{"title":"对与ADHD相关基因3’UTR SNPs相关的miRNA靶位点的计算分析","authors":"Adel Abdi, Mina Zafarpiran, Z. S. Farsani","doi":"10.2174/1871524919666191014104843","DOIUrl":null,"url":null,"abstract":"Background: Attention-deficit/hyperactivity disorder (ADHD) is a frequent chronic neuropsychiatric disorder in which different factors including environmental, genetic, and epigenetic factors play an important role in its pathogenesis. One of the effective epigenetic factors is recognized as MicroRNAs (miRNAs). On the other hand, it has been indicated that the single nucleotide polymorphism (SNPs) present within 3'UTR (3' untranslated region) of mRNAs can influence the regulation of miRNA-mediated gene and susceptibility to a diversity of human diseases. Methods: The purpose of this study was to analyze the SNPs within the 3'UTR of miRNA target genes associated with ADHD . 3'UTR genetic variants were identified in all genes associated with ADHD using DisGeNET, dbGaP, Ovid, DAVID, Web of knowledge, and SNPs databases. miRNA's target prediction databases were applied in order to predict the miRNA binding sites. 124 SNPs with MAF>0.05 were identified located in the binding site of the miRNA of 35 genes amongst 51 genes associated with ADHD. Results: Bioinformatics analysis predicted 81 MRE (miRNA recognition elements)-creating SNPs, 101 MRE-breaking SNPs, 61 MRE-enhancing SNPs, and finally predicted 41 MRE-decreasing SNPs in the 3'UTR of ADHD-implicated genes. These candidate SNPs within these genes miRNA binding sites can alter the miRNAs binding, and consequently, lead to mRNA gene regulation. Conclusion: Therefore, these miRNA and MRE-SNPs may play important roles in ADHD, and because of that, they would be valuable for further investigation in the field of functional verification.","PeriodicalId":9799,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":"20 1","pages":"58 - 75"},"PeriodicalIF":0.0000,"publicationDate":"2020-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1871524919666191014104843","citationCount":"6","resultStr":"{\"title\":\"The Computational Analysis Conducted on miRNA Target Sites in Association with SNPs at 3’UTR of ADHD-implicated Genes\",\"authors\":\"Adel Abdi, Mina Zafarpiran, Z. S. Farsani\",\"doi\":\"10.2174/1871524919666191014104843\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Background: Attention-deficit/hyperactivity disorder (ADHD) is a frequent chronic neuropsychiatric disorder in which different factors including environmental, genetic, and epigenetic factors play an important role in its pathogenesis. One of the effective epigenetic factors is recognized as MicroRNAs (miRNAs). On the other hand, it has been indicated that the single nucleotide polymorphism (SNPs) present within 3'UTR (3' untranslated region) of mRNAs can influence the regulation of miRNA-mediated gene and susceptibility to a diversity of human diseases. Methods: The purpose of this study was to analyze the SNPs within the 3'UTR of miRNA target genes associated with ADHD . 3'UTR genetic variants were identified in all genes associated with ADHD using DisGeNET, dbGaP, Ovid, DAVID, Web of knowledge, and SNPs databases. miRNA's target prediction databases were applied in order to predict the miRNA binding sites. 124 SNPs with MAF>0.05 were identified located in the binding site of the miRNA of 35 genes amongst 51 genes associated with ADHD. Results: Bioinformatics analysis predicted 81 MRE (miRNA recognition elements)-creating SNPs, 101 MRE-breaking SNPs, 61 MRE-enhancing SNPs, and finally predicted 41 MRE-decreasing SNPs in the 3'UTR of ADHD-implicated genes. These candidate SNPs within these genes miRNA binding sites can alter the miRNAs binding, and consequently, lead to mRNA gene regulation. Conclusion: Therefore, these miRNA and MRE-SNPs may play important roles in ADHD, and because of that, they would be valuable for further investigation in the field of functional verification.\",\"PeriodicalId\":9799,\"journal\":{\"name\":\"Central nervous system agents in medicinal chemistry\",\"volume\":\"20 1\",\"pages\":\"58 - 75\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2020-04-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.2174/1871524919666191014104843\",\"citationCount\":\"6\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Central nervous system agents in medicinal chemistry\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.2174/1871524919666191014104843\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"Psychology\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Central nervous system agents in medicinal chemistry","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2174/1871524919666191014104843","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"Psychology","Score":null,"Total":0}
引用次数: 6
摘要
背景:注意力缺陷/多动障碍(ADHD)是一种常见的慢性神经精神障碍,包括环境、遗传和表观遗传因素在内的多种因素在其发病机制中发挥着重要作用。有效的表观遗传因子之一被认为是微小RNA(miRNA)。另一方面,已经表明存在于mRNA的3'UTR(3'非翻译区)内的单核苷酸多态性(SNPs)可以影响miRNA介导的基因的调节和对多种人类疾病的易感性。方法:本研究的目的是分析与多动症相关的miRNA靶基因3'UTR内的SNPs。使用DisGeNET、dbGaP、Ovid、DAVID、Web of knowledge和SNPs数据库在所有与多动症相关的基因中鉴定了3’UTR基因变体。应用miRNA的靶预测数据库来预测miRNA结合位点。在51个ADHD相关基因中,有124个MAF>0.05的SNPs位于35个基因的miRNA结合位点。结果:生物信息学分析预测了81个MRE(miRNA识别元件)产生SNPs,101个MRE破坏SNPs,61个MRE增强SNPs,并最终预测了41个MRE降低SNPs在ADHD相关基因的3'UTR中。这些基因中的这些候选SNPs miRNA结合位点可以改变miRNA的结合,从而导致mRNA基因调控。结论:因此,这些miRNA和MRE SNPs可能在多动症中发挥重要作用,因此,它们对功能验证领域的进一步研究具有价值。
The Computational Analysis Conducted on miRNA Target Sites in Association with SNPs at 3’UTR of ADHD-implicated Genes
Background: Attention-deficit/hyperactivity disorder (ADHD) is a frequent chronic neuropsychiatric disorder in which different factors including environmental, genetic, and epigenetic factors play an important role in its pathogenesis. One of the effective epigenetic factors is recognized as MicroRNAs (miRNAs). On the other hand, it has been indicated that the single nucleotide polymorphism (SNPs) present within 3'UTR (3' untranslated region) of mRNAs can influence the regulation of miRNA-mediated gene and susceptibility to a diversity of human diseases. Methods: The purpose of this study was to analyze the SNPs within the 3'UTR of miRNA target genes associated with ADHD . 3'UTR genetic variants were identified in all genes associated with ADHD using DisGeNET, dbGaP, Ovid, DAVID, Web of knowledge, and SNPs databases. miRNA's target prediction databases were applied in order to predict the miRNA binding sites. 124 SNPs with MAF>0.05 were identified located in the binding site of the miRNA of 35 genes amongst 51 genes associated with ADHD. Results: Bioinformatics analysis predicted 81 MRE (miRNA recognition elements)-creating SNPs, 101 MRE-breaking SNPs, 61 MRE-enhancing SNPs, and finally predicted 41 MRE-decreasing SNPs in the 3'UTR of ADHD-implicated genes. These candidate SNPs within these genes miRNA binding sites can alter the miRNAs binding, and consequently, lead to mRNA gene regulation. Conclusion: Therefore, these miRNA and MRE-SNPs may play important roles in ADHD, and because of that, they would be valuable for further investigation in the field of functional verification.
期刊介绍:
Central Nervous System Agents in Medicinal Chemistry aims to cover all the latest and outstanding developments in medicinal chemistry and rational drug design for the discovery of new central nervous system agents. Containing a series of timely in-depth reviews written by leaders in the field covering a range of current topics, Central Nervous System Agents in Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments in the field.