Download or read book Mapping Genetic Interactions written by Franco Joseph Vizeacoumar and published by . This book was released on 2021 with total page 361 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume details methods of identifying synthetic lethal, genetic interactions by various approaches in different model systems including human cancer cells. Chapters guide readers through genetic interactions in model organisms, RNA interference, CRISPR/Cas9 based genome editing technologies, drug-gene interactions, mapping chemical genetic interactions, synergistic drug-gene relations, single cell sequencing, gene expression profiling, and novel genetic interactions. Written in the format of the highly successful Methods in Molecular Biology series, each chapter includes an introduction to the topic, lists necessary materials and reagents, includes tips on troubleshooting and known pitfalls, and step-by-step, readily reproducible protocols. Authoritative and cutting-edge, Genetic Interaction Mapping aims to be a useful practical guide to researches to help further their study in this field.

Download or read book Mapping Genetic Interaction Networks in Yeast written by Anastasija Baryshnikova and published by . This book was released on 2013 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Mapping and Sequencing the Human Genome written by National Research Council and published by National Academies Press. This book was released on 1988-01-01 with total page 128 pages. Available in PDF, EPUB and Kindle. Book excerpt: There is growing enthusiasm in the scientific community about the prospect of mapping and sequencing the human genome, a monumental project that will have far-reaching consequences for medicine, biology, technology, and other fields. But how will such an effort be organized and funded? How will we develop the new technologies that are needed? What new legal, social, and ethical questions will be raised? Mapping and Sequencing the Human Genome is a blueprint for this proposed project. The authors offer a highly readable explanation of the technical aspects of genetic mapping and sequencing, and they recommend specific interim and long-range research goals, organizational strategies, and funding levels. They also outline some of the legal and social questions that might arise and urge their early consideration by policymakers.

Download or read book Mapping Genetic Interactions for Rare Disease Associated Genes written by Kristin Kantautas and published by . This book was released on 2020 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Over 7,000 rare diseases have been identified in the human population that, in aggregate, affect over 400 million people worldwide. The majority of rare diseases that have been identified are genetic in origin. However, a key challenge in developing therapies is that the functions of many rare disease-associated genes are poorly understood and consequently, their role in disease pathogenesis. There is strong appreciation that genes do not act in isolation and many disease phenotypes may arise from complex genetic interactions (GIs). Systematic mapping of GIs offers a wealth of information about gene function and advancements in gene-editing technology, such as clustered regularly interspaced short palindromic repeats (CRISPR), allows for GI mapping in human cells. In this thesis, I describe how lentiviral-based genome-wide pooled CRISPR/Cas9 screens offer insight into the function of rare disease-associated genes including NGLY1 and the genes encoding the complement regulatory proteins (CRPs): CD46, CD55, and CD59. Autosomal recessive mutations in NGLY1 give rise to NGLY1-deficiency, a congenital disorder of deglycosylation. How the loss of NGLY1 function contributes to disease pathogenesis is poorly understood. The CRPs are key inhibitors of the complement cascade and their impaired function contributes to a wide range of common and rare diseases. Similar to NGLY1, the functions of the CRPs independent of complement-regulation and roles in disease have not been explored using functional genomics approaches. To further our functional understanding of NGLY1 and the genes encoding the CRPs, I performed pooled genome-wide CRISPR/Cas9 screens to identify GIs, and uncovered a novel genetic relationship between the CRPs and the NGLY1 pathway involving genes in the secretory pathway that may coordinate different aspects of intracellular cholesterol trafficking. My work demonstrates the utility in mapping GIs in order to reveal functional relationships with rare disease genes, offering critical insight into the genetic underpinnings of NGLY1-deficiency and complement-independent functions of the CRPs. As the functions of many rare disease-associated genes are poorly characterized, mapping genetic interactions in co-isogenic human cell lines using genome-wide CRISPR screening approaches offers a powerful framework that may be exploited to gain insight into gene function and direct future therapeutic efforts.

Download or read book Large scale Mapping of Genetic Interactions in Saccharomyces Cerevisiae microform written by Amy Hin Yan Tong and published by Library and Archives Canada = Bibliothèque et Archives Canada. This book was released on 2005 with total page 474 pages. Available in PDF, EPUB and Kindle. Book excerpt: In chapter four, I describe the application of SGA analysis to the large-scale mapping of genetic interactions. A genetic interaction network containing & sim;1000 genes and & sim;4000 interactions was mapped by crossing mutations in 132 different query genes into a set of & sim;4700 viable gene deletion mutants and scoring the double mutant progeny for fitness defects. Network connectivity is predictive of function because interactions often occur among functionally related genes. Genetic interactions are largely orthogonal (non-overlapping) with protein-protein interactions, but genes coding for proteins that occur in the same pathway or complex display similar patterns of genetic interactions. The genetic network shows dense local neighbourhoods, implying the position of a gene on a partially mapped network is predictive of interactions. Because genetic networks are likely conserved, synthetic genetic interactions may underlie the complex genetics associated with inherited phenotypes in other organisms. In chapter three, I describe the development of a new method for automated identification of genetic interactions, termed synthetic genetic array (SGA) analysis. SGA analysis allows systematic construction of double mutants and examination of their fitness on a genome-wide scale. Functional genomics approaches have provided the opportunity for systematic examination of all genes in a genome, generating functional information such as gene expression profiles, protein expression and localization profiles, protein-protein interaction networks, and systematic characterization of mutants. Budding yeast has been the organism of choice for many of these pioneering studies because of its facile genetics. Large-scale studies have made significant contributions to our understanding of complex biological systems, and this trend is continuously fueled by new development of high-throughput technologies. In this thesis, I describe a general strategy to study protein-protein interaction modules (chapter two). A protein-protein interaction network was generated by focusing on yeast SH3 domains and combining data derived from phage-display ligand consensus sequences and large-scale two-hybrid physical interactions. This study produced a network that is depleted of most false positive interactions and enriched for biologically relevant interactions.

Download or read book Mapping and Targeting Genetic and Physical Interactions at Scale written by Kyle Ford and published by . This book was released on 2022 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Biological phenotypes are mediated by a network of functional interactions between genes, proteins, and other biomolecules present in the cell. While high-throughput screening efforts have largely mapped the role of individual genes in controlling phenotypes such as cellular proliferation, interactions between genes/proteins remain largely unmapped and untargeted. In this dissertation, we develop and apply novel screening methodologies to map and exploit interactions between genes/proteins. We use pairwise CRISPR-Cas9 mediated gene knockouts to map the full set of genetic interactions among cyclin-dependent kinases (CDKs) and interacting proteins, identifying several synthetic-lethal and synergistic relationships. We perform single-cell RNA sequencing on the CDK knockout populations, quantifying the cell-cycle effects and cell states mediated by individual CDK proteins. While CDKs are readily druggable via small molecules, many cancer drivers have structures which are not amenable to traditional pharmacological inhibition approaches. To address this challenge, we developed a peptide tiling (PepTile) approach to engineer protein inhibitors of cancer drivers and protein-protein interactions in general. By overexpressing pooled libraries of peptides within cancer cells, we map bioactive protein domains and identify peptides derived from key protein-protein interaction (PPI) interfaces which have strong anti-proliferative effects. We show that these peptides can be modified for extracellular delivery, functioning as anticancer drugs with micromolar IC50s. Finally, we demonstrated the versatility of the PepTile approach to alternative contexts, mining physical interactions to improve delivery of therapeutic payloads in vivo. We show our screening datasets can be used to train predictive models, with applications for future engineering efforts towards targeting and delivery of therapeutic biomolecules.

Download or read book Systems Genetics written by Florian Markowetz and published by Cambridge University Press. This book was released on 2015-07-02 with total page 287 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Download or read book Large scale Mapping of Chemical genetic Interaction Phenotypes in Human Cells written by Christian Scheeder and published by . This book was released on 2022* with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Phenotypes and Genotypes written by Florian Frommlet and published by Springer. This book was released on 2016-02-12 with total page 232 pages. Available in PDF, EPUB and Kindle. Book excerpt: This timely text presents a comprehensive guide to genetic association, a new and rapidly expanding field that aims to elucidate how our genetic code (genotypes) influences the traits we possess (phenotypes). The book provides a detailed review of methods of gene mapping used in association with experimental crosses, as well as genome-wide association studies. Emphasis is placed on model selection procedures for analyzing data from large-scale genome scans based on specifically designed modifications of the Bayesian information criterion. Features: presents a thorough introduction to the theoretical background to studies of genetic association (both genetic and statistical); reviews the latest advances in the field; illustrates the properties of methods for mapping quantitative trait loci using computer simulations and the analysis of real data; discusses open challenges; includes an extensive statistical appendix as a reference for those who are not totally familiar with the fundamentals of statistics.

Download or read book Mapping of Signaling Networks Through Synthetic Genetic Interaction Analysis by RNAi written by Thomas Horn and published by . This book was released on 2010 with total page 244 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Dissecting Genotype phenotype Relationships Through Integration and Analysis of Differential Genetic Interaction Maps written by Rohith Kannappan Srivas and published by . This book was released on 2012 with total page 179 pages. Available in PDF, EPUB and Kindle. Book excerpt: Epistasis, refers to the phenomenon, in which the phenotypic effect of one gene depends on or is modified by a secondary gene. High-throughput screening of genetic interactions has been made possible through a variety of methods such as Synthetic Genetic Array, combinatorial RNAi and genome-wide association studies. However, thus far the majority of data has been generated in standard laboratory conditions. Yet in the course of their lives, cells are exposed to a wide-array of environmental stresses. How genetic interaction networks are re-wired in response to such stimuli remains an open question. In this thesis, I describe the generation and analysis of differential genetic interaction data, in response to numerous genotoxic stresses and demonstrate how this data can be used to elucidate cellular pathways required for the response to these stresses. In Chapter 2, I describe the development of computational and visualization algorithms designed to integrate physical and differential genetic interaction data. This integrative approach enables the automatic assembly of raw interactions into pathway models and maps the higher-order functional relationships between such pathways. In Chapter 3, I map changes in the cell's genetic network across a panel of mechanistically distinct DNA-damaging agents. This multi-conditional genetic interaction map identifies both agent-specific and general DNA damage response pathways. More over, we anticipate that this data will be an important resource for the study of the DDR and its associated diseases. In Chapters 4 and 5, I describe our efforts to analyze genetic interactions derived from forward genetic screening approaches, such as genome-wide association studies (GWAS). We develop a novel computational algorithm, which greatly increases our power to detect such interactions and furthermore, through projection of these genetic interactions within and across protein complexes, demonstrate that such pathway-based interpretations of GWAS data provide novel hypothesis regarding the mechanism through which combinations of polymorphisms may affect a phenotype.

Download or read book Microevolution Rate Pattern Process written by Andrew P. Hendry and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 528 pages. Available in PDF, EPUB and Kindle. Book excerpt: From guppies to Galapagos finches and from adaptive landscapes to haldanes, this compilation of contributed works provides reviews, perspectives, theoretical models, statistical developments, and empirical demonstrations exploring the tempo and mode of microevolution on contemporary to geological time scales. New developments, and reviews, of classic and novel empirical systems demonstrate the strength and diversity of evolutionary processes producing biodiversity within species. Perspectives and theoretical insights expand these empirical observations to explore patterns and mechanisms of microevolution, methods for its quantification, and implications for the evolution of biodiversity on other scales. This diverse assemblage of manuscripts is aimed at professionals, graduate students, and advanced undergraduates who desire a timely synthesis of current knowledge, an illustration of exciting new directions, and a springboard for future investigations in the study of microevolution in the wild.

Download or read book Genetic Analysis of Complex Disease written by William K. Scott and published by John Wiley & Sons. This book was released on 2021-12-06 with total page 340 pages. Available in PDF, EPUB and Kindle. Book excerpt: Genetic Analysis of Complex Diseases An up-to-date and complete treatment of the strategies, designs and analysis methods for studying complex genetic disease in human beings In the newly revised Third Edition of Genetic Analysis of Complex Diseases, a team of distinguished geneticists delivers a comprehensive introduction to the most relevant strategies, designs and methods of analysis for the study of complex genetic disease in humans. The book focuses on concepts and designs, thereby offering readers a broad understanding of common problems and solutions in the field based on successful applications in the design and execution of genetic studies. This edited volume contains contributions from some of the leading voices in the area and presents new chapters on high-throughput genomic sequencing, copy-number variant analysis and epigenetic studies. Providing clear and easily referenced overviews of the considerations involved in genetic analysis of complex human genetic disease, including sampling, design, data collection, linkage and association studies and social, legal and ethical issues. Genetic Analysis of Complex Diseases also provides: A thorough introduction to study design for the identification of genes in complex traits Comprehensive explorations of basic concepts in genetics, disease phenotype definition and the determination of the genetic components of disease Practical discussions of modern bioinformatics tools for analysis of genetic data Reflecting on responsible conduct of research in genetic studies, as well as linkage analysis and data management New expanded chapter on complex genetic interactions This latest edition of Genetic Analysis of Complex Diseases is a must-read resource for molecular biologists, human geneticists, genetic epidemiologists and pharmaceutical researchers. It is also invaluable for graduate students taking courses in statistical genetics or genetic epidemiology.

Download or read book Integrating Physical and Genetic Interaction Networks for Biological Pathway Discovery written by Sourav Bandyopadhyay and published by . This book was released on 2010 with total page 316 pages. Available in PDF, EPUB and Kindle. Book excerpt: The goal of understanding complex biological systems and how they are perturbed to cause disease has long been a central focus of biology. The past decade has seen the creation and maturation of a number of new technologies designed to study biological pathways on a genome-wide scale. Rather than obtaining information about the function of one gene or protein at a time, such approaches can offer insight into the activity of every gene and protein in the cell all in the context of one experiment. One fundamental mode of gathering biological insight is through identifying which proteins in the cell interact physically, such as those which form protein complexes or biochemical pathways. Techniques such as yeast-two hybrid and co-immunoprecipitation followed by mass spectrometry allow the determination of a physical interaction map which details binding interactions between proteins on a large scale. Another fundamental mode of biological discovery is through assaying genetic interactions which arise when mutations in two genes produce a phenotype that is surprising in light of each mutation's individual effects. For example a synthetic lethal genetic interaction is indicated when deletions in two genes which are not essential for viability cause lethality when deleted together. Genetic interaction maps can be determined in high-throughput via SGA (Synthetic Genetic Array) technology. In Chapter 2 we derive and analyze a large physical protein interaction map centered on a set of human protein kinases and show how biological insight can be derived from such large-scale screens. In Chapter 3, we develop methods for the comparison of such physical protein interaction maps between species in order to identify proteins whose function is conserved throughout millions of years of evolution. In Chapter 4 we develop algorithms to integrate both physical and genetic interactions together for the purpose of biological pathway discovery. Moreover, our approaches create maps of genetic interactions that provide a picture of the global organization of pathways and complexes within the cell, which we apply to create a map of functional relationships among protein complexes involved in chromosomal biology. In Chapter 6, we apply this approach in two different yeast species and discover that while physical protein interactions are largely conserved across species, many genetic interactions are rewired which gives us valuable insight into pathway architecture. Finally in Chapter 7, we focus on the discovery of genetic interactions involved in the DNA damage response by assaying how different gene mutants respond to a drug which causes DNA damage and then demonstration how this elucidates pathways involved in this process.

Download or read book Genetic Mapping and Marker Assisted Selection written by N. Manikanda Boopathi and published by Springer Nature. This book was released on 2020-04-07 with total page 504 pages. Available in PDF, EPUB and Kindle. Book excerpt: The first edition of this book, Genetic Mapping and Marker Assisted Selection: Basics, Practice and Benefits, was widely appreciated as the first of its kind on this topic and has been listed as a reference work in several agricultural universities’ curricula. A great deal has happened over the last five years, making it high time to incorporate recent developments in genetic mapping and report on novel strategies in marker assisted selection in crop plants as a second edition. This book addresses a range of topics, including: new marker types and their genotyping methods based on high-throughput technologies, advances in genomics and their role in new marker development, improvements in genetic mapping strategies and software updates, developments in phenomics and their applications in QTL mapping, and how to incorporate these developments and advances in marker assisted selection in crop plants. Similar to the first edition, each technique and method is explained using a step-by-step method, allowing the book to serve as a self-study guide for scholars whose work involves the genetic improvement of crop plants for any trait of interest, particularly for biotic and abiotic stress resistance. In addition, the book offers a valuable guide for undergraduate and graduate students at agricultural universities and institutes that are interested and/or involved in the genetic improvement of crop plants using modern tools. In addition, the bibliography includes a list of suggested works for pursuing further research on the topics covered.

Download or read book Epistasis and the Evolutionary Process written by Jason B. Wolf and published by Oxford University Press, USA. This book was released on 2000 with total page 348 pages. Available in PDF, EPUB and Kindle. Book excerpt: Over the last two decades, research into epistasis has seen explosive growth and has moved the focus of research in evolutionary genetics from a traditional additive approach. We now know the effects of genes are rarely independent, and to reach a fuller understanding of the process of evolution we need to look at gene interactions as well as gene-environment interactions. This book is an overview of non-additive evolutionary genetics, integrating all work to date on all levels of evolutionary investigation of the importance of epistasis in the evolutionary process in general. It includes a historical perspective on this emerging field, in-depth discussion of terminology, discussions of the effects of epistasis at several different levels of biological organization and combinations of theoretical and experimental approaches to analysis.

Download or read book Plant Molecular Evolution written by J.J. Doyle and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 272 pages. Available in PDF, EPUB and Kindle. Book excerpt: Plant molecular biology has produced an ever-increasing flood of data about genes and genomes. Evolutionary biology and systematics provides the context for synthesizing this information. This book brings together contributions from evolutionary biologists, systematists, developmental geneticists, biochemists, and others working on diverse aspects of plant biology whose work touches to varying degrees on plant molecular evolution. The book is organized in three parts, the first of which introduces broad topics in evolutionary biology and summarizes advances in plant molecular phylogenetics, with emphasis on model plant systems. The second segment presents a series of case studies of gene family evolution, while the third gives overviews of the evolution of important plant processes such as disease resistance, nodulation, hybridization, transposable elements and genome evolution, and polyploidy.