scholarly journals Association of a Functional Single Nucleotide Polymorphism (rs874040) in the RBPJ Gene with Susceptibility to Rheumatoid Arthritis in Iranian Population

2021 ◽  
Author(s):  
Mansour Salesi ◽  
Mahdieh Oboodiyat ◽  
Rasoul Salehi ◽  
Bahram Pakzad
Keyword(s):  
Rheumatoid Arthritis ◽  
Single Nucleotide Polymorphism ◽  
Association Studies ◽  
Notch Pathway ◽  
Iranian Population ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Immunoglobulin Kappa ◽  
Functional Single Nucleotide Polymorphism

Background: Rheumatoid Arthritis (RA) is a progressive, heterogeneous, and common multifactorial autoimmune disease. Several Genome-Wide Association Studies (GWASs) have revealed more than 100 risk loci for RA. One of these loci is a functional single nucleotide polymorphism (rs874040; G>C) near the recombination signal-binding protein for the immunoglobulin kappa J region (RBPJ) gene. RBPJ can convert into a transcriptional activator upon activation of the canonical Notch pathway. Notch signaling has recently emerged as an important regulator of immune responses in inflammation and autoimmune diseases. In the present study, the possible association between SNP rs874040 (G>C) upstream of the RBPJ gene with RA risk was assessed in Iranian population.   Methods: A case-control study including 60 RA patients and 44 control subjects was conducted to estimate rs874040 genotypes using real‑time polymerase chain reaction High Resolution Melting (HRM) method.   Results: Logistic regression analysis indicated that homozygous CC and heterozygous GC genotypes increase the risk of RA compared with GG genotype (CC vs. GG; OR=11.36; 95% CI [3.93-33.33] and CG vs. GG; OR=3.78; 95% CI [1.30-10. 98]). Besides, subjects with C allele were more frequently affected with RA than subjects with G allele (OR=10.42; 95% CI [5.21-20.83]). Furthermore, in the patient group, a significant correlation was found between C-reactive protein concentrations and rs874040 polymorphism (p<0.05).   Conclusion: Our findings propose a substantial correlation between rs874040 polymorphism and RA risk in Iranian population.  

scholarly journals THE EFFECT OF SINGLE NUCLEOTIDE POLYMORPHISM (SNP) IN GLIOBLASTOMA MULTIFORME

2021 ◽  
Author(s):  
Asmita Ghosh ◽  
Dattatreya Mukherjee ◽  
Parth Patel ◽  
Debraj Mukhopadhyay
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Glioblastoma Multiforme ◽  
Association Studies ◽  
Disease Onset ◽  
Genetic Alterations ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Coding Region ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide

Single nucleotide polymorphism is a genetic substitution of a base pair at a single position of the genome. SNPs are a common phenomenon and influence mRNA expression. Half of the SNPs occur in the non-coding region with 25% being mis-sense mutation and 25% being silent mutations. SNPs belong to the last generation of molecular markers which is identified through SNP mapping. SNPs are extensively studied to distinguish genetic expression and protein synthesis. These genetic differences are a major source of diseases in humans like cancers. One of the most common types of cancer of the brain is the Glioblastoma Multiforme that accounts for more than 80% of the malignant primary brain tumors (PBT). Researchers have found out a potential role of various SNPs in the genome to have a strong relation with Glioma formation and proliferation. Most SNPs are either not discovered, or their biological mechanisms are unknown, making it difficult to link putative associations with disease onset. The given review aims to identify some of the most common SNPs associated with GBM and classify the genetic basis along with future prospects. These SNPs are pioneer in Genome Wide Association studies to help in cancer research and identification of specific genetic alterations liked to GBM. Single Nucleotide Polymorphisms in a gene can be used as genetic biomarkers to aid better understanding of the mechanism of cancer formation, its aetiology, progression and metastatic behaviour.

scholarly journals The Risk G Allele of the Single-Nucleotide Polymorphism rs928413 Creates a CREB1-Binding Site That Activates IL33 Promoter in Lung Epithelial Cells

2018 ◽  
Vol 19 (10) ◽  
pp. 2911 ◽  
Author(s):  
Alisa Gorbacheva ◽  
Kirill Korneev ◽  
Dmitry Kuprash ◽  
Nikita Mitkin
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Binding Site ◽  
Association Studies ◽  
Lung Epithelial Cells ◽  
Atopic Asthma ◽  
Genome Wide Association Studies ◽  
Dependent Manner ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Proinflammatory Mediators

Cytokine interleukin 33 (IL-33) is constitutively expressed by epithelial barrier cells, and promotes the development of humoral immune responses. Along with other proinflammatory mediators released by the epithelium of airways and lungs, it plays an important role in a number of respiratory pathologies. In particular, IL-33 significantly contributes to pathogenesis of allergy and asthma; genetic variations in the IL33 locus are associated with increased susceptibility to asthma. Large-scale genome-wide association studies have identified minor “G” allele of the single-nucleotide polymorphism rs928413, located in the IL33 promoter area, as a susceptible variant for early childhood and atopic asthma development. Here, we demonstrate that the rs928413(G) allele creates a binding site for the cAMP response element-binding protein 1 (CREB1) transcription factor. In a pulmonary epithelial cell line, activation of CREB1, presumably via the p38 mitogen-activated protein kinases (MAPK) cascade, activates the IL33 promoter containing the rs928413(G) allele specifically and in a CREB1-dependent manner. This mechanism may explain the negative effect of the rs928413 minor “G” allele on asthma development.

scholarly journals FSHB  Transcription is Regulated by a Novel 5′ Distal Enhancer With a Fertility-Associated Single Nucleotide Polymorphism

Endocrinology ◽  
2020 ◽  
Vol 162 (1) ◽  
Author(s):  
Stephanie C Bohaczuk ◽  
Varykina G Thackray ◽  
Jia Shen ◽  
Dorota Skowronska-Krawczyk ◽  
Pamela L Mellon
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Polycystic Ovary ◽  
Function Analysis ◽  
Association Studies ◽  
Female Fertility ◽  
Open Chromatin ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Conserved Region

Abstract The pituitary gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone, signal the gonads to regulate male and female fertility. FSH is critical for female fertility as it regulates oocyte maturation, ovulation, and hormone synthesis. Multiple genome-wide association studies (GWAS) link a 130 Kb locus at 11p14.1, which encompasses the FSH beta-subunit (FSHB) gene, with fertility-related traits that include polycystic ovary syndrome, age of natural menopause, and dizygotic twinning. The most statistically significant single nucleotide polymorphism from several GWAS studies (rs11031006) resides within a highly conserved 450 bp region 26 Kb upstream of the human FSHB gene. Given that sequence conservation suggests an important biological function, we hypothesized that the region could regulate FSHB transcription. In luciferase assays, the conserved region enhanced FSHB transcription and gel shifts identified a binding site for Steroidogenic factor 1 (SF1) contributing to its function. Analysis of mouse pituitary single-cell ATAC-seq demonstrated open chromatin at the conserved region exclusive to a gonadotrope cell-type cluster. Additionally, enhancer-associated histone markers were identified by immunoprecipitation of chromatin from mouse whole pituitary and an immortalized mouse gonadotrope-derived LβT2 cell line at the conserved region. Furthermore, we found that the rs11031006 minor allele upregulated FSHB transcription via increased SF1 binding to the enhancer. All together, these results identify a novel upstream regulator of FSHB transcription and indicate that rs11031006 can modulate FSH levels.

scholarly journals Replication of Top Loci From COL4A1/2 Associated With White Matter Hyperintensity Burden in Patients With Ischemic Stroke

Stroke ◽  
2020 ◽  
Vol 51 (12) ◽  
pp. 3751-3755
Author(s):  
Jiang Li ◽  
Vida Abedi ◽  
Ramin Zand ◽  
Christoph J. Griessenauer ◽  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Ischemic Stroke ◽  
Odds Ratio ◽  
Association Studies ◽  
Genome Wide Association ◽  
White Matter Hyperintensity ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Genome Wide

Background and Purpose: The purpose of this study was to replicate the top loci associated with white matter hyperintensity (WMH) phenotypes identified by large genome-wide association studies and the loci identified from the previous candidate gene studies. Methods: A total of 946 Geisinger MyCode patients with acute ischemic stroke with validated European ancestry and magnetic resonance imaging data were included in this study. Log-transformed WMH volume, as a quantitative trait, was calculated by a fully automated quantification process. The genome-wide association studies was carried out by a linear mixed regression model (GEMMA). A candidate-single nucleotide polymorphism analysis by including known single nucleotide polymorphisms, reported from a meta-analysis and several large GWAS for WMH, was conducted in all cases and binary converted extreme cases. Results: No genome-wide significantly associated variants were identified. In a candidate-single nucleotide polymorphism study, rs9515201 ( COL4A2 ) and rs3744028 ( TRIM65 ), 2 known genetic loci, showed nominal or trend of association with the WMH volume (β=0.13 and P =0.001 for rs9515201; β=0.094 and P =0.094 for rs3744028), and replicated in a subset of extreme cases versus controls (odds ratio=1.78, P =7.74×10 − 4 for rs9515201; odds ratio=1.53, P =0.047 for rs3744028, respectively). MTHFR677 cytosine/thymine (rs1801133) also showed an association with the binary WMH with odds ratio=1.47 for T allele ( P =0.019). Conclusions: Replication of COL4A1/2 associated with WMH reassures that the genetic risk factors for monogenic and polygenic ischemic stroke are shared at gene level.

scholarly journals An Analysis Pipeline for Genome-wide Association Studies

2008 ◽  
Vol 6 ◽  
pp. CIN.S966 ◽  
Author(s):  
Stefan Stefanov ◽  
James Lautenberger ◽  
Bert Gold
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Missing Values ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Population Difference ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Genome Wide ◽  
And Control

We developed an efficient pipeline to analyze genome-wide association study single nucleotide polymorphism scan results. Perl scripts were used to convert genotypes called using the BRLMM algorithm into a modified PB format. We computed summary statistics characteristic of our case and control populations including allele counts, missing values, heterozygosity, measures of compliance with Hardy-Weinberg equilibrium, and several population difference statistics. In addition, we computed association tests, including exact tests of association for genotypes, alleles, the Cochran-Armitage linear trend test, and dominant, recessive, and overdominant models at every single nucleotide polymorphism (SNP). In addition, pairwise linkage disequilbrium statistics were elaborated, using the command line version of HaploView, which was possible by writing a reformatting script. Additional Perl scripts permit loading the results into a MySQL database conjoined with a Generic Genome Browser (gbrowse) for comprehensive visualization. This browser incorporates a download feature that provides actual case and control genotypes to users in associated genomic regions. Thus, re-analysis “on the fly” is possible for casual browser users from anywhere on the Internet.

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