Dataset Information

Single nucleotide polymorphisms in the 3'UTR of VPAC-1 cooperate in modulating gene expression and impact differently on the interaction with miR525-5p.

ABSTRACT: Complex immune and neurodegenerative disorders are the result of multiple interactions between common genetic variations having, individually, a weak effect on the disease susceptibility or resistance. Interestingly, some genes have been found to be associated with more than one disease although not necessarily the same SNPs are involved. In this context, single nucleotide polymorphisms in the 3'UTR region of type 1 receptor (VPAC-1) for vasoactive intestinal peptide (VIP) have been reported to be associated with some immune-mediated as well as with neurodegenerative diseases such as Alzheimer's Disease (AD). Here, we demonstrate that variations at the 3'UTR of the VPAC-1 gene act synergistically to affect the expression of the luciferase as well as of the GFP reporter genes expressed in HEK293T cells. Moreover, the miRNA 525-5p, previously shown by us to target the 3'UTR of VPAC-1, is more efficient in decreasing GFP expression when co-expressed with constructs carrying the allele C at rs896 (p<10(-3)) suggesting that this miRNA regulates VPAC-1 expression at different levels depending on rs896 polymorphism and thus adding complexity to the network of disease susceptibility.

SUBMITTER: Paladini F

PROVIDER: S-EPMC4229240 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Single nucleotide polymorphisms in the 3'UTR of VPAC-1 cooperate in modulating gene expression and impact differently on the interaction with miR525-5p.

Paladini Fabiana F Porciello Nicla N Camilli Giorgio G Tuncer Sinem S Cocco Elisa E Fiorillo Maria Teresa MT Sorrentino Rosa R

PloS one 20141112 11

Complex immune and neurodegenerative disorders are the result of multiple interactions between common genetic variations having, individually, a weak effect on the disease susceptibility or resistance. Interestingly, some genes have been found to be associated with more than one disease although not necessarily the same SNPs are involved. In this context, single nucleotide polymorphisms in the 3'UTR region of type 1 receptor (VPAC-1) for vasoactive intestinal peptide (VIP) have been reported to ...[more]

PMID: 25390694

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Project description:Single-nucleotide polymorphisms (SNPs) provide an abundant source of DNA polymorphisms in a number of eukaryotic species. Information on the frequency, nature, and distribution of SNPs in plant genomes is limited. Thus, our objectives were (1) to determine SNP frequency in coding and noncoding soybean (Glycine max L. Merr.) DNA sequence amplified from genomic DNA using PCR primers designed to complete genes, cDNAs, and random genomic sequence; (2) to characterize haplotype variation in these sequences; and (3) to provide initial estimates of linkage disequilibrium (LD) in soybean. Approximately 28.7 kbp of coding sequence, 37.9 kbp of noncoding perigenic DNA, and 9.7 kbp of random noncoding genomic DNA were sequenced in each of 25 diverse soybean genotypes. Over the >76 kbp, mean nucleotide diversity expressed as Watterson's theta was 0.00097. Nucleotide diversity was 0.00053 and 0.00111 in coding and in noncoding perigenic DNA, respectively, lower than estimates in the autogamous model species Arabidopsis thaliana. Haplotype analysis of SNP-containing fragments revealed a deficiency of haplotypes vs. the number that would be anticipated at linkage equilibrium. In 49 fragments with three or more SNPs, five haplotypes were present in one fragment while four or less were present in the remaining 48, thereby supporting the suggestion of relatively limited genetic variation in cultivated soybean. Squared allele-frequency correlations (r(2)) among haplotypes at 54 loci with two or more SNPs indicated low genome-wide LD. The low level of LD and the limited haplotype diversity suggested that the genome of any given soybean accession is a mosaic of three or four haplotypes. To facilitate SNP discovery and the development of a transcript map, subsets of four to six diverse genotypes, whose sequence analysis would permit the discovery of at least 75% of all SNPs present in the 25 genotypes as well as 90% of the common (frequency >0.10) SNPs, were identified.

Project description:BackgroundEsophageal, stomach, and colorectal cancers are commonly lethal gastrointestinal tract (GIT) neoplasms, causing almost two million deaths worldwide each year. some environmental risk factors are acknowledged; however, genetic defects can significantly contribute to predisposition to GIT cancers. Accordingly, recent works have shown that single-nucleotide polymorphisms (SNPs) within miRNAs coding sequence (miR-SNPs) and miRNA target sites (target-SNPs) may further contribute to increased risk of developing cancer.ObjectivesIn this study, we comprehensively identified miRNA-target gene pairs implicated in GIT cancers and catalogued the presence of potentially functional miR-SNPs and target-SNPs that impair the correct functional recognition.Materials and methodsUsing bioinformatics tools, manual literature review, and a highly accurate dataset of experimentally validated miRNA-target gene interactions, we compiled a list of miRNA-target genes pairs related to GIT cancers and prioritized them into different groups based on the levels of experimental support. Functional annotations (gene ontology) were applied to these pairs in each group to gain further information.ResultsWe identified 97 pairs in which both miRNAs and target genes were implicated in GIT cancers. Several pairs, denoted as highly polymorphic pairs, had both miR-SNPs and target-SNPs. In addition, more than 5000 miRNA-target gene pairs were identified in which, according to the previous reports, either the miRNAs or the target genes had a direct involvement in GIT cancers. More than 800 target-SNPs are located in regulatory regions that were extracted from the ENCODE project through the RegulomeDB database. Of these, 20 were classified as expression quantitative trait loci (eQTLs).ConclusionsOur work provided a comprehensive source of prioritized and annotated candidate polymorphisms inside miRNAs and their target sites in GIT cancers, which would facilitate the process of choosing right candidate miRNA-target genes and related polymorphisms for future association or functional studies.

Dataset Information

Single nucleotide polymorphisms in the 3'UTR of VPAC-1 cooperate in modulating gene expression and impact differently on the interaction with miR525-5p.

Publications

Single nucleotide polymorphisms in the 3'UTR of VPAC-1 cooperate in modulating gene expression and impact differently on the interaction with miR525-5p.

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