Structure of tumor necrosis factor-alpha haploblocks in European populations

Merino, Aimee; Zhang, Kui; Kaslow, Richard A.; Aissani, Brahim

doi:10.1007/s00251-013-0700-2

Cited by 10 publications

(7 citation statements)

References 62 publications

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“…Based on our previous haplotyping data for the present study population, the risk G-A-G-A haplotype is most likely carried on the TNF-α superhaplotype VI ( Supplementary Table S3 ( 24 )).…”

Section: Discussionmentioning

confidence: 84%

SNP screening of central MHC-identified HLA-DMB as a candidate susceptibility gene for HIV-related Kaposi’s sarcoma

et al. 2014

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The major histocompatibility complex (MHC) region on chromosome 6p21.3 is suspected to host susceptibility loci for HIV-related Kaposi’s sarcoma (HIV-KS). A nested case-control study in the Multicenter AIDS Cohort Study was designed to conduct fine genetic association mapping across central MHC. Individuals co-infected with HIV-1 and HHV-8 who later developed KS were defined as cases (n=354) and were matched 1:1 with co-infected KS-free controls. We report data for new independent MHC class II and III susceptibility loci. In particular, class II HLA-DMB emerged as a strong candidate, with the intronic variant rs6902982 A>G associated with a 4-fold increase of risk (OR= 4.09; 95% CI: 1.90–8.80; p= 0.0003). A striking multiplicative effect on the estimated risk was associated with further carriage of two non-synonymous variants, rs1800453 A>G (Asp697Gly) and rs4148880 A>G (Ile393Val), in the linked TAP1 gene (OR=10.5; 95% CI: 2.54–43.6; p=0.0012). The class III susceptibility variant is moderately associated with HIV-KS and lies within a 120 Kb-long haplotype (OR=1.52; 95% CI: 1.01–2.28; p=0.047) formed by rs7029 A>G (GPANK1 3’UTR), rs1065356 G>A (LY6G6C), rs3749953 A>G (MSH5-SAPCD1 readthrough) and rs707926 G>A (VARS). Our data suggest that antigen processing by MHC class II molecules is a target pathway in the pathogenesis of HIV-KS.

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Section: Discussionmentioning

confidence: 84%

SNP screening of central MHC-identified HLA-DMB as a candidate susceptibility gene for HIV-related Kaposi’s sarcoma

et al. 2014

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“… 52 The fusion gene 7.1323 could produce 17 fusion isoforms in pigs while it only produced two transcripts in humans and might induce immunologic and infectious diseases. 53 …”

Section: Resultsmentioning

confidence: 99%

A survey of transcriptome complexity in Sus scrofa using single-molecule long-read sequencing

Yao

Cui

et al. 2018

DNA Research

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Alternative splicing (AS) and fusion transcripts produce a vast expansion of transcriptomes and proteomes diversity. However, the reliability of these events and the extend of epigenetic mechanisms have not been adequately addressed due to its limitation of uncertainties about the complete structure of mRNA. Here we combined single-molecule real-time sequencing, Illumina RNA-seq and DNA methylation data to characterize the landscapes of DNA methylation on AS, fusion isoforms formation and lncRNA feature and further to unveil the transcriptome complexity of pig. Our analysis identified an unprecedented scale of high-quality full-length isoforms with over 28,127 novel isoforms from 26,881 novel genes. More than 92,000 novel AS events were detected and intron retention predominated in AS model, followed by exon skipping. Interestingly, we found that DNA methylation played an important role in generating various AS isoforms by regulating splicing sites, promoter regions and first exons. Furthermore, we identified a large of fusion transcripts and novel lncRNAs, and found that DNA methylation of the promoter and gene body could regulate lncRNA expression. Our results significantly improved existed gene models of pig and unveiled that pig AS and epigenetic modify were more complex than previously thought.

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“…There are two alleles at the polymorphic site, TNF-α -308G and TNF-α -308A. In normal populations, TNF-α-308G homozygosity is the predominant genotype [ 110 ]. The A allele of this polymorphism can lead to high binding affinity of nuclear factors to the TNF promoter, resulting in a high level of transcription activity and secretion levels of TNF-α [ 111 , 112 , 113 ].…”

Section: The Genetic Polymorphism Of Tnf-α In Mddmentioning

confidence: 99%

Pathogenetic and Therapeutic Applications of Tumor Necrosis Factor-α (TNF-α) in Major Depressive Disorder: A Systematic Review

Zhang

Baloch

2016

IJMS

168

100

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Major depressive disorder (MDD) is characterized by mood, vegetative, cognitive, and even psychotic symptoms and signs that can cause substantial impairments in quality of life and functioning. Up to now, the exact pathogenesis of MDD remains poorly understood. Recent research has begun to reveal that the pro-inflammatory cytokines, particularly, tumor necrosis factor-α (TNF-α), play an integral role in the pathophysiology of depressive disorders and the mechanism of antidepressant treatment. On the base of several observations: it is found that subsets of MDD patients have enhanced plasma levels TNF-α; antidepressant treatments had linked with the decline of TNF-α; central administration of TNF-α gives rise to sickness behavior which shares features with depression; and a blockade of it can ameliorate depressive symptomatology in animal models and clinical trials. In this review article, we focus on recent evidence linking TNF-α and MDD looking at data from animal and clinical studies, illustrating the pathophysiological role, susceptibility and its therapeutic application in depression. We conclude by discussing future directions for research, in particular the opportunities for the development of novel therapeutics that target TNF-α. This will be very important for designing preventative strategies and for the identification of new drug targets and preventative strategies.

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Structure of tumor necrosis factor-alpha haploblocks in European populations

Cited by 10 publications

References 62 publications

SNP screening of central MHC-identified HLA-DMB as a candidate susceptibility gene for HIV-related Kaposi’s sarcoma

SNP screening of central MHC-identified HLA-DMB as a candidate susceptibility gene for HIV-related Kaposi’s sarcoma

A survey of transcriptome complexity in Sus scrofa using single-molecule long-read sequencing

Pathogenetic and Therapeutic Applications of Tumor Necrosis Factor-α (TNF-α) in Major Depressive Disorder: A Systematic Review

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