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表观基因组学和转录组学在儿童哮喘预测与诊断中的应用:我们做到了吗?

Epigenomics and Transcriptomics in the Prediction and Diagnosis of Childhood Asthma: Are We There Yet?

作者信息

Forno Erick, Celedón Juan C

机构信息

Division of Pulmonary Medicine, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, United States.

Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.

出版信息

Front Pediatr. 2019 Apr 2;7:115. doi: 10.3389/fped.2019.00115. eCollection 2019.

Abstract

Asthma is the most common non-communicable chronic disease of childhood. Despite its high prevalence, to date we lack methods that are both efficient and accurate in diagnosing asthma. Most traditional approaches have been based on garnering clinical evidence, such as risk factors and exposures. Given the high heritability of asthma, more recent approaches have looked at genetic polymorphisms as potential "risk factors." However, genetic variants explain only a small proportion of asthma risk, and have been less than optimal at predicting risk for individual subjects. Epigenomic studies offer significant advantages over previous approaches. Epigenetic regulation is highly tissue-specific, and can induce both short- and long-term changes in gene expression. Such changes can start , can vary throughout the life span, and in some instances can be passed on from one generation to another. Most importantly, the epigenome can be modified by environmental factors and exposures, and thus epigenetic and transcriptomic profiling may yield the most accurate risk estimates for a given patient by incorporating environmental (and treatment) effects throughout the lifespan. Here we will review the most recent advances in the use of epigenetic and transcriptomic analysis for the early diagnosis of asthma and atopy, as well as challenges and future directions in the field as it moves forward. We will particularly focus on DNA methylation, the most studied mechanism of epigenetic regulation.

摘要

哮喘是儿童期最常见的非传染性慢性病。尽管其患病率很高,但迄今为止,我们仍缺乏高效且准确的哮喘诊断方法。大多数传统方法都基于收集临床证据,如风险因素和暴露情况。鉴于哮喘的高遗传性,最近的方法着眼于基因多态性作为潜在的“风险因素”。然而,基因变异仅解释了一小部分哮喘风险,在预测个体受试者的风险方面并不理想。表观基因组学研究比以前的方法具有显著优势。表观遗传调控具有高度的组织特异性,可诱导基因表达的短期和长期变化。这种变化可以启动,可以在整个生命周期中变化,并且在某些情况下可以代代相传。最重要的是,表观基因组可以被环境因素和暴露所修饰,因此表观遗传学和转录组学分析通过纳入整个生命周期的环境(和治疗)影响,可能为特定患者产生最准确的风险估计。在这里,我们将回顾表观遗传学和转录组学分析在哮喘和特应性疾病早期诊断中的最新进展,以及该领域在向前发展过程中的挑战和未来方向。我们将特别关注DNA甲基化,这是研究最多的表观遗传调控机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d5d/6454089/62529673bc6e/fped-07-00115-g0001.jpg

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