High-throughput phenotyping has opened whole new perspectives for crop improvement and better understanding of quantitative traits in plants. Generation of loss-of-function and gain-of-function plant
Although a phenotype is the ensemble of observable characteristics displayed by an organism, the word phenome is sometimes used to refer to a collection of traits, while the simultaneous study of such a collection is referred to as phenomics.[12][13] Phenomics is an important field of study because it can be used to figure out which genomic variants affect phenotypes which then can be used to explain things like health, disease, and evolutionary fitness.[14] Phenomics forms a large part of the Human Genome Project[15]. Phenomics has widespread applications in the agricultural industry. With an exponentially growing population and inconsistent weather patterns due to global warming, it has become increasingly difficult to cultivate enough crops to support the worlds population. Advantageous genomic variations, like drought and heat resistance, can be identified through the use of phenomics to create more durable GMOs.[16][17]. Phenomics is also a crucial stepping stone towards personalized ...
Autor: Müller, Oliver et al.; Genre: Zeitschriftenartikel; Im Druck veröffentlicht: 2004; Keywords: bioorganic chemistry • combinatorial chemistry • library screening • medicinal chemistry • signal transduction; Titel: Identification of potent Ras signaling inhibitors by pathway-selective phenotype-based screening
The Mammalian Phenotype (MP) Ontology is a community effort to provide standard terms for annotating phenotypic data. You can use this browser to view terms, definitions, and term relationships in a hierarchical display. Links to summary annotated phenotype data at MGI are provided in Term Detail reports.
The Mammalian Phenotype (MP) Ontology is a community effort to provide standard terms for annotating phenotypic data. You can use this browser to view terms, definitions, and term relationships in a hierarchical display. Links to summary annotated phenotype data at MGI are provided in Term Detail reports.
Rice, Oryza sativa L., is one of the most important crops in the world. With the rising world population, feeding people in a more sustainable and environment-friendly way becomes increasingly important. Therefore, rice research community needs to share resources to better understand functions of rice genes that are the foundation for future agricultural biotechnology development, and one way to achieve this goal is via the extensive study of insertional mutants.|br| We have constructed a large rice insertional mutant population in a japonica rice variety, Tainung 67. The collection contains about 93,000 mutant lines, among them 85% with phenomics data and 65% with flanking sequence data. We screened the phenotypes of 12 individual plants for each line grown under field conditions according to 68 subcategories and 3 quantitative traits. Both phenotypes and integration sites are searchable in the database at Taiwan Rice Insertional Mutants Database (http://trim.sinica.edu.tw).|br| Detailed analyses of
Rice, Oryza sativa L., is one of the most important crops in the world. With the rising world population, feeding people in a more sustainable and environment-friendly way becomes increasingly important. Therefore, rice research community needs to share resources to better understand functions of rice genes that are the foundation for future agricultural biotechnology development, and one way to achieve this goal is via the extensive study of insertional mutants.|br| We have constructed a large rice insertional mutant population in a japonica rice variety, Tainung 67. The collection contains about 93,000 mutant lines, among them 85% with phenomics data and 65% with flanking sequence data. We screened the phenotypes of 12 individual plants for each line grown under field conditions according to 68 subcategories and 3 quantitative traits. Both phenotypes and integration sites are searchable in the database at Taiwan Rice Insertional Mutants Database (http://trim.sinica.edu.tw).|br| Detailed analyses of
Tables displaying phenotype data. Phenotype terms and chemical names that occur within any tables of phenotype data (e.g., on the Phenotype Details page showing mutant phenotypes for a single gene, as well as in tables of phenotype search results) provide access to additional related phenotypes and the genes associated with them. Clicking on a hyperlinked phenotype term will take you to a list of all annotations to that phenotype, with the associated genes. Clicking on the name of a chemical will take you to a list of all phenotypes and genes associated with that chemical. ...
Everyone who does computational biology and has wrote at least one Python script probably knows about the BioPython library. I personally remember going "Oh!" some years ago when I gave up writing my own (horrible, terrible, clunky) GenBank file parser and discovered it. Since then it has been a central part of almost all small scripts I needed to write. Recent versions have become even more useful, with the inclusion of a very cool KEGG API wrapper, which has the side-effect of putting together two well-designed bioinformatics software together!. It is then with great pleasure that Im announcing the addition of the Bio.phenotype module to BioPython, starting from version 1.67. The module allows to parse and write the outputs of Phenotype Microarray experiments, as well as to run some simple analysis on the raw data. Even though I have published another software in the past to run the same analysis (plus some more), I thought that a simpler library would prove useful for many, and that having ...
How to interpret the nature of biological processes, which when perturbed cause certain phenotype changes, such as human disease, is a major challenge. The completion of sequencing the genomics of many model organisms has made "reverse genetic approaches" efficient and comprehensive ways to identify the causal genes for a given phenotype under investigation. For instance, genome-wide knockout strains are now available for S. cerevisiae, and diverse high throughput RNAi knockdown experiments have been performed for multiple higher organisms. Although very useful, these high throughput screening approaches are associated with two main problems: 1) the underlying biology, i.e., how genetic perturbation leads to the change of phenotypes in the complex of biological systems is unclear; 2) the screening results could be very noisy with high false positive and false negative rates.; As genomic data from different sources accumulates, integrating screening results with other genomic information, ...
How to interpret the nature of biological processes, which when perturbed cause certain phenotype changes, such as human disease, is a major challenge. The completion of sequencing the genomics of many model organisms has made "reverse genetic approaches" efficient and comprehensive ways to identify the causal genes for a given phenotype under investigation. For instance, genome-wide knockout strains are now available for S. cerevisiae, and diverse high throughput RNAi knockdown experiments have been performed for multiple higher organisms. Although very useful, these high throughput screening approaches are associated with two main problems: 1) the underlying biology, i.e., how genetic perturbation leads to the change of phenotypes in the complex of biological systems is unclear; 2) the screening results could be very noisy with high false positive and false negative rates.; As genomic data from different sources accumulates, integrating screening results with other genomic information, ...
TY - JOUR. T1 - Lineage determination in mixed phenotype acute leukemia. T2 - Response to marcondes et al.. AU - Fuda, Franklin. AU - Chen, Weina. PY - 2014/5. Y1 - 2014/5. UR - http://www.scopus.com/inward/record.url?scp=84898544513&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=84898544513&partnerID=8YFLogxK. U2 - 10.1002/cyto.b.21159. DO - 10.1002/cyto.b.21159. M3 - Letter. C2 - 24470224. AN - SCOPUS:84898544513. VL - 86. SP - 150. EP - 151. JO - Cytometry Part B - Clinical Cytometry. JF - Cytometry Part B - Clinical Cytometry. SN - 1552-4949. IS - 3. ER - ...
The R package opm includes tools for analysing OmniLog(R) Phenotype Microarray (PM) data as produced by the device distributed by BiOLOG Inc., including plotting, aggregating (estimating curve parameters) and comparing PM data, integrating metadata, using the YAML format for the storage of data and metadata, and batch conversion of large numbers of files.
This OPMS object contains all measurements from the study by Vaas et al. (2012). Metadata have been added to fully describe the conducted OmniLog(R) phenotype microarray (PM) experiments. The plate type is Generation III, but the running mode was as for the usual PM plates. Four bacterial strains from two species were considered in the study. For the three publicly accessible ones, the web links to their DSMZ catalogue entries are given below.
We have designed a system for targeted gene expression that allows the selective activation of any cloned gene in a wide variety of tissue- and cell-specific patterns. The gene encoding the yeast transcriptional activator GAL4 is inserted randomly into the Drosophila genome to drive GAL4 expression from one of a diverse array of genomic enhancers. It is then possible to introduce a gene containing GAL4 binding sites within its promoter, to activate it in those cells where GAL4 is expressed, and to observe the effect of this directed misexpression on development. We have used GAL4-directed transcription to expand the domain of embryonic expression of the homeobox protein even-skipped. We show that even-skipped represses wingless and transforms cells that would normally secrete naked cuticle into denticle secreting cells. The GAL4 system can thus be used to study regulatory interactions during embryonic development. In adults, targeted expression can be used to generate dominant phenotypes for use ...
Berger AH, Brooks AN, Wu X, Shrestha Y, Chouinard C, Piccioni F, Bagul M, Kamburov A, Imielinski M, Hogstrom L, Zhu C, Yang X, Pantel S, Sakai R, Watson J, Kaplan N, Campbell JD, Singh S, Root DE, Narayan R, Natoli T, Lahr DL, Tirosh I, Tamayo P, Getz G, Wong B, Doench J, Subramanian A, Golub TR, Meyerson M, Boehm ...
Chromatin immunoprecipitation followed by genome-wide chip hybridization (ChIP-chip), provides a tool for identifying transcription factor (TF) binding sites in the upstream regulatory regions of genes that are differentially expressed in alternative phenotypes or under different environmental conditions (Sun et al. 2010; Qin et al. 2011; Vernes et al. 2011; Yu et al. 2011; Cho et al. 2012; Kwon et al. 2012; Federowicz et al. 2014). By combining ChIP-chip hybridization analyses with mutational analyses and genome-wide transcription profiling, transcriptional networks regulating phenotypic transitions and the expression of alternative phenotypes can be developed (Sun et al. 2010; Qin et al. 2011; Vernes et al. 2011; Wang et al. 2011; Cho et al. 2012; Kwon et al. 2012; Federowicz et al. 2014). However, while ChIP-chip analyses provide the locations of binding sites, they do not assess functionality (Anderson et al. 1989; Li et al. 2008; Cooke et al. 2009; Ucar et al. 2009; Qin et al. 2011; Carey ...
The next round of Postgraduate Internship Awards at the Australian Plant Phenomics Facility (APPF) will close 30 November, 2017. Internships are offered at the…
Quite alot of questions - Ill try and tackle at least some!. ,evolution can be described as descent with modification; a change that builds up in a population over time. The changes involved are random mutations to the DNA that is not directed. I also imagine that that change is established in the population before the next change occurs, Not so. Populations harbour a lot of genetic variance arising ultimately from mutations. Mutations are arising all the time and ultimately proceed to fixation (the mutant allele becomes the only variant in the population) or loss (it disappears from the population). Selection plays a big role here but so does random chance. At any one time there will be lots of mutations at lots of genes at all sorts of different frequencies in a population. So its definitely not a sequential process at all!. ,Are small changes (that have no effect on phenotype) able to be part of this process?. Absolutely, much genetic evolution has no detectable effect on phenotype and ...
Results This study analysed 1111 consecutive patients. Of these, 224 (20.2%) met the criteria for HCAP (39.3% hospitalised within 3 months, 37.5% nursing home residents, 10.7% recent outpatient appointments, 12.5% other). 96.4% of HCAP patients received standard CAP antibiotic therapy without coverage of Pseudomonas aeruginosa or MRSA. Demographic comparison of HCAP and CAP patients showed HCAP patients were significantly older (median age 76 vs 64, p,0.0001) and more likely to have co-morbidities, for example, congestive cardiac failure (30% vs 17%, p,0.0001), COPD (33.5% vs 20.8%, p,0.0001). HCAP patients had higher markers of severity and worse outcomes on univariate analysis. Mean admission CURB65 score was greater (2.32 vs 1.78, p,0.0001), median length of stay was longer (7 vs 5 days, p=0.01) and 30-day mortality was double that of CAP patients (16.5% vs 8.2%, p=0.0004). Kaplain-Meier analysis showed higher mortality for HCAP patients (Log rank test χ2 13.24 df=1, p=0.0003) as shown ...
RNAi is a convenient, widely used tool for screening for genes of interest. We have recently used this technology to screen roughly 750 candidate genes, in C. elegans, for potential roles in regulating muscle protein degradation in vivo. To maximize confidence and assess reproducibility, we have only used previously validated RNAi constructs and have included time courses and replicates. To maximize mechanistic understanding, we have examined multiple sub-cellular phenotypes in multiple compartments in muscle. We have also tested knockdowns of putative regulators of degradation in the context of mutations or drugs that were previously shown to inhibit protein degradation by diverse mechanisms. Here we discuss how assaying multiple phenotypes, multiplexing RNAi screens with use of mutations and drugs, and use of bioinformatics can provide more data on rates of potential false positives and negatives as well as more mechanistic insight than simple RNAi screening.
RNAi is a convenient, widely used tool for screening for genes of interest. We have recently used this technology to screen roughly 750 candidate genes, in C. elegans, for potential roles in regulating muscle protein degradation in vivo. To maximize confidence and assess reproducibility, we have only used previously validated RNAi constructs and have included time courses and replicates. To maximize mechanistic understanding, we have examined multiple sub-cellular phenotypes in multiple compartments in muscle. We have also tested knockdowns of putative regulators of degradation in the context of mutations or drugs that were previously shown to inhibit protein degradation by diverse mechanisms. Here we discuss how assaying multiple phenotypes, multiplexing RNAi screens with use of mutations and drugs, and use of bioinformatics can provide more data on rates of potential false positives and negatives as well as more mechanistic insight than simple RNAi screening.
Im opening up this thread to be a place for the lit review on phenotype definition sub-team, led by @mattspotnitz, @rchen and @Gowtham_Rao, can have team discussions and share progress. Thanks for all your efforts!
BACKGROUND:. Hypertension, an exceedingly common trait in most developed countries, imparts an increased risk of cardiovascular, cerebrovascular and renal diseases. Nevertheless, the primary determinants of elevated blood pressure in most patients are unknown. Recognizing that a sizable portion of variation in blood pressure is genetically determined, one line of research has focused on identifying genetic variants that contribute to the pathogenesis of hypertension. However, standard genetic linkage analysis using hypertension as a phenotype may lack power due to the multifactorial nature of the disorder. A way to overcome this challenge is to subdivide hypertensive subjects into more homogenous subgroups.. DESIGN NARRATIVE:. The overall goal, which is to define the underlying genetics of hypertension in an Asian population by studying intermediate phenotypes, can be divided into three parts. First, the rural Chinese population will be characterized by the collection of intermediate phenotype ...
A. There are plausible disease-causing mutations(i) within, affecting or encompassing an interpretable functional region(ii) of this gene identified in multiple (,3) unrelated cases/families with the phenotype(iii).. OR. B. There are plausible disease-causing mutations(i) within, affecting or encompassing cis-regulatory elements convincingly affecting the expression of a single gene identified in multiple (,3) unrelated cases/families with the phenotype(iii).. OR. C. As definitions A or B but in 2 or 3 unrelated cases/families with the phenotype, with the addition of convincing bioinformatic or functional evidence of causation e.g. known inborn error of metabolism with mutation in orthologous gene which is known to have the relevant deficient enzymatic activity in other species; existence of an animal model which recapitulates the human phenotype.. AND. D. Evidence indicates that disease-causing mutations follow a Mendelian pattern of causation appropriate for reporting in a diagnostic ...
Despite considerable progress in understanding the molecular origins of hereditary human diseases, the molecular basis of several thousand genetic diseases still remains unknown. High-throughput phenotype studies are underway to systematically assess the phenotype outcome of targeted mutations in model organisms. Thus, comparing the similarity between experimentally identified phenotypes and the phenotypes associated with human diseases can be used to suggest causal genes underlying a disease. In this manuscript, we present a method for disease gene prioritization based on comparing phenotypes of mouse models with those of human diseases. For this purpose, either human disease phenotypes are
Author Summary The molecular evolution of any organism is described by changes in the genotype resulting from genetic drift or selection to maintain or establish fitness under the given environmental conditions. Identification of phenotype-defining changes and their distinction from (near-) neutral (hitchhikers) ones is a fundamental challenge in genome research. The standard approach involves time- and cost-intensive mutation experiments, which are typically low throughput, due to their experimental nature. We have developed a computational method for the inference of phenotypic impact of genotypic changes that is applicable to any system, within or across species, where homologous genetic sequences and associated pairwise phenotype distances are available. We demonstrate the accuracy of our method by application to the human influenza A (H3N2) virus. This exemplary system is of particular interest, as recognizing changes in the antigenic phenotype and a viral strains capability to evade pre
The Hickey lab conducts discovery and applied research on Australias most important cereal crops - wheat and barley. The group is situated within the Queensland Alliance for Agriculture and Food Innovation at The University of Queensland, Brisbane, Australia. Our research is focused on key abiotic and biotic factors that limit grain production, as well as development of novel breeding tools and methodologies.. Our germplasm pipeline takes advantage of large nested-association mapping (NAM) populations, speed breeding technology, high-throughput phenotyping methods, and genotyping-by-sequencing (GBS) marker platforms. We develop novel pre-breeding germplasm with adapted genetic backgrounds, along with validated marker-trait associations. Our genetic studies improve understanding of gene effects, trait interactions, and interactions with specific environments. Such information and tools better equip breeders to assemble improved cultivars for farmers.. ...
The Hickey lab conducts discovery and applied research on Australias most important cereal crops - wheat and barley. The group is situated within the Queensland Alliance for Agriculture and Food Innovation at The University of Queensland, Brisbane, Australia. Our research is focussed on key abiotic and biotic factors that limit grain production, as well as development of novel breeding tools and methodologies. Our germplasm pipeline takes advantage of large nested-association mapping (NAM) populations, speed breeding technology, high-throughput phenotyping methods, and genotyping-by-sequencing (GBS) marker platforms. We develop novel pre-breeding germplasm with adapted genetic backgrounds, along with validated marker-trait associations. Our genetic studies improve understanding of gene effects, trait interactions, and interactions with specific environments. Such information and tools better equip breeders to assemble improved cultivars for farmers ...
Crop production has to increase faster to meet the global food demand in the near future. Phenotyping, i.e. the monitoring crop state variables and canopy functioning quantitatively, was recognized as the bottleneck to accelerate genetic progress to increase the yield. Field phenotyping is mandatory since it allows evaluating the genotypes under natural field conditions. The technological advances of sensors, communication and computing foster the development of high-throughput phenotyping systems during the last decade. However, only limited attentions was paid in the interpretation of phenotyping measurements, leading to an under-exploitation of the potentials of current systems. This thesis focuses on advancing the interpretation of field phenotyping measurements over wheat crops. It includes three complementary aspects that illustrate the potentials of advanced image processing, model inversion and data assimilation for the interpretation of phenotyping measurements to access new traits or improve
Representation and depiction of phenotype information at SOC and HLT level. (A) We used the hierarchical information of the MedDRA ontology to map all phenotypi
Identification of functional SNPs in genes and their effects on plant phenotypes - Functional SNPs;Genetic diversity;Phenotypic variation;Biotic and abiotic stresses;
Degree to which an organisms phenotype changes depending upon its current or past environment. Two organisms with the same genotype (e.g., identical twins) may have different phenotypes (e.g., one may be taller or heavier) if raised in different environments; those differences represent phenotypic plasticity. All organisms exhibit some degree of phenotypic plasticity (e.g., an animal that receives more food will generally be heavier than a genetically identical animal that receives less food), but sometimes phenotypic plasticity can be extreme (e.g., some fish become either male or female depending upon the temperatures they were exposed to as an egg). For more details, see our news story on the topic of phenotypic plasticity ...
Because of potential chemotherapeutic (sensitization of chemoresistant cells to death; refs. 3, 4) and chemopreventive (skin cancer prevention; ref. 35) implications, ATR pathway inhibitors have long been sought. Caffeine has been widely used as an ATM/ATR inhibitor, but caffeine requires millimolar levels to inhibit ATR and has several other targets (12, 36). Previous attempts to discover novel DNA damage response inhibitors have focused on finding better ATP-competitive inhibitors of kinases in this pathway. In the present study, we used a phenotype-based screening approach to identify ATR pathway inhibitors, potentially mechanistically distinct from typical ATP-competitive kinase inhibitors. Because the ATR activation mechanism is complex and requires multiple proteins to be recruited to damaged DNA, any of these components of the ATR pathway could potentially be a target of the identified small-molecule inhibitors. Specifically, unlike traditional biochemical screening, this phenotype-based ...
Genetic researchers often collect disease related quantitative traits in addition to disease status because they are interested in understanding the pathophysiology of disease processes. In genome-wide association (GWA) studies, these quantitative phenotypes may be relevant to disease development and serve as intermediate phenotypes or they could be behavioral or other risk factors that predict disease risk. Statistical tests combining both disease status and quantitative risk factors should be more powerful than case-control studies, as the former incorporates more information about the disease. In this paper, we proposed a modified inverse-variance weighted meta-analysis method to combine disease status and quantitative intermediate phenotype information. The simulation results showed that when an intermediate phenotype was available, the inverse-variance weighted method had more power than did a case-control study of complex diseases, especially in identifying susceptibility loci having minor ...
Objective: The possibility that a subset of persons who are obese may be metabolically healthy-referred to as the metabolically healthy obese (MHO) phenotype-has attracted attention recently. However, few studies have followed individuals with MHO or other obesity phenotypes over time to assess change in their metabolic profiles. The aim of the present study was to examine transitions over a 6-year period among different states defined simultaneously by body mass index (BMI) and the presence/absence of the metabolic syndrome (MetS).. Methods: We used repeated measurements available for a subcohort of participants enrolled in the Womens Health Initiative (N=3512) and followed for an average of 6 years to examine the frequency of different metabolic obesity phenotypes at baseline, the 6-year transition probabilities to other states and predictors of the risk of different transitions. Six phenotypes were defined by cross-tabulating BMI (18.5-,25.0, 25.0-,30.0 ...
Linear mixed models are a core statistical approach used in several key areas of genetics. In particular, they provide state-of-the-art solutions for genome-wide association studies, heritability estimation and phenotype prediction. However, one of the fundamental assumptions of these models. that the noise is Gaussian distributed. rarely holds in practice. We show that as a result, standard approaches yield sub-optimal performance, resulting in significant losses in power for GWAS, increased bias in heritability estimation, and reduced accuracy for phenotype predictions. One way to mitigate this problem is to apply an appropriate transformation (e.g., log transform) as a preprocessing step of the phenotypic data. However, choosing the right. transformation is challenging because of the need to manually define a set of transformations, and choose one over another, without a clear objective function that could be used to guide this decision. Thus, the problem has only been partially, and ...
Tissue inhibitors of metalloproteinases (TIMPs) are a family of closely related proteins that inhibit matrix metalloproteinases (MMPs). In the central nervous system (CNS), TIMPs 2, 3, and 4 are constitutively expressed at high levels, whereas TIMP1 can be induced by various stimuli. Here, we studied the effects of constitutive expression of TIMP1 in the CNS in transgenic mice. Transgene expression started prenatally and persisted throughout lifetime at high levels. Since MMP activity has been implicated in CNS development, in proper function of the adult CNS, and in inflammatory disorders, we investigated Timp1-induced CNS alterations. Despite sufficient MMP inhibition, high expressor transgenic mice had a normal phenotype. The absence of compensatory up-regulation of MMP genes in the CNS of Timp1 transgenic mice indicates that development, learning, and memory functions do not require the entire MMP arsenal. To elucidate the effects of strong Timp1 expression in CNS inflammation, we induced ...
Campbell HB, Oscar-Berman M, Giordano J, Blum K, Barh D and Downs BW-Common Phenotype in Patients with Both Food and Substance Dependence: Case Reports
Instead of relying on natural variation, a more direct forward genetic approach is to randomly mutagenize the genome and to systematically screen for mutants with phenotypes of interest. Such screens may uncover novel and unexpected genes without any bias or assumptions. Mutants sharing a similar phenotype may indeed point to an underlying network of genes that potentially affect the same biological process or genetic pathway. Furthermore, mutations showing differences in phenotypic severity will allow us to identify key players of a pathway. An important aspect of a phenotype-driven screen is that it allows genome-wide interrogation. The strength and broad application of these approaches have been demonstrated in many other model organisms, including yeast, worms, flies, fish and Arabidopsis. For example, the large-scale screen for embryonic lethals in Drosophila melanogaster by Eric Wieschaus and Christine Nüsslein-Volhard led to the discovery of genes that regulate embryonic development and ...
Our lab addresses a fundamental question in biology: how do novel phenotypic traits originate and diversify in nature? We use a wide range of approaches to address this question from different perspectives, and on different levels of biological organization. We use behavioral and ecological approaches in the lab and field on experimental and natural populations to understand when and how ecological processes can drive phenotypic evolution. We employ standard developmental techniques and growth manipulations to address physiological mechanisms of phenotype formation and evolution. Lastly, we rely on an increasing range of developmental-genetic and molecular tools (in-situ hybridization, immunohistochemistry, EST libraries, RNAinterference, microarrays, 2d-Protein-gel electrophoresis) to investigate the genetic and genomic regulation of phenotype expression and diversification. While each of these approaches has provided valuable insights, it has been most of all the integration across these ...
Through reverse genetics we will deduce the function of a gene starting with its sequence and working back to its phenotype. There are many genes in the genome whose phenotype when mutated is lethal; therefore, its impossible (or very difficult) to tie function to a particular gene in the traditional forward genetics manner of creating random mutations, looking for phenotype changes, and then finding the defective gene responsible for that function. In our reverse genetics study of some interesting C. elegans genes, two different strains of worms, wild-type and rrf-3 (RNAi enhanced), are fed bacteria expressing dsRNA specific to a particular worm gene. Ingesting dsRNA initiates cascade of events that leads to the destruction of the mRNA of the target gene. An altered phenotype in the progeny of RNAi-treated worms indicates what happens when the normal function of this gene is lost or significantly downregulated ...
Biological systems are robust, meaning that they can maintain relatively stable phenotypic outputs over a range of perturbing genetic and environmental inputs. Genetic buffering refers to the gene activities within a cell that confer phenotypic stability. Research in the lab is aimed at discovering how the arrangement of gene circuitry provides robustness through global analysis of genetic interactions. Genetic interaction is defined by the phenotypic effect of altering one gene being non-additive with the effect of a second perturbation. By this definition, when a gene interacts the phenotypic response to perturbation is dependent upon the activity of that gene, and therefore the gene has the capacity to modify phenotypic robustness to the perturbation, or to buffer the perturbation. To measure gene interaction globally, we perturb an array of ~5000 isogenic yeast deletion strains, and use cell proliferation as a phenotypic readout to quantify the interacting effects between the perturbation ...
Figure 4. Summary of phenotype caused by mutations of six3 gene. All targeted mutations showed a similar phenotype. (a-d) Phenotype variations seen in st.40 embryos targeted with the sgRNA for coding region site 1. By this stage, the obvious phenotype is significantly reduced eye size, but a brain defect (see below) is not yet obvious. The phenotype is six3-specific because it was partially rescued by coinjection of six3 mRNA (b, c). Severity of phenotype was scored as +++ (most severe, no eye or tiny piece of eye), ++ (severe, small and malformed eye), + (modest, small relatively normal looking eye), and - (no or little phenotype) (a�c). As observed with the tyr target injections, toxicity of injected RNAs varied greatly depending on batch of embryos. For example, in different experiments, the percentage of normal embryos recovered after the same RNA doses were injected (six3 target 1) varied from 43% to 87% (see Supporting Information Table S1). (d) Chromatograms of the DSP assay from an ...
A rare point mutation in the core promoter -270GC-rich box of PIGM, a housekeeping gene, disrupts binding of the generic transcription factor (TF) Sp1 and causes inherited glycosylphosphatidylinositol (GPI) deficiency (IGD). We show that whereas PIGM messenger RNA levels and surface GPI expression in IGD B cells are low, GPI expression is near normal in IGD erythroid cells. This divergent phenotype results from differential promoter chromatin accessibility and binding of Sp1. Specifically, whereas PIGM transcription in B cells is dependent on Sp1 binding to the -270GC-rich box and is associated with lower promoter accessibility, in erythroid cells, Sp1 activates PIGM transcription by binding upstream of (but not to) the -270GC-rich box. These findings explain intact PIGM transcription in IGD erythroid cells and the lack of clinically significant intravascular hemolysis in patients with IGD. Furthermore, they provide novel insights into tissue-specific transcriptional control of a housekeeping gene by a
Molecular Quantitative Genetics Postdoctoral Associate A postdoctoral position is available to work on the molecular basis of quantitative variation in maize and its ancestor, teosinte. The project involves an analysis of the teosinte branched1 (tb1) gene [see Genetics 141, 333-346 (1995); Nature 386, 485-488 (1997)]. One component of the project will measure the phenotypic effects of a set of tb1 alleles isolated from maize and teosinte and transferred into an isogenic background. The goal is to associate polymorphisms in the DNA sequences of these alleles with their variant phenotypes. The second component will involve the generation of a series of intragenic recombinants between a maize and a teosinte allele of tb1. These recombinant alleles will be used to map the genic regions that confer the different phenotypes of maize and teosinte. Both components of the project will involve statistical analysis of quantitative data and gene expression assays using northerns and tissue in situ ...
Q9CQF9.1,Pcyox1,Pcyox1, prenylcysteine oxidase 1 [Source:MGI Symbol;Acc:MGI:1914131]Mice homozygous for a knock-out allele are viable, fertile and free of obvious pathology despite a striking accumulation of both farnesylcysteine and geranylgeranylcysteine in brain and liver., , ,
Australian agriculture operates in a largely harsh, resource limited (nutrients, water) environment so the role of plant roots is even more vital to crop…
I think this is being somewhat misleading - classical arch-selectionists (self-styled "Darwinists" in the non-slur sense, such as Dawkins, Trivers, etc.) fully acknowledge that natural selection requires the existence of variation created through mutation and is powerless without the needed variation. (see the "Constraints on Perfection" chapter in "The Extended Phenotype" for example) What they dont believe is that any complexity at the phenotypic level can be created by anything other than selection. The paper of Lynchs that you link to is (pardon the pun) "neutral" on that issue, suggesting that the neutral processes merely provide a substrate for selection to act upon - hardly different from what Dawkins would say.. I personally think that we *will* find cases of phenotypic complexity created by neutral forces, but we havent found any convincing cases yet.. ...
In the terminology of evolutionary quantitative genetics, hybrid phenotypes can be considered as correlated responses to changes in the conspecific phenotypes (Johnson and Wade 1996; Johnson 2000). Unfortunately, we rarely know how evolutionary forces have acted upon conspecific phenotypes to generate the observed hybrid dysfunction. Indeed, we seldom know which conspecific phenotypes correlate with phenotypes of hybrid dysfunction.. Muller also realized that one consequence of these models is that all hybrid incompatibilities must be initially asymmetric. Recall the model above where combinations of the alleles a and b together are incompatible and the nascent species I and II are aaBB and AAbb, respectively. While a (species I) is incompatible with b (II), A (II) cannot be incompatible with B (I). Indeed, AABB is the ancestral genotype. It is possible that taxa I and II could further diverge at these loci to A1A1B1B1 and A2A2B2B2 where the A1-B2 and the A2-B1 combinations are both ...
Phenotypes are used for a multitude of purposes such as defining species, reconstructing phylogenies, diagnosing diseases or improving crop and animal productivity, but most of this phenotypic data is published in free-text narratives that are not computable. This means that the complex relationship between the genome, the environment and phenotypes is largely inaccessible to analysis and important questions related to the evolution of organisms, their diseases or their response to climate change cannot be fully addressed. It takes great effort to manually convert free-text narratives to a computable format before they can be used in large-scale analyses. We argue that this manual curation approach is not a sustainable solution to produce computable phenotypic data for three reasons: 1) it does not scale to all of biodiversity; 2) it does not stop the publication of free-text phenotypes that will continue to need manual curation in the future and, most importantly, 3) It does not solve the problem of
Our Biomedical Research Group (BRG) integrates research into the genotypic and phenotypic relationships underpinning our understanding of health, disease and ageing.
By Pranay Reddy 11. WINSTON-SALEM, NC-This summer I have done research at the Rheumatology lab at Wake Forest. I am working at the same location as last year but I have gained more responsiblity this year and can actually make an impact on the research. We are working with various Lupus phenotype mice that have various genes knocked out. Ultimately the Lupus phenotype mice are more prone to aterosclerosis, inflammation, skin disease and other lupus-like symptoms. We are mainly focusing on the cholesterol absorption of these mice in comparison to healthy, non-Lupus mice. We isolate the blood, and centrifuge it to seperate the blood from the plasma. We test the plasma for total cholesterol, free cholesterol, and triglyceride content. We also measure food intake by collecting the stool, and weighing both the mice and the food. The interesting discovery arises when we look at one particular phenotype. Because the paper is not yet published, my boss insists I keep the exact gene name quiet. Anyway, ...
Kayagaki N, Stowe IB, Lee BL, ORourke K, Anderson K, Warming S, Cuellar T, Haley B, Roose-Girma M, Phung QT, Liu PS, Lill JR, Li H, Wu J, Kummerfeld S, Zhang J, Lee WP, Snipas SJ, Salvesen GS, Morris LX, Fitzgerald L, Zhang Y, Bertram EM, Goodnow CC, Dixit VM.. READ. ...
Here, we report that the progeny of irradiated HMEC are dramatically sensitized to undergo TGFβ-induced EMT. IR and TGFβ cooperated to induce a phenotypic transition that occurred in the progeny of cells irradiated once and persisted even in the absence of TGFβ. This resulted in increased motility, enhanced invasion, and disrupted epithelial morphogenesis and was accompanied by a distinct pattern of gene expression.. TGFβ has long been considered as both a positive and a negative effector of mammary tumorigenesis, acting early as a tumor suppressor but later as a stimulator of tumor invasion ( 8). Overexpression of constitutively active TGFβ can induce EMT during tumor progression in vivo ( 33), and the overexpression of TGFβ has been associated with poor prognosis of many human cancers ( 8). The phenotypes of breast cancer micrometastases in lymph nodes and the bone marrow have been interpreted as evidence that EMT occurs in primary tumors ( 34). However, in vivo verification of EMT has ...
This harmonises the phenotype data with genotype data, and also extract the relevant columns from a larger phenotype matrix, and also pre-calculates stratification indices and residuals. This is called by mPhen function, but quicker to do this just once for batched genotype data.
Contributed by: MarkU This week we had 4 prs.. pr. 1 7/9 RFP+ and no phenotype. pr. 2 23/30 RFP+ and no phenotype. pr.3 23/29 RFP+ and no phenotype. pr. 4 19/27 RFP+ and no phenotype. There were no observable phenotypes this week for this line.. Comments (0). ...
We have described GECKO, a simple method for constraining metabolic fluxes with enzymatic data that can be implemented for any GEM. Our method shares elements with previous approaches but stands out as the first method developed for implementing enzyme constraints on a genome‐scale model using experimentally measured turnover numbers and enabling the direct integration of absolute proteomic measurements. GECKO is based on the FBAwMC approach (Beg et al, 2007) but extended to limit each individual enzyme, thereby giving a physiologically constrained and thus more feasible solution. On the other hand, as GECKO uses inequalities instead of equalities, it is less constrained than RBA (Goelzer et al, 2015), thus relying less on the quality of the experimental data. Finally, GECKO does not require a detailed description of protein synthesis, and therefore, its implementation to model eukaryal organisms is less demanding compared to the ME‐modeling strategy (OBrien et al, 2013). Furthermore, the ...
Genotype-phenotype correlations exist for homozygous or compound heterozygous mutations in ABCA3. Frameshift or nonsense ABCA3 mutations are predictive of neonatal presentation and poor outcome, whereas missense, splice site, and insertion/deletions are less reliably associated with age of presentat …
The Carpenter paper1 is a review of the overall methods and individual steps for conducting a high content screening(HCS). First the author briefly introduced the key concepts of visual assays and its development to HCS. In visual assays, cells are labeled flurescently and can be observed using a microscope of their phenotype changes. The recent…
(i) Higher fitness should be considered a characteristic of metabolically healthy but obese phenotype. (ii) Once fitness is accounted for, the metabolically healthy but obese phenotype is a benign condition, with a better prognosis for mortality and morbidity than metabolically abnormal obese indivi …
We explain Traits with video tutorials and quizzes, using our Many Ways(TM) approach from multiple teachers.This lesson will explain how traits are passed down by alleles, and that one particular genotype determines one particular phenotype
Frew, A J and ODonnell, R A (2002) Is there more than one inflammatory phenotype in asthma? Thorax, 57 (7). pp. 566-568. ISSN 0040-6376 Full text not available from this repository ...
Accessories and Reagents for Mammalian Cells Catalog # Phenotype MicroArray OmniLog Accessories 90931-O Validation Manual and Supplies (for Ovation Pipettes) 90931-M Validation Manual and Supplies (for Matrix Pipettes) 90701 OmniLog Trays - Type A MicroPlate footprint 3711 Ovation Electronic Pipettor (8-channel, repe
For many aspects of health, the critical issue is not whether an individual "has" the disorder, but "how much of it" [9]. Studies of clinically diagnosed disorder, which are often complex disorders with a range of signs, symptoms, and levels of severity, typically lump together individuals with very heterogeneous phenotypes into one category, often due to statistical constraints (a study would require a large number of participants to look at subtypes of a disorder). Heterogeneity of the case definition for these complex disorders is problematic for etiologic research because different etiologic factors may be at play for the various traits that are included in the diagnostic criteria. This has been cited as a major limitation for research on ASD [10] and the research community has responded with an effort to create new dimensional classifications of mental disorders based on pathophysiology through the Research Domain Criteria (RDoC) initiative [11]. Heterogeneity in current categorical ...
It is the SpotNet ebook, which matches Launch with Sickbeard, CouchPotato, SABnzbd, and NAS media. The relocation is a non HTTPS reload. new linked some devices Writing the NZBStars functionality is every five resources, but that is to use published down frequently that of 2018.
pr.1- 19/27 RFP+, no phenotype.. pr.2- 22/30 RFP+, no phenotype.. pr.3- 15/27 RFP+, no phenotype.. pr. 4- 22/28 RFP+, no phenotype.. ...
Carcinomas account for most tumors and arise from the aberrant control of proliferation and the preceding dedifferentiation of epithelial cells. Upon progression of epithelial tumors to more malignant stages, carcinoma cells lose specific intercellular contacts, which are required to maintain the regular turnover and typical architecture of epithelial structures in the adult. The dissociation of cell-to-cell contacts and the concomitant acquisition of a fibroblastoid morphology is accompanied by the rearrangement of the cytoskeleton and the secretion of extracellular matrix proteins, which facilitates the adoption of a migratory and invasive phenotype at later steps of carcinogenesis ( Birchmeier et al., 1995; Hay, 1990). A similar morphogenetic process, referred to as epithelial to mesenchymal (fibroblastoid) transition, occurs under precise spatio-temporal control during embryonic development, and it is conceivable that mechanisms contributing to this process might be reactivated upon ...
Definition: The most common phenotype or genotype in a natural population; also, a phenotype or genotype arbitrarily designed as a standard for comparison. Source: Essential Genetics: A genomics perspective (2006) 4th Ed. ...
Délétion du gène et surexpression de la protéine sont des méthodes courantes pour létude des fonctions des protéines. Dans cet...
Classifying evolution as an ontogeny relieves the environment from having to account for phenotypes, something the authors insist that it cannot do. They assert, ". . . multiple levels of internal constraints on possible phenotypes make the notion of evolution as the product of external selection operating on phenotypic variations generated at random radically untenable." In a developmental model of evolution, however, the environment doesnt bestow medals of fitness on adaptive phenotypes, but functions as it does in ontogeny. A developmental model of evolution demotes the environment, subordinating it to the needs of ontogenetic programs. In this supportive role, it can function well or poorly, and in so doing facilitate or retard phenotypic expression. Nature in this model cannot select, as in the Darwinian model; it can only nurture or neglect. The environment does not pick any particular path, but it will feed or starve whoever ventures ...
Sep 15, 2014 at 4:02pm
Please help me complete this assignment.
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In the clinic, both the selection of patients for some treatments and the development of new therapies relies heavily on the underlying genetic profile of a particular tumor (14). Implicit in this approach is the hypothesis that specific mutations produce predictable phenotypes that can be targeted by a single method in a variety of cancer types. This hypothesis has also been applied to metabolism, where stereotyped driver mutation-metabolic phenotype relationships based largely on in vitro studies have been described (15-17). Our findings, however, suggest that tissue of origin and tumor environment, in addition to genetics, are important factors that influence metabolic weaknesses for a given tumor. Consistent with this idea, administration of chemotherapies that target nucleotide metabolism has historically been based on tumor type rather than genetics (18).. Using mouse and human data, we have explored metabolic interactions between nascent tumors and their host environment, both local and ...
This is a version of MIEP CD4+ T Cell computational model released on Feburary 5th, 2014. The model is available for download in CellDesigner xml format. We have tested that the model is compatible with Cell Designer 4.3. Here is the release note: The new phenotypes of Th9, Th22, Tr1 and Tfh were added via interactions with new nodes for IL-22, AhR, IL-9, PU.1, BLIMP1, BCL-6, c-MAF, and IL-27. Th9 relies on the presence of IL-4 and TGF-beta in the PU-1 pathway and produces IL-10, IL-9, and IL-21. Cytokines TGF-beta and IL-4 induce the PU.1 transcription factor, which then upregulates IL-9. It also promotes IL-21 via the BCL-6 pathway. IL-21 then promotes c-MAF phosphorylation which upregulates IL-10. Th22 results from the AHR pathway requiring IL-6 and TNF-alpha and upregulates TNF-alpha and IL-22. TNF-alpha and IL-6 work together to promote AhR phosphorylation, which is also promoted by IL-27. AhR then increases IL-6 and IL-22 production. IL-10 promotes the Tr1 phenotype. Tfh results from the ...
This is a version of MIEP CD4+ T Cell computational model released on Feburary 5th, 2014. The model is available for download in CellDesigner xml format. We have tested that the model is compatible with Cell Designer 4.3. Here is the release note: The new phenotypes of Th9, Th22, Tr1 and Tfh were added via interactions with new nodes for IL-22, AhR, IL-9, PU.1, BLIMP1, BCL-6, c-MAF, and IL-27. Th9 relies on the presence of IL-4 and TGF-beta in the PU-1 pathway and produces IL-10, IL-9, and IL-21. Cytokines TGF-beta and IL-4 induce the PU.1 transcription factor, which then upregulates IL-9. It also promotes IL-21 via the BCL-6 pathway. IL-21 then promotes c-MAF phosphorylation which upregulates IL-10. Th22 results from the AHR pathway requiring IL-6 and TNF-alpha and upregulates TNF-alpha and IL-22. TNF-alpha and IL-6 work together to promote AhR phosphorylation, which is also promoted by IL-27. AhR then increases IL-6 and IL-22 production. IL-10 promotes the Tr1 phenotype. Tfh results from the ...
Correlates variation within the meta-genome to target species phenotype variations in meta-genome with association studies. Follows the pipeline described in Chaston, J.M. et al. (2014) ,doi:10.1128/mBio.01631-14,.. ...
Restoration of a normal cellular phenotype in CHM1 RPE following transduction with AAV2/5-CAG-CHM. (a) A representative in vitro prenylation, followed by wester
Barcelona: divine CLIE, 2015. Contact Us using online default raison is to become predetermined into process when core surfaces have phenomics for magazine requests. only to Liberal new signals should in be dispatched as formulations for apostolic pop.
Woody Allen, Elizabeth Shue and Billy Crystal.Film: Deconstructing WoodyBy Sally Ogle DavisRemember when Woody Allen, following the Soon Yi scandal, wasask
Interrogating conserved elements of diseases using Boolean combinations of orthologous phenotypes John O Woods , Matthew Z Tien , Edward M Marcotte doi: http://dx.doi.org/10.1101/017947 Conserved genetic programs often predate the homologous structures and phenotypes to which they give rise; eyes, for example, have evolved several dozen times, but their development seems to involve a common…
Question is ⇒ The tumor phenotype, which can be maintained indefinitely in tissue culture, results from the expression of genes on the, Options are ⇒ (A) T-DNA, (B) c-DNA, (C) r-DNA, (D) m-RNA, (E) , Leave your comments or Download question paper.
The results of this study show that the level of Her2 expression is variable in prostate cancer and that an increased Her2 expression level is associated with unfavorable tumor phenotype, rapid tumor cell proliferation, and poor prognosis.. In this study, a TMA containing one 0.6-mm tissue core per cancer was used. The ability to independently detect significant associations with tumor phenotype and prognosis with two different immunohistochemistry protocols highlights the power of this TMA approach for identification of clinically relevant associations. It seems that the high number of cases analyzed in combination with high level of standardization of both immunostaining and analysis compensates for the low amount of tissue analyzed per patient. Literally, all previous studies using large TMAs had succeeded to identify previously well-established associations between molecular findings and tumor phenotype and prognosis (31-33).. Two different antibodies were used in this study to minimize the ...
The Flexible Phenotype attempts a true synthesis of animal physiology, behavior, and ecology by developing an empirical argument that describes the intimate connections between animal phenotype and environment. It starts with a synthesis of the principles guiding current research in ecophysiology, behavior, and ecology, illustrating each aspect with the detailed results of empirical work on as wide a range of organisms as possible.
From 29 June until 3 July, PHENOTYPE will be present during the Making Cities Liveable Conference focussing on Achieving Green, Healthy Cities. The...
Perhaps the most enduring lesson to be drawn from these three efforts is the demonstrated importance of phenotype, and specifically, of a carefully phenotyped population.
And the "one gene, one trait" model violates everything we do know about the phenotype and genotype. Every gene is pleiotropic - it influences multiple traits to varying degrees. Every trait is multigenic - multiple genes contribute to the expression of every phenotypic detail. The bean-bag model is totally inadequate for describing the relationship of genes to physiology and morphology. Instead of a bean-bag, I prefer to think of the genome as comparable to a power spectrum, an expression of the organism in a completely different domain. But I wrote about that previously, and Ill make this explanation a little simpler.. Heres the problem: you cant always reliably predict the phenotype from the genotype. We have a skewed perspective on the problem, because historically, genetics has first searched for strong phenotypes, and then gone looking for the genetic cause. Weve been effectively blind to many subtle phenotypic effects, simply because we dont know how to find them. When we go the ...
The mass download-function of openSNP allows you to easily download the full genotyping raw-data in the file formats that are provided by 23andMe, deCODEme and FamilyTreeDNA. As the files can be grouped by their variations for specific phenotypes it is easy to get datasets that are already usable for association studies.. ...
The mass download-function of openSNP allows you to easily download the full genotyping raw-data in the file formats that are provided by 23andMe, deCODEme and FamilyTreeDNA. As the files can be grouped by their variations for specific phenotypes it is easy to get datasets that are already usable for association studies.. ...
phenotype - relating to how an organism behaves, based on how its genotype relates to the environment. Phenotypic resistance tests look at whether HIV continues to grow in a test tube after increasing concentrations of a drug are added. See genotype.. ...
Gene reports include a comprehensive description of function and biological process as well as disease, expression, regulation and phenotype information.
When two alleles are codominant to each other, the appearance of the heterozygotes is different from both of the homozygotes. There are many synonyms for codominant, such as incomplete dominant, semidominant, partially dominant, mostly dominant, etc. What all of these terms have in common is that they specify a relationship where the different pairings of two genes can create three distinct phenotypes, as opposed to a dominant/recessive relationship where only two phenotypes exist. For all practical purposes, as far as this distinction is concerned, the above terms mean the same thing ...
Imagine if we could compute across phenotype data as easily as genomic data; this article calls for efforts to realize this vision and discusses the potential benefits.. ...
Cardiovascular disease is the leading cause of death in the United States and other Western countries. Although many factors add to the risk of cardiovascular d...
The idea of an extended phenotype refers to the expression of genes in the behavior of an organism rather than its physical composition. The way a beaver makes a dam is influenced by the genetic...
PT-3295 Selecting from the quick search suggestions a phenotype that is already selected and had details attached appears to cause the loss of the details ...
Selecting from the quick search suggestions a phenotype that is already selected and had details attached appears to cause the loss of the ...
Because I couldnt think of a better word to describe them, Phenotypes in this RP refers to the modifications or abilities that a particular character may poss
The idea about Phenotype was to achieve a unique visual effect by touching serifs. Characters form ligatures, but every combination looks different. Touchi
Sometimes you just want to know the few, essential markers for phenotyping and identifying your immune cells in flow cytometry (rather than every CD marker it expresses). Our new page lists the hallmark markers typically used to phenotype several popular immune cells in research. BioLegend develops and manufactures world-class, cutting-edge immunological reagents for biomedical research, offered at an outstanding value.
Sometimes you just want to know the few, essential markers for phenotyping and identifying your immune cells in flow cytometry (rather than every CD marker it expresses). Our new page lists the hallmark markers typically used to phenotype several popular immune cells in research.