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Forward genetics

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https://www.readbyqxmd.com/read/29684753/reviewing-the-evidence-for-viruses-as-environmental-risk-factors-for-als-a-new-perspective
#1
REVIEW
Daniel B Celeste, Matthew S Miller
Amyotrophic lateral sclerosis is a devastating neurodegenerative disease whose etiology remains poorly understood. Since the genetic basis of disease is known in only a small subset of cases, there has been substantial interest in determining whether environmental factors act as triggers of ALS. Viruses have received longstanding attention as potential ALS triggers. Yet, existing studies have not provided a compelling case for causation. This review summarizes the evidence supporting a link between viral infection and motor neuron disease, with a focus on ALS...
April 20, 2018: Cytokine
https://www.readbyqxmd.com/read/29684672/epigenetic-modulation-by-small-molecule-compounds-for-neurodegenerative-disorders
#2
REVIEW
Akash Kumar Singh, Sarmistha Halder Sinha, James P Clement, Tapas K Kundu
The accumulation of somatic and genetic mutations which altered the structure and coding information of the DNA are the major cause of neurological disorders. However, our recent understanding of molecular mechanisms of 'epigenetic' phenomenon reveals that the modifications of chromatin play a significant role in the development and severity of neurological disorders. These epigenetic processes are dynamic and reversible as compared to genetic ablations which are stable and irreversible. Therefore, targeting these epigenetic processes through small molecule modulators are of great therapeutic potential...
April 20, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29681477/a-forward-genetic-screen-in-zebrafish-identifies-the-g-protein-coupled-receptor-casr-as-a-modulator-of-sensorimotor-decision-making
#3
Roshan A Jain, Marc A Wolman, Kurt C Marsden, Jessica C Nelson, Hannah Shoenhard, Fabio A Echeverry, Christina Szi, Hannah Bell, Julianne Skinner, Emilia N Cobbs, Keisuke Sawada, Amy D Zamora, Alberto E Pereda, Michael Granato
Animals continuously integrate sensory information and select contextually appropriate responses. Here, we show that zebrafish larvae select a behavioral response to acoustic stimuli from a pre-existing choice repertoire in a context-dependent manner. We demonstrate that this sensorimotor choice is modulated by stimulus quality and history, as well as by neuromodulatory systems-all hallmarks of more complex decision making. Moreover, from a genetic screen coupled with whole-genome sequencing, we identified eight mutants with deficits in this sensorimotor choice, including mutants of the vertebrate-specific G-protein-coupled extracellular calcium-sensing receptor (CaSR), whose function in the nervous system is not well understood...
April 6, 2018: Current Biology: CB
https://www.readbyqxmd.com/read/29678862/natural-variation-within-a-species-for-traits-underpinning-c4-photosynthesis
#4
Gregory Reeves, Pallavi Singh, Timo A Rossberg, Deedi Sogbohossou, M Eric Schranz, Julian M Hibberd
Engineering C4 photosynthesis into C3 crops could substantially increase their yield by alleviating photorespiratory losses. This objective is challenging because the C4 pathway involves complex modifications to the biochemistry, cell biology and anatomy of leaves. Forward genetics has provided limited insight into the mechanistic basis of these properties, and there have been no reports of significant quantitative intra-specific variation of C4 attributes that would allow trait mapping. Here, we show that accessions of the C4 species Gynandropsis gynandra collected from locations across Africa and Asia exhibit natural variation in key characteristics of C4 photosynthesis...
April 20, 2018: Plant Physiology
https://www.readbyqxmd.com/read/29676642/immunomethylomics-a-novel-cancer-risk-prediction-tool
#5
Karl T Kelsey, John K Wiencke
There is emerging evidence that the immune biology associated with lung and other solid tumors, as well as patient immune genetic traits, contributes to individual survival. At this time, dramatic advances in immunologic approaches to the study and management of human cancers are taking place, including lung and head and neck squamous cell carcinoma. However, major obstacles for therapies are the profound immune alterations in blood and in the tumor microenvironment that arise in tandem with the cancer. Although there is a significant current effort underway across the cancer research community to probe the tumor environment to uncover the dynamics of the immune response, little similar work is being done to understand the dynamics of immune alterations in peripheral blood, despite evidence showing the prognostic relevance of the neutrophil/lymphocyte ratio for these cancers...
April 2018: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/29675900/virus-inspired-nanogenes-free-from-man-made-materials-for-host-specific-transfection-and-bio-aided-mr-imaging
#6
Jing-Yi Zhu, Ming-Kang Zhang, Xian-Guang Ding, Wen-Xiu Qiu, Wu-Yang Yu, Jun Feng, Xian-Zheng Zhang
Many viruses have a lipid envelope derived from the host cell membrane that contributes much to the host specificity and the cellular invasion. This study puts forward a virus-inspired technology that allows targeted genetic delivery free from man-made materials. Genetic therapeutics, metal ions, and biologically derived cell membranes are nanointegrated. Vulnerable genetic therapeutics contained in the formed "nanogene" can be well protected from unwanted attacks by blood components and enzymes. The surface envelope composed of cancer cell membrane fragments enables host-specific targeting of the nanogene to the source cancer cells and homologous tumors while effectively inhibiting recognition by macrophages...
April 20, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29673930/amelioration-of-neurosensory-structure-and-function-in-animal-and-cellular-models-of-a-congenital-blindness
#7
Ji Yun Song, Puya Aravand, Sergei Nikonov, Lanfranco Leo, Arkady Lyubarsky, Jeannette L Bennicelli, Jieyan Pan, Zhangyong Wei, Ivan Shpylchak, Pamela Herrera, Daniel J Bennett, Nicoletta Commins, Albert M Maguire, Jennifer Pham, Anneke I den Hollander, Frans P M Cremers, Robert K Koenekoop, Ronald Roepman, Patsy Nishina, Shangzhen Zhou, Wei Pan, Gui-Shuang Ying, Tomas S Aleman, Jimmy de Melo, Ilan McNamara, Junwei Sun, Jason Mills, Jean Bennett
Most genetically distinct inherited retinal degenerations are primary photoreceptor degenerations. We selected a severe early onset form of Leber congenital amaurosis (LCA), caused by mutations in the gene LCA5, in order to test the efficacy of gene augmentation therapy for a ciliopathy. The LCA5-encoded protein, Lebercilin, is essential for the trafficking of proteins and vesicles to the photoreceptor outer segment. Using the AAV serotype AAV7m8 to deliver a human LCA5 cDNA into an Lca5 null mouse model of LCA5, we show partial rescue of retinal structure and visual function...
March 21, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29673375/stages-of-behavioural-change-after-direct-to-consumer-disease-risk-profiling-study-protocol-of-two-integrated-controlled-pragmatic-trials
#8
Kelly F J Stewart, Anke Wesselius, Annemie M W J Schols, Maurice P Zeegers
BACKGROUND: The incidence and prevalence of chronic diseases have reached epidemic proportions during the last decades and are not expected to diminish. Chronic diseases increasingly affect younger individuals too, with over 40% of all deaths due to non-communicable diseases occurring before the age of 70. This has led to the development of information services aimed at preventive health care, such as Health Potential®. This counselling service estimates a personal disease risk of a carefully selected list of preventable common chronic diseases that have both a genetic and a lifestyle component of development...
April 19, 2018: Trials
https://www.readbyqxmd.com/read/29673314/a-site-specific-model-and-analysis-of-the-neutral-somatic-mutation-rate-in-whole-genome-cancer-data
#9
Johanna Bertl, Qianyun Guo, Malene Juul, Søren Besenbacher, Morten Muhlig Nielsen, Henrik Hornshøj, Jakob Skou Pedersen, Asger Hobolth
BACKGROUND: Detailed modelling of the neutral mutational process in cancer cells is crucial for identifying driver mutations and understanding the mutational mechanisms that act during cancer development. The neutral mutational process is very complex: whole-genome analyses have revealed that the mutation rate differs between cancer types, between patients and along the genome depending on the genetic and epigenetic context. Therefore, methods that predict the number of different types of mutations in regions or specific genomic elements must consider local genomic explanatory variables...
April 19, 2018: BMC Bioinformatics
https://www.readbyqxmd.com/read/29670134/detection-of-functional-protein-domains-by-unbiased-genome-wide-forward-genetic-screening
#10
Mareike Herzog, Fabio Puddu, Julia Coates, Nicola Geisler, Josep V Forment, Stephen P Jackson
Establishing genetic and chemo-genetic interactions has played key roles in elucidating mechanisms by which certain chemicals perturb cellular functions. In contrast to gene disruption/depletion strategies to identify mechanisms of drug resistance, searching for point-mutational genetic suppressors that can identify separation- or gain-of-function mutations has been limited. Here, by demonstrating its utility in identifying chemical-genetic suppressors of sensitivity to the DNA topoisomerase I poison camptothecin or the poly(ADP-ribose) polymerase inhibitor olaparib, we detail an approach allowing systematic, large-scale detection of spontaneous or chemically-induced suppressor mutations in yeast or haploid mammalian cells in a short timeframe, and with potential applications in other haploid systems...
April 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29670001/epigenetic-programming-of-synthesis-release-and-or-receptor-expression-of-common-mediators-participating-in-the-risk-resilience-for-comorbid-stress-related-disorders-and-coronary-artery-disease
#11
REVIEW
Carlos Manuel Zapata-Martín Del Campo, Martín Martínez-Rosas, Verónica Guarner-Lans
Corticotrophin releasing factor, vasopressin, oxytocin, natriuretic hormones, angiotensin, neuregulins, some purinergic substances, and some cytokines contribute to the long-term modulation and restructuring of cardiovascular regulation networks and, at the same time, have relevance in situations of comorbid abnormal stress responses. The synthesis, release, and receptor expression of these mediators seem to be under epigenetic control since early stages of life, possibly underlying the comorbidity to coronary artery disease (CAD) and stress-related disorders (SRD)...
April 18, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29669291/a-cyfip2-dependent-excitatory-interneuron-pathway-establishes-the-innate-startle-threshold
#12
Kurt C Marsden, Roshan A Jain, Marc A Wolman, Fabio A Echeverry, Jessica C Nelson, Katharina E Hayer, Ben Miltenberg, Alberto E Pereda, Michael Granato
Sensory experiences dynamically modify whether animals respond to a given stimulus, but it is unclear how innate behavioral thresholds are established. Here, we identify molecular and circuit-level mechanisms underlying the innate threshold of the zebrafish startle response. From a forward genetic screen, we isolated five mutant lines with reduced innate startle thresholds. Using whole-genome sequencing, we identify the causative mutation for one line to be in the fragile X mental retardation protein (FMRP)-interacting protein cyfip2...
April 17, 2018: Cell Reports
https://www.readbyqxmd.com/read/29666236/synthetically-engineered-medea-gene-drive-system-in-the-worldwide-crop-pest-drosophila-suzukii
#13
Anna Buchman, John M Marshall, Dennis Ostrovski, Ting Yang, Omar S Akbari
Synthetic gene drive systems possess enormous potential to replace, alter, or suppress wild populations of significant disease vectors and crop pests; however, their utility in diverse populations remains to be demonstrated. Here, we report the creation of a synthetic Medea gene drive system in a major worldwide crop pest, Drosophila suzukii We demonstrate that this drive system, based on an engineered maternal "toxin" coupled with a linked embryonic "antidote," is capable of biasing Mendelian inheritance rates with up to 100% efficiency...
April 17, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29663366/a-genomic-copy-number-signature-predicts-radiation-exposure-in-post-chernobyl-breast-cancer
#14
Christina M Wilke, Herbert Braselmann, Julia Hess, Sergiy V Klymenko, Vadim V Chumak, Liubov M Zakhartseva, Elena V Bakhanova, Axel K Walch, Martin Selmansberger, Daniel Samaga, Peter Weber, Ludmila Schneider, Falko Fend, Hans C Bösmüller, Horst Zitzelsberger, Kristian Unger
Breast cancer is the second leading cause of cancer death among women worldwide and besides life-style, age and genetic risk factors, exposure to ionising radiation is known to increase the risk for breast cancer. Further, DNA copy number alterations (CNAs), which can result from radiation-induced double-strand breaks, are frequently occurring in breast cancer cells. We set out to identify a signature of CNAs discriminating breast cancers from radiation-exposed and non-exposed female patients. We analysed resected breast cancer tissues from 68 exposed female Chernobyl clean-up workers and evacuees and 68 matched non-exposed control patients for CNAs by array comparative genomic hybridisation analysis (aCGH)...
April 16, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29662166/signatures-of-negative-selection-in-the-genetic-architecture-of-human-complex-traits
#15
Jian Zeng, Ronald de Vlaming, Yang Wu, Matthew R Robinson, Luke R Lloyd-Jones, Loic Yengo, Chloe X Yap, Angli Xue, Julia Sidorenko, Allan F McRae, Joseph E Powell, Grant W Montgomery, Andres Metspalu, Tonu Esko, Greg Gibson, Naomi R Wray, Peter M Visscher, Jian Yang
We develop a Bayesian mixed linear model that simultaneously estimates single-nucleotide polymorphism (SNP)-based heritability, polygenicity (proportion of SNPs with nonzero effects), and the relationship between SNP effect size and minor allele frequency for complex traits in conventionally unrelated individuals using genome-wide SNP data. We apply the method to 28 complex traits in the UK Biobank data (N = 126,752) and show that on average, 6% of SNPs have nonzero effects, which in total explain 22% of phenotypic variance...
April 16, 2018: Nature Genetics
https://www.readbyqxmd.com/read/29660854/the-butanol-producing-microbe-clostridium-beijerinckii-ncimb-14988-manipulated-using-forward-and-reverse-genetic-tools
#16
Gareth T Little, Benjamin J Willson, John T Heap, Klaus Winzer, Nigel P Minton
The solventogenic anaerobe Clostridium beijerinckii has potential for use in the sustainable bioconversion of plant-derived carbohydrates into solvents, such as butanol or acetone. However, relatively few strains have been extensively characterised either at the genomic level or through exemplification of a complete genetic toolkit. To remedy this situation, a new strain of C. beijerinckii, NCIMB 14988, was selected from amongst a total of 55 new clostridial isolates capable of growth on hexose and pentose sugars...
April 16, 2018: Biotechnology Journal
https://www.readbyqxmd.com/read/29659762/activation-of-%C3%AF-20-dependent-recombination-and-horizontal-gene-transfer-in-mycoplasma-genitalium
#17
Sergi Torres-Puig, Carlos Martínez-Torró, Ignasi Granero-Moya, Enrique Querol, Jaume Piñol, Oscar Q Pich
In the human pathogen Mycoplasma genitalium, homologous recombination is under the control of σ20, an alternative sigma factor that boosts the generation of genetic and antigenic diversity in the population. Under laboratory growth conditions, σ20 activation is rare and the factors governing its intermittent activity are unknown. Two σ20-regulated genes, rrlA and rrlB, showed to be important for recombination of homologous DNA sequences in this bacterium. Herein, we demonstrate that rrlA and rrlB code for two small proteins that participate in a feed-forward loop essential for σ20 function...
April 11, 2018: DNA Research: An International Journal for Rapid Publication of Reports on Genes and Genomes
https://www.readbyqxmd.com/read/29656834/controlling-ticks-and-tick-borne-diseases%C3%A2-looking-forward
#18
EDITORIAL
José de la Fuente
Tick-borne diseases (TBDs) represent a growing burden for human and animal health worldwide. Several approaches including the use of chemicals with repellency and parasiticidal activity, habitat management, genetic selection of hosts with higher resistance to ticks, and vaccines have been implemented for reducing the risk of TBDs. However, the application of latest gene editing technologies in combination with vaccines likely combining tick and pathogen derived antigens and other control measures should result in the development of effective, safe, and environmentally sound integrated control programs for the prevention and control of TBDs...
April 10, 2018: Ticks and Tick-borne Diseases
https://www.readbyqxmd.com/read/29651978/tracking-the-rules-of-transmission-and-introgression-with-networks
#19
Chloé Vigliotti, Cédric Bicep, Eric Bapteste, Philippe Lopez, Eduardo Corel
Understanding how an animal organism and its gut microbes form an integrated biological organization, known as a holobiont, is becoming a central issue in biological studies. Such an organization inevitably involves a complex web of transmission processes that occur on different scales in time and space, across microbes and hosts. Network-based models are introduced in this chapter to tackle aspects of this complexity and to better take into account vertical and horizontal dimensions of transmission. Two types of network-based models are presented, sequence similarity networks and bipartite graphs...
April 2018: Microbiology Spectrum
https://www.readbyqxmd.com/read/29629209/rapid-and-simultaneous-prediction-of-eight-diesel-quality-parameters-through-atr-ftir-analysis
#20
Maurilio Gustavo Nespeca, Rafael Rodrigues Hatanaka, Danilo Luiz Flumignan, José Eduardo de Oliveira
Quality assessment of diesel fuel is highly necessary for society, but the costs and time spent are very high while using standard methods. Therefore, this study aimed to develop an analytical method capable of simultaneously determining eight diesel quality parameters (density; flash point; total sulfur content; distillation temperatures at 10% (T10), 50% (T50), and 85% (T85) recovery; cetane index; and biodiesel content) through attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy and the multivariate regression method, partial least square (PLS)...
2018: Journal of Analytical Methods in Chemistry
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