Molecular Portrait of Potential Attention Deficit/ Hyperactivity Disorder Candidate Genes and Regulating Micrornas Expression in Normal Human Developing Brain Tissues
Main Article Content
Abstract
Attention-deficit/hyperactivity disorder (ADHD) is the most common neuropsychiatric disorder in childhood affecting 5-6% of children, and is a major global health concern, which seems to increase in magnitude. The etiology of ADHD is still poorly understood, however; there are indications of genetic as well as environmental and epigenetic factors contributing to the development of the disorder. The objectives of this study was i) to identify potential ADHD candidate genes; ii) to explore spatial and temporal transcriptional fluctuation of the identified ADHD candidate genes in normal developing human brain tissues, and iii) to identify miRNAs regulating the identified ADHD candidate genes and explore how these miRNAs are expressed in normal developing human brain tissues.
From search in literature and publicly available databases, we identified 103 shared potential ADHD candidate genes. These genes were expressed and enriched in several human brain regions and developmental stages. Clustering analysis of these genes based on their expression levels showed a clear difference between fetal stage and the other developmental stages. There was no clear gender or brain region differences between samples. Further, functional analysis of these genes revealed that they participate in a variety of different and widely distributed functional pathways implicated with ADHD.
From miRNA-target prediction analysis, we identified twenty miRNAs regulating the identified 103 genes, and the expression pattern of these miRNAs was developmental stage dependent. These miRNAs were enriched in functional pathways and disease ontologies relevant to neurodevelopment.
The knowledge of the expression pattern of potential ADHD candidate genes and miRNAs, which regulate these genes across different stages of brain development, is essential for understanding normal brain development and subsequent disease development of the brain. In addition, identification of miRNA-regulated ADHD candidate genes can be used to develop blood-based molecular markers to be investigated in future studies of ADHD patients.
Keywords:
Attention-deficit/hyperactivity disorder, ADHD, microRNA, epigenetics, neurodevelopment, transcription
Article Details
How to Cite
DYPÅS, Lene B. et al.
Molecular Portrait of Potential Attention Deficit/ Hyperactivity Disorder Candidate Genes and Regulating Micrornas Expression in Normal Human Developing Brain Tissues.
Medical Research Archives, [S.l.], v. 8, n. 9, sep. 2020.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/2214>. Date accessed: 25 apr. 2024.
doi: https://doi.org/10.18103/mra.v8i9.2214.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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22. Camkurt MA, Karababa F, Erdal ME, Bayazıt H, Kandemir SB, Ay ME, et al. Investigation of Dysregulation of Several MicroRNAs in Peripheral Blood of Schizophrenia Patients. Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology. 2016;14(3):256-60.
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28. Kovács-Nagy R, Hu J, Rónai Z, Sasvári-Székely M. SNAP-25: a novel candidate gene in psychiatric genetics. Neuropsychopharmacologia Hungarica : a Magyar Pszichofarmakologiai Egyesulet lapja = official journal of the Hungarian Association of Psychopharmacology. 2009;11(2):89-94.
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32. Aydin SU, Kabukcu Basay B, Cetin GO, Gungor Aydin A, Tepeli E. Altered microRNA 5692b and microRNA let-7d expression levels in children and adolescents with attention deficit hyperactivity disorder. Journal of psychiatric research. 2019;115:158-64.
33. Sánchez-Mora C, Soler Artigas M, Garcia-Martínez I, Pagerols M, Rovira P, Richarte V, et al. Epigenetic signature for attention-deficit/hyperactivity disorder: identification of miR-26b-5p, miR-185-5p, and miR-191-5p as potential biomarkers in peripheral blood mononuclear cells. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 2019;44(5):890-7.
34. Cao P, Wang L, Cheng Q, Sun X, Kang Q, Dai L, et al. Changes in serum miRNA-let-7 level in children with attention deficit hyperactivity disorder treated by repetitive transcranial magnetic stimulation or atomoxetine: An exploratory trial. Psychiatry research. 2019;274:189-94.
35. Zhang L, Chang S, Li Z, Zhang K, Du Y, Ott J, et al. ADHDgene: a genetic database for attention deficit hyperactivity disorder. Nucleic Acids Res. 2012;40(Database issue):D1003-9.
36. Piñero J, Bravo À, Queralt-Rosinach N, Gutiérrez-Sacristán A, Deu-Pons J, Centeno E, et al. DisGeNET: a comprehensive platform integrating information on human disease-associated genes and variants. Nucleic Acids Res. 2017;45(D1):D833-d9.
37. Stelzer G, Rosen N, Plaschkes I, Zimmerman S, Twik M, Fishilevich S, et al. The GeneCards Suite: From Gene Data Mining to Disease Genome Sequence Analyses. Current protocols in bioinformatics. 2016;54:1.30.1-1..3.
38. Alonso-Gonzalez A, Calaza M, Rodriguez-Fontenla C, Carracedo A. Gene-based analysis of ADHD using PASCAL: a biological insight into the novel associated genes. BMC medical genomics. 2019;12(1):143.
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