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Epistasis

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https://www.readbyqxmd.com/read/29333607/arabidopsis-mlo2-is-a-negative-regulator-of-sensitivity-to-extracellular-ros
#1
Fuqiang Cui, Hongpo Wu, Omid Safronov, Panpan Zhang, Rajeev Kumar, Hannes Kollist, Jarkko Salojärvi, Ralph Panstruga, Kirk Overmyer
The atmospheric pollutant ozone (O3 ) is a strong oxidant that causes extracellular reactive oxygen species (ROS) formation, has significant ecological relevance, and is used here as a non-invasive ROS inducer to study plant signalling. Previous genetic screens identified several mutants exhibiting enhanced O3- sensitivity, but few with enhanced tolerance. We found that loss-of-function mutants in Arabidopsis MLO2, a gene implicated in susceptibility to powdery mildew disease, exhibit enhanced dose-dependent tolerance to O3 and extracellular ROS, but a normal response to intracellular ROS...
January 15, 2018: Plant, Cell & Environment
https://www.readbyqxmd.com/read/29330348/weak-epistasis-may-drive-adaptation-in-recombining-bacteria
#2
Brian J Arnold, Michael U Gutmann, Yonatan H Grad, Samuel K Sheppard, Jukka Corander, Marc Lipsitch, William P Hanage
The impact of epistasis on the evolution of multilocus traits depends on recombination. While sexually-reproducing eukaryotes recombine so frequently that epistasis between polymorphisms is not considered to play a large role in short-term adaptation, many bacteria also recombine, some to the degree that their populations are described as 'panmictic' or 'freely recombining'. However, whether this recombination is sufficient to limit the ability of selection to act on epistatic contributions to fitness is unknown...
January 12, 2018: Genetics
https://www.readbyqxmd.com/read/29323662/crispr-cas9-based-genome-wide-screening-of-toxoplasma-gondii
#3
Saima M Sidik, Diego Huet, Sebastian Lourido
Apicomplexan parasites, such as Toxoplasma gondii, cause extensive morbidity and mortality in humans and livestock, highlighting the need for a deeper understanding of their molecular biology. Although techniques for the generation of targeted gene disruptions have long been available for apicomplexans, such methods are not readily scalable to the entire genome. We recently used CRISPR-Cas9 to disrupt all nuclear protein-coding genes in T. gondii using a pooled format. The method relies on transfection of a guide RNA library into parasites constitutively expressing Cas9...
January 2018: Nature Protocols
https://www.readbyqxmd.com/read/29317470/network-guided-discovery-of-extensive-epistasis-between-transcription-factors-involved-in-aliphatic-glucosinolate-biosynthesis
#4
Baohua Li, Michelle Tang, Ayla Nelson, Hart Caligagan, Xue Zhou, Caitlin Clark Wiest, Richard Ngo, Siobhan M Brady, Daniel J Kliebenstein
Plants use diverse mechanisms influenced by vast regulatory networks of indefinite scale to adapt to their environment. These regulatory networks have an unknown potential for epistasis between genes within and across networks. To test for epistasis within an adaptive trait genetic network, we generated and tested 47 Arabidopsis thaliana double mutant combinations for 20 transcription factors, which all influence the accumulation of aliphatic glucosinolates, the defense metabolites that control fitness. The epistatic combinations were used to test if there is more or less epistasis depending on gene membership within the same or different phenotypic sub-networks...
January 9, 2018: Plant Cell
https://www.readbyqxmd.com/read/29304028/high-density-single-nucleotide-polymorphism-snp-mapping-and-quantitative-trait-loci-qtl-analysis-in-a-biparental-spring-triticale-population-localized-major-and-minor-effect-fusarium-head-blight-resistance-and-associated-traits-qtl
#5
Raman Dhariwal, George Fedak, Yves Dion, Curtis Pozniak, André Laroche, François Eudes, Harpinder Singh Randhawa
Triticale (xTriticosecale Wittmack) is an important feed crop which suffers severe yield, grade and end-use quality losses due to Fusarium head blight (FHB). Development of resistant triticale cultivars is hindered by lack of effective genetic resistance sources. To dissect FHB resistance, a doubled haploid spring triticale population produced from the cross TMP16315/AC Ultima using a microspore culture method, was phenotyped for FHB incidence, severity, visual rating index (VRI), deoxynivalenol (DON) and some associated traits (ergot, grain protein content, test weight, yield, plant height and lodging) followed by single nucleotide polymorphism (SNP) genotyping...
January 5, 2018: Genes
https://www.readbyqxmd.com/read/29296205/angiotensin-ii-receptor-type-1-a1166c-modifies-the-association-between-angiotensinogen-m235t-and-chronic-kidney-disease
#6
Sui-Lung Su, Wei-Teing Chen, Po-Jen Hsiao, Kuo-Cheng Lu, Yuh-Feng Lin, Chin Lin, Wen Su, Shih-Jen Yeh, Hung Chang, Fu-Huang Lin
Single nucleotide polymorphisms (SNPs) in renin-angiotensin system (RAS) genes are associated with RAS imbalance and chronic kidney disease (CKD). We performed a case-control study and meta-analysis to investigate the association between angiotensinogen (AGT) M235T polymorphism and CKD. A total of 634 patients with end-stage renal disease and 739 healthy controls were studied. We also searched PubMed and the Cochrane Library to identify prospective observational studies published before December 2015. We found that the TT and MT genotypes were associated with a higher risk of CKD than the MM genotype (odds ratio [OR]: 3...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29281674/convergent-evolution-and-topologically-disruptive-polymorphisms-among-multidrug-resistant-tuberculosis-in-peru
#7
Louis Grandjean, Robert H Gilman, Tomatada Iwamoto, Claudio U Köser, Jorge Coronel, Mirko Zimic, M Estee Török, Diepreye Ayabina, Michelle Kendall, Christophe Fraser, Simon Harris, Julian Parkhill, Sharon J Peacock, David A J Moore, Caroline Colijn
BACKGROUND: Multidrug-resistant tuberculosis poses a major threat to the success of tuberculosis control programs worldwide. Understanding how drug-resistant tuberculosis evolves can inform the development of new therapeutic and preventive strategies. METHODS: Here, we use novel genome-wide analysis techniques to identify polymorphisms that are associated with drug resistance, adaptive evolution and the structure of the phylogenetic tree. A total of 471 samples from different patients collected between 2009 and 2013 in the Lima suburbs of Callao and Lima South were sequenced on the Illumina MiSeq platform with 150bp paired-end reads...
2017: PloS One
https://www.readbyqxmd.com/read/29279302/genetic-evidence-for-roles-of-yeast-mitotic-cyclins-at-single-stranded-gaps-created-by-dna-replication
#8
Laurence Signon
Paused/stalled replication forks are major threats to genome integrity; unraveling the complex pathways that contribute to fork stability/restart is crucial. Experimentally, fork stalling is induced by growth in presence of hydroxyurea (HU), which depletes the pool of deoxynucleoside triphosphates (dNTPs) and slows down replication progression in yeast. Here, I report an epistasis analysis, based on sensitivity to HU, between CLB2, the principal mitotic cyclin gene in S. cerevisiae, and genes involved in fork stability and recombination...
December 26, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29273888/identification-of-pleiotropic-genetic-variants-affecting-osteoporosis-risk-in-a-korean-elderly-cohort
#9
Eun Pyo Hong, Ka Hyun Rhee, Dong Hyun Kim, Ji Wan Park
Pleiotropy has important implications for understanding the genetic basis and risk assessment of osteoporosis. Our aim was to identify pleiotropic genetic variants associated with the development of osteoporosis and predict osteoporosis risk by leveraging pleiotropic variants. We evaluated the effects of 21 conventional risk factors and 185 single-nucleotide polymorphisms (SNPs) in 63 inflammation- and metabolism-related genes on osteoporosis risk in a community-based Korean cohort study of 1025 participants, the Hallym Aging Study...
December 22, 2017: Journal of Bone and Mineral Metabolism
https://www.readbyqxmd.com/read/29261740/percolation-in-protein-sequence-space
#10
Patrick C F Buchholz, Silvia Fademrecht, Jürgen Pleiss
The currently known protein sequences are not distributed equally in sequence space, but cluster into families. Analyzing the cluster size distribution gives a glimpse of the large and unknown extant protein sequence space, which has been explored during evolution. For six protein superfamilies with different fold and function, the cluster size distributions followed a power law with slopes between 2.4 and 3.3, which represent upper limits to the cluster distribution of extant sequences. The power law distribution of cluster sizes is in accordance with percolation theory and strongly supports connectedness of extant sequence space...
2017: PloS One
https://www.readbyqxmd.com/read/29260711/inferring-genetic-interactions-from-comparative-fitness-data
#11
Kristina Crona, Alex Gavryushkin, Devin Greene, Niko Beerenwinkel
Darwinian fitness is a central concept in evolutionary biology. In practice, however, it is hardly possible to measure fitness for all genotypes in a natural population. Here, we present quantitative tools to make inferences about epistatic gene interactions when the fitness landscape is only incompletely determined due to imprecise measurements or missing observations. We demonstrate that genetic interactions can often be inferred from fitness rank orders, where all genotypes are ordered according to fitness, and even from partial fitness orders...
December 20, 2017: ELife
https://www.readbyqxmd.com/read/29240818/genetic-dissection-of-main-and-epistatic-effects-of-qtl-based-on-augmented-triple-test-cross-design
#12
Xueli Zhang, Congwei Sun, Zheng Zhang, Zhijun Dai, Yuan Chen, Xiong Yuan, Zheming Yuan, Wenbang Tang, Lanzhi Li, Zhongli Hu
The use of heterosis has considerably increased the productivity of many crops; however, the biological mechanism underpinning the technique remains elusive. The North Carolina design III (NCIII) and the triple test cross (TTC) are powerful and popular genetic mating design that can be used to decipher the genetic basis of heterosis. However, when using the NCIII design with the present quantitative trait locus (QTL) mapping method, if epistasis exists, the estimated additive or dominant effects are confounded with epistatic effects...
2017: PloS One
https://www.readbyqxmd.com/read/29234160/inheritance-patterns-in-metabolism-and-growth-in-diallel-crosses-of-arabidopsis-thaliana-from-a-single-growth-habitat
#13
Andrés Eduardo Rodriguez Cubillos, Hao Tong, Saleh Alseekh, Francisco de Abreu E Lima, Jing Yu, Alisdair R Fernie, Zoran Nikoloski, Roosa A E Laitinen
Metabolism is a key determinant of plant growth and modulates plant adaptive responses. Increased metabolic variation due to heterozygosity may be beneficial for highly homozygous plants if their progeny is to respond to sudden changes in the habitat. Here, we investigate the extent to which heterozygosity contributes to the variation in metabolism and size of hybrids of Arabidopsis thaliana whose parents are from a single growth habitat. We created full diallel crosses among seven parents, originating from Southern Germany, and analysed the inheritance patterns in primary and secondary metabolism as well as in rosette size in situ...
December 13, 2017: Heredity
https://www.readbyqxmd.com/read/29233914/had1-is-required-for-cell-wall-integrity-and-fungal-virulence-in-cryptococcus-neoformans
#14
Won-Hee Jung, Ye-Eun Son, Sang-Hun Oh, Ci Fu, Hye Shin Kim, Jin-Hwan Kwak, Maria E Cardenas, Joseph Heitman, Hee-Soo Park
Calcineurin modulates environmental stress survival and virulence of the human fungal pathogen Cryptococcus neoformans Previously, we identified 44 putative calcineurin substrates and proposed that the calcineurin pathway is branched to regulate targets including Crz1, Pbp1, and Puf4 in C. neoformans In this study we characterized Had1, which is one of the putative calcineurin substrates and belongs to a ubiquitously conserved haloacid dehalogenase β-phosphoglucomutase protein super-family. Growth of the had1∆ mutant was found to be compromised at 38°C or higher...
December 12, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29229921/phenotypic-plasticity-promotes-recombination-and-gene-clustering-in-periodic-environments
#15
Davorka Gulisija, Joshua B Plotkin
While theory offers clear predictions for when recombination will evolve in changing environments, it is unclear what natural scenarios can generate the necessary conditions. The Red Queen hypothesis provides one such scenario, but it requires antagonistic host-parasite interactions. Here we present a novel scenario for the evolution of recombination in finite populations: the genomic storage effect due to phenotypic plasticity. Using analytic approximations and Monte-Carlo simulations, we demonstrate that balanced polymorphism and recombination evolve between a target locus that codes for a seasonally selected trait and a plasticity modifier locus that modulates the effects of target-locus alleles...
December 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/29218913/leveraging-putative-enhancer-promoter-interactions-to-investigate-two-way-epistasis-in-type-2-diabetes-gwas
#16
Elisabetta Manduchi, Alessandra Chesi, Molly A Hall, Struan F A Grant, Jason H Moore
We utilized evidence for enhancer-promoter interactions from functional genomics data in order to build biological filters to narrow down the search space for two-way Single Nucleotide Polymorphism (SNP) interactions in Type 2 Diabetes (T2D) Genome Wide Association Studies (GWAS). This has led us to the identification of a reproducible statistically significant SNP pair associated with T2D. As more functional genomics data are being generated that can help identify potentially interacting enhancer-promoter pairs in larger collection of tissues/cells, this approach has implications for investigation of epistasis from GWAS in general...
2018: Pacific Symposium on Biocomputing
https://www.readbyqxmd.com/read/29218911/convergent-downstream-candidate-mechanisms-of-independent-intergenic-polymorphisms-between-co-classified-diseases-implicate-epistasis-among-noncoding-elements
#17
Jiali Han, Jianrong Li, Ikbel Achour, Lorenzo Pesce, Ian Foster, Haiquan Li, Yves A Lussier
Eighty percent of DNA outside protein coding regions was shown biochemically functional by the ENCODE project, enabling studies of their interactions. Studies have since explored how convergent downstream mechanisms arise from independent genetic risks of one complex disease. However, the cross-talk and epistasis between intergenic risks associated with distinct complex diseases have not been comprehensively characterized. Our recent integrative genomic analysis unveiled downstream biological effectors of disease-specific polymorphisms buried in intergenic regions, and we then validated their genetic synergy and antagonism in distinct GWAS...
2018: Pacific Symposium on Biocomputing
https://www.readbyqxmd.com/read/29214224/mutation-network-based-understanding-of-pleiotropic-and-epistatic-mutational-behavior-of-enterococcus-faecalis-fmn-dependent-azoreductase
#18
Jinyan Sun, Ohgew Kweon, Jinshan Jin, Gui-Xin He, Xiyu Li, Carl E Cerniglia, Huizhong Chen
We previously identified a highly active homodimeric FMN-dependent NADH-preferred azoreductase (AzoA) from Enterococcus faecalis, which cleaves the azo bonds (R-N˭N-R) of diverse azo dyes, and determined its crystal structure. The preliminary network-based mutational analysis suggested that the two residues, Arg-21 and Asn-121, have an apparent mutational potential for fine-tuning of AzoA, based on their beneficial pleiotropic feedbacks. However, epistasis between the two promising mutational spots in AzoA has not been obtained in terms of substrate binding and azoreductase activity...
December 2017: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/29203697/frontiers-of-knowledge-an-interview-with-2017-edward-novitski-prize-recipient-jonathan-hodgkin
#19
Jonathan Hodgkin
The Genetics Society of America's Edward Novitski Prize recognizes a single experimental accomplishment or a body of work in which an exceptional level of creativity and intellectual ingenuity has been used to design and execute scientific experiments to solve a difficult problem in genetics. The 2017 winner, Jonathan Hodgkin, used elegant genetic studies to unravel the sex determination pathway in Caenorhabditis elegans He inferred the order of genes in the pathway and their modes of regulation using epistasis analyses-a powerful tool that was quickly adopted by other researchers...
December 2017: Genetics
https://www.readbyqxmd.com/read/29198859/selecting-among-three-basic-fitness-landscape-models-additive-multiplicative-and-stickbreaking
#20
Craig R Miller, James T Van Leuven, Holly A Wichman, Paul Joyce
Fitness landscapes map genotypes to organismal fitness. Their topographies depend on how mutational effects interact-epistasis-and are important for understanding evolutionary processes such as speciation, the rate of adaptation, the advantage of recombination, and the predictability versus stochasticity of evolution. The growing amount of data has made it possible to better test landscape models empirically. We argue that this endeavor will benefit from the development and use of meaningful basic models against which to compare more complex models...
November 30, 2017: Theoretical Population Biology
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