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Epistasis

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https://www.readbyqxmd.com/read/28799976/effect-of-gene-gene-and-gene-environment-interactions-associated-with-antituberculosis-drug-induced-hepatotoxicity
#1
Julián G Chamorro, Jorge P Castagnino, Omar Aidar, Rosa M Musella, Ana Frías, Mabel Visca, Mabel Nogueras, Lucas Costa, Alessandro Perez, Fabio Caradonna, Gabriela F de Larrañaga
OBJECTIVES: This study evaluated the association between environmental factors and genetic variations in enzymes that metabolize antituberculosis (anti-TB) drugs [arylamine N-acetyltransferase 2, cytochrome P450 2E1 (CYP2E1), glutathione S-transferase theta 1 (GSTT1), and glutathione S-transferase mu 1] with antituberculosis drug-induced hepatotoxicity (ATDH). We also investigated the potential gene-gene and gene-environment interactions as well as their association with ATDH development in a population of hospitalized TB patients from Buenos Aires...
August 9, 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28798062/when-does-frequency-independent-selection-maintain-genetic-variation
#2
Sebastian Novak, Nicholas H Barton
Frequency-independent selection is generally considered as a force that acts to reduce the genetic variation in evolving populations, yet rigorous arguments for this idea are scarce. When selection fluctuates in time, it is unclear whether frequency-independent selection may maintain genetic polymorphism without invoking additional mechanisms. We show that constant frequency-independent selection with arbitrary epistasis on a well-mixed haploid population eliminates genetic variation if we assume linkage equilibrium between alleles...
August 10, 2017: Genetics
https://www.readbyqxmd.com/read/28776950/genetics-of-dispersal
#3
Marjo Saastamoinen, Greta Bocedi, Julien Cote, Delphine Legrand, Frédéric Guillaume, Christopher W Wheat, Emanuel A Fronhofer, Cristina Garcia, Roslyn Henry, Arild Husby, Michel Baguette, Dries Bonte, Aurélie Coulon, Hanna Kokko, Erik Matthysen, Kristjan Niitepõld, Etsuko Nonaka, Virginie M Stevens, Justin M J Travis, Kathleen Donohue, James M Bullock, Maria Del Mar Delgado
Dispersal is a process of central importance for the ecological and evolutionary dynamics of populations and communities, because of its diverse consequences for gene flow and demography. It is subject to evolutionary change, which begs the question, what is the genetic basis of this potentially complex trait? To address this question, we (i) review the empirical literature on the genetic basis of dispersal, (ii) explore how theoretical investigations of the evolution of dispersal have represented the genetics of dispersal, and (iii) discuss how the genetic basis of dispersal influences theoretical predictions of the evolution of dispersal and potential consequences...
August 3, 2017: Biological Reviews of the Cambridge Philosophical Society
https://www.readbyqxmd.com/read/28746338/detecting-epistasis-with-the-marginal-epistasis-test-in-genetic-mapping-studies-of-quantitative-traits
#4
Lorin Crawford, Ping Zeng, Sayan Mukherjee, Xiang Zhou
Epistasis, commonly defined as the interaction between multiple genes, is an important genetic component underlying phenotypic variation. Many statistical methods have been developed to model and identify epistatic interactions between genetic variants. However, because of the large combinatorial search space of interactions, most epistasis mapping methods face enormous computational challenges and often suffer from low statistical power due to multiple test correction. Here, we present a novel, alternative strategy for mapping epistasis: instead of directly identifying individual pairwise or higher-order interactions, we focus on mapping variants that have non-zero marginal epistatic effects-the combined pairwise interaction effects between a given variant and all other variants...
July 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28743817/bacterial-signaling-nucleotides-inhibit-yeast-cell-growth-by-impacting-mitochondrial-and-other-specifically-eukaryotic-functions
#5
Andy Hesketh, Marta Vergnano, Chris Wan, Stephen G Oliver
We have engineered Saccharomyces cerevisiae to inducibly synthesize the prokaryotic signaling nucleotides cyclic di-GMP (cdiGMP), cdiAMP, and ppGpp in order to characterize the range of effects these nucleotides exert on eukaryotic cell function during bacterial pathogenesis. Synthetic genetic array (SGA) and transcriptome analyses indicated that, while these compounds elicit some common reactions in yeast, there are also complex and distinctive responses to each of the three nucleotides. All three are capable of inhibiting eukaryotic cell growth, with the guanine nucleotides exhibiting stronger effects than cdiAMP...
July 25, 2017: MBio
https://www.readbyqxmd.com/read/28733416/genetic-interaction-screens-in-schizosaccharomyces-pombe-using-the-pombe-epistasis-mapper-pem-system-and-a-manual-colony-replicator
#6
Isabelle Colson, Edgar Hartsuiker
In laboratories in which a colony-replicating robot is not available, manual replication provides a good, low-cost alternative for genetic interaction screening using the Pombe Epistasis Mapper (PEM) system. The protocol presented here describes the minimum number of steps required to identify genetic interactions. First, a query deletion is introduced to a library of deletion mutants by mating. Through a series of subsequent selection steps, single and double mutants are isolated and analyzed.
July 21, 2017: Cold Spring Harbor Protocols
https://www.readbyqxmd.com/read/28733404/high-throughput-quantitative-genetic-interaction-mapping-in-the-fission-yeast-schizosaccharomyces-pombe
#7
Assen Roguev, Colm J Ryan, Edgar Hartsuiker, Nevan J Krogan
Epistasis mapping, in which the phenotype that emerges from combining pairs of mutations is measured quantitatively, is a powerful tool for unbiased study of gene function. When performed at a large scale, this approach has been used to assign function to previously uncharacterized genes, define functional modules and pathways, and study their cross talk. These experiments rely heavily on methods for rapid sampling of binary combinations of mutant alleles by systematic generation of a series of double mutants...
July 21, 2017: Cold Spring Harbor Protocols
https://www.readbyqxmd.com/read/28733394/genetic-interaction-mapping-in-schizosaccharomyces-pombe-using-the-pombe-epistasis-mapper-pem-system-and-a-rotor-hda-colony-replicating-robot-in-a-1536-array-format
#8
Assen Roguev, Jiewei Xu, Nevan Krogan
This protocol describes an optimized high-throughput procedure for generating double deletion mutants in Schizosaccharomyces pombe using the colony replicating robot ROTOR HDA and the PEM (pombe epistasis mapper) system. The method is based on generating high-density colony arrays (1536 colonies per agar plate) and passaging them through a series of antidiploid and mating-type selection (ADS-MTS) and double-mutant selection (DMS) steps. Detailed program parameters for each individual replication step are provided...
July 21, 2017: Cold Spring Harbor Protocols
https://www.readbyqxmd.com/read/28724085/quantitative-trait-loci-mapping-for-spike-characteristics-in-hexaploid-wheat
#9
Yaopeng Zhou, Benjamin Conway, Daniela Miller, David Marshall, Aaron Cooper, Paul Murphy, Shiaoman Chao, Gina Brown-Guedira, José Costa
Wheat ( L.) spike characteristics determine the number of grains produced on each spike and constitute key components of grain yield. Understanding of the genetic basis of spike characteristics in wheat, however, is limited. In this study, genotyping-by-sequencing (GBS) and the iSelect 9K assay were used on a doubled-haploid (DH) soft red winter wheat population that showed a wide range of phenotypic variation for spike traits. A genetic map spanning 2934.1 cM with an average interval length of 3.4 cM was constructed...
July 2017: Plant Genome
https://www.readbyqxmd.com/read/28720710/application-of-response-surface-methods-to-determine-conditions-for-optimal-genomic-prediction
#10
Réka Howard, Alicia L Carriquiry, William D Beavis
An epistatic genetic architecture can have a significant impact on prediction accuracies of genomic prediction (GP) methods. Machine learning methods predict traits composed of epistatic genetic architectures more accurately than statistical methods based on additive mixed linear models. The differences between these types of GP methods suggest a diagnostic for revealing genetic architectures underlying traits of interest. In addition to genetic architecture, the performance of GP methods may be influenced by the sample size of the training population, the number of QTL, and the proportion of phenotypic variability due to genotypic variability (heritability)...
July 18, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28720700/hitchhiking-and-epistasis-give-rise-to-cohort-dynamics-in-adapting-populations
#11
Sean W Buskirk, Ryan Emily Peace, Gregory I Lang
Beneficial mutations are the driving force of adaptive evolution. In asexual populations, the identification of beneficial alleles is confounded by the presence of genetically linked hitchhiker mutations. Parallel evolution experiments enable the recognition of common targets of selection; yet these targets are inherently enriched for genes of large target size and mutations of large effect. A comprehensive study of individual mutations is necessary to create a realistic picture of the evolutionarily significant spectrum of beneficial mutations...
July 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28709611/the-case-epistasis-and-urolithiasis
#12
Nathalie Tabibzadeh, Lynda Cheddani, Michel Daudon, Jean-Philippe Haymann, Aurélie Toussaint, Caroline Silve, Emmanuel Letavernier
No abstract text is available yet for this article.
August 2017: Kidney International
https://www.readbyqxmd.com/read/28703322/the-drosophila-simulans-y-chromosome-interacts-with-the-autosomes-to-influence-male-fitness
#13
C Ruth Archer, Robert M Stephens, Manmohan D Sharma, David J Hosken
The Y chromosome should degenerate because it cannot recombine. However, male limited transmission increases selection efficiency for male benefit alleles on the Y, and therefore Y-chromosomes should contribute significantly to variation in male-fitness. This means that although the Drosophila Y chromosome is small and gene-poor, Y-linked genes are vital for male fertility in D. melanogaster and the Y chromosome has large male-fitness effects. It is unclear if the same pattern is seen in the closely related D...
July 13, 2017: Journal of Evolutionary Biology
https://www.readbyqxmd.com/read/28703045/the-role-of-human-host-genetics-in-tuberculosis-resistance
#14
Craig Kinnear, Eileen G Hoal, Haiko Schurz, Paul D van Helden, Marlo Möller
Tuberculosis (TB) remains a public health problem: the latest estimate of new incident cases per year is a staggering 10.4 million. Despite this overwhelming number, the majority of the immunocompetent population can control infection with Mycobacterium tuberculosis. The human genome underlies the immune response and contributes to the outcome of TB infection. Areas covered: Investigations of TB resistance in the general population have closely mirrored those of other infectious diseases and initially involved epidemiological observations...
July 20, 2017: Expert Review of Respiratory Medicine
https://www.readbyqxmd.com/read/28694848/epiaco-a-method-for-identifying-epistasis-based-on-ant-colony-optimization-algorithm
#15
Yingxia Sun, Junliang Shang, Jin-Xing Liu, Shengjun Li, Chun-Hou Zheng
BACKGROUND: Identifying epistasis or epistatic interactions, which refer to nonlinear interaction effects of single nucleotide polymorphisms (SNPs), is essential to understand disease susceptibility and to detect genetic architectures underlying complex diseases. Though many works have been done for identifying epistatic interactions, due to their methodological and computational challenges, the algorithmic development is still ongoing. RESULTS: In this study, a method epiACO is proposed to identify epistatic interactions, which based on ant colony optimization algorithm...
2017: BioData Mining
https://www.readbyqxmd.com/read/28678836/epistasis-in-genomic-and-survival-data-of-cancer-patients
#16
Dariusz Matlak, Ewa Szczurek
Cancer aggressiveness and its effect on patient survival depends on mutations in the tumor genome. Epistatic interactions between the mutated genes may guide the choice of anticancer therapy and set predictive factors of its success. Inhibitors targeting synthetic lethal partners of genes mutated in tumors are already utilized for efficient and specific treatment in the clinic. The space of possible epistatic interactions, however, is overwhelming, and computational methods are needed to limit the experimental effort of validating the interactions for therapy and characterizing their biomarkers...
July 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28674544/the-interactions-between-the-long-non-coding-rna-nerdl-and-its-target-gene-affect-wood-formation-in-populus-tomentosa
#17
Wan Shi, Mingyang Quan, Qingzhang Du, Deqiang Zhang
Long non-coding RNAs (lncRNAs) are important regulatory factors for plant growth and development, but little is known about the allelic interactions of lncRNAs with mRNA in perennial plants. Here, we analyzed the interaction of the NERD (Needed for RDR2-independent DNA methylation) Populus tomentosa gene PtoNERD with its putative regulator, the lncRNA NERDL (NERD-related lncRNA), which partially overlaps with the promoter region of this gene. Expression analysis in eight tissues showed a positive correlation between NERDL and PtoNERD (r = 0...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28659968/the-human-microbiome-and-the-missing-heritability-problem
#18
Santiago Sandoval-Motta, Maximino Aldana, Esperanza Martínez-Romero, Alejandro Frank
The "missing heritability" problem states that genetic variants in Genome-Wide Association Studies (GWAS) cannot completely explain the heritability of complex traits. Traditionally, the heritability of a phenotype is measured through familial studies using twins, siblings and other close relatives, making assumptions on the genetic similarities between them. When this heritability is compared to the one obtained through GWAS for the same traits, a substantial gap between both measurements arise with genome wide studies reporting significantly smaller values...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28655969/the-immunosignature-of-mother-fetus-couples-in-gestational-diabetes-mellitus-role-of-hla-g-14%C3%A2-bp-ins-del-and-papp-a-a-c-polymorphisms-in-the-uterine-inflammatory-milieu
#19
Miryam Martinetti, Fausta Beneventi, Cristina Capittini, Elena Locatelli, Margherita Simonetta, Chiara Cavagnoli, Irene De Maggio, Annalisa De Silvestri, Annamaria Pasi, Arsenio Spinillo
We enrolled 151 healthy mother/newborn couples and 26 with gestational diabetes mellitus (GDM). HLA-G and PAPP-A plasma levels were measured by ELISA at first and second trimesters, at delivery, and in cord blood. HLA-G 14 bp ins/del and PAPP-A A/C polymorphisms were genotyped. HLA-G del/del and PAPP-A C/C genotypes were more frequent among GDM mothers than controls. We observed a genetic epistasis between the two polymorphisms: the HLA-G del/del and PAPP-A C/C combination was carried by 8% of GDM mothers and 1...
2017: Disease Markers
https://www.readbyqxmd.com/read/28654546/sex-specific-effect-of-rnasel-rs486907-and-mir-146a-rs2910164-polymorphisms-interaction-as-a-susceptibility-factor-for-melanoma-skin-cancer
#20
Antonella Sangalli, Elisa Orlandi, Albino Poli, Andrea Maurichi, Mario Santinami, Morena Nicolis, Silvia Ferronato, Giovanni Malerba, Monica Rodolfo, Macarena Gomez Lira
The genetics of melanoma is complex and, in addition to environmental influences, numerous genes are involved or contribute toward melanoma predisposition. In this study, we evaluated the possible interaction between miR-146a and one of its putative targets ribonuclease L (RNASEL) in the risk of sporadic melanoma. Polymorphisms rs2910164 in miR-146a and rs486907 in the RNASEL gene have both independently been associated with the risk of different cancers, and an interaction between them has been observed in nonmelanoma skin cancer...
August 2017: Melanoma Research
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