The mTOR Signaling Pathway Activity and Vitamin D Availability Control the Expression of Most Autism Predisposition Genes

Autism spectrum disorder (ASD) has a strong and complex genetic component with an estimate of more than 1000 genes implicated cataloged in SFARI (Simon's Foundation Autism Research Initiative) gene database. A significant part of both syndromic and idiopathic autism cases can be attributed to d...

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Bibliographic Details
Published in:International journal of molecular sciences 2019-12, Vol.20 (24), p.6332
Main Authors: Trifonova, Ekaterina A, Klimenko, Alexandra I, Mustafin, Zakhar S, Lashin, Sergey A, Kochetov, Alex V
Format: Article
Language:English
Subjects:
Autism
Autism Spectrum Disorder - genetics
Autistic Disorder - genetics
Availability
Calciferol
Chromosomes
Deregulation
Epigenetics
Fragile X syndrome
Gene Regulatory Networks - genetics
Genes
Humans
Intellectual disabilities
Kinases
Mutation
Network analysis
Phosphatase
Proteins
Rapamycin
Signal transduction
Signal Transduction - genetics
Signs and symptoms
TOR protein
TOR Serine-Threonine Kinases - genetics
Vitamin D
Vitamin D - genetics
Vitamin D3
Vitamin deficiency
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Summary:Autism spectrum disorder (ASD) has a strong and complex genetic component with an estimate of more than 1000 genes implicated cataloged in SFARI (Simon's 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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms20246332