keyword
MENU ▼
Read by QxMD icon Read
search

Epistasis

keyword
https://www.readbyqxmd.com/read/28100592/detecting-high-order-epistasis-in-nonlinear-genotype-phenotype-maps
#1
Zachary R Sailer, Michael J Harms
High-order epistasis has been observed in many genotype-phenotype maps. These multi-way interactions between mutations may be useful for dissecting complex traits and could have profound implications for evolution. Alternatively, they could be a statistical artifact. High-order epistasis models assume the effects of mutations should add, when they could in fact multiply or combine in some other nonlinear way. A mismatch in the "scale" of the epistasis model and the scale of the underlying map would lead to spurious epistasis...
January 18, 2017: Genetics
https://www.readbyqxmd.com/read/28092658/mutation-effects-predicted-from-sequence-co-variation
#2
Thomas A Hopf, John B Ingraham, Frank J Poelwijk, Charlotta P I Schärfe, Michael Springer, Chris Sander, Debora S Marks
Many high-throughput experimental technologies have been developed to assess the effects of large numbers of mutations (variation) on phenotypes. However, designing functional assays for these methods is challenging, and systematic testing of all combinations is impossible, so robust methods to predict the effects of genetic variation are needed. Most prediction methods exploit evolutionary sequence conservation but do not consider the interdependencies of residues or bases. We present EVmutation, an unsupervised statistical method for predicting the effects of mutations that explicitly captures residue dependencies between positions...
January 16, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28092574/dynamics-in-epistasis-analysis
#3
Aseel Awdeh, Hilary Phenix, Mads Kaern, Theodore Perkins
Finding regulatory relationships between genes, including the direction and nature of influence between them, is a fundamental challenge in the field of molecular genetics. One classical approach to this problem is epistasis analysis. Broadly speaking, epistasis analysis infers the regulatory relationships between a pair of genes in a genetic pathway by considering the patterns of change in an observable trait resulting from single and double deletion of genes. While classical epistasis analysis has yielded deep insights on numerous genetic pathways, it is not without limitations...
January 16, 2017: IEEE/ACM Transactions on Computational Biology and Bioinformatics
https://www.readbyqxmd.com/read/28090739/obesity-related-genetic-polymorphisms-and-adiposity-indices-in-a-young-italian-population
#4
Laura Bordoni, Francesca Marchegiani, Marco Piangerelli, Valerio Napolioni, Rosita Gabbianelli
Pediatric obesity develops when a complex biological predisposition collides with an obesogenic environment. To further elucidate the role of genetics in obesity onset, we performed a candidate-gene association study in a young and sportive Italian population by testing the association of functional polymorphisms in ACE (rs4646994), FTO (rs9939609), MC4R (rs17782313) and PPARG (rs1801282) genes with body mass index (BMI) and waist-to-height ratio (WHtR). We also tested the combinations of identified risk genotypes and epistatic interactions among them to determine the existence of cumulative effects in predicting the predisposition to gain weight...
January 16, 2017: IUBMB Life
https://www.readbyqxmd.com/read/28087769/enzyme-efficiency-but-not-thermostability-drives-cefotaxime-resistance-evolution-in-tem-1-%C3%AE-lactamase
#5
Jennifer Knies, Fei Cai, Daniel M Weinreich
A leading intellectual challenge in evolutionary genetics is to identify the specific phenotypes that drive adaptation. Enzymes offer a particularly promising opportunity to pursue this question, because many enzymes' contributions to organismal fitness depend on a comparatively small number of experimentally accessible properties. Moreover, on first principles the demands of enzyme thermostability stand in opposition to the demands of catalytic activity. This observation, coupled with the fact that enzymes are only marginally thermostable, motivates the widely held hypothesis that mutations conferring functional improvement require compensatory mutations to restore thermostability...
January 12, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28087639/vegfd-modulates-both-angiogenesis-and-lymphangiogenesis-during-zebrafish-embryonic-development
#6
Neil I Bower, Adam J Vogrin, Ludovic Le Guen, Huijun Chen, Steven A Stacker, Marc G Achen, Benjamin M Hogan
Vascular endothelial growth factors (VEGFs) control angiogenesis and lymphangiogenesis during development and in pathological conditions. In the zebrafish trunk, Vegfa controls the formation of intersegmental arteries by primary angiogenesis and Vegfc is essential for secondary angiogenesis, the formation of veins and lymphatics. VEGFD has been largely thought of as dispensable for vascular development in vertebrates. Here, we generated a zebrafish vegfd mutant by genome editing. vegfd mutants display significant defects in facial lymphangiogenesis independent of vegfc function...
January 13, 2017: Development
https://www.readbyqxmd.com/read/28087633/the-abl-pathway-bifurcates-to-balance-enabled-and-rac-signaling-in-axon-patterning-in-drosophila
#7
Ramakrishnan Kannan, Jeong-Kuen Song, Tatiana Karpova, Akanni Clarke, Madhuri Shivalkar, Benjamin Wang, Lyudmila Kotlyanskaya, Irina Kuzina, Qun Gu, Edward Giniger
The Abl tyrosine kinase signaling network controls cell migration, epithelial organization, axon patterning and other aspects of development. While individual components are known, the relationships among them remain mysterious. We now use FRET measurements of pathway activity, analysis of protein localization and genetic epistasis to dissect the structure of this network in Drosophila We find that the adaptor protein Disabled stimulates Abl kinase activity. Abl suppresses the actin regulatory factor Enabled, and we find that Abl also acts through the GEF Trio to stimulate the signaling activity of Rac GTPase: Abl gates the activity of the spectrin repeats of Trio, allowing them to relieve intramolecular repression of Trio GEF activity by the Trio N-terminal domain...
January 13, 2017: Development
https://www.readbyqxmd.com/read/28079101/comparing-gwas-results-of-complex-traits-using-full-genetic-model-and-additive-models-for-revealing-genetic-architecture
#8
Md Mamun Monir, Jun Zhu
Most of the genome-wide association studies (GWASs) for human complex diseases have ignored dominance, epistasis and ethnic interactions. We conducted comparative GWASs for total cholesterol using full model and additive models, which illustrate the impacts of the ignoring genetic variants on analysis results and demonstrate how genetic effects of multiple loci could differ across different ethnic groups. There were 15 quantitative trait loci with 13 individual loci and 3 pairs of epistasis loci identified by full model, whereas only 14 loci (9 common loci and 5 different loci) identified by multi-loci additive model...
January 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28076348/reverse-pathway-genetic-approach-identifies-epistasis-in-autism-spectrum-disorders
#9
Ileena Mitra, Alinoë Lavillaureix, Erika Yeh, Michela Traglia, Kathryn Tsang, Carrie E Bearden, Katherine A Rauen, Lauren A Weiss
Although gene-gene interaction, or epistasis, plays a large role in complex traits in model organisms, genome-wide by genome-wide searches for two-way interaction have limited power in human studies. We thus used knowledge of a biological pathway in order to identify a contribution of epistasis to autism spectrum disorders (ASDs) in humans, a reverse-pathway genetic approach. Based on previous observation of increased ASD symptoms in Mendelian disorders of the Ras/MAPK pathway (RASopathies), we showed that common SNPs in RASopathy genes show enrichment for association signal in GWAS (P = 0...
January 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28063628/separate-effects-of-the-ankylosing-spondylitis-associated-erap1-and-erap2-aminopeptidases-determine-the-influence-of-their-combined-phenotype-on-the-hla-b-27-peptidome
#10
Adrian Martín-Esteban, Alejandro Sanz-Bravo, Pablo Guasp, Eilon Barnea, Arie Admon, José A López de Castro
Ankylosing spondylitis (AS) is an inflammatory disease strongly associated with the Major Histocompatibility Complex class I (MHC-I) allotype HLA-B*27. The endoplasmic reticulum aminopeptidases (ERAP)1 and 2, which trim peptides to their optimal length for MHC-I binding, are also susceptibility factors for this disease. Both highly active ERAP1 variants and ERAP2 expression favor AS, whereas loss-of-function ERAP1 and loss-of-expression ERAP2 variants are protective. Yet, only ERAP1 is in epistasis with HLA-B*27...
January 4, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28060815/consequences-of-epistasis-on-growth-in-an-erhualian-%C3%A3-white-duroc-pig-cross
#11
Lucy Crooks, Yuanmei Guo
Epistasis describes an interaction between the effects of loci. We included epistasis in quantitative trait locus (QTL) mapping of growth at a series of ages in a cross of a Chinese pig breed, Erhualian, with a commercial line, White Duroc. Erhualian pigs have much lower growth rates than White Duroc. We improved a method for genomewide testing of epistasis and present a clear analysis workflow. We also suggest a new approach for interpreting epistasis results where significant additive and dominance effects of a locus in specific backgrounds are determined...
2017: PloS One
https://www.readbyqxmd.com/read/28057356/cell-wall-synthesis-and-central-carbohydrate-metabolism-are-interconnected-by-the-snf1-mig1-pathway-in-kluyveromyces-lactis
#12
Dorthe Rippert, Katja Backhaus, Rosaura Rodicio, Jürgen J Heinisch
The trimeric AMP-activated kinase complex (AMPK) is conserved from yeast to humans and is best known for its role in balancing energy metabolism. Additional functions, including the regulation of cell wall biosynthesis, have been proposed for the SNF1 complex, the baker's yeast homolog of AMPK. We here demonstrate that this function is conserved in the Crabtree-negative milk yeast Kluyveromyces lactis. Deletion mutants in the genes encoding the subunits of the trimeric complex (Klsnf1, Klgal83, Klsnf4) displayed increased sensitivities towards cell wall stress agents and a mutant lacking the kinase subunit had a thinner cell wall in transmission electron micrographs as compared to wild type...
December 28, 2016: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28054091/constrained-evolution-of-a-bispecific-enzyme-lessons-for-biocatalyst-design
#13
E Sugrue, C Scott, C J Jackson
One of the central goals of protein design and engineering is to be able to accurately predict the effects of a mutation on stability and activity. However, the genetic context into which mutations are introduced can lead to complex interactions between the mutation and other amino acids and unpredictable, non-additive, effects. This phenomenon is known as intramolecular epistasis and has been shown to restrict evolutionary paths through laboratory directed evolution experiments and ancestral protein reconstruction, but has rarely been studied at a quantitative level in naturally evolving enzymes...
January 5, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28053228/diverse-evolutionary-patterns-of-pneumococcal-antigens-identified-by-pangenome-wide-immunological-screening
#14
Nicholas J Croucher, Joseph J Campo, Timothy Q Le, Xiaowu Liang, Stephen D Bentley, William P Hanage, Marc Lipsitch
Characterizing the immune response to pneumococcal proteins is critical in understanding this bacterium's epidemiology and vaccinology. Probing a custom-designed proteome microarray with sera from 35 healthy US adults revealed a continuous distribution of IgG affinities for 2,190 potential antigens from the species-wide pangenome. Reproducibly elevated IgG binding was elicited by 208 "antibody binding targets" (ABTs), which included 109 variants of the diverse pneumococcal surface proteins A and C (PspA and PspC) and zinc metalloprotease A and B (ZmpA and ZmpB) proteins...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28053116/dna-dependent-protease-activity-of-human-spartan-facilitates-replication-of-dna-protein-crosslink-containing-dna
#15
Mónika Mórocz, Eszter Zsigmond, Róbert Tóth, Márton Zs Enyedi, Lajos Pintér, Lajos Haracska
Mutations in SPARTAN are associated with early onset hepatocellular carcinoma and progeroid features. A regulatory function of Spartan has been implicated in DNA damage tolerance pathways such as translesion synthesis, but the exact function of the protein remained unclear. Here, we reveal the role of human Spartan in facilitating replication of DNA-protein crosslink-containing DNA. We found that purified Spartan has a DNA-dependent protease activity degrading certain proteins bound to DNA. In concert, Spartan is required for direct DPC removal in vivo; we also show that the protease Spartan facilitates repair of formaldehyde-induced DNA-protein crosslinks in later phases of replication using the bromodeoxyuridin (BrdU) comet assay...
January 3, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28053111/evolutionary-interplay-between-structure-energy-and-epistasis-in-the-coat-protein-of-the-%C3%AF-x174-phage-family
#16
Rodrigo A F Redondo, Harold P de Vladar, Tomasz Włodarski, Jonathan P Bollback
Viral capsids are structurally constrained by interactions among the amino acids (AAs) of their constituent proteins. Therefore, epistasis is expected to evolve among physically interacting sites and to influence the rates of substitution. To study the evolution of epistasis, we focused on the major structural protein of the ϕX174 phage family by first reconstructing the ancestral protein sequences of 18 species using a Bayesian statistical framework. The inferred ancestral reconstruction differed at eight AAs, for a total of 256 possible ancestral haplotypes...
January 2017: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/28049709/widespread-historical-contingency-in-influenza-viruses
#17
Jean Claude Nshogozabahizi, Jonathan Dench, Stéphane Aris-Brosou
In systems biology and genomics, epistasis characterizes the impact that a substitution at a particular location in a genome can have on a substitution at another location. This phenomenon is often implicated in the evolution of drug resistance or to explain why particular "disease-causing" mutations do not have the same outcome in all individuals. Hence, uncovering these mutations and their locations in a genome is a central question in biology. However, epistasis is notoriously difficult to uncover, especially in fast-evolving organisms...
January 2017: Genetics
https://www.readbyqxmd.com/read/28049412/genomic-prediction-with-epistasis-models-on-the-marker-coding-dependent-performance-of-the-extended-gblup-and-properties-of-the-categorical-epistasis-model-ce
#18
Johannes W R Martini, Ning Gao, Diercles F Cardoso, Valentin Wimmer, Malena Erbe, Rodolfo J C Cantet, Henner Simianer
BACKGROUND: Epistasis marker effect models incorporating products of marker values as predictor variables in a linear regression approach (extended GBLUP, EGBLUP) have been assessed as potentially beneficial for genomic prediction, but their performance depends on marker coding. Although this fact has been recognized in literature, the nature of the problem has not been thoroughly investigated so far. RESULTS: We illustrate how the choice of marker coding implicitly specifies the model of how effects of certain allele combinations at different loci contribute to the phenotype, and investigate coding-dependent properties of EGBLUP...
January 3, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28025271/no-evidence-that-protein-noise-induced-epigenetic-epistasis-constrains-gene-expression-evolution
#19
Gábor Boross, Balázs Papp
Changes in gene expression can affect phenotypes and therefore both its level and stochastic variability are frequently under selection. It has recently been proposed that epistatic interactions influence gene expression evolution: gene pairs where simultaneous knockout is more deleterious than expected should evolve reduced expression noise to avoid concurrent low expression of both proteins. In apparent support, yeast genes with many epistatic partners have low expression variation both among isogenic individuals and between species...
November 8, 2016: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28025057/a-generalization-of-kingman-s-model-of-selection-and-mutation-and-the-lenski-experiment
#20
Linglong Yuan
Kingman's model of selection and mutation studies the limit type value distribution in an asexual population of discrete generations and infinite size undergoing selection and mutation. This paper generalizes the model to analyze the long-term evolution of Escherichia. coli in Lenski experiment. Weak assumptions for fitness functions are proposed and the mutation mechanism is the same as in Kingman's model. General macroscopic epistasis are designable through fitness functions. Convergence to the unique limit type distribution is obtained...
December 23, 2016: Mathematical Biosciences
keyword
keyword
5224
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"