Variant functional impact
-
Genetic studies have been tremendously successful in identifying genomic regions associated with a wide variety of phenotypes, although the success of these studies in identifying causal genes, their variants, and their functional impacts has been more limited.
21p vibransone 28-03-2024 2 1 Download
-
Gain-of-function (GOF) variants give rise to increased/novel protein functions whereas loss-of-function (LOF) variants lead to diminished protein function. Experimental approaches for identifying GOF and LOF are generally slow and costly, whilst available computational methods have not been optimized to discriminate between GOF and LOF variants.
19p vicwell 29-02-2024 3 2 Download
-
5’ untranslated regions (5’UTRs) are essential modulators of protein translation. Predicting the impact of 5’UTR variants is challenging and rarely performed in routine diagnostics. Here, we present a combined approach of a comprehensive prioritization strategy and functional assays to evaluate 5’UTR variation in two large cohorts of patients with inherited retinal diseases (IRDs).
21p vicwell 29-02-2024 3 1 Download
-
Adsorption of carbon dioxide on elastic layered metal-organic frameworks (ELMs) was investigated during and after exposure to water. Two ELM variants, ELM-11 and ELM-12, were contacted with water vapor and the impact of cyclical exposure on the CO2 capacity of the adsorbents was observed.
7p vironald 15-12-2022 6 2 Download
-
To independently assess the impact of mandatory testing using an extended DPYD variant panel (ToxNav®) and consequent dose adjustment of Capecitabine/5-FU on recorded quantitative toxicity, symptoms of depression, and hospital costs.
11p vikolindagrabar 27-07-2022 3 1 Download
-
Functional characterization of the noncoding genome is essential for biological understanding of gene regulation and disease. Here, we introduce the computational framework PINES (Phenotype-Informed Noncoding Element Scoring), which predicts the functional impact of noncoding variants by integrating epigenetic annotations in a phenotype-dependent manner.
17p vigalileogalilei 27-02-2022 6 1 Download
-
Most cancer risk-associated single nucleotide polymorphisms (SNPs) identified by genome-wide association studies (GWAS) are noncoding and it is challenging to assess their functional impacts. To systematically identify the SNPs that affect gene expression by modulating activities of distal regulatory elements, we adapt the self-transcribing active regulatory region sequencing (STARR-seq) strategy, a high-throughput technique to functionally quantify enhancer activities.
14p vialfrednobel 29-01-2022 6 0 Download
-
H3K27ac is well recognized as a marker for active enhancers and a great indicator of enhancer activity. However, its functional impact on transcription has not been characterized. By substituting lysine 27 in histone variant H3.3 with arginine in mouse embryonic stem cells, we diminish the vast majority of H3K27ac at enhancers.
7p viarchimedes 26-01-2022 8 0 Download
-
RNA-binding proteins (RBPs) play key roles in post-transcriptional regulation and disease. Their binding sites cover more of the genome than coding exons; nevertheless, most noncoding variant prioritization methods only focus on transcriptional regulation. Here, we integrate the portfolio of ENCODE-RBP experiments to develop RADAR, a variant-scoring framework.
13p viarchimedes 26-01-2022 13 0 Download
-
β -arrestins are responsible for termination of G protein-coupled receptor (GPCR)-mediated signaling. Association of single nucleotide variants with onset of crucial diseases has made this protein family hot targets in the field of GPCR-mediated pharmacology. However, impact of these mutations on function of these variants has remained elusive. In this study, structural and dynamical properties of one of β -arrestin2 (arrestin 3) variants, A248T, which has been identified in some cancer tissue samples, were investigated via molecular dynamics simulations.
12p tudichquannguyet 29-11-2021 3 1 Download
-
Aim of the present study was first to identify genetic variants associated with egg number (EN) in female broilers, second to describe the mode of their gene action (additive and/or dominant) and third to provide a list with implicated candidate genes for the trait.
12p vijeeni2711 24-07-2021 11 0 Download
-
Reference-guided read alignment and variant genotyping are prone to reference allele bias, particularly for samples that are greatly divergent from the reference genome. A Hereford-based assembly is the widely accepted bovine reference genome.
17p vilichoo2711 23-06-2021 8 1 Download
-
Transposable elements (TEs) are DNA sequences that are able to move from their location in the genome by cutting or copying themselves to another locus. As such, they are increasingly recognized as impacting all aspects of genome function.
16p vikentucky2711 26-11-2020 7 1 Download
-
Deep mutational scanning is a technique to estimate the impacts of mutations on a gene by using deep sequencing to count mutations in a library of variants before and after imposing a functional selection. The impacts of mutations must be inferred from changes in their counts after selection.
13p vikentucky2711 24-11-2020 10 1 Download
-
Molecular simulations are used to provide insight into protein structure and dynamics, and have the potential to provide important context when predicting the impact of sequence variation on protein function.
8p vijisoo2711 27-10-2020 9 0 Download
-
Over the last 10 years, there have been over 3300 genome-wide association studies (GWAS). Almost every GWAS study provides a Manhattan plot either as a main figure or in the supplement. Several software packages can generate a Manhattan plot, but they are all limited in the extent to which they can annotate genenames, allele frequencies, and variants having high impact on gene function or provide any other added information or flexibility.
5p vicolorado2711 23-10-2020 18 0 Download
-
Precision medicine promises to improve both the efficacy and safety of therapeutic products by better informing why some patients respond well to a drug, and some experience adverse reactions, while others do not. Pharmacogenomics is a key component of precision medicine and can be utilized to select optimal doses for patients, more precisely identify individuals who will respond to a treatment and avoid serious drug-related toxicities.
5p caothientrangnguyen 09-05-2020 10 1 Download
-
Three point mutations R335S, L336V and V476L, distin-guish the sequence of a cytochrome P450CYP6A2 variant assumed to be responsible for 1,1,1-trichloro-2,2-bis-(4¢-chlorophenyl)ethane (DDT) resistance in theRDDT R strain ofDrosophila melanogaster. To determine the impact of each mutation on the function of CYP6A2, the wild-type enzyme (CYP6A2wt) ofCyp6a2was expressed inEscheri-chia colias well as three variants carrying a single mutation, the double mutant CYP6A2vSV and the triple mutant CYP6A2vSVL. All CYP6A2 variants were less stable than the CYP6A2wt protein. ...
8p dell39 03-04-2013 46 2 Download
-
This study characterized the human apolipoprotein H [APOH; b2-glycopro-tein I (b2GPI)] promoter and its variants byin vitro functional experiments and investigated their relationship with human plasmab2GPI levels. We examined the individual effects of 12 APOHpromoter single nucleotide polymorphisms in the 5¢ flanking region ofAPOH(1.4 kb) on luciferase activity in COS-1 cells and HepG2 cells and their impact on plasma...
13p mobifone23 18-01-2013 47 2 Download
-
Controlling the impact of stress on brewing biomass, predicting yeast activity and ensuring consistent fermentation performance through successive fermentations remain areas of active interest for the brewing industry. To be able to control and perhaps even manipulate yeast activity, it is necessary to identify factors that affect its functionality during fermentation. Genetic stability and integrity are crucial to maintaining predictable performance.
321p qdung92ct 27-10-2012 87 21 Download