scholarly journals Approaching Shared Pathophysiology in Immune-Mediated Diseases through Functional Genomics

Genes ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 1482
Author(s):  
David González-Serna ◽  
Gonzalo Villanueva-Martin ◽  
Marialbert Acosta-Herrera ◽  
Ana Márquez ◽  
Javier Martín
Keyword(s):  
Functional Genomics ◽  
Genetic Factors ◽  
Regulatory Elements ◽  
Experimental Characterization ◽  
Risk Variants ◽  
Immune Mediated ◽  
Pathological Mechanism ◽  
Genetic Pattern ◽  
Shared Genetic

Immune-mediated diseases (IMDs) are complex pathologies that are strongly influenced by environmental and genetic factors. Associations between genetic loci and susceptibility to these diseases have been widely studied, and hundreds of risk variants have emerged during the last two decades, with researchers observing a shared genetic pattern among them. Nevertheless, the pathological mechanism behind these associations remains a challenge that has just started to be understood thanks to functional genomic approaches. Transcriptomics, regulatory elements, chromatin interactome, as well as the experimental characterization of genomic findings, constitute key elements in the emerging understandings of how genetics affects the etiopathogenesis of IMDs. In this review, we will focus on the latest advances in the field of functional genomics, centering our attention on systemic rheumatic IMDs.

scholarly journals What functional genomics has taught us about transcriptional regulation in malaria parasites

2019 ◽  
Vol 18 (5) ◽  
pp. 290-301 ◽  
Author(s):  
Christa G Toenhake ◽  
Richárd Bártfai
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Life Cycle ◽  
Functional Genomics ◽  
Expression Patterns ◽  
Regulatory Elements ◽  
Complex Life Cycle ◽  
Malaria Parasites ◽  
Gene Regulatory

Abstract Malaria parasites are characterized by a complex life cycle that is accompanied by dynamic gene expression patterns. The factors and mechanisms that regulate gene expression in these parasites have been searched for even before the advent of next generation sequencing technologies. Functional genomics approaches have substantially boosted this area of research and have yielded significant insights into the interplay between epigenetic, transcriptional and post-transcriptional mechanisms. Recently, considerable progress has been made in identifying sequence-specific transcription factors and DNA-encoded regulatory elements. Here, we review the insights obtained from these efforts including the characterization of core promoters, the involvement of sequence-specific transcription factors in life cycle progression and the mapping of gene regulatory elements. Furthermore, we discuss recent developments in the field of functional genomics and how they might contribute to further characterization of this complex gene regulatory network.

Shared genetic factors may not explain the raised risk of comorbid inflammatory diseases in multiple sclerosis

2012 ◽  
Vol 18 (10) ◽  
pp. 1430-1436 ◽  
Author(s):  
H Roshanisefat ◽  
S Bahmanyar ◽  
J Hillert ◽  
T Olsson ◽  
S Montgomery
Keyword(s):  
Multiple Sclerosis ◽  
Genetic Factors ◽  
Cox Regression ◽  
Disease Risk ◽  
Inflammatory Diseases ◽  
Inflammatory Conditions ◽  
Disease Characteristics ◽  
Immune Mediated ◽  
Risk Patients ◽  
Shared Genetic

Background: Comorbid inflammatory conditions in multiple sclerosis (MS) patients suggest shared risks with MS. Objective: To estimate if the risk of immune-mediated disease in MS patients and their parents is increased. Methods: Swedish register data were analysed using Cox regression to estimate immune-mediated disease risk among 11284 fathers and 12006 mothers of MS patients, compared with 123158 fathers and 129409 mothers of index subjects without MS. Similar analyses were conducted among 20276 index subjects with MS and 203951 without. Results: Parents of patients with MS did not have a significantly altered immune-mediated disease risk. Patients with MS had a consistently raised risk for several immune-mediated diseases: ulcerative colitis, Crohn’s disease, type 1 diabetes, psoriasis, polyarthritis nodosa and pemphigoid. The risk was more pronounced for diseases diagnosed subsequent to MS onset. Conclusion: The increased occurrence of other immune-mediated diseases in MS patients may not be due to shared genetic factors and surveillance bias is likely to be the main or possibly the entire explanation. If not entirely explained by surveillance bias, a modestly raised occurrence of comorbid diseases may be due to shared environmental risks or factors related to MS disease characteristics.

scholarly journals Pan-Cancer Study Detects Novel Genetic Risk Variants and Shared Genetic Basis in Two Large Cohorts

2019 ◽  
Author(s):  
Sara R. Rashkin ◽  
Rebecca E. Graff ◽  
Linda Kachuri ◽  
Khanh K. Thai ◽  
Stacey E. Alexeeff ◽  
...  
Keyword(s):  
Genetic Basis ◽  
Association Studies ◽  
Large Population ◽  
Regulatory Elements ◽  
European Ancestry ◽  
Genome Wide Association Studies ◽  
Risk Variants ◽  
Genome Wide ◽  
Pan Cancer ◽  
Shared Genetic

AbstractDeciphering the shared genetic basis of distinct cancers has the potential to elucidate carcinogenic mechanisms and inform broadly applicable risk assessment efforts. However, no studies have investigated pan-cancer pleiotropy within single, well-defined populations unselected for phenotype. We undertook novel genome-wide association studies (GWAS) and comprehensive evaluations of heritability and pleiotropy across 18 cancer types in two large, population-based cohorts: the UK Biobank (413,870 European ancestry individuals; 48,961 cancer cases) and the Kaiser Permanente Genetic Epidemiology Research on Adult Health and Aging cohorts (66,526 European ancestry individuals; 16,001 cancer cases). The GWAS detected 21 novel genome-wide significant risk variants. In addition, numerous cancer sites exhibited clear heritability. Investigations of pleiotropy identified 12 cancer pairs exhibiting either positive or negative genetic correlations and 43 pleiotropic loci. We identified 158 pleiotropic variants, many of which were enriched for regulatory elements and influenced cross-tissue gene expression. Our findings demonstrate widespread pleiotropy and offer further insight into the complex genetic architecture of cross-cancer susceptibility.

scholarly journals In Silico Identification and Experimental Characterization of Regulatory Elements Controlling the Expression of the Salmonella csrB and csrC Genes

2013 ◽  
Vol 196 (2) ◽  
pp. 325-336 ◽  
Author(s):  
L. C. Martinez ◽  
I. Martinez-Flores ◽  
H. Salgado ◽  
M. Fernandez-Mora ◽  
A. Medina-Rivera ◽  
...  
Keyword(s):  
In Silico ◽  
Regulatory Elements ◽  
Experimental Characterization ◽  
In Silico Identification

Experimental Characterization of the Reliability of 3-Terminal Dual-Damascene Copper Interconnect Trees

2002 ◽  
Vol 716 ◽  
Author(s):  
C. L. Gan ◽  
C. V. Thompson ◽  
K. L. Pey ◽  
W. K. Choi ◽  
F. Wei ◽  
...  
Keyword(s):  
Stress Conditions ◽  
Experimental Characterization ◽  
Contact Lines ◽  
Tree Structures ◽  
Similar Test ◽  
Dual Damascene ◽  
Copper Interconnect ◽  
Test Conditions

AbstractElectromigration experiments have been carried out on simple Cu dual-damascene interconnect tree structures consisting of straight via-to-via (or contact-to-contact) lines with an extra via in the middle of the line. As with Al-based interconnects, the reliability of a segment in this tree strongly depends on the stress conditions of the connected segment. Beyond this, there are important differences in the results obtained under similar test conditions for Al-based and Cu-based interconnect trees. These differences are thought to be associated with variations in the architectural schemes of the two metallizations. The absence of a conducting electromigrationresistant overlayer in Cu technology, and the possibility of liner rupture at stressed vias lead to significant differences in tree reliabilities in Cu compared to Al.

Experimental Characterization of Mechanical Behavior of Cord-Rubber Composites

1982 ◽  
Vol 10 (1) ◽  
pp. 37-54 ◽  
Author(s):  
M. Kumar ◽  
C. W. Bert
Keyword(s):  
Response Characteristic ◽  
Cord Compression ◽  
Complete Characterization ◽  
Strain Response ◽  
Strain Gages ◽  
Experimental Characterization ◽  
Rubber Composites ◽  
Stress Strain ◽  
Strain Data

Abstract Unidirectional cord-rubber specimens in the form of tensile coupons and sandwich beams were used. Using specimens with the cords oriented at 0°, 45°, and 90° to the loading direction and appropriate data reduction, we were able to obtain complete characterization for the in-plane stress-strain response of single-ply, unidirectional cord-rubber composites. All strains were measured by means of liquid mercury strain gages, for which the nonlinear strain response characteristic was obtained by calibration. Stress-strain data were obtained for the cases of both cord tension and cord compression. Materials investigated were aramid-rubber, polyester-rubber, and steel-rubber.

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