The Effect Of Natural Variation On Perturbed Phenotypes In Caenorhabditis Elegans PDF Download
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| Author | : Victoria Vu |
| Publisher | : |
| Total Pages | : |
| Release | : 2018 |
| Genre | : |
| ISBN | : |
Download The Effect of Natural Variation on Perturbed Phenotypes in Caenorhabditis Elegans Book in PDF, ePub and Kindle
A common problem in the study of human disease genetics is that the severity of symptoms can vary greatly between individuals, even when the underlying disease mutations are identical. Natural variation in genetic background is recognized as one of the contributors to variation in phenotype severity, but our understanding of the underlying mechanisms is limited. Here, I endeavour to explore why differences in genetic background lead to phenotypic variations by systematically examining a large set of single-gene perturbations in Caenorhabditis elegans. In the first section of this thesis, I broadly examine the effect of genetic background on these perturbed phenotypes employing RNAi in two C. elegans isolates, the canonical lab strain N2 and a commonly used wild-type CB4856 for comparison. This screen yielded 120 genes that produced a more severe phenotype in N2 and 127 genes that produced a more severe phenotype in CB4856 (p-value ≤0.05), with notable enrichments in specific functional groups. These differences in phenotypic severity are recapitulated in both genetic mutants and animals chemically treated to perturb the same functional networks. In the latter part of my thesis, I explore the genetics of variation in perturbed phenotypes and find that they are complex, affected by both the expression level of the gene itself and that of genes within the same functional group. For instance, a gene that has lower expression in N2 will likely exhibit a more severe phenotype in N2, and experimentally lowering the gene expression of the gene itself or genes within the same functional group will increase the severity of the phenotype. I further explore the genetics underlying the phenotypic variation of a subset of these gene perturbations using quantitative trait loci (QTL) mapping. With this approach, I identified a broad trend of four QTLs that repeatedly underlie the phenotypic variations in a set of functionally unrelated genes and that most perturbation variations between N2 and CB4856 have more than one underlying genetic cause. Together, these data show that genetic backgrounds frequently modify perturbed phenotype severities and that the genetics underlying this variation is complex.
| Author | : Takanori Ueda |
| Publisher | : Springer |
| Total Pages | : 0 |
| Release | : 2018-09-11 |
| Genre | : Medical |
| ISBN | : 9789811098444 |
Download Chemotherapy for Leukemia Book in PDF, ePub and Kindle
This book focuses on the latest progress in chemotherapy for leukemia and related diseases, including still-ongoing but promising studies. The effectiveness of treatment for chronic myeloid leukemia and acute promyelocytic leukemia has been dramatically improved in recent years. This improvement has been made possible with the development of molecular targeted agents such as bcr-abl tyrosine kinase inhibitors and all-trans retinoic acid. The antibody for the unique target of chemokine receptor 4 for adult T-cell leukemia/lymphoma, or FLT3 inhibitors (signaling inhibitors) has been applied to other leukemias. Also, chemotherapeutic agents including antimetabolite analogues such as clofarabine, and azacitidine (an epigenetic regulator) have undergone progressive development. Meanwhile, the novel concept of therapy targeting leukemic stem cells has been developed. The contributors discuss prospective results of basic and preclinical studies and clinical possibilities based on the effects for leukemic stem cells. This work facilitates a comprehensive understanding of modern treatment methodology for leukemia. The volume therefore will greatly benefit not only hematologists but also oncologists, all physicians who specialize in blood cancer, and pharmacologists who are involved in the development of therapeutic agents for leukemia.
| Author | : Ian A. Hope |
| Publisher | : OUP Oxford |
| Total Pages | : 306 |
| Release | : 1999-12-09 |
| Genre | : Science |
| ISBN | : 019159198X |
Download C. elegans Book in PDF, ePub and Kindle
Caenorhabditis Elegans has been a popular model organism for biological research for over thirty years and has been used to investigate many aspects of animal development, for example apoptosis, the Hox genes, signal transduction pathways, and the development of the nervous system. It has recently taken on new importance with the publication of the entire genome sequence in 1998. The first chapter gives all the basic information on C. elegans required to use it: it's natural history, anatomy, life cycle, development, and evolution. Information on how to obtain, grow, and maintain C. elegans for use as a model system is given in Chapter 4. Chapters 2 and 3 describe the genome project and show how to use genome sequence information by searching the database for homologues using different search methods and then how to analyse the search data. The next chapter gives the essential practical details of transformation and common uses for the technique. Chapter 6 covers reverse genetics and describes strategies for gene inactivation that are known to work in C elegans: epigenetic inactivation and mutational germ line inactivation. Chapter 7 is designed to help the user analyse phenotype by microscopy and includes Normaski, fluorescence, 4-dimensional, and electron microscopy. Techniques for studying the neurobiology of C. elegans are given in chapter 8. Chapter 9 describes the three commonly used approaches for studying gene expression and Chapter 10 deals with the common methods of molecular biology essential for gene characterization. C. elegans is not the ideal organism for biochemical studies, but chapter 11 describes several procedures for producing biochemically useful quantities of pure tissues. The final chapter is about conventional genetics and details the standard procedures for selfing and crossing; mutagenesis and mutant screening; characterization of mutants; gene mapping; temperature-shift experiments and mosaic analysis. Caenorhabditis Elegans: A Practical Approach will therefore provide all the background information necessary for use of C. elegans as a model system.
| Author | : Michal Polak |
| Publisher | : Oxford University Press, USA |
| Total Pages | : 488 |
| Release | : 2003 |
| Genre | : Language Arts & Disciplines |
| ISBN | : 9780195143454 |
Download Developmental Instability Book in PDF, ePub and Kindle
The field of developmental instability has generated a large amount of controversy recently, mostly because of fierce disagreement over the genetic basis of fluctuating asymmetry and its role in mate selection. This book is a timely and innovative critical evaluation of a burgeoning field. The book explores the premise that complex organismal, ecological and evolutionary processes can be understood as emergent properties of the "epigenetic machine," that is, the mechanisms fundamental to all organisms responsible for building and organizing phenotypes from information translated from DNA.
| Author | : National Research Council |
| Publisher | : National Academies Press |
| Total Pages | : 348 |
| Release | : 2000-12-21 |
| Genre | : Nature |
| ISBN | : 0309070864 |
Download Scientific Frontiers in Developmental Toxicology and Risk Assessment Book in PDF, ePub and Kindle
Scientific Frontiers in Developmental Toxicology and Risk Assessment reviews advances made during the last 10-15 years in fields such as developmental biology, molecular biology, and genetics. It describes a novel approach for how these advances might be used in combination with existing methodologies to further the understanding of mechanisms of developmental toxicity, to improve the assessment of chemicals for their ability to cause developmental toxicity, and to improve risk assessment for developmental defects. For example, based on the recent advances, even the smallest, simplest laboratory animals such as the fruit fly, roundworm, and zebrafish might be able to serve as developmental toxicological models for human biological systems. Use of such organisms might allow for rapid and inexpensive testing of large numbers of chemicals for their potential to cause developmental toxicity; presently, there are little or no developmental toxicity data available for the majority of natural and manufactured chemicals in use. This new approach to developmental toxicology and risk assessment will require simultaneous research on several fronts by experts from multiple scientific disciplines, including developmental toxicologists, developmental biologists, geneticists, epidemiologists, and biostatisticians.
| Author | : Timothy G. Geary |
| Publisher | : Springer Science & Business Media |
| Total Pages | : 246 |
| Release | : 2011-01-13 |
| Genre | : Medical |
| ISBN | : 1441969020 |
Download Neuropeptide Systems as Targets for Parasite and Pest Control Book in PDF, ePub and Kindle
The need to continually discover new agents for the control or treatment of invertebrate pests and pathogens is undeniable. Agriculture, both animal and plant, succeeds only to the extent that arthropod and helminth consumers, vectors and pathogens can be kept at bay. Humans and their companion animals are also plagued by invertebrate parasites. The deployment of chemical agents for these purposes inevitably elicits the selection of resistant populations of the targets of control, necessitating a regular introduction of new kinds of molecules. Experience in other areas of chemotherapy has shown that a thorough understanding of the biology of disease is an essential platform upon which to build a discovery program. Unfortunately, investment of research resources into understanding the basic physiology of invertebrates as a strategy to illuminate new molecular targets for pesticide and parasiticide discovery has been scarce, and the pace of introduction of new molecules for these indications has been slowed as a result. An exciting and so far unexploited area to explore in this regard is invertebrate neuropeptide physiology. This book was assembled to focus attention on this promising field by compiling a comprehensive review of recent research on neuropeptides in arthropods and helminths, with contributions from many of the leading laboratories working on these systems.
| Author | : Y. Pichon |
| Publisher | : Birkhäuser |
| Total Pages | : 445 |
| Release | : 2013-03-08 |
| Genre | : Science |
| ISBN | : 3034872658 |
Download Comparative Molecular Neurobiology Book in PDF, ePub and Kindle
It is generally accepted that all living organisms present on earth derive from one single primordial cell born several billion years ago. One important step in the evolution occurred some 1. 5 billion years ago with the transition from small procaryote cells with relatively simple internal structures such as bacteria to larger and more compleX: eucaryotic cells such as those found in higher animals and plants. Large membrane proteins which enable the cells to communicate appeared early in evolution, and it is believed that the nerve membrane receptors and ionic channels which are observed today in both invertebrate and vertebrate species derive from a common ancestor. Basically, the three identified superfamilies, 1) ionotropic receptors (i. e. receptors containing an integral ionic channel), 2) metabotropic receptors (receptors coupled to G proteins) and 3) voltage-dependent ionic channels (Na+, K + and Ca2+ channels) were already well differentiated when vertebrates separated from invertebrate species. The large number of subtypes which are observed in each superfamily may be of more recent evolutionary origin. To understand how this happened, the best approach was to compare the sequences and the properties of the receptors and ionic channels in species sufficiently distant in the evolutionary tree. In the present volume, many of the best specialists in the field of comparative molecular neurobiology, several of them working on vertebrate and invertebrate species, have accepted to report their most recent findings.
| Author | : Klaus Ebnet |
| Publisher | : Springer |
| Total Pages | : 228 |
| Release | : 2015-02-24 |
| Genre | : Science |
| ISBN | : 3319144669 |
Download Cell Polarity 2 Book in PDF, ePub and Kindle
This work provides a state-of-the art overview on the most relevant aspects of cell polarity. Volume 2 discusses the physiological and pathophysiological relevance of cell polarity. It especially focuses on pathophysiological conditions in which one or several aspects of cell polarity are impaired, and in which a loss of cell polarity possibly contributes to disease (e.g. epithelial-to-mesenchymal transition in cancer, role of polarity proteins in cancer). Both volumes are intended for professors, group leaders and researchers in cell biology as well as for medical professionals working in anatomy, cell biology, physiology, pathology and tumor biology.
| Author | : Florian Markowetz |
| Publisher | : Cambridge University Press |
| Total Pages | : 287 |
| Release | : 2015-07-02 |
| Genre | : Science |
| ISBN | : 131638098X |
Download Systems Genetics Book in PDF, ePub and Kindle
Whereas genetic studies have traditionally focused on explaining heritance of single traits and their phenotypes, recent technological advances have made it possible to comprehensively dissect the genetic architecture of complex traits and quantify how genes interact to shape phenotypes. This exciting new area has been termed systems genetics and is born out of a synthesis of multiple fields, integrating a range of approaches and exploiting our increased ability to obtain quantitative and detailed measurements on a broad spectrum of phenotypes. Gathering the contributions of leading scientists, both computational and experimental, this book shows how experimental perturbations can help us to understand the link between genotype and phenotype. A snapshot of current research activity and state-of-the-art approaches to systems genetics are provided, including work from model organisms such as Saccharomyces cerevisiae and Drosophila melanogaster, as well as from human studies.
| Author | : |
| Publisher | : ScholarlyEditions |
| Total Pages | : 96 |
| Release | : 2012-12-26 |
| Genre | : Science |
| ISBN | : 1481605674 |
Download Advances in Rhabditida Research and Treatment: 2012 Edition Book in PDF, ePub and Kindle
Advances in Rhabditida Research and Treatment / 2012 Edition is a ScholarlyBrief™ that delivers timely, authoritative, comprehensive, and specialized information about Rhabditida in a concise format. The editors have built Advances in Rhabditida Research and Treatment / 2012 Edition on the vast information databases of ScholarlyNews.™ You can expect the information about Rhabditida in this eBook to be deeper than what you can access anywhere else, as well as consistently reliable, authoritative, informed, and relevant. The content of Advances in Rhabditida Research and Treatment / 2012 Edition has been produced by the world’s leading scientists, engineers, analysts, research institutions, and companies. All of the content is from peer-reviewed sources, and all of it is written, assembled, and edited by the editors at ScholarlyEditions™ and available exclusively from us. You now have a source you can cite with authority, confidence, and credibility. More information is available at http://www.ScholarlyEditions.com/.
