Exome Sequencing to identify novel candidate genes for autism

• Project/Area Number: 25461728
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: イスメール サンシーム 浜松医科大学, 医学部, 特任研究員 (60569846)
• Co-Investigator(Kenkyū-buntansha): 大坪 正史 浜松医科大学, メディカルフォトニクス研究センター, 助教 (10327653) ; Anitha A (ANITHA A) 浜松医科大学, 子どものこころの発達研究センター, 特任助教 (70377753)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Discontinued (Fiscal Year 2014)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
• Keywords: 児童・思春期精神医学 / 自閉症スペクトラム / コピー数多型解析 / エクソーム配列解析 / エクソ－ム配列解析

Outline of Annual Research Achievements

Recent advances in next-generation sequencing techniques have made the large-scale analysis of human genomes possible. In contrast with the array-based analysis of large CNVs, this approach has a greater potential to reveal single genes associated with ASDs. We sequenced the exome of 20 patients with sporadic autism and their parents (60 individuals in total), reasoning that these families would be enriched for de novo mutations of severe impact. In the sporadic or simplex families with no previous history of ASD or related phenotypes, de novo mutations underlie a substantial fraction of the risk to develop ASD.
As a result, we discovered several novel/ultra-rare de novo variations, many of them are potentially deleterious, in the first ever exome sequencing study in Japanese autism subjects; further highlighting the genetic heterogeneity of the disorder. Estimation of the exact functional consequences of rare mutations, and the translation of this knowledge to support clinical decisions towards personalized pharmacological interventions is a real future challenge.

Research Products

• [Journal Article] Zinc finger protein 804A (ZNF804A) and verbal deficits in individuals with autism. (2014)
  • Author(s): Anitha A, Thanseem I, Nakamura K, Vasu MM, Yamada K, Ueki T, Iwayama Y, Toyota T, Tsuchiya KJ, Iwata Y, Suzuki K, Sugiyama T, Tsujii M, Yoshikawa T, Mori N.
  • Journal Title: J Psychiatry Neurosci Volume: 39 Issue: 5 Pages: 294-303
  • DOI: 10.1503/jpn.130126
  • Peer Reviewed / Open Access