scholarly journals Previously Identified Genetic Variants in ADGRL3 Are not Associated with Risk for Equine Degenerative Myeloencephalopathy across Breeds

Genes ◽  
2019 ◽  
Vol 10 (9) ◽  
pp. 681 ◽  
Author(s):  
Sabin A. Marquardt ◽  
Callie V. Wilcox ◽  
Erin N. Burns ◽  
Janel A. Peterson ◽  
Carrie J. Finno
Keyword(s):  
Missense Mutation ◽  
Missense Variant ◽  
Genomic Region ◽  
Neuroaxonal Dystrophy ◽  
Nucleotide Polymorphisms ◽  
Nonsynonymous Variant ◽  
Single Nucleotide ◽  
Wide Range ◽  
Young Horses ◽  
G Protein Coupled

Equine neuroaxonal dystrophy/equine degenerative myeloencephalopathy (eNAD/EDM) is a neurologic disease that has been reported in young horses from a wide range of breeds. The disease is inherited and associated with vitamin E deficiency during the first two years of life, resulting in bilateral symmetric ataxia. A missense mutation (chr3:71,917,591 C > T) within adhesion G protein-coupled receptor L3 (ADGRL3) was recently associated with risk for EDM in the Caspian breed. In order to confirm these findings, genotyping of this missense mutation, along with the three other associated single nucleotide polymorphisms (SNPs) in the genomic region, was carried out on 31 postmortem-confirmed eNAD/EDM cases and 43 clinically phenotyped controls from various breeds. No significant association was found between eNAD/EDM confirmed cases and genotype at any of the four identified SNPs (P > 0.05), including the nonsynonymous variant (EquCab2.0 chr3:71,917,591; allelic P = 0.85). These findings suggest that the four SNPs, including the missense variant in the ADGRL3 region, are not associated with risk for eNAD/EDM across multiple breeds of horses.

EPCO-02. GERMLINE SINGLE NUCLEOTIDE POLYMORPHISM rs55705857 AT 8q24 INTERACTS WITH SOMATIC IDH1 MUTATION TO ENHANCE HUMAN GLIOMA FORMATION

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi1-vi1
Author(s):  
Kristen Drucker ◽  
Connor Yanchus ◽  
Thomas Kollmeyer ◽  
Asma Ali ◽  
Decker Paul ◽  
...  
Keyword(s):  
Fine Mapping ◽  
Dna Interaction ◽  
Genomic Region ◽  
Idh1 Mutation ◽  
Normal Brain ◽  
Nucleotide Polymorphisms ◽  
Human Glioma ◽  
Single Nucleotide ◽  
Coding Regions ◽  
Chromatin Immunoprecipitation Sequencing

Abstract BACKGROUND Determination of the causation of germline single nucleotide polymorphisms (SNPs) located in non-coding regions of the genome is challenging. The genomic region of 8q24 has been identified as important in many kinds of cancer, linked to a topologically associated domain (TAD) encompassing MYC; this TAD contains a GWAS SNP (rs55705857) associated with IDH-mutant glioma. METHODS Germline genotyping data from 622 IDH-mutant glioma and 668 controls were used to fine map the rs55705857 locus by detailed haplotype analysis. Chromatin immunoprecipitation sequencing (ChIP-seq) of histone markers H3K4me1, H3K4me3, H3K27ac and H3K36me3 was performed on normal brain samples (n=8) and human glioma samples (n=11 IDH-wt and 52 IDH-mut). RNAseq from 9 normal and 83 brain tumors (n=26 IDH-wt and 55 IDH-mut) were used to assess differential gene expression. RESULTS Fine-mapping identified rs55705857 SNP as the most likely causative allele (OR=8.69; p<0.001) within 8q24 for the development of IDH-mutant glioma. At rs55705857, both H3K27ac and H3K4me1 in IDH-mutant vs IDH-wt tumors were increased 3.05- and 1.58-fold, respectively (DiffBind; p=5.81×10-7 and p=2.31×10-3). ChromHMM analysis of the marks indicated that promoter and enhancer functions were significantly increased, and the activity broadened at rs55705857 in IDH-mut gliomas compared to IDH-wt tumors and normal brain samples. This enhancement correlated with significant increased MYC expression in IDH-mut gliomas (p=3.1×10-13), as well as alterations of Myc signaling targets. Publicly available ATACseq, ChIPseq and long-range DNA interaction data demonstrated that the rs55705857 locus is open and interacts with the MYC promoter. CONCLUSIONS Fine-mapping of the 8q24 locus provided strong evidence that rs55705857 is the causative 8q24 locus associated with IDH-mut glioma. Functional experiments suggest that IDH mutation facilitates rs55705857 interaction with MYC to alter downstream MYC targets.

scholarly journals simuG: a general-purpose genome simulator

2019 ◽  
Vol 35 (21) ◽  
pp. 4442-4444 ◽  
Author(s):  
Jia-Xing Yue ◽  
Gianni Liti
Keyword(s):  
Copy Number Variants ◽  
General Purpose ◽  
Supplementary Information ◽  
Nucleotide Polymorphisms ◽  
Bioinformatics Analyses ◽  
Full Spectrum ◽  
Single Nucleotide ◽  
Genomic Variants ◽  
Wide Range ◽  
Simulation Based

Abstract Summary Simulated genomes with pre-defined and random genomic variants can be very useful for benchmarking genomic and bioinformatics analyses. Here we introduce simuG, a lightweight tool for simulating the full-spectrum of genomic variants (single nucleotide polymorphisms, Insertions/Deletions, copy number variants, inversions and translocations) for any organisms (including human). The simplicity and versatility of simuG make it a unique general-purpose genome simulator for a wide-range of simulation-based applications. Availability and implementation Code in Perl along with user manual and testing data is available at https://github.com/yjx1217/simuG. This software is free for use under the MIT license. Supplementary information Supplementary data are available at Bioinformatics online.

Association Between Two Single-nucleotide Polymorphism of TAAR1 Gene and Suicide Attempts

2017 ◽  
Vol 41 (S1) ◽  
pp. S103-S103
Author(s):  
A. Zdanowicz ◽  
A. Sakowicz ◽  
E. Kusidel ◽  
P. Wierzbinski
Keyword(s):  
Suicide Attempts ◽  
Statistical Tests ◽  
Control Group ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Hardy Weinberg Equilibrium ◽  
The Mean ◽  
Competing Interest ◽  
G Protein Coupled ◽  
The Brain

IntroductionTAAR1 is a G protein-coupled receptor expressed broadly throughout the brain. Recently, TAAR1 has been demonstrated to be an important modulator of the dopaminergic, serotonergic and glutamatergic activity.AimsAssessment of the relation between two single-nucleotide polymorphisms of TAAR1 gene, suicide attempts and alcohol abuse.MethodsA total of 150 Polish patients were included, 59 subjects after suicide attempt vs. 91 controls. The chosen SNPs (rs759733834 and rs9402439) were studied using RFLP-PCR methods. The Hardy-Weinberg equilibrium was tested in control group.Statistical testsChi2 or Yeates Chi2 Test were used.ResultsThe mean age of study subjects and controls was: 38 ± 12.3 and 42 ± 12.8 respectively; 49% study males vs. 54% male controls. We did not observe the association between the carriage of the genotypes GG, GA and AA of rs759733834 polymorphisms in either of the groups. The distribution of genotypes in respect to rs9402439 polymorphism (CC, CG, GG) was also insignificant. Among patients with alcohol dependence, the frequency G allele of rs9402439 polymorphism was lower compared to non-addicted ones (27 vs. 47%) P < 0.01.ConclusionsTAAR1 polymorphisms rs759733834 and rs9402439 are not related to suicide attempts. The carriage of allele G of rs9402439 polymorphism is related to lower risk of alcohol addiction OR 0.40 95%Cl 0.20–0.81. To our knowledge, this is the first study on the TAAR1 receptor and the risk of suicide and it might offer a new insight into genetic etiology of TAAR1 receptor.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Structural and Functional Features of the P2X4 Receptor: An Immunological Perspective

2021 ◽  
Vol 12 ◽  
Author(s):  
Jean M. Kanellopoulos ◽  
Cássio Luiz Coutinho Almeida-da-Silva ◽  
Sirje Rüütel Boudinot ◽  
David M. Ojcius
Keyword(s):  
Plasma Membrane ◽  
P2y Receptors ◽  
Potential Interaction ◽  
The Body ◽  
Extracellular Nucleotides ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Functional Features ◽  
G Protein Coupled

Extracellular nucleotides are important mediators of activation, triggering various responses through plasma membrane P2 and P1 receptors. P2 receptors are further subdivided into ionotropic P2X receptors and G protein-coupled P2Y receptors. P2X4 is an ATP-gated cation channel broadly expressed in most tissues of the body. Within the P2X family, P2X4 has a unique subcellular distribution, being preferentially localized in lysosomes. In these organelles, high ATP concentrations do not trigger P2X4 because of the low pH. However, when the pH increases to 7.4, P2X4 can be stimulated by intra-lysosomal ATP, which is in its active, tetra-anionic form. Elucidation of P2X4, P2X3 and P2X7 structures has shed some light on the functional differences between these purinergic receptors. The potential interaction between P2X4 and P2X7 has been extensively studied. Despite intensive effort, it has not been possible yet to determine whether P2X4 and P2X7 interact as heterotrimers or homotrimers at the plasma membrane. However, several publications have shown that functional interactions between P2X4 and P2X7 do occur. Importantly, these studies indicate that P2X4 potentiates P2X7-dependent activation of inflammasomes, leading to increased release of IL-1β and IL-18. The role of P2X4 in various diseases could be beneficial or deleterious even though the pathophysiological mechanisms involved are still poorly defined. However, in diseases whose physiopathology involves activation of the NLRP3 inflammasome, P2X4 was found to exacerbate severity of disease. The recent production of monoclonal antibodies specific for the human and mouse P2X4, some of which are endowed with agonist or antagonist properties, raises the possibility that they could be used therapeutically. Analysis of single nucleotide polymorphisms of the human P2RX4 gene has uncovered the association of P2RX4 gene variants with susceptibility to several human diseases.

PSXIV-25 Search for the association of SNP in GRM8 gene with sperm quality in stallions

2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 257-257
Author(s):  
Elena Nikitkina ◽  
Anna Krutikova ◽  
Artem Musidray
Keyword(s):  
Volume Concentration ◽  
Sperm Quality ◽  
Nucleotide Polymorphisms ◽  
Nucleotide Substitutions ◽  
Single Nucleotide ◽  
Progressive Motility ◽  
Wide Range ◽  
Sperm Volume ◽  
Polymorphic Variants ◽  
Genetic Analyzer

Abstract The formation and functioning of the animal reproductive system occurs as a result of the coordinated interaction of a wide range of genes. To search for causal mutations, work was carried out to search for polymorphic variants in the marker regions detected using GWAS. The four single-nucleotide substitutions in the exon of the GRM8 gene identified during the studies and the association of these SNPs with sperm quality was carried out. Semen from 22 stallions was collected. Sperm volume, concentration and progressive motility were assessed. Sequencing of the sections of the candidate GRM8 gene was carried out using an Applied Biosystems 3500 genetic analyzer. For the rs1138419111 genotype, no significant differences were found in the studied parameters. According to the identified single nucleotide substitution rs1147388106, the highest ejaculate volume was in stallions with the GG genotype (55.9±26.5 ml) compared to stallions with the GA genotypes (32.5±13.9 ml) and AA (18.0±33,6) (p &lt; 0.05). When analyzing data on SNP rs395286150, stallions with a heterozygous CT genotype had the best sperm quality. Thus, the cell concentration was 317.0±66.5 million/ml in stallions with the CT genotype, 209.6±58.2 and 189.5±74.9 % with the CC and TT genotypes, respectively (P &lt; 0.05). The progressive sperm motility of stallions with the CT genotype was 65.5±20.5% versus 48.7±22.0% in stallions with the TT genotype and 48.4±18.6% with CC. Analysis of data on SNP rs394524550 revealed a significant effect of the genotype on progressive motility. Stallions with the AG genotype had a progressive motility of 64.6±16.3%, and those with GG and AA 32.7±15.7 and 49.6±18.1%, respectively (P &lt; 0.05). Thus, as a result four single nucleotide polymorphisms were identified in the exon of the GRM gene. Three of them were significantly associated with such indicators of sperm quality as ejaculate volume, concentration and progressive motility. Project No. 0445-2021-0011.

SRG extractor: a skinny reference genome approach for reduced-representation sequencing

2019 ◽  
Vol 35 (17) ◽  
pp. 3160-3162
Author(s):  
Davoud Torkamaneh ◽  
Jérôme Laroche ◽  
Istvan Rajcan ◽  
François Belzile
Keyword(s):  
Reference Genome ◽  
Computing Time ◽  
Supplementary Information ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Scanning Method ◽  
Reduced Representation ◽  
A Genome ◽  
Wide Range ◽  
Reduced Representation Sequencing

Abstract Motivation Reduced-representation sequencing is a genome-wide scanning method for simultaneous discovery and genotyping of thousands to millions of single nucleotide polymorphisms that is used across a wide range of species. However, in this method a reproducible but very small fraction of the genome is captured for sequencing, while the resulting reads are typically aligned against the entire reference genome. Results Here we present a skinny reference genome approach in which a simplified reference genome is used to decrease computing time for data processing and to increase single nucleotide polymorphism counts and accuracy. A skinny reference genome can be integrated into any reduced-representation sequencing analytical pipeline. Availability and implementation https://bitbucket.org/jerlar73/SRG-Extractor. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals From Single Nucleotide Polymorphisms to Constant Immunosuppression: Mesenchymal Stem Cell Therapy for Autoimmune Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Raghavan Chinnadurai ◽  
Edmund K. Waller ◽  
Jacques Galipeau ◽  
Ajay K. Nooka
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Autoimmune Diseases ◽  
Association Studies ◽  
Autoimmune Disorders ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Mesenchymal Stem Cell Therapy ◽  
Immune Mediated ◽  
Wide Range

The regenerative abilities and the immunosuppressive properties of mesenchymal stromal cells (MSCs) make them potentially the ideal cellular product of choice for treatment of autoimmune and other immune mediated disorders. Although the usefulness of MSCs for therapeutic applications is in early phases, their potential clinical use remains of great interest. Current clinical evidence of use of MSCs from both autologous and allogeneic sources to treat autoimmune disorders confers conflicting clinical benefit outcomes. These varied results may possibly be due to MSC use across wide range of autoimmune disorders with clinical heterogeneity or due to variability of the cellular product. In the light of recent genome wide association studies (GWAS), linking predisposition of autoimmune diseases to single nucleotide polymorphisms (SNPs) in the susceptible genetic loci, the clinical relevance of MSCs possessing SNPs in the critical effector molecules of immunosuppression is largely undiscussed. It is of further interest in the allogeneic setting, where SNPs in the target pathway of MSC's intervention may also modulate clinical outcome. In the present review, we have discussed the known critical SNPs predisposing to disease susceptibility in various autoimmune diseases and their significance in the immunomodulatory properties of MSCs.

Sign in / Sign up

Export Citation Format

Share Document