Variation in the Untranslated Genome and Susceptibility to Infections.
Variation in the Untranslated Genome and Susceptibility to Infections.
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DOI：
10.3389/fimmu.2018.02046
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发表时间：
2018
影响因子：
7.3
通讯作者：
Kulkarni S
中科院分区：
文献类型：
--
作者：
Ramsuran V;Ewy R;Nguyen H;Kulkarni S
感染的临床结果在个体之间是高度可变的，并由复杂的宿主-病原体相互作用决定。全基因组关联研究（GWAS）是揭示与疾病风险和临床结果相关的常见遗传变异的有力工具。然而，GWAS很少揭示确切的遗传元素及其关联背后的影响，因为大多数命中都在非编码区域。一些变异或相关多态性现在被发现具有功能意义，如蛋白质编码基因启动子和增强子区域的调控元件或蛋白质编码基因3 '非翻译区microRNA结合位点，它们影响蛋白质编码基因的转录、RNA稳定性和翻译。然而，整个转录组中只有3%是蛋白质编码的，这表明非编码rna代表了大多数转录本。因此，以前鉴定的基因间GWAS单核苷酸多态性（snp）的很大一部分是在非编码rna中。非编码rna在转录组中形成了一个大规模的调控网络，极大地扩展了基因调控的复杂性。越来越多的证据还表明，“非编码”基因组区域积极调节高度动态的三维（3D）染色质结构，这对基因组功能至关重要。表观遗传调控如DNA甲基化和组蛋白修饰进一步影响染色质可及性和基因表达，为与疾病结果相关的遗传变异的功能解释增加了另一层复杂性。我们概述了人类基因组这些“未翻译”区域的变异对传染病的影响的当前信息。本文综述的重点是传染病相关的多态性及其与病理生理相关的基因调控机制。
The clinical outcomes of infections are highly variable among individuals and are determined by complex host-pathogen interactions. Genome-wide association studies (GWAS) are powerful tools to unravel common genetic variations that are associated with disease risk and clinical outcomes. However, GWAS has only rarely revealed information on the exact genetic elements and their effects underlying an association because the majority of the hits are within non-coding regions. Some of the variants or the linked polymorphisms are now being discovered to have functional significance, such as regulatory elements in the promoter and enhancer regions or the microRNA binding sites in the 3′untranslated region of the protein-coding genes, which influence transcription, RNA stability, and translation of the protein-coding genes. However, only 3% of the entire transcriptome is protein-coding, signifying that non-coding RNAs represent most of the transcripts. Thus, a large portion of previously identified intergenic GWAS single nucleotide polymorphisms (SNPs) is in the non-coding RNAs. The non-coding RNAs form a large-scale regulatory network across the transcriptome, greatly expanding the complexity of gene regulation. Accumulating evidence also suggests that the “non-coding” genome regions actively regulate the highly dynamic three dimensional (3D) chromatin structures, which are critical for genome function. Epigenetic modulation like DNA methylation and histone modifications further affect chromatin accessibility and gene expression adding another layer of complexity to the functional interpretation of genetic variation associated with disease outcomes. We provide an overview of the current information on the influence of variation in these “untranslated” regions of the human genome on infectious diseases. The focus of this review is infectious disease-associated polymorphisms and gene regulatory mechanisms of pathophysiological relevance.
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影响因子：
3.8
作者：
Cezar-de-Mello PF;Toledo-Pinto TG;Marques CS;Arnez LE;Cardoso CC;Guerreiro LT;Antunes SL;Jardim MM;Covas Cde J;Illaramendi X;Dias-Baptista IM;Rosa PS;Durães SM;Pacheco AG;Ribeiro-Alves M;Sarno EN;Moraes MO
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6.4
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影响因子：
64.5
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通讯作者：
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影响因子：
9.8
作者：
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通讯作者：
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影响因子：
6.4
作者：
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通讯作者：
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