Comparison of genomic and epigenomicexpression in monozygotic twins using next-generation sequencing.

2012 Fiscal Year Final Research Report

• Project/Area Number: 23659519
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: University of Yamanashi
• Principal Investigator: KUBOTA Takeo 山梨大学, 医学工学総合研究部, 教授 (70293511)
• Co-Investigator(Kenkyū-buntansha): TOYODA Atsushi 国立遺伝学研究所, 生物遺伝資源情報総合センター, 特任准教授 (10267495) ; SASAKI Masayuki 国立精神, 神経医療研究センター病院, 部長 (60235273)
• Project Period (FY): 2011 – 2012
• Keywords: ゲノム / 遺伝子 / 精神発達障害 / 双生児 / 次世代シーケンサー

Research Abstract

Discordance in disease manifestation between affected monozygotic twins has been attributed to either environmental factors or different patterns of X chromosome inactivation (XCI). However, recent studies have identified genetic and epigenetic differences between monozygotic twins, thereby challenging the accepted experimental model for distinguishing the effects of nature andnurture. Here, we report the genomic and epigenomic sequences in skin fibroblasts of a discordant monozygotic twin pair with Rett syndrome, an X-linked neurodevelopmental disorder characterized by autistic features, epileptic seizures, gait ataxia and stereotypical hand movements. In the twins, no reproducible differences were detected between the twins in single nucleotide polymorphisms (SNPs), insertion-deletion polymorphisms (indels), or copy number variations. Differences in DNA methylation between the twins were detected in fibroblasts in the upstream regions of genes involved in brain function and skeletal tissues, and thus, the differences in DNA methylation patterns likely underlie the discordance in Rett phenotypes between the twins.

Research Products

• [Journal Article] Comparison of genomic and epigenomic expression in monozygotic twins discordant for Rett syndrome (2013)
  • Author(s): Miyake K,Yang C,Minakuchi Y, OhoriK,Soutome M,HirasawaT,KazukiY, Adachi N,Suzuki S, Itoh M, Goto Y, Andoh T, KurosawaH, OshimuraM, SasakiM, Toyoda A, Kubota T
  • Journal Title: PLoS ONE Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] subtelomere deletion with congenital glaucoma, severe mental retardation, and growth impairment (2013)
  • Author(s): Nakane T, Nakamura K, Hata S, Kamiya Y, Sato H, Kubota T, Sugita K
  • Journal Title: Pediatr Int Volume: Vol.55、No.3 Pages: 376-381
  • Peer Reviewed
• [Presentation] 母子分離ストレスによるマウス脳海馬領域のグルココルチコイド受容体の発現変化 (2012)
  • Author(s): 平澤孝枝、石田哲史、田原佑里子、三宅邦夫、久保田健夫
  • Organizer: 第6回日本エピジェエティクス研究会
  • Place of Presentation: 東京
  • Year and Date: 20120514-15
• [Presentation] The epigenetic regulation of glucocorticoid receptors in juvenile maternal separation stress (2011)
  • Author(s): Hirasawa T, Ishida I, Miyake K, Endo A, Kubota T
  • Organizer: The 32nd Naito Conference (Yamanashi)
  • Place of Presentation: Yamanashi
  • Year and Date: 20111018-21
• [Presentation] Idenfiticaiton of MeCP2-target synaptic molecules associated with pathogenesis of Rett syndrome (2011)
  • Author(s): Miyake K, Hirasawa T, Kubota T
  • Organizer: 第34回日本分子生物学会年年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-14
• [Book] Chapter: Epigenetic Modulation of Human Neurobiological Disorders (2012)
  • Author(s): Kubota T, Miyake K, Hirasawa T, Onaka T, Yamasue H
  • Publisher: Elisevier(印刷中)
• [Book] The Mechanisms of DNA Replictaion (2012)
  • Author(s): Kubota T, Miyake K, Hirasawa T. Section 4
  • Total Pages: 333-350
  • Publisher: Chromatin and Epigenetic Influences on DNA Replication, Chapter 13: The Mechanism of Epigenetic Modifications during DNA Replication
• [Remarks] (山梨大学医学部環境遺伝医学講座)
  • URL: http://www.epigenetmed.com