Development And Application Of A General Method For Somatic Cell Genetics
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Development And Application Of A General Method For Somatic Cell Genetics
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Author : Tim Wang (Ph. D.)
language : en
Publisher:
Release Date : 2017
Development And Application Of A General Method For Somatic Cell Genetics written by Tim Wang (Ph. D.) and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017 with categories.
Genetic analysis, or genetic screening, is an efficient method for identifying the set of genes involved in a biological process. In microorganisms, powerful techniques enable systematic loss-of-function screens, which have yielded critical insights into the molecular basis of many fundamental cellular pathways. In human cells, however, prevailing screening methods fall short - leaving our understanding of human genes incomplete. Here, I describe the development of a general method for genetic screening in mammalian cells using the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system. In this approach, libraries of knockout mutants can be generated in any cultured cell line using large-scale lentiviral single-guide RNA (sgRNA) pools and screened under both positive and negative selection. After the initial, proof-of-principle experiments, I constructed a genome-wide sgRNA library and screened for genes required for the proliferation and survival of the nearhaploid chronic myeloid leukemia cell line, KBM7. The unusual karyotype of these cells also allowed an independent screening approach, involving gene-trap insertional mutagenesis, to find cell-essential genes. Together, these screens converged on a highly overlapping gene set that was enriched for genes that encode components of fundamental pathways, are expressed at high levels, and contain few inactivating polymorphisms in the human population. To broadly survey patterns of human gene essentiality, I conducted CRISPR-based screens across many more cell lines and cancer types. Overall, these studies revealed a large set of common essential genes involved in housekeeping processes but, interestingly, also pinpointed differences specific to each cell line that reflected its developmental origin, oncogenic drivers, paralogous gene expression pattern, and chromosomal structure. By mapping sets of genes displaying variable but correlated essentiality across lines, I uncovered functionally interacting gene networks. Using this dataset, I also identified genetic vulnerabilities associated with oncogenic Ras which may be exploited for anti-cancer therapy. Last, in collaboration with Bruce Walker and Nir Hacohen's labs, I have conducted a screen for host factors (i.e. human genes) that are required to support HIV infection in a physiologically relevant cell line model. Collectively, these results establish CRISPR-based screens as a powerful tool for systematic genetic analysis in mammalian cells.
Techniques In Somatic Cell Genetics
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Author : Jerry W. Shay
language : en
Publisher: Springer Science & Business Media
Release Date : 2013-11-21
Techniques In Somatic Cell Genetics written by Jerry W. Shay and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2013-11-21 with Medical categories.
Somatic cell genetics is an exciting and rapidly expanding field of research. Since descriptions of the major experimental techniques in the field are scattered throughout various journals and other publications, there is a real need for a single reference source for both established investigators and students in the field. In addition, technical reports are frequently abridged such that many researchers are discouraged from attempting to adopt the appropriate methodology. This book, therefore, describes in detail the many recent technical advances in such areas of somatic cell genetics as transfer mediated by liposomes, erythrocyte ghosts, chromosomes, micro cells, mito chondria, and isolated nuclear DNA. These techniques have increased our understanding of the organization and regulation of eukaryotic cells. The production of antibiotic-resistant cell lines and their use in studying cytoplasmic inheritance are also included. Evidence for the cytoplasmic regulation of nuclear gene expression in eukaryotic cells is rapidly accumu lating following the characterization of cytoplasmic mutations. The produc tion of nuclear-coded mutations, their use in standard cell hybridization, and recent advances in techniques for fusing whole cells or cell components are also described.
Human Genome Editing
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Author : National Academies of Sciences, Engineering, and Medicine
language : en
Publisher: National Academies Press
Release Date : 2017-08-13
Human Genome Editing written by National Academies of Sciences, Engineering, and Medicine and has been published by National Academies Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017-08-13 with Medical categories.
Genome editing is a powerful new tool for making precise alterations to an organism's genetic material. Recent scientific advances have made genome editing more efficient, precise, and flexible than ever before. These advances have spurred an explosion of interest from around the globe in the possible ways in which genome editing can improve human health. The speed at which these technologies are being developed and applied has led many policymakers and stakeholders to express concern about whether appropriate systems are in place to govern these technologies and how and when the public should be engaged in these decisions. Human Genome Editing considers important questions about the human application of genome editing including: balancing potential benefits with unintended risks, governing the use of genome editing, incorporating societal values into clinical applications and policy decisions, and respecting the inevitable differences across nations and cultures that will shape how and whether to use these new technologies. This report proposes criteria for heritable germline editing, provides conclusions on the crucial need for public education and engagement, and presents 7 general principles for the governance of human genome editing.
Somatic Gene Therapy
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Author : P.L. Chang
language : en
Publisher: CRC Press
Release Date : 2018-01-17
Somatic Gene Therapy written by P.L. Chang and has been published by CRC Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2018-01-17 with Science categories.
As human gene therapy becomes a clinical reality, a new era in medicine dawns. Novel and innovative developments in molecular genetics now provide opportunities to treat the genetic bases of diseases often untreatable before. Somatic Gene Therapy documents these historical clinical trials, reviews current advances in the field, evaluates the use of the many different cell types and organs amenable to gene transfer, and examines the prospects of various exciting strategies for gene therapy.
Heritable Human Genome Editing
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Author : The Royal Society
language : en
Publisher: National Academies Press
Release Date : 2021-01-16
Heritable Human Genome Editing written by The Royal Society and has been published by National Academies Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2021-01-16 with Medical categories.
Heritable human genome editing - making changes to the genetic material of eggs, sperm, or any cells that lead to their development, including the cells of early embryos, and establishing a pregnancy - raises not only scientific and medical considerations but also a host of ethical, moral, and societal issues. Human embryos whose genomes have been edited should not be used to create a pregnancy until it is established that precise genomic changes can be made reliably and without introducing undesired changes - criteria that have not yet been met, says Heritable Human Genome Editing. From an international commission of the U.S. National Academy of Medicine, U.S. National Academy of Sciences, and the U.K.'s Royal Society, the report considers potential benefits, harms, and uncertainties associated with genome editing technologies and defines a translational pathway from rigorous preclinical research to initial clinical uses, should a country decide to permit such uses. The report specifies stringent preclinical and clinical requirements for establishing safety and efficacy, and for undertaking long-term monitoring of outcomes. Extensive national and international dialogue is needed before any country decides whether to permit clinical use of this technology, according to the report, which identifies essential elements of national and international scientific governance and oversight.
Molecular Biology Of The Cell
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Author : Bruce Alberts
language : en
Publisher:
Release Date : 2002
Molecular Biology Of The Cell written by Bruce Alberts and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2002 with Cytology categories.
Safety Of Genetically Engineered Foods
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Author : National Research Council
language : en
Publisher: National Academies Press
Release Date : 2004-07-08
Safety Of Genetically Engineered Foods written by National Research Council and has been published by National Academies Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2004-07-08 with Science categories.
Assists policymakers in evaluating the appropriate scientific methods for detecting unintended changes in food and assessing the potential for adverse health effects from genetically modified products. In this book, the committee recommended that greater scrutiny should be given to foods containing new compounds or unusual amounts of naturally occurring substances, regardless of the method used to create them. The book offers a framework to guide federal agencies in selecting the route of safety assessment. It identifies and recommends several pre- and post-market approaches to guide the assessment of unintended compositional changes that could result from genetically modified foods and research avenues to fill the knowledge gaps.
Mammography And Beyond
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Author : National Research Council
language : en
Publisher: National Academies Press
Release Date : 2001-06-04
Mammography And Beyond written by National Research Council and has been published by National Academies Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2001-06-04 with Medical categories.
X-ray mammography screening is the current mainstay for early breast cancer detection. It has been proven to detect breast cancer at an earlier stage and to reduce the number of women dying from the disease. However, it has a number of limitations. These current limitations in early breast cancer detection technology are driving a surge of new technological developments, from modifications of x-ray mammography such as computer programs that can indicate suspicious areas, to newer methods of detection such as magnetic resonance imaging (MRI) or biochemical tests on breast fluids. To explore the merits and drawbacks of these new breast cancer detection techniques, the Institute of Medicine of the National Academy of Sciences convened a committee of experts. During its year of operation, the committee examined the peer-reviewed literature, consulted with other experts in the field, and held two public workshops. In addition to identifying promising new technologies for early detection, the committee explored potential barriers that might prevent the development of new detection methods and their common usage. Such barriers could include lack of funding from agencies that support research and lack of investment in the commercial sector; complicated, inconsistent, or unpredictable federal regulations; inadequate insurance reimbursement; and limited access to or unacceptability of breast cancer detection technology for women and their doctors. Based on the findings of their study, the committee prepared a report entitled Mammography and Beyond: Developing Technology for Early Detection of Breast Cancer, which was published in the spring of 2001. This is a non-technical summary of that report.
Mapping And Sequencing The Human Genome
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Author : National Research Council
language : en
Publisher: National Academies Press
Release Date : 1988-01-01
Mapping And Sequencing The Human Genome written by National Research Council and has been published by National Academies Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 1988-01-01 with Science categories.
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.
Essentials Of Stem Cell Biology
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Author : Robert Lanza
language : en
Publisher: Academic Press
Release Date : 2009-06-05
Essentials Of Stem Cell Biology written by Robert Lanza and has been published by Academic Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2009-06-05 with Science categories.
First developed as an accessible abridgement of the successful Handbook of Stem Cells, Essentials of Stem Cell Biology serves the needs of the evolving population of scientists, researchers, practitioners and students that are embracing the latest advances in stem cells. Representing the combined effort of seven editors and more than 200 scholars and scientists whose pioneering work has defined our understanding of stem cells, this book combines the prerequisites for a general understanding of adult and embryonic stem cells with a presentation by the world's experts of the latest research information about specific organ systems. From basic biology/mechanisms, early development, ectoderm, mesoderm, endoderm, methods to application of stem cells to specific human diseases, regulation and ethics, and patient perspectives, no topic in the field of stem cells is left uncovered. Selected for inclusion in Doody's Core Titles 2013, an essential collection development tool for health sciences libraries Contributions by Nobel Laureates and leading international investigators Includes two entirely new chapters devoted exclusively to induced pluripotent stem (iPS) cells written by the scientists who made the breakthrough Edited by a world-renowned author and researcher to present a complete story of stem cells in research, in application, and as the subject of political debate Presented in full color with glossary, highlighted terms, and bibliographic entries replacing references