Table 1 The most important differentially methylated genes in ASD-Placenta with predictive or pathways relevance value
From: Placental DNA methylation profile as predicting marker for autism spectrum disorder (ASD)
Gene | Chromosome | Methylation | Product | Gene function | SFARI | Significance | Relevance | References |
|---|---|---|---|---|---|---|---|---|
NOS1AP | 1q23.3 | Increased | Neuronal nitric oxide synthase 1 adaptor protein | Functions as an adapter protein connecting nNOS to specific targets like synapsins | N | GWS | Predictive | Bahado-Singh et al. (2021b) |
WNT2B | 1p13.2 | Increased | Wnt Family Member 2B | Play a role in the canonical Wnt/beta-catenin signaling pathway | N | GWS | Microtubule dynamics pathway | Bahado-Singh et al. (2021b) |
WNT10A | 2q35 | Decreased | Wnt Family Member 10A | Functions in the canonical Wnt/beta-catenin signaling pathway | N | GWS | Microtubule dynamics pathway | Bahado-Singh et al. (2021b) |
CAMK2D | 4q26 | Increased | Calcium/Calmodulin-Dependent Protein Kinase Type II Delta Chain | Intracellular calcium signaling | N | GWS | Quantity of synapse pathway | Bahado-Singh et al. (2021b) |
NEUROG2 | 4q25 | Decreased | Neural-specific basic helix-loop-helix (bHLH) transcription factor | Specify progenitors to a neuronal fate on ectodermal cells and reprograms early postnatal astroglia to develop neurons | N | NS | Abnormal morphology of neurons pathway | Bahado-Singh et al. (2021b) |
NKX2-5 | 5q35.1 | Increased | Homeobox Protein Nkx-2.5 transcription factor | Functions in heart and the spleen development | N | GWS | Predictive | Bahado-Singh et al. (2021a) |
DLL1 | 6q27 | Increased/decreased | Encodes the Delta-like1 ligand of Notch receptors | Regulates neurogenesis, neurons differentiation, quiescence of neural stem cells and plays a role as a fate determinant during neural stem cells mitosis | Y | GWS | Predictive | |
POU3F2 | 6q16.1 | Decreased | POU Domain, Class 3, Transcription Factor 2 | Neuronal differentiation and promoting the activation of corticotropin-releasing hormone regulated genes | N | NS | Abnormal morphology of neurons pathway | Bahado-Singh et al. (2021b) |
NRN1 | 6p25.1 | Increased | Neuritin | Promotes neurite outgrowth and arborisation during neuritogenesis | N | GWS | Predictive | Bahado-Singh et al. (2021a) |
AUTS2 | 7q11.22 | Decreased | Autism Susceptibility Gene 2 Protein | Contributes to dendrite and axon elongation and neuronal migration. It enhances rearrangement of the actin cytoskeleton, lamellipodia shaping and neurite elongation | Y | GWS | Neuritogenesis pathway | |
CUX1 | 7q22.1 | Increased | Homeobox Protein Cux-1 | Encodes a transcription factor that controls neuronal differentiation in the brain, regulates dendrite development and branching, and dendritic spine formation in cortical layers II-III. It also play a controlling role during synaptogenesis | Y | GWS | Neuritogenesis pathway | Bahado-Singh et al. (2021b) |
WNT2 | 7q31.2 | Decreased | Wnt Family Member 2 | Functions in the canonical Wnt/beta-catenin signaling pathway and likely involved in embryonic brain development by controlling the proliferation of dopaminergic precursors and neurons | N | GWS | Microtubule dynamics pathway | Bahado-Singh et al. (2021b) |
GPNMB | 7p15.3 | Increased | Glycoprotein Nonmetastatic Melanoma Protein B | May be involved in growth delay and reduction of metastatic potential and could be a melanogenic enzyme | N | GWS | Predictive | Bahado-Singh et al. (2021a) |
MYC | 8q24.21 | Decreased | Nuclear phosphoprotein (BHLH Transcription Factor) | Plays a role in cell cycle progression, apoptosis and cellular transformation | N | GWS | Microtubule dynamics pathway | Bahado-Singh et al. (2021b) |
CYP2E1 | 10q26.3 | Decreased | A member of cytochrome P450 superfamily | Contributes to catalysing reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids Involved in the metabolism of drugs | N | GWS | Abnormal morphology of neurons pathway | Bahado-Singh et al. (2021a), Bahado-Singh et al. (2021b), Zhu et al. (2019) |
AFAP1L2 | 10q25.3 | Increased | Actin Filament-Associated Protein 1-Like 2 | Plays several roles including positive regulation of epidermal growth factor receptor signaling pathway, regulation of gene expression; and controlling mitotic cell cycle | N | GWS | Predictive | Bahado-Singh et al. (2021b) |
DGKZ | 11p11.2 | Decreased | Diacylglycerol Kinase Zeta | Reduces protein kinase C activity by controlling diacylglycerol levels in intracellular signaling cascade and signal transduction | N | NS only in maternal side | Predictive | |
CHST11 | 12q23.3 | NA | Carbohydrate Sulfotransferase 11 | Catalyzes the transfer of sulfate to N-acetylgalactosamine (GalNAc) residue of chondroitin in cartilage and on the surfaces of cells and extracellular matrices | N | GWS in one CpG site, cg09418354 | Predictive | Santos Jr et al. (2020) |
WNT1 | 12q13.12 | Decreased | Wnt Family Member 1 | Functions in the canonical Wnt/beta-catenin signaling pathway and play a key role in the developing embryonic brain and central nervous system (CNS) | Y | GWS | Microtubule dynamics pathway | Bahado-Singh et al. (2021b) |
IRS2 | 13q34 | Increased/decreased | Encodes insulin receptor substrate 2 | A cytoplasmic signalling molecule that mediates the influence of insulin and insulin-like growth factor 1 (IGF1) and cytokine receptors | N | GWS | Predictive | |
ZNF267 | 16p11.2 | Increased | Zinc Finger Protein 267 | Activates DNA-binding transcription activator function, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity | N | GWS | Predictive | Bahado-Singh et al. (2021a) |
ZNF217 | 20q13.2 | Increased | Zinc Finger Protein 217 | Activates DNA-binding transcription repressor function, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity and regulates neuron-specific genes such as CoREST and HDAC2 | N | GWS | Predictive | Bahado-Singh et al. (2021a) |
NHIP | 22q13.33 | Decreased | lncRNA | Hypoxia responsive regulatory gene | N | GWS | Predictive | Zhu et al. (2022) |
WNT7B | 22q13.31 | Increased | Wnt Family Member 7B | Functions in the canonical Wnt/beta-catenin signaling pathway and is necessary for central nervous system (CNS) angiogenesis and blood–brain barrier regulation | N | GWS | Microtubule dynamics pathway | Bahado-Singh et al. (2021b) |
GRIPAP1 | Xp11.23 | Increased | GRIP1 Associated Protein 1 | Involved in neuronal cytoskeleton organization | N | GWS | Predictive | Bahado-Singh et al. (2021b) |
MOSPD1 | Xq26.3 | Increased | Motile Sperm Domain Containing 1 | Mesenchymal stem cells (MSCs) proliferation and differentiation | N | GWS | Predictive | Bahado-Singh et al. (2021b) |