Rare sequence variation and DNA methylation : effects on alcohol and tobacco use phenotypes

2019 ◽  
Author(s):  
◽  
Jacqueline Marisa Otto
Keyword(s):  
Dna Methylation ◽  
Tobacco Use ◽  
Sequence Variation ◽  
Rare Variants ◽  
Cpg Islands ◽  
Protein Coding ◽  
University Of Missouri ◽  
Rare Variation ◽  
The University ◽  
Regulatory Dna

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] Alcohol and tobacco use and dependence are known to be influenced by the effects of common variants enriched in non-coding gene regulatory regions, as well as rare protein-coding variation. In contrast, the role of rare non-coding regulatory variation is unknown. Epigenetic factors such as DNA methylation also influence gene expression, and some of these effects are under genomic control. The current study investigated the effects of rare coding and non-coding variation in regions susceptible to DNA methylation, and whether differential levels of methylation mediated their effects in association with alcohol and tobacco use and dependence. Data from whole-genome sequencing and DNA methylation microarrays for participants in the UCSF Family Alcoholism Study (N = 1,852) were used for set-based tests of rare variation, region-based differential methylation, and epigenetic mediation in relation to quantitative measures of alcohol and tobacco use and DSM-IV dependence diagnoses. Rare variants in exonic and intronic regions, as well as CpG islands, were weighted by a measure of deleteriousness and were significantly associated with alcohol and tobacco use phenotypes. Similarly, differential levels of DNA methylation exhibited significant association with lifetime and current measures of use and dependence. However, there was a relative lack of evidence for epigenetic mediation of rare variation, likely due to a lack of power. Findings from the current study suggest that rare regulatory DNA sequence variation and differential levels of DNA methylation influence risk for alcohol and tobacco use, but whether there exists epigenetic mediation of rare variation requires larger sample sizes in future studies.

TEM study of boron additions to cobalt aluminide

1988 ◽  
Vol 46 ◽  
pp. 546-547
Author(s):  
Gerald B. Feldewerth
Keyword(s):  
High Temperature ◽  
Turbine Engines ◽  
Major Drawback ◽  
University Of Missouri ◽  
Specific Strength ◽  
Aerospace Applications ◽  
Wide Range ◽  
Ordered Alloys ◽  
The University ◽  
Very High

In recent years an increasing emphasis has been placed on the study of high temperature intermetallic compounds for possible aerospace applications. One group of interest is the B2 aiuminides. This group of intermetaliics has a very high melting temperature, good high temperature, and excellent specific strength. These qualities make it a candidate for applications such as turbine engines. The B2 aiuminides exist over a wide range of compositions and also have a large solubility for third element substitutional additions, which may allow alloying additions to overcome their major drawback, their brittle nature.One B2 aluminide currently being studied is cobalt aluminide. Optical microscopy of CoAl alloys produced at the University of Missouri-Rolla showed a dramatic decrease in the grain size which affects the yield strength and flow stress of long range ordered alloys, and a change in the grain shape with the addition of 0.5 % boron.

MARS — Its Tenth Anniversary of Operation and its Future

1980 ◽  
Vol 19 (03) ◽  
pp. 125-132
Author(s):  
G. S. Lodwick ◽  
C. R. Wickizer ◽  
E. Dickhaus
Keyword(s):  
Conceptual Development ◽  
Administrative Support ◽  
Final Section ◽  
Economic Benefits ◽  
Hospital Environment ◽  
Computer Scientist ◽  
University Of Missouri ◽  
Complete Bibliography ◽  
The University ◽  
Economic Considerations

The Missouri Automated Radiology System recently passed its tenth year of clinical operation at the University of Missouri. This article presents the views of a radiologist who has been instrumental in the conceptual development and administrative support of MARS for most of this period, an economist who evaluated MARS from 1972 to 1974 as part of her doctoral dissertation, and a computer scientist who has worked for two years in the development of a Standard MUMPS version of MARS. The first section provides a historical perspective. The second deals with economic considerations of the present MARS system, and suggests those improvements which offer the greatest economic benefits. The final section discusses the new approaches employed in the latest version of MARS, as well as areas for further application in the overall radiology and hospital environment. A complete bibliography on MARS is provided for further reading.

Data Mining Technique Applied To DNA Sequencing

2015 ◽  
Vol 2 (7) ◽  
pp. 18
Author(s):  
R. Jamuna
Keyword(s):  
Data Mining ◽  
Dna Methylation ◽  
Markov Chain ◽  
Human Genome ◽  
Transition Probabilities ◽  
Markov Chain Model ◽  
Effective Means ◽  
Cpg Islands ◽  
Chain Model ◽  
The Given

CpG islands (CGIs) play a vital role in genome analysis as genomic markers.  Identification of the CpG pair has contributed not only to the prediction of promoters but also to the understanding of the epigenetic causes of cancer. In the human genome [1] wherever the dinucleotides CG occurs the C nucleotide (cytosine) undergoes chemical modifications. There is a relatively high probability of this modification that mutates C into a T. For biologically important reasons the mutation modification process is suppressed in short stretches of the genome, such as ‘start’ regions. In these regions [2] predominant CpG dinucleotides are found than elsewhere. Such regions are called CpG islands. DNA methylation is an effective means by which gene expression is silenced. In normal cells, DNA methylation functions to prevent the expression of imprinted and inactive X chromosome genes. In cancerous cells, DNA methylation inactivates tumor-suppressor genes, as well as DNA repair genes, can disrupt cell-cycle regulation. The most current methods for identifying CGIs suffered from various limitations and involved a lot of human interventions. This paper gives an easy searching technique with data mining of Markov Chain in genes. Markov chain model has been applied to study the probability of occurrence of C-G pair in the given   gene sequence. Maximum Likelihood estimators for the transition probabilities for each model and analgously for the  model has been developed and log odds ratio that is calculated estimates the presence or absence of CpG is lands in the given gene which brings in many  facts for the cancer detection in human genome.

scholarly journals Common and rare genetic variants that could contribute to severe otitis media in an Australian Aboriginal population

2021 ◽  
Author(s):  
Sarra E Jamieson ◽  
Michaela Fakiola ◽  
Dave Tang ◽  
Elizabeth Scaman ◽  
Genevieve Syn ◽  
...  
Keyword(s):  
Hair Cell ◽  
Otitis Media ◽  
Genetic Risk ◽  
Transforming Growth Factor ◽  
Rare Variants ◽  
Protein Coding ◽  
Gene Sets ◽  
Growth Factor Signalling ◽  
Rare Genetic Variants ◽  
And Function

Abstract Background Our goal was to identify genetic risk factors for severe otitis media (OM) in Aboriginal Australians. Methods Illumina ® Omni2.5 BeadChip and imputed data were compared between 21 children with severe OM (multiple episodes chronic suppurative OM and/or perforations or tympanic sclerosis) and 370 individuals without this phenotype, followed by FUnctional Mapping and Annotation (FUMA). Exome data filtered for common (EXaC_all≥0.1) putative deleterious variants influencing protein coding (CADD-scaled scores ≥ 15) were used to compare 15 severe OM cases with 9 mild cases (single episode of acute OM recorded over ≥ 3 consecutive years). Rare (ExAC_all≤0.01) such variants were filtered for those present only in severe OM. Enrichr was used to determine enrichment of genes contributing to pathways/processes relevant to OM. Results FUMA analysis identified two plausible genetic risk loci for severe OM: NR3C1 (Pimputed_1000G=3.62x10 -6) encoding the glucocorticoid receptor, and NREP (Pimputed_1000G=3.67x10 -6) encoding neuronal regeneration related protein. Exome analysis showed: (i) association of severe OM with variants influencing protein coding (CADD-scaled ≥ 15) in a gene-set (GRXCR1, CDH23, LRP2, FAT4, ARSA, EYA4) enriched for Mammalian Phenotype Level 4 abnormal hair cell stereociliary bundle morphology and related phenotypes; (ii) rare variants influencing protein coding only seen in severe OM provided gene-sets enriched for “abnormal ear” (LMNA, CDH23, LRP2, MYO7A, FGFR1), integrin interactions, transforming growth factor signalling, and cell projection phenotypes including hair cell stereociliary bundles and cilium assembly. Conclusions This study highlights interacting genes and pathways related to cilium structure and function that may contribute to extreme susceptibility to OM in Aboriginal Australian children.

scholarly journals Androgenic-Induced Transposable Elements Dependent Sequence Variation in Barley

2021 ◽  
Vol 22 (13) ◽  
pp. 6783
Author(s):  
Renata Orłowska ◽  
Katarzyna A. Pachota ◽  
Wioletta M. Dynkowska ◽  
Agnieszka Niedziela ◽  
Piotr T. Bednarek
Keyword(s):  
Dna Methylation ◽  
Transposable Elements ◽  
Dna Sequence ◽  
Sequence Variation ◽  
Nuclear Dna ◽  
Point Mutations ◽  
Mobile Elements ◽  
Dna Demethylation ◽  
Plant Genome

A plant genome usually encompasses different families of transposable elements (TEs) that may constitute up to 85% of nuclear DNA. Under stressful conditions, some of them may activate, leading to sequence variation. In vitro plant regeneration may induce either phenotypic or genetic and epigenetic changes. While DNA methylation alternations might be related, i.e., to the Yang cycle problems, DNA pattern changes, especially DNA demethylation, may activate TEs that could result in point mutations in DNA sequence changes. Thus, TEs have the highest input into sequence variation (SV). A set of barley regenerants were derived via in vitro anther culture. High Performance Liquid Chromatography (RP-HPLC), used to study the global DNA methylation of donor plants and their regenerants, showed that the level of DNA methylation increased in regenerants by 1.45% compared to the donors. The Methyl-Sensitive Transposon Display (MSTD) based on methylation-sensitive Amplified Fragment Length Polymorphism (metAFLP) approach demonstrated that, depending on the selected elements belonging to the TEs family analyzed, varying levels of sequence variation were evaluated. DNA sequence contexts may have a different impact on SV generated by distinct mobile elements belonged to various TE families. Based on the presented study, some of the selected mobile elements contribute differently to TE-related SV. The surrounding context of the TEs DNA sequence is possibly important here, and the study explained some part of SV related to those contexts.

scholarly journals DNA methylation differentiates smoking from vaping and non-combustible tobacco use

Epigenetics ◽  
2021 ◽  
pp. 1-13 ◽  
Author(s):  
Allan Andersen ◽  
Rachel Reimer ◽  
Kelsey Dawes ◽  
Ashley Becker ◽  
Natasha Hutchens ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Tobacco Use

scholarly journals Two competing mechanisms of DNMT3A recruitment regulate the dynamics of de novo DNA methylation at PRC1-targeted CpG islands

2021 ◽  
Author(s):  
Daniel N. Weinberg ◽  
Phillip Rosenbaum ◽  
Xiao Chen ◽  
Douglas Barrows ◽  
Cynthia Horth ◽  
...  
Keyword(s):  
Dna Methylation ◽  
De Novo ◽  
Cpg Islands

scholarly journals DNA Methylation of Human Choline Kinase Alpha Promoter-Associated CpG Islands in MCF-7 Cells

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 853
Author(s):  
Siti Aisyah Faten Mohamed Sa’dom ◽  
Sweta Raikundalia ◽  
Shaharum Shamsuddin ◽  
Wei Cun See Too ◽  
Ling Ling Few
Keyword(s):  
Dna Methylation ◽  
Transcription Factor ◽  
Binding Site ◽  
Promoter Activity ◽  
Cytosine Methylation ◽  
Cpg Island ◽  
Cpg Islands ◽  
Site Directed Mutagenesis ◽  
Choline Kinase ◽  
Mcf 7

Choline kinase (CK) is the enzyme catalyzing the first reaction in CDP-choline pathway for the biosynthesis of phosphatidylcholine. Higher expression of the α isozyme of CK has been implicated in carcinogenesis, and inhibition or downregulation of CKα (CHKA) is a promising anticancer approach. This study aimed to investigate the regulation of CKα expression by DNA methylation of the CpG islands found on the promoter of this gene in MCF-7 cells. Four CpG islands have been predicted in the 2000 bp promoter region of ckα (chka) gene. Six CpG island deletion mutants were constructed using PCR site-directed mutagenesis method and cloned into pGL4.10 vectors for promoter activity assays. Deletion of CpG4C region located between –225 and –56 significantly increased the promoter activity by 4-fold, indicating the presence of important repressive transcription factor binding site. The promoter activity of methylated full-length promoter was significantly lower than the methylated CpG4C deletion mutant by 16-fold. The results show that DNA methylation of CpG4C promotes the binding of the transcription factor that suppresses the promoter activity. Electrophoretic mobility shift assay analysis showed that cytosine methylation at MZF1 binding site in CpG4C increased the binding of putative MZF1 in nuclear extract. In conclusion, the results suggest that DNA methylation decreased the promoter activity by promoting the binding of putative MZF1 transcription factor at CpG4C region of the ckα gene promoter.

scholarly journals Sequence Variation in Two Protein-Coding Genes Correlates with Mycelial Compatibility Groupings in Sclerotium rolfsii

2013 ◽  
Vol 103 (5) ◽  
pp. 479-487 ◽  
Author(s):  
Efrén Remesal ◽  
Blanca B. Landa ◽  
María del Mar Jiménez-Gasco ◽  
Juan A. Navas-Cortés
Keyword(s):  
Rna Polymerase Ii ◽  
Sequence Variation ◽  
Geographic Origin ◽  
Sclerotium Rolfsii ◽  
Nuclear Ribosomal Dna ◽  
Causal Organism ◽  
Protein Coding ◽  
Protein Coding Genes ◽  
Wide Range ◽  
Mycelial Compatibility

Populations of Sclerotium rolfsii, the causal organism of Sclerotium root-rot on a wide range of hosts, can be placed into mycelial compatibility groups (MCGs). In this study, we evaluated three different molecular approaches to unequivocally identify each of 12 previously identified MCGs. These included restriction fragment length polymorphism (RFLP) patterns of the internal transcribed spacer (ITS) region of nuclear ribosomal DNA (rDNA) and sequence analysis of two protein-coding genes: translation elongation factor 1α (EF1α) and RNA polymerase II subunit two (RPB2). A collection of 238 single-sclerotial isolates representing 12 MCGs of S. rolfsii were obtained from diseased sugar beet plants from Chile, Italy, Portugal, and Spain. ITS-RFLP analysis using four restriction enzymes (AluI, HpaII, RsaI, and MboI) displayed a low degree of variability among MCGs. Only three different restriction profiles were identified among S. rolfsii isolates, with no correlation to MCG or to geographic origin. Based on nucleotide polymorphisms, the RPB2 gene was more variable among MCGs compared with the EF1α gene. Thus, 10 of 12 MCGs could be characterized utilizing the RPB2 region only, while the EF1α region resolved 7 MCGs. However, the analysis of combined partial sequences of EF1α and RPB2 genes allowed discrimination among each of the 12 MCGs. All isolates belonging to the same MCG showed identical nucleotide sequences that differed by at least in one nucleotide from a different MCG. The consistency of our results to identify the MCG of a given S. rolfsii isolate using the combined sequences of EF1α and RPB2 genes was confirmed using blind trials. Our study demonstrates that sequence variation in the protein-coding genes EF1α and RPB2 may be exploited as a diagnostic tool for MCG typing in S. rolfsii as well as to identify previously undescribed MCGs.

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