The mTOR signaling pathway activity and vitamin d availability control the expression of most autism predisposition genes

Ekaterina A. Trifonova, Alexandra I. Klimenko, Zakhar S. Mustafin, Sergey A. Lashin, Alex V. Kochetov

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Autism spectrum disorder (ASD) has a strong and complex genetic component with an estimate of more than 1000 genes implicated cataloged in SFARI (Simons Foundation Autism Research Initiative) gene database. A significant part of both syndromic and idiopathic autism cases can be attributed to disorders caused by the mechanistic target of rapamycin (mTOR)-dependent translation deregulation. We conducted gene-set analyses and revealed that 606 out of 1053 genes (58%) included in the SFARI Gene database and 179 out of 281 genes (64%) included in the first three categories of the database (“high confidence”, “strong candidate”, and “suggestive evidence”) could be attributed to one of the four groups: 1. FMRP (fragile X mental retardation protein) target genes, 2. mTOR signaling network genes, 3. mTOR-modulated genes, 4. vitamin D3 sensitive genes. The additional gene network analysis revealed 43 new genes and 127 new interactions, so in the whole 222 out of 281 (79%) high scored genes from SFARI Gene database were connected with mTOR signaling activity and/or dependent on vitamin D3 availability directly or indirectly. We hypothesized that genetic and/or environment mTOR hyperactivation, including provocation by vitamin D deficiency, might be a common mechanism controlling the expressivity of most autism predisposition genes and even core symptoms of autism.

Original languageEnglish
Article number6332
Number of pages14
JournalInternational Journal of Molecular Sciences
Volume20
Issue number24
DOIs
Publication statusPublished - 15 Dec 2019

Keywords

  • Autism spectrum disorder (ASD)
  • Bioinformatics
  • FMRP
  • Genetics
  • MTOR signaling pathway
  • SFARI Gene database
  • Vitamin D3
  • mTOR signaling pathway
  • TARGET
  • SPECTRUM DISORDER
  • D DEFICIENCY
  • CYTOSCAPE
  • SYMPTOMS
  • GUT MICROBIOTA
  • ANGELMAN SYNDROME
  • TRANSLATION
  • FEATURES
  • genetics
  • bioinformatics
  • vitamin D3
  • autism spectrum disorder (ASD)

Fingerprint Dive into the research topics of 'The mTOR signaling pathway activity and vitamin d availability control the expression of most autism predisposition genes'. Together they form a unique fingerprint.

Cite this