Review Volume 11, Issue 22 pp 10742—10770
Association of genes with phenotype in autism spectrum disorder
- 1 Research Branch, Sidra Medicine, Doha, Qatar
- 2 Department of Psychiatry, Sidra Medicine, Doha, Qatar
- 3 Weill Cornell Medicine, Doha, Qatar
- 4 Translational Research Institute, Hamad Medical Corporation, Doha, Qatar
- 5 Center for Magnetic Resonance and Optical Imaging, Department of Radiology, Perelman School of Medicine at The University of Pennsylvania, Philadelphia, PA 19104, USA
- 6 Laboratory Animal Research Center, Qatar University, Doha, Qatar
Received: August 5, 2019 Accepted: November 8, 2019 Published: November 19, 2019
https://doi.org/10.18632/aging.102473How to Cite
Copyright © 2019 Nisar et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Autism spectrum disorder (ASD) is a genetic heterogeneous neurodevelopmental disorder that is characterized by impairments in social interaction and speech development and is accompanied by stereotypical behaviors such as body rocking, hand flapping, spinning objects, sniffing and restricted behaviors. The considerable significance of the genetics associated with autism has led to the identification of many risk genes for ASD used for the probing of ASD specificity and shared cognitive features over the past few decades. Identification of ASD risk genes helps to unravel various genetic variants and signaling pathways which are involved in ASD. This review highlights the role of ASD risk genes in gene transcription and translation regulation processes, as well as neuronal activity modulation, synaptic plasticity, disrupted key biological signaling pathways, and the novel candidate genes that play a significant role in the pathophysiology of ASD. The current emphasis on autism spectrum disorders has generated new opportunities in the field of neuroscience, and further advancements in the identification of different biomarkers, risk genes, and genetic pathways can help in the early diagnosis and development of new clinical and pharmacological treatments for ASD.
Abbreviations
ASD: autism spectrum disorder; FXS: fragile-X Syndrome; CNV: copy number variation; CDFE: cortical Dysplasia-focal Epilepsy; GWAS: genome-wide association studies; SNP: single nucleotide polymorphism; GABARAPL1: GABA type A receptor associated protein; DBI: Diazepam binding inhibitor; DYRK1A: dual-specificity tyrosine phosphorylation-regulated kinase 1A; ASS: argininosuccinate synthetase; NO: nitric Oxide; PC: Purkinje cells; NT: neurotrophin; PSD: postsynaptic density; NETBAG: network-based analysis of genetic associations; DCC: deleted in colorectal carcinoma; PAK: p21-activated kinase; LIMK: LIM-domain containing protein kinase; LCR: low copy repeats; CACNA1C: calcium voltage-gated channel subunit alpha1 C; Pk2: Prickle2; COX-2: cyclooxygenase-2; SV: synaptic vesicle; HGF: hepatocyte growth factor; LTP: long term synaptic potentiation; CaN: calcineurin; PKC: protein kinase-C; CaM: calmodulin; SHH: sonic hedgehog; CNS: central nervous system; PTCHD: patched domain-containing 1; EN2: engrailed-2; DHCR7: 7-dehydrocholesterol reductase; RORA: retinoic acid-related orphan receptor alpha; RAR: retinoic acid receptor; RXR: retinoid X receptor; FGF: fibroblast growth factor; BMP: bone morphogenetic protein; DLX: distal-less homeobox; Bmper: BMP-binding endothelial regulator; CMA: chromosomal microarray; NGS: next generation sequencing; WGS: whole-genome sequencing; WES: whole-exome sequencing; GSK3: glycogen synthase kinase 3; CK1: casein kinase 1; APC: adenomatous polyposis coli; DVL: Dishevelled; FZD9-Frizzled 9; TCF: T cell factor; MET: hepatocyte growth factor receptor; NMDAR: N-methyl-D-aspartate receptor; TSC1/2: Tuberous sclerosis 1 and 2; DISC1: Disrupted in Schizophrenia 1; NRXN: Neurexin; NLGN: Neuroligin; SYN1: Synapsin 1; SYT: Synaptotagmin; CaN: Calcineurin; CREB: cAMP response element binding; PP1: Protein phosphatase 1; PP2A: Protein phosphatase 2A; DOCK4: dedicator of cytokinesis 4; KATNAL2: katanin catalytic Subunit A1 Like 2; KCNQ4: potassium voltage-gated channel subfamily Q member 4; CNTNAP2: contactin associated protein 2; COL11A1: collagen type XI alpha 1 chain; FMR1: fragile-X mental retardation 1; FOXP1: forkhead box P1; GJB6: gap junction protein beta 6; GRIN2B: glutamate ionotropic receptor NMDA type subunit 2B; MYH14: myosin heavy chain 14; SCN1A: sodium voltage-gated channel alpha subunit 1; SCN2A: sodium voltage-gated channel alpha subunit 2; SHANK3: SH3 and multiple ankyrin repeat domains 3; Syngap1: synaptic ras GTPase activating protein 1; THRA: thyroid hormone receptor, alpha; UBE3A: ubiquitin protein ligase E3A; Wnt: wingless-type; ANK3: Ankyrin-3; PGE2: prostaglandin E2; CTNNB1: catenin beta 1; TBR1: T-box, brain 1; MOCOS: molybdenum cofactor sulfurase; TBL1XR1: transducin beta like 1 X-linked receptor 1; CYFIP1: cytoplasmic FMR1 interacting protein 1; CNTN3: contactin 3; PCDH10: protocadherin 10; DIA1: deleted in autism 1; SLC9A9: solute carrier family 9 member A9; GLRA2: glycine receptor alpha 2; SEMA5A: semaphorin 5A; MACROD2: mono-ADP ribosylhydrolase 2; CHD2: chromodomain helicase DNA binding protein 2; HDAC: histone deacetylase 4; HDAC9: histone deacetylase 9; GDI1: GDP dissociation inhibitor 1; SETD5: SET domain containing 5; MIR137: microRNA 137; SLC6A11: solute carrier family 6 member 11; SLC6A8: solute carrier family 6 member 8.