scholarly journals Genetic variants and underlying mechanisms influencing variance heterogeneity in maize

2020 ◽  
Vol 103 (3) ◽  
pp. 1089-1102 ◽  
Author(s):  
Hui Li ◽  
Min Wang ◽  
Weijun Li ◽  
Linlin He ◽  
Yuanyuan Zhou ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Variance Heterogeneity ◽  
Underlying Mechanisms

scholarly journals Genetic variants influencing phenotypic variance heterogeneity

2018 ◽  
Vol 27 (5) ◽  
pp. 799-810 ◽  
Author(s):  
Weronica E Ek ◽  
Mathias Rask-Andersen ◽  
Torgny Karlsson ◽  
Stefan Enroth ◽  
Ulf Gyllensten ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Phenotypic Variance ◽  
Variance Heterogeneity

scholarly journals ESC - a comprehensive resource for SARS-CoV-2 immune escape variants

2021 ◽  
Author(s):  
Mercy Rophina ◽  
Kavita Pandhare ◽  
Afra Shamnath ◽  
Mohamed Imran ◽  
Bani Jolly ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Viral Genome ◽  
Neutralizing Antibodies ◽  
Large Scale ◽  
Immune Escape ◽  
Spike Protein ◽  
Genomic Research ◽  
Disease Pathogenesis ◽  
Underlying Mechanisms ◽  
Gain Access

ABSTRACTEver since the breakout of COVID-19 disease, ceaseless genomic research to inspect the epidemiology and evolution of the pathogen has been undertaken globally. Large scale viral genome sequencing and analysis have uncovered the functional impact of numerous genetic variants in disease pathogenesis and transmission. Emerging evidence of mutations in spike protein domains escaping antibody neutralization is reported. We have a precise collation of manually curated variants in SARS-CoV-2 from literature with potential escape mechanisms from a range of neutralizing antibodies. This comprehensive repository encompasses a total of 532 variants accounting for 146 unique variants tested against 75 antibodies and patient convalescent plasma. This resource enables the user to gain access to an extensive annotation of SARS-CoV-2 escape mutations which we hope would contribute to exploring and understanding the underlying mechanisms of immune response against the pathogen. The resource is available at http://clingen.igib.res.in/esc/.

scholarly journals Conflicting Roles of 20-HETE in Hypertension and Stroke

2019 ◽  
Vol 20 (18) ◽  
pp. 4500 ◽  
Author(s):  
Shashank Shekhar ◽  
Kevin Varghese ◽  
Man Li ◽  
Letao Fan ◽  
George Booz ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Genetic Variants ◽  
Reduce Blood Pressure ◽  
The Other ◽  
Eicosatetraenoic Acid ◽  
Vascular Response ◽  
Barrier Integrity ◽  
Underlying Mechanisms ◽  
Blood Brain Barrier Integrity

Hypertension is the most common modifiable risk factor for stroke, and understanding the underlying mechanisms of hypertension and hypertension-related stroke is crucial. 20-hydroxy-5, 8, 11, 14-eicosatetraenoic acid (20-HETE), which plays an important role in vasoconstriction, autoregulation, endothelial dysfunction, angiogenesis, inflammation, and blood-brain barrier integrity, has been linked to hypertension and stroke. 20-HETE can promote hypertension by potentiating the vascular response to vasoconstrictors; it also can reduce blood pressure by inhibition of sodium transport in the kidney. The production of 20-HETE is elevated after the onset of both ischemic and hemorrhagic strokes; on the other hand, subjects with genetic variants in CYP4F2 and CYP4A11 that reduce 20-HETE production are more susceptible to stroke. This review summarizes recent genetic variants in CYP4F2, and CYP4A11 influencing 20-HETE production and discusses the role of 20-HETE in hypertension and the susceptibility to the onset, progression, and prognosis of ischemic and hemorrhagic strokes.

scholarly journals Noise-augmented directional clustering of genetic association data identifies distinct mechanisms underlying obesity

2021 ◽  
Author(s):  
Andrew J Grant ◽  
Dipender Gill ◽  
Paul DW Kirk ◽  
Stephen Burgess
Keyword(s):  
Body Mass Index ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Body Mass ◽  
Genetic Variants ◽  
Disease Risk ◽  
Biological Pathways ◽  
Mixture Model Approach ◽  
Association Data ◽  
Underlying Mechanisms

Clustering genetic variants based on their associations with different traits can provide insight into their underlying biological mechanisms. Existing clustering approaches typically group variants based on the similarity of their association estimates for various traits. We present a new procedure for clustering variants based on their proportional associations with different traits, which is more reflective of the underlying mechanisms to which they relate. The method is based on a mixture model approach for directional clustering and includes a noise cluster that provides robustness to outliers. The procedure performs well across a range of simulation scenarios. In an applied setting, clustering genetic variants associated with body mass index generates groups reflective of distinct biological pathways. Mendelian randomization analyses support that the clusters vary in their effect on coronary heart disease, including one cluster that represents elevated body mass index with a favourable metabolic profile and reduced coronary heart disease risk. Analysis of the biological pathways underlying this cluster identifies inflammation as playing a key role in mediating the effects of increased body mass index on coronary heart disease.

scholarly journals TRPM8 genetic variant is associated with chronic migraine and allodynia

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Yu-Hsiang Ling ◽  
Shih-Pin Chen ◽  
Cathy Shen-Jang Fann ◽  
Shuu-Jiun Wang ◽  
Yen-Feng Wang
Keyword(s):  
Chronic Migraine ◽  
Genetic Variants ◽  
Genetic Variant ◽  
Nucleotide Polymorphisms ◽  
Susceptibility Loci ◽  
Replication Cohort ◽  
Discovery Cohort ◽  
Single Nucleotide ◽  
Female Ratio ◽  
Underlying Mechanisms

Abstract Background Many single nucleotide polymorphisms (SNPs) have been reported to be associated with migraine susceptibility. However, evidences for their associations with migraine endophenotypes or subtypes are scarce. We aimed to investigate the associations of pre-identified migraine susceptibility loci in Taiwanese with migraine endophenotypes or subtypes, including chronic migraine and allodynia. Methods The associations of six SNPs identified from our previous study, including TRPM8 rs10166942, LRP1 rs1172113, DLG2 rs655484, GFRA1 rs3781545, UPP2 rs7565931, and GPR39 rs10803531, and migraine endophenotypes, including chronic migraine and allodynia were tested. Significant associations in the discovery cohort were validated in the replication cohort. The adjusted odds ratios (aOR) were calculated after controlling for confounders. Results In total, 1904 patients (mean age 37.5 ± 12.2 years old, female ratio: 77.7%) including 1077 in the discovery cohort and 827 in the replication cohort were recruited. Of them, 584 (30.7%) had chronic migraine. Of the 6 investigated SNPs, TRPM8 rs10166942 T allele-carrying patients were more likely to have chronic migraine than non-T allele carriers in both discovery and replication cohorts and combined samples (33.7% vs. 25.8%, p = 0.004, aOR = 1.62). In addition, T allele carriers reported more allodynic symptoms than non-T allele carriers (3.5 ± 3.7 vs. 2.6 ± 2.8, p < 0.001). However, allodynia severity did not differ between episodic and chronic migraine patients. No further correlations between genetic variants and endophenotypes were noted for the other SNPs. Conclusions TRPM8 may contribute to the pathogenesis of chronic migraine. However, our study did not support allodynia as a link between them. The underlying mechanisms deserve further investigations.

Capitalizing on Insights from Human Genetics to Identify Novel Therapeutic Targets for Coronary Artery Disease

2019 ◽  
Vol 70 (1) ◽  
pp. 19-32 ◽  
Author(s):  
Erica P. Young ◽  
Nathan O. Stitziel
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Genetic Variants ◽  
Human Genetics ◽  
Disease Risk ◽  
Therapeutic Targets ◽  
Disease Pathogenesis ◽  
Artery Disease ◽  
Underlying Mechanisms ◽  
Novel Therapeutic

Coronary artery disease (CAD) is a major cause of morbidity and mortality. Unfortunately, despite decades of research focused on disease pathogenesis, we still lack a sufficient pharmacopeia for preventing CAD. The failure of many novel cardiovascular drugs to improve clinical outcomes reflects the major substantial challenge of drug development: identifying causal mechanisms that can be therapeutically manipulated to lower disease risk. Identifying genetic variants that are associated with risk of CAD has emerged as a clear path toward improving our understanding of the underlying mechanisms that lead to disease and to the development of new therapies. Here, we review the potential utility and limitations of using human genetics to guide the identification of therapeutic targets for CAD.

The limits of human performance

2008 ◽  
Vol 44 ◽  
pp. 11-26 ◽  
Author(s):  
Ralph Beneke ◽  
Dieter Böning
Keyword(s):  
Human Performance ◽  
Safety Margin ◽  
Afferent Input ◽  
Metabolic Energy ◽  
Human Organism ◽  
Mechanical Resistance ◽  
As Doping ◽  
Gene And Protein Expression ◽  
Underlying Mechanisms ◽  
Biochemical Research

Human performance, defined by mechanical resistance and distance per time, includes human, task and environmental factors, all interrelated. It requires metabolic energy provided by anaerobic and aerobic metabolic energy sources. These sources have specific limitations in the capacity and rate to provide re-phosphorylation energy, which determines individual ratios of aerobic and anaerobic metabolic power and their sustainability. In healthy athletes, limits to provide and utilize metabolic energy are multifactorial, carefully matched and include a safety margin imposed in order to protect the integrity of the human organism under maximal effort. Perception of afferent input associated with effort leads to conscious or unconscious decisions to modulate or terminate performance; however, the underlying mechanisms of cerebral control are not fully understood. The idea to move borders of performance with the help of biochemicals is two millennia old. Biochemical findings resulted in highly effective substances widely used to increase performance in daily life, during preparation for sport events and during competition, but many of them must be considered as doping and therefore illegal. Supplements and food have ergogenic potential; however, numerous concepts are controversially discussed with respect to legality and particularly evidence in terms of usefulness and risks. The effect of evidence-based nutritional strategies on adaptations in terms of gene and protein expression that occur in skeletal muscle during and after exercise training sessions is widely unknown. Biochemical research is essential for better understanding of the basic mechanisms causing fatigue and the regulation of the dynamic adaptation to physical and mental training.

Genetic Variation: Impact on Folate (and Choline) Bioefficacy

2010 ◽  
Vol 80 (45) ◽  
pp. 319-329 ◽  
Author(s):  
Allyson A. West ◽  
Marie A. Caudill
Keyword(s):  
Carbon Metabolism ◽  
Genetic Variants ◽  
Plasma Homocysteine ◽  
Water Soluble ◽  
Gene Interactions ◽  
Dietary Folate ◽  
Methyl Donors ◽  
Common Genetic Variants ◽  
One Carbon Metabolism ◽  
The Impact

Folate and choline are water-soluble micronutrients that serve as methyl donors in the conversion of homocysteine to methionine. Inadequacy of these nutrients can disturb one-carbon metabolism as evidenced by alterations in circulating folate and/or plasma homocysteine. Among common genetic variants that reside in genes regulating folate absorptive and metabolic processes, homozygosity for the MTHFR 677C > T variant has consistently been shown to have robust effects on status markers. This paper will review the impact of genetic variants in folate-metabolizing genes on folate and choline bioefficacy. Nutrient-gene and gene-gene interactions will be considered along with the need to account for these genetic variants when updating dietary folate and choline recommendations.

Orienting and Focusing in Voluntary and Involuntary Visuospatial Attention Conditions

2010 ◽  
Vol 24 (3) ◽  
pp. 198-209 ◽  
Author(s):  
Yan Wang ◽  
Jianhui Wu ◽  
Shimin Fu ◽  
Yuejia Luo
Keyword(s):  
Gain Control ◽  
Event Related Potentials ◽  
Stimulus Onset ◽  
Orientation Discrimination ◽  
Involuntary Attention ◽  
Attention Condition ◽  
Voluntary Attention ◽  
Visual Spatial ◽  
Related Potentials ◽  
Underlying Mechanisms

In the present study, we used event-related potentials (ERPs) and behavioral measurements in a peripherally cued line-orientation discrimination task to investigate the underlying mechanisms of orienting and focusing in voluntary and involuntary attention conditions. Informative peripheral cue (75% valid) with long stimulus onset asynchrony (SOA) was used in the voluntary attention condition; uninformative peripheral cue (50% valid) with short SOA was used in the involuntary attention condition. Both orienting and focusing were affected by attention type. Results for attention orienting in the voluntary attention condition confirmed the “sensory gain control theory,” as attention enhanced the amplitude of the early ERP components, P1 and N1, without latency changes. In the involuntary attention condition, compared with invalid trials, targets in the valid trials elicited larger and later contralateral P1 components, and smaller and later contralateral N1 components. Furthermore, but only in the voluntary attention condition, targets in the valid trials elicited larger N2 and P3 components than in the invalid trials. Attention focusing in the involuntary attention condition resulted in larger P1 components elicited by targets in small-cue trials compared to large-cue trials, whereas in the voluntary attention condition, larger P1 components were elicited by targets in large-cue trials than in small-cue trials. There was no interaction between orienting and focusing. These results suggest that orienting and focusing of visual-spatial attention are deployed independently regardless of attention type. In addition, the present results provide evidence of dissociation between voluntary and involuntary attention during the same task.

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