Exome Sequencing to identify novel candidate genes for autism

2013 Fiscal Year Research-status Report

• Project/Area Number: 25461728
• Research Category: Grant-in-Aid for Scientific Research (C)
• 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 浜松医科大学, 子どものこころの発達研究センター, 助教 (70377753)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 自閉症スペクトラム / コピー数多型解析 / エクソ－ム配列解析

Research Abstract

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.

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

There was no apparent problem on progress of the research.

Strategy for Future Research Activity

We are currently preparing a manuscript on the results.
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.

Expenditure Plans for the Next FY Research Funding

The number of control samples that had been corrected and analysed was smaller than expected.
We will continue to recruit control samples. Incurring amount will be used for purchasing Kits for exome capture and target enrichment, Illumina MiSeq Reagent kits, and Agencourt AMPure XP beads for sample purification.