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Epistasis

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https://www.readbyqxmd.com/read/28636612/laminin-211-inhibits-protein-kinase-a-in-schwann-cells-to-modulate-neuregulin-1-type-iii-driven-myelination
#1
Monica Ghidinelli, Yannick Poitelon, Yoon Kyoung Shin, Dominique Ameroso, Courtney Williamson, Cinzia Ferri, Marta Pellegatta, Kevin Espino, Amit Mogha, Kelly Monk, Paola Podini, Carla Taveggia, Klaus-Armin Nave, Lawrence Wrabetz, Hwan Tae Park, Maria Laura Feltri
Myelin is required for proper nervous system function. Schwann cells in developing nerves depend on extrinsic signals from the axon and from the extracellular matrix to first sort and ensheathe a single axon and then myelinate it. Neuregulin 1 type III (Nrg1III) and laminin α2β1γ1 (Lm211) are the key axonal and matrix signals, respectively, but how their signaling is integrated and if each molecule controls both axonal sorting and myelination is unclear. Here, we use a series of epistasis experiments to show that Lm211 modulates neuregulin signaling to ensure the correct timing and amount of myelination...
June 2017: PLoS Biology
https://www.readbyqxmd.com/read/28634159/a-role-for-the-nonsense-mediated-mrna-decay-pathway-in-maintaining-genome-stability-in-caenorhabditis-elegans
#2
Víctor González-Huici, Bin Wang, Anton Gartner
Ionizing radiation (IR) is commonly used in cancer therapy and is a main source of DNA double-strand-breaks (DSBs), one of the most toxic forms of DNA damage. We have used Caenorhabditis elegans as an invertebrate model to identify novel factors required for repair of DNA damage inflicted by IR. We have performed an unbiased genetic screen, finding that smg-1 mutations confer strong hypersensitivity to IR. SMG-1 is a phosphoinositide-3 kinase (PI3K) kinase involved in mediating nonsense-mediated mRNA decay (NMD) of transcripts containing premature stop codons and related to the ATM and ATR kinases which are at the apex of DNA damage signalling pathways...
June 20, 2017: Genetics
https://www.readbyqxmd.com/read/28619819/yorkie-and-hedgehog-independently-restrict-bmp-production-in-escort-cells-to-permit-germline-differentiation-in-the-drosophila-ovary
#3
Jianhua Huang, Amy Reilein, Daniel Kalderon
Multiple signaling pathways guide the behavior and differentiation of both germline stem cells (GSCs) and somatic stem cells (FSCs) in the Drosophila germarium, necessitating careful control of signal generation, range and responses. Signal integration involves Escort Cells (ECs), which promote differentiation of the GSC derivatives they envelop, provide niche signals for FSCs and derive directly from FSCs in adults. Hedgehog (Hh) signaling induces the Hippo pathway effector Yorkie (Yki) to promote proliferation and maintenance of FSCs but Hh also signals to ECs, which are quiescent...
June 15, 2017: Development
https://www.readbyqxmd.com/read/28618270/diversity-of-functionally-permissive-sequences-in-the-receptor-binding-site-of-influenza-hemagglutinin
#4
Nicholas C Wu, Jia Xie, Tianqing Zheng, Corwin M Nycholat, Geramie Grande, James C Paulson, Richard A Lerner, Ian A Wilson
Influenza A virus hemagglutinin (HA) initiates viral entry by engaging host receptor sialylated glycans via its receptor-binding site (RBS). The amino acid sequence of the RBS naturally varies across avian and human influenza virus subtypes and is also evolvable. However, functional sequence diversity in the RBS has not been fully explored. Here, we performed a large-scale mutational analysis of the RBS of A/WSN/33 (H1N1) and A/Hong Kong/1/1968 (H3N2) HAs. Many replication-competent mutants not yet observed in nature were identified, including some that could escape from an RBS-targeted broadly neutralizing antibody...
June 14, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28608555/epistasis-%C3%A3-environment-interactions-among-arabidopsis-thaliana-glucosinolate-genes-impact-complex-traits-and-fitness-in-the-field
#5
Rachel E Kerwin, Julie Feusier, Alise Muok, Catherine Lin, Brandon Larson, Daniel Copeland, Jason A Corwin, Matthew J Rubin, Marta Francisco, Baohua Li, Bindu Joseph, Cynthia Weinig, Daniel J Kliebenstein
Despite the growing number of studies showing that genotype × environment and epistatic interactions control fitness, the influences of epistasis × environment interactions on adaptive trait evolution remain largely uncharacterized. Across three field trials, we quantified aliphatic glucosinolate (GSL) defense chemistry, leaf damage, and relative fitness using mutant lines of Arabidopsis thaliana varying at pairs of causal aliphatic GSL defense genes to test the impact of epistatic and epistasis × environment interactions on adaptive trait variation...
June 13, 2017: New Phytologist
https://www.readbyqxmd.com/read/28607034/tctex-1-controls-ciliary-resorption-by-regulating-branched-actin-polymerization-and-endocytosis
#6
Masaki Saito, Wataru Otsu, Kuo-Shun Hsu, Jen-Zen Chuang, Teruyuki Yanagisawa, Vincent Shieh, Taku Kaitsuka, Fan-Yan Wei, Kazuhito Tomizawa, Ching-Hwa Sung
The primary cilium is a plasma membrane-protruding sensory organelle that undergoes regulated assembly and resorption. While the assembly process has been studied extensively, the cellular machinery that governs ciliary resorption is less well understood. Previous studies showed that the ciliary pocket membrane is an actin-rich, endocytosis-active periciliary subdomain. Furthermore, Tctex-1, originally identified as a cytoplasmic dynein light chain, has a dynein-independent role in ciliary resorption upon phosphorylation at Thr94...
June 12, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28606944/cytonuclear-epistasis-controls-the-density-of-symbiont-wolbachia-pipientis-in-non-gonadal-tissues-of-mosquito-culex-quinquefasciatus
#7
Kevin J Emerson, Robert L Glaser
Wolbachia pipientis, a bacterial symbiont infecting arthropods and nematodes, is vertically transmitted through the female germline and manipulates its host's reproduction to favor infected females. Wolbachia also infects somatic tissues where it can cause non-reproductive phenotypes in its host, including resistance to viral pathogens. Wolbachia-mediated phenotypes are strongly associated with the density of Wolbachia in host tissues. Little is known, however, about how Wolbachia density is regulated in native or heterologous hosts...
June 12, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28605458/prioritizing-tests-of-epistasis-through-hierarchical-representation-of-genomic-redundancies
#8
Tyler Cowman, Mehmet Koyutürk
Epistasis is defined as a statistical interaction between two or more genomic loci in terms of their association with a phenotype of interest. Epistatic loci that are identified using data from Genome-Wide Association Studies (GWAS) provide insights into the interplay among multiple genetic factors, with applications including assessment of susceptibility to complex diseases, decision making in precision medicine, and gaining insights into disease mechanisms. Since the number of genomic loci assayed by GWAS is extremely large (usually in the order of millions), identification of epistatic loci is a statistically difficult and computationally intensive problem...
June 9, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28604770/pervasive-antagonistic-interactions-among-hybrid-incompatibility-loci
#9
Rafael F Guerrero, Christopher D Muir, Sarah Josway, Leonie C Moyle
Species barriers, expressed as hybrid inviability and sterility, are often due to epistatic interactions between divergent loci from two lineages. Theoretical models indicate that the strength, direction, and complexity of these genetic interactions can strongly affect the expression of interspecific reproductive isolation and the rates at which new species evolve. Nonetheless, empirical analyses have not quantified the frequency with which loci are involved in interactions affecting hybrid fitness, and whether these loci predominantly interact synergistically or antagonistically, or preferentially involve loci that have strong individual effects on hybrid fitness...
June 12, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28596757/time-resolved-tracking-of-mutations-reveals-diverse-allele-dynamics-during-escherichia-coli-antimicrobial-adaptive-evolution-to-single-drugs-and-drug-pairs
#10
Rachel A Hickman, Christian Munck, Morten O A Sommer
Understanding the evolutionary processes that lead to antibiotic resistance can help to achieve better treatment strategies. Yet, little is known about the dynamics of the resistance alleles during adaptation. Here, we use population sequencing to monitor genetic changes in putative resistance loci at several time-points during adaptive evolution experiments involving five different antibiotic conditions. We monitor the mutational spectra in lineages evolved to be resistant to single antibiotics [amikacin (AMK), chloramphenicol (CHL), and ciprofloxacin (CIP)], as well as antibiotic combinations (AMK + CHL and CHL + CIP)...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28592644/epistasis-searching-for-interacting-genetic-variants-using-crosses
#11
Ian M Ehrenreich
No abstract text is available yet for this article.
June 7, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28592500/epistatic-networks-jointly-influence-phenotypes-related-to-metabolic-disease-and-gene-expression-in-diversity-outbred-mice
#12
Anna L Tyler, Bo Ji, Daniel M Gatti, Steven C Munger, Gary A Churchill, Karen L Svenson, Gregory W Carter
Genetic studies of multidimensional phenotypes can potentially link genetic variation, gene expression, and physiological data to create multi-scale models of complex traits. The challenge of reducing these data to specific hypotheses has become increasingly acute with the advent of genome-scale data resources. Multi-parent populations derived from model organisms provide a resource for developing methods to understand this complexity. In this study, we simultaneously modeled body composition, serum biomarkers, and liver transcript abundances from 474 Diversity Outbred mice...
June 2017: Genetics
https://www.readbyqxmd.com/read/28592494/epistasis-searching-for-interacting-genetic-variants-using-crosses
#13
Ian M Ehrenreich
No abstract text is available yet for this article.
June 2017: Genetics
https://www.readbyqxmd.com/read/28589859/integrative-information-theoretic-network-analysis-for-genome-wide-association-study-of-aspirin-exacerbated-respiratory-disease-in-korean-population
#14
Sehee Wang, Hyun-Hwan Jeong, Dokyoon Kim, Kyubum Wee, Hae-Sim Park, Seung-Hyun Kim, Kyung-Ah Sohn
BACKGROUND: Aspirin Exacerbated Respiratory Disease (AERD) is a chronic medical condition that encompasses asthma, nasal polyposis, and hypersensitivity to aspirin and other non-steroidal anti-inflammatory drugs. Several previous studies have shown that part of the genetic effects of the disease may be induced by the interaction of multiple genetic variants. However, heavy computational cost as well as the complexity of the underlying biological mechanism has prevented a thorough investigation of epistatic interactions and thus most previous studies have typically considered only a small number of genetic variants at a time...
May 24, 2017: BMC Medical Genomics
https://www.readbyqxmd.com/read/28578406/ancestral-protein-resurrection-and-engineering-opportunities-of-the-mamba-aminergic-toxins
#15
Guillaume Blanchet, Doria Alili, Adèle Protte, Gregory Upert, Nicolas Gilles, Livia Tepshi, Enrico A Stura, Gilles Mourier, Denis Servent
Mamba venoms contain a multiplicity of three-finger fold aminergic toxins known to interact with various α-adrenergic, muscarinic and dopaminergic receptors with different pharmacological profiles. In order to generate novel functions on this structural scaffold and to avoid the daunting task of producing and screening an overwhelming number of variants generated by a classical protein engineering strategy, we accepted the challenge of resurrecting ancestral proteins, likely to have possessed functional properties...
June 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28549456/association-mapping-of-loci-controlling-genetic-and-environmental-interaction-of-soybean-flowering-time-under-various-photo-thermal-conditions
#16
Tingting Mao, Jinyu Li, Zixiang Wen, Tingting Wu, Cunxiang Wu, Shi Sun, Bingjun Jiang, Wensheng Hou, Wenbin Li, Qijian Song, Dechun Wang, Tianfu Han
BACKGROUND: Soybean (Glycine max (L.) Merr.) is a short day plant. Its flowering and maturity time are controlled by genetic and environmental factors, as well the interaction between the two factors. Previous studies have shown that both genetic and environmental factors, mainly photoperiod and temperature, control flowering time of soybean. Additionally, these studies have reported gene × gene and gene × environment interactions on flowering time. However, the effects of quantitative trait loci (QTL) in response to photoperiod and temperature have not been well evaluated...
May 26, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28547213/evolutionary-dynamics-in-the-two-locus-two-allele-model-with-weak-selection
#17
Martin Pontz, Josef Hofbauer, Reinhard Bürger
Two-locus two-allele models are among the most studied models in population genetics. The reason is that they are the simplest models to explore the role of epistasis for a variety of important evolutionary problems, including the maintenance of polymorphism and the evolution of genetic incompatibilities. Many specific types of models have been explored. However, due to the mathematical complexity arising from the fact that epistasis generates linkage disequilibrium, few general insights have emerged. Here, we study a simpler problem by assuming that linkage disequilibrium can be ignored...
May 25, 2017: Journal of Mathematical Biology
https://www.readbyqxmd.com/read/28541468/a-fast-and-exhaustive-method-for-heterogeneity-and-epistasis-analysis-based-on-multi-objective-optimization
#18
Xiong Li
Motivation: The existing epistasis analysis approaches have been criticized mainly for their: 1) ignoring heterogeneity during epistasis analysis; 2) high computational costs; and 3) volatility of performances and results. Therefore, they will not perform well in general, leading to lack of reproducibility and low power in complex disease association studies. Method: In this work, a fast scheme is proposed to accelerate exhaustive searching based on multi-objective optimization named ESMO for concurrently analyzing heterogeneity and epistasis phenomena...
May 24, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28535795/turtle-interacts-with-borderless-in-regulating-glial-extension-and-axon-ensheathment
#19
Yixu Chen, Scott Cameron, Wen-Tzu Chang, Yong Rao
Proper recognition between axons and glial processes is required for the establishment of axon ensheathment in the developing nervous system. Recent studies have begun to reveal molecular events underlying developmental control of axon-glia recognition. In our previous work, we showed that the transmembrane protein Borderless (Bdl) is specifically expressed in wrapping glia (WG), and is required for the extension of glial processes and the ensheathment of photoreceptor axons in the developing Drosophila visual system...
May 23, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28535292/adaptive-radiation-of-p-fluorescens-sbw25-in-experimental-microcosms-provides-an-understanding-of-the-evolutionary-ecology-and-molecular-biology-of-a-l-interface-biofilm-formation
#20
Anna Koza, Anna Kusmierska, Kimberley McLaughlin, Olena Moshynets, Andrew J Spiers
Combined experimental evolutionary and molecular biology approaches have been used to investigate the adaptive radiation of Pseudomonas fluorescens SBW25 in static microcosms leading to the colonisation of the air-liquid interface by biofilm-forming mutants such as the Wrinkly Spreader. In these microcosms, the ecosystem engineering of the early wild-type colonists establish the niche space for subsequent WS evolution and colonisation. Random WS mutations occurring in the developing population that de-regulate diguanylate cyclases and c-di-GMP homeostasis result in cellulose-based biofilms at the air-liquid interface...
May 23, 2017: FEMS Microbiology Letters
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