
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 網膜色素変性症を伴う家族性片麻痺性片頭痛における病因遺伝子探索． (2015)
  • Author(s): 高橋 祐二，滝澤 歩武，古澤 嘉彦，石浦 浩之，三井 純，森下 真一，辻 省次，村田 美穂
  • Organizer: 第43回日本頭痛学会総会
  • Place of Presentation: 東京
  • Year and Date: 2015-11-13
• [Presentation] Genetic epidemiological study on migraine and episodic ataxia in the Japanese population (2013)
  • Author(s): Yuji Takahashi, Hiroyuki Ishiura, Jun Goto and Shoji Tsuji
  • Organizer: American Society of Human Genetics 63rd Annual Meeting
  • Place of Presentation: Boston Convention & Exhibition Center, Boston, MA, USA