論文

査読有り 国際誌
2020年9月

Integrated DNA methylation analysis reveals a potential role for ANKRD30B in Williams syndrome.

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
  • Ryo Kimura
  • ,
  • Roy Lardenoije
  • ,
  • Kiyotaka Tomiwa
  • ,
  • Yasuko Funabiki
  • ,
  • Masatoshi Nakata
  • ,
  • Shiho Suzuki
  • ,
  • Tomonari Awaya
  • ,
  • Takeo Kato
  • ,
  • Shin Okazaki
  • ,
  • Toshiya Murai
  • ,
  • Toshio Heike
  • ,
  • Bart P F Rutten
  • ,
  • Masatoshi Hagiwara

45
10
開始ページ
1627
終了ページ
1636
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/s41386-020-0675-2

Williams syndrome (WS) is a rare genetic disorder, caused by a microdeletion at the 7q11.23 region. WS exhibits a wide spectrum of features including hypersociability, which contrasts with social deficits typically associated with autism spectrum disorders. The phenotypic variability in WS likely involves epigenetic modifications; however, the nature of these events remains unclear. To better understand the role of epigenetics in WS phenotypes, we integrated DNA methylation and gene expression profiles in blood from patients with WS and controls. From these studies, 380 differentially methylated positions (DMPs), located throughout the genome, were identified. Systems-level analysis revealed multiple co-methylation modules linked to intermediate phenotypes of WS, with the top-scoring module related to neurogenesis and development of the central nervous system. Notably, ANKRD30B, a promising hub gene, was significantly hypermethylated in blood and downregulated in brain tissue from individuals with WS. Most CpG sites of ANKRD30B in blood were significantly correlated with brain regions. Furthermore, analyses of gene regulatory networks (GRNs) yielded master regulator transcription factors associated with WS. Taken together, this systems-level approach highlights the role of epigenetics in WS, and provides a possible explanation for the complex phenotypes observed in patients with WS.

リンク情報
DOI
https://doi.org/10.1038/s41386-020-0675-2
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/32303053
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7419304

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