A global map for dissecting phenotypic variants in human lincRNAs

Ning, Shangwei; Wang, Peng; Ye, Jingrun; Li, Xiang; Li, Ronghong; Zhao, Zhenqun; Huo, Xiao; Wang, Li; Li, Feng; Li, Xia

doi:10.1038/ejhg.2013.7

Cited by 25 publications

(20 citation statements)

References 45 publications

(51 reference statements)

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“…200 nt that do not contain an open reading frame; although their biological meaning and function still need to be elucidated, ample evidence, including specific subcellular localization, tissue specificity, and association with disease, indicates that they may be essential regulators of cell function (27)(28)(29). The importance of lncRNAs in MS is highlighted by recent studies showing that various SNPs associated with MS in GWAS are located in genomic regions that code for lncRNAs (30) or regulate lncRNA expression in cis in human monocytes (31). Abundant expression of ANKRD55 007 in CD4 + T cells may be an indication of the unique cell-specific functional role for this noncoding RNA; it is an intriguing finding that merits further investigation.…”

Section: Discussionmentioning

confidence: 99%

Novel Insights into the Multiple Sclerosis Risk Gene ANKRD55

Lapuente

Feliú

Ugidos

et al. 2016

The Journal of Immunology

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An intronic variant in ANKRD55, rs6859219, is a genetic risk factor for multiple sclerosis, but the biological reasons underlying this association are unknown. We characterized the expression of ANKRD55 in human PBMCs and cell lines. Three ANKRD55 transcript variants (Ensembl isoforms 001, 005, and 007) could be detected in PBMCs and CD4+ T cells but were virtually absent in CD8+, CD14+, CD19+, and CD56+ cells. Rs6859219 was significantly associated with ANKRD55 transcript levels in PBMCs and CD4+ T cells and, thus, coincides with a cis-expression quantitative trait locus. The processed noncoding transcript 007 was the most highly expressed variant in CD4+ T cells, followed by 001 and 005, respectively, but it was not detected in Jurkat, U937, and SH-SY5Y cell lines. Homozygotes for the risk allele produced more than four times more transcript copies than did those for the protective allele. ANKRD55 protein isoforms 005 and 001 were predominantly located in the nucleus of CD4+ T cells and Jurkat and U937 cells. ANKRD55 was produced by primary cultures of murine hippocampal neurons and microglia, as well as by the murine microglial cell line BV2, and it was induced by inflammatory stimuli. ANKRD55 protein was increased in the murine mouse model of experimental autoimmune encephalomyelitis. Flow cytometric analysis of CNS-infiltrating mononuclear cells showed that CD4+ T cells and monocytes expressed ANKRD55 in experimental autoimmune encephalomyelitis mice, with the higher fluorescence intensity found in CD4+ cells. A low percentage of microglia also expressed ANKRD55. Together, these data support an important role for ANKRD55 in multiple sclerosis and neuroinflammation.

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Section: Discussionmentioning

confidence: 99%

Novel Insights into the Multiple Sclerosis Risk Gene ANKRD55

Lapuente

Feliú

Ugidos

et al. 2016

The Journal of Immunology

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“…47 A number of studies examined the implication of lincRNAs in complex diseases based on GWAS studies (LincPoly 48 , LincSNP 49 ). These studies represent initial efforts to integrate disease-associated SNPs and human lincRNAs, but both datasets do not include complete GWAS SNP data, and focus on only a few thousand lincRNAs.…”

Section: The Tools Of Functional Genomicsmentioning

confidence: 99%

From Loci to Biology

Nürnberg

Zhang

Hand

et al. 2016

Circulation Research

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Genome-wide association studies (GWAS) have provided a rich collection of ~58 CAD loci that suggest the existence of previously unsuspected new biology relevant to atherosclerosis. However, these studies only identify genomic loci associated with CAD and many questions remain even after a genomic locus is definitively implicated, including the nature of the causal variant(s) and the causal gene(s), as well as the directionality of effect. There are a number of tools that can be employed for investigation of the functional genomics of these loci, and progress has been made on a limited number of novel CAD loci. New biology regarding atherosclerosis and CAD will be learned through the functional genomics of these loci and the hope is that at least some of these new pathways relevant to CAD pathogenesis will yield new therapeutic targets for the prevention and treatment of CAD.

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“…For example, rs6475606, rs564398 and rs496892, rs1063192, and rs2151280 modify susceptibility to intracranial aneurysm, large-vessel ischemic stroke, glioma, and plexiform neurofibroma, respectively. Other correlations between lncRNA polymorphisms and disease are actively being investigated [79]. One study analyzed data from the Alzheimer Disease (AD) Neuroimaging Initiative and reported that the rs7990916:T> C polymorphism in the brain-specific, rapidly evolving lincRNA, TCONS_00021856/linc-SLITRK5-11, is associated with regional cortical gray matter volumes in normal controls and in patients with mild cognitive impairment and AD [80].…”

Section: Establishing Paradigms For Lncrna-related Pathologymentioning

confidence: 99%

Long Non-coding RNAs: Novel Targets for Nervous System Disease Diagnosis and Therapy

2013

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The human genome encodes tens of thousands of long non-coding RNAs (lncRNAs), a novel and important class of genes. Our knowledge of lncRNAs has grown exponentially since their discovery within the last decade. lncRNAs are expressed in a highly cell-and tissue-specific manner, and are particularly abundant within the nervous system. lncRNAs are subject to post-transcriptional processing and inter-and intra-cellular transport. lncRNAs act via a spectrum of molecular mechanisms leveraging their ability to engage in both sequence-specific and conformational interactions with diverse partners (DNA, RNA, and proteins). Because of their size, lncRNAs act in a modular fashion, bringing different macromolecules together within the three-dimensional context of the cell. lncRNAs thus coordinate the execution of transcriptional, post-transcriptional, and epigenetic processes and critical biological programs (growth and development, establishment of cell identity, and deployment of stress responses). Emerging data reveal that lncRNAs play vital roles in mediating the developmental complexity, cellular diversity, and activitydependent plasticity that are hallmarks of brain. Corresponding studies implicate these factors in brain aging and the pathophysiology of brain disorders, through evolving paradigms including the following: (i) genetic variation in lncRNA genes causes disease and influences susceptibility; (ii) epigenetic deregulation of lncRNAs genes is associated with disease; (iii) genomic context links lncRNA genes to disease genes and pathways; and (iv) lncRNAs are otherwise interconnected with known pathogenic mechanisms. Hence, Electronic supplementary material The online version of this article

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A global map for dissecting phenotypic variants in human lincRNAs

Cited by 25 publications

References 45 publications

Novel Insights into the Multiple Sclerosis Risk Gene ANKRD55

Novel Insights into the Multiple Sclerosis Risk Gene ANKRD55

From Loci to Biology

Long Non-coding RNAs: Novel Targets for Nervous System Disease Diagnosis and Therapy

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