Do autism spectrum and autoimmune disorders share predisposition gene signature due to mtor signaling pathway controlling expression?

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Do autism spectrum and autoimmune disorders share predisposition gene signature due to mtor signaling pathway controlling expression? / Trifonova, Ekaterina A.; Klimenko, Alexandra I.; Mustafin, Zakhar S. et al.

In: International Journal of Molecular Sciences, Vol. 22, No. 10, 5248, 16.05.2021.

Research output: Contribution to journal › Article › peer-review

BibTeX

@article{c2f5905a05964bc8b451363c2de8f18e,

title = "Do autism spectrum and autoimmune disorders share predisposition gene signature due to mtor signaling pathway controlling expression?",

abstract = "Autism spectrum disorder (ASD) is characterized by uncommon genetic heterogeneity and a high heritability concurrently. Most autoimmune disorders (AID), similarly to ASD, are characterized by impressive genetic heterogeneity and heritability. We conducted gene-set analyses and revealed that 584 out of 992 genes (59%) included in a new release of the SFARI Gene database and 439 out of 871 AID-associated genes (50%) could be attributed to one of four groups: 1. FMRP (fragile X mental retardation protein) target genes, 2. mTOR signaling network genes, 3. mTOR-modulated genes, and 4. vitamin D3-sensitive genes. With the exception of FMRP targets, which are obviously associated with the direct involvement of local translation disturbance in the pathological mechanisms of ASD, the remaining categories are represented among AID genes in a very similar percentage as among ASD predisposition genes. Thus, mTOR signaling pathway genes make up 4% of ASD and 3% of AID genes, mTOR-modulated genes—31% of both ASD and AID genes, and vitamin D-sensitive genes—20% of ASD and 23% of AID genes. The network analysis revealed 3124 interactions between 528 out of 729 AID genes for the 0.7 cutoff, so the great majority (up to 67%) of AID genes are related to the mTOR signaling pathway directly or indirectly. Our present research and available published data allow us to hypothesize that both a certain part of ASD and AID comprise a connected set of disorders sharing a common aberrant pathway (mTOR signaling) rather than a vast set of different disorders. Furthermore, an immune subtype of the autism spectrum might be a specific type of autoimmune disorder with an early manifestation of a unique set of predominantly behavioral symptoms.",

keywords = "Autism spectrum disorder (ASD), Autoimmune disorders (AID), Bioinformatics, FMRP, MTOR, SFARI Gene database, Vitamin D3, Genetic Predisposition to Disease, Fragile X Mental Retardation Protein/genetics, Autism Spectrum Disorder/genetics, Humans, Signal Transduction/genetics, Autoimmune Diseases/genetics, Databases, Genetic, Gene Regulatory Networks, TOR Serine-Threonine Kinases/genetics, Cholecalciferol/genetics",

author = "Trifonova, {Ekaterina A.} and Klimenko, {Alexandra I.} and Mustafin, {Zakhar S.} and Lashin, {Sergey A.} and Kochetov, {Alex V.}",

note = "Funding Information: Funding: This research was supported by the Russian State Budget (project No. 0259-2019-0008). Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

month = may,

day = "16",

doi = "10.3390/ijms22105248",

language = "English",

volume = "22",

journal = "International Journal of Molecular Sciences",

issn = "1661-6596",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "10",