Alternative splicing and gene co-expression network-based analysis of dizygotic twins with autism-spectrum disorder and their parents

Okay, Kaan; Varış, Pelin Ünal; Miral, Süha; Ekinci, Burcu; Yaraş, Tutku; Karakülah, Gökhan; Oktay, Yavuz

doi:10.1016/j.ygeno.2021.05.038

Cited by 6 publications

(2 citation statements)

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“…Here we will review only those that were associated with ASD. Out of 1053 genes in the SFARI gene database (gene score 1,2 or S), 22 are directly related to splicing regulation (Abrahams et al, 2013; Banerjee‐Basu & Packer, 2010; Okay et al, 2021). In six of them, ASD‐associated variants were found only in large ASD cohort studies: ELAVL3 (Iossifov et al, 2014; Zhou et al, 2022), ELAVL2 (Iossifov et al, 2014; Zhou et al, 2022), KHDRBS2 (Girirajan et al, 2013; Woodbury‐Smith et al, 2022), PTBP2 (De Rubeis et al, 2014; Doan et al, 2016; Iossifov et al, 2014), SF3B1 and SRSF11 (De Rubeis et al, 2014; Zhou et al, 2022).…”

Section: Splicing Factors Mutated In Asdmentioning

confidence: 99%

The spectrum of pre‐mRNA splicing in autism

Engal,

Zhang,

Geminder

et al. 2024

WIREs RNA

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Disruptions in spatiotemporal gene expression can result in atypical brain function. Specifically, autism spectrum disorder (ASD) is characterized by abnormalities in pre‐mRNA splicing. Abnormal splicing patterns have been identified in the brains of individuals with ASD, and mutations in splicing factors have been found to contribute to neurodevelopmental delays associated with ASD. Here we review studies that shed light on the importance of splicing observed in ASD and that explored the intricate relationship between splicing factors and ASD, revealing how disruptions in pre‐mRNA splicing may underlie ASD pathogenesis. We provide an overview of the research regarding all splicing factors associated with ASD and place a special emphasis on five specific splicing factors—HNRNPH2, NOVA2, WBP4, SRRM2, and RBFOX1—known to impact the splicing of ASD‐related genes. In the discussion of the molecular mechanisms influenced by these splicing factors, we lay the groundwork for a deeper understanding of ASD's complex etiology. Finally, we discuss the potential benefit of unraveling the connection between splicing and ASD for the development of more precise diagnostic tools and targeted therapeutic interventions.This article is categorized under: RNA in Disease and Development > RNA in Disease RNA Evolution and Genomics > RNA and Ribonucleoprotein Evolution RNA Evolution and Genomics > Computational Analyses of RNA RNA‐Based Catalysis > RNA Catalysis in Splicing and Translation

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Section: Splicing Factors Mutated In Asdmentioning

confidence: 99%

The spectrum of pre‐mRNA splicing in autism

Engal,

Zhang,

Geminder

et al. 2024

WIREs RNA

View full text Add to dashboard Cite

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“…Alternative splicing and co-expression analyses of total RNA from PBMC isolated from ASD twins and their parents has shown that zinc finger protein 322 ( ZNF322) and nuclear receptor subfamily 4 group A member 1 ( NR4A1) display differentially alternative splicing ( 154 ). ZNF322 is a member of the zinc-finger transcription factor family with a putative role in regulation of the ubiquitous MAPK signaling pathways ( 155 ) while NR4A1 is a key general regulator in the induction of T cell dysfunction ( 156 ).…”

Section: Immune System Involvement In Asdmentioning

confidence: 99%

Re-emerging concepts of immune dysregulation in autism spectrum disorders

et al. 2022

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Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by communication and social interaction deficits, and by restricted interests and stereotyped, repetitive behavior patterns. ASD has a strong genetic component and a complex architecture characterized by the interplay of rare and common genetic variants. Recently, increasing evidence suggest a significant contribution of immune system dysregulation in ASD. The present paper reviews the latest updates regarding the altered immune landscape of this complex disorder highlighting areas with potential for biomarkers discovery as well as personalization of therapeutic approaches. Cross-talk between the central nervous system and immune system has long been envisaged and recent evidence brings insights into the pathways connecting the brain to the immune system. Disturbance of cytokine levels plays an important role in the establishment of a neuroinflammatory milieu in ASD. Several other immune molecules involved in antigen presentation and inflammatory cellular phenotypes are also at play in ASD. Maternal immune activation, the presence of brain-reactive antibodies and autoimmunity are other potential prenatal and postnatal contributors to ASD pathophysiology. The molecular players involved in oxidative-stress response and mitochondrial system function, are discussed as contributors to the pro-inflammatory pattern. The gastrointestinal inflammation pathways proposed to play a role in ASD are also discussed. Moreover, the body of evidence regarding some of the genetic factors linked to the immune system dysregulation is reviewed and discussed. Last, but not least, the epigenetic traits and their interactions with the immune system are reviewed as an expanding field in ASD research. Understanding the immune-mediated pathways that influence brain development and function, metabolism, and intestinal homeostasis, may lead to the identification of robust diagnostic or predictive biomarkers for ASD individuals. Thus, novel therapeutic approaches could be developed, ultimately aiming to improve their quality of life.

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