An important milestone in medicine has been the recent completion of the Human Genome Project. The identification of 30,000 genes and their regulatory proteins provides the framework for understanding the metabolic basis of disease. This advance has also laid the foundation for a broad range of genomic tools that have opened the way for targeted genetic testing in a number of medical disorders. This book is designed to be the first major text to discuss genomics-based advances in disease susceptibility, diagnosis, prognostication, and prediction of treatment outcomes in various areas of medicine. After building a strong underpinning in the basic concepts of genomics, the authors of this book, all leaders in the field, proceed to discuss a wide range of clinical areas and the applications now afforded by genomic analysis.

Basic Properties of the Actin Molecule and Actin-Based Microfilament Systems.- Vibrational Modes of G-Actin.- Combining Electron Microscopy and X-Ray Crystallography Data to Study the Structure of F-Actin and its Implications for Thin-Filament Regulation in Muscle.- Evidence for an F-Actin Like Conformation in the Actin: DNase I Complex.- Actin-Bound Nucleotide/Divalent Cation Interactions.- Influence of the High Affinity Divalent Cation on Actin Tryptophan Fluorescence.- C-Terminus on Actin: Spectroscopic and Immunochemical Examination of its Role in Actinomycin Interactions.- Actin Polymerization: Regulation by Divalent Metal Ion and Nucleotide Binding, ATP Hydrolysis and Binding of Myosin.- Actin-Associated Proteins and Control of Filament-Based Assembly-Disassembly.- Structural Requirements of Tropomyosin for Binding to Filamentous Actin.- Actin-Gelsolin Interaction.- Actin Regulation and Surface Catalysis.- Caldesmon: Possible Functions in Microfilament Reorganization During Mitosis and Cell Transformation.- Cytoskeleton, Motile Structures and Macromolecular Crowding.- Cellular Functions of the Microfilament System.- Actin Filament Dynamics in Cell Motility.- Changes in Adhesion Plaque Protein Levels Regulate Cell Motility and Tumorigenicity.- Induction of Collagen Synthesis in Response to Adhesion and TGF? is Dependent on the Actin-Containing Cytoskeleton.- Gelsolin Expression in Normal Human Keratinocytes is a Function of Induced Differentiation.- Actin Filaments and the Spatial Positioning of mRNA.- Redistribution of p52(PAI-l) mRNA to the Cytoskeletal Framework Accompanies Increased p52(PAI-l) Expression in Cytochalasin D-Stimulated Rat Kidney Cells.- Brush Border Myosin I Has a Calmodulin/Phosphatidylserine Switch and Tail Actin-Binding.- Control of p52(PAI-l) Gene Expression in Normal and Transformed Rat Kidney Cells: Relationship Between p52(PAI-l) Induction and Actin Cytoarchitecture.- Contributors

This volume shares technologies that detect common epigenetic changes which are very important in the early detection, progression, and prognosis of cancer as well as the design of new therapeutic tools against cancer cells. Beginning with a bit of background on epigenetic mechanisms, Cancer Epigenetics: Risk Assessment, Diagnosis, Treatment, and Prognosis continues with cancer specific type epigenetic change, methods and technologies used for detecting epigenetic changes, factors that influence epigenetic changes in cancer, as well as a final section on future directions in the field. Written for the highly successful Methods in Molecular Biology series, chapters in this volume include the kind of detailed implementation advice that guarantees easily reproducible results. Comprehensive and practical, Cancer Epigenetics: Risk Assessment, Diagnosis, Treatment, and Prognosis provides the most up-to-date knowledge of epigenetics and its implication in cancer prevention by risk assessment and screening and cancer control by treatment.

The study of molecular events leading to cellular transformation and cancer has progressed considerably during the 1990s. It has become apparent that many genes subject to modification in cancer are, in fact, transcription factors that govern the execution of the genetic programme of the cell. Transcription factors can behave either as oncogenes or as tumor supressor genes. To date only a very limited number of transcription factors have been associated with cancer. This volume gives molecular information on several oncogenes, tumor suppressor genes or chromosomal translocations. Each chapter contains a description of the structure of such transcription factors, the nature of target genes, the regulation of their activities and an explaination of how they can deregulate cell growth and differentiation. This book should be suitable for the specialist scientist and the advanced student

This volume introduces software used for gene prediction with focus on eukaryotic genomes. The chapters in this book describe software and web server usage as applied in common use-cases, and explain ways to simplify re-annotation of long available genome assemblies. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary computational requirements, step-by-step, readily reproducible computational protocols, and tips on troubleshooting and avoiding known pitfalls. Cutting-edge and thorough, Gene Prediction: Methods and Protocols is a valuable resource for researchers and research groups working on the assembly and annotation of single species or small groups of species. Chapter 3 is available open access under a CC BY 4.0 license via link.springer.com.

Review Questions of Clinical Molecular Genetics presents a comprehensive study guide for the board and certificate exams presented by the American College of Medical Genetics and Genomics (ACMG) and the American Board of Medical Genetics and Genomics (ABMGG). It provides residents and fellows in genetics and genomics with over 1,000 concise questions, ranging from topics in cystic fibrosis, to genetic counseling, to trinucleotide repeat expansion disorders. It puts key points in the form of questions, thus challenging the reader to retain knowledge. As board and certificate exams require knowledge of new technologies and applications, this book helps users meet that challenge.

This book is aimed at analyzing the foundations of medical ethics by considering different moral theories and their implications for judgments in clinical practice and policy-making. It provides a review of the major types of ethical theory that can be applied to medical and bioethical issues concerning reproductive genetics. In response to the debate on the most adequate ethical doctrine to guide biomedical decisions, this book formulates views that capture the best elements in each, bearing in mind their differences and taking into account the specific character of medicine. No historically influential position in ethics is by itself adequate to be applied to reproductive decisions. Thus, this book attempts to offer a pluralistic approach to biomedical research and medical practice. One usually claims that there are some basic principles (non-maleficence, beneficence, confidentiality, autonomy, and justice) which constitute the foundations of bioethics and medical ethics. Yet these principles conflict with each other and one needs some criteria to solve these conflicts and to specify the scope of application of these principles. Exploring miscellaneous ethical approaches as introduced to biomedicine, particularly to reproductive genetics, the book shall elucidate their different assumptions concerning human nature and the relations between healthcare providers, recipients, and other affected parties (e.g. progeny, relatives, other patients, society). The book attempts to answer the question of whether the tension between these ethical doctrines generates conflict in the field of biomedicine or if these competing approaches could in some way complement each other. In this respect, lecturers and researchers in bioethics would be interested in this reading this book.

This book provides a unique overview on the most recent developments in initially diverse areas of behavioral genomic research that now start to intertwine to provide more detailed insights into the complex nature of behavior in health and disease. It focuses on our current understanding of genetic and epigenetic mechanisms of brain function and how they contribute to the complex formation of behavioral traits and psychiatric disorders. Readers experience diverse perspectives of the contributing authors starting from the genetic viewpoint and the effort to establish functional connection between genetic variants and behavioral phenotypes. Particular attention is given to the broad spectrum of epigenetic mechanisms and behavior. The chapter 'Role of MicoRNAs in Anxiety and Anxiety-Related Disorders' is available open access under a CC BY 4.0 license at link.springer.com

Evolution's Clinical Guidebook: Translating Ancient Genes into Precision Medicine demonstrates, through well-documented examples, how an understanding of the phylogenetic ancestry of humans allows us to make sense out of the flood of genetic data streaming from modern laboratories and how it can lead us to new ways to prevent, diagnose and treat diseases. Topics cover evolution and human genome, meiosis and other recombinants events, embryology, speciation, phylogeny, rare and common diseases, and the evolution of aging. This book is a valuable source for bioinformaticians and those in the biomedical field who need knowledge, down to gene level, to fully comprehend currently available data.

This book illustrates the activities of mammalian sirtuin SIRT6 in connection with DNA damage repair and premature aging. It mainly presents research on the nuclear lamin A, notably the upregulation of p53 and acetylation etc. Taken together, these studies reveal the various regulatory roles of SIRT6, which are of substantial biological relevance in DNA damage repair, aging and longevity, and can have significant implications in devising therapeutic strategies to combat age-associated pathologies. Given its scope, the book offers a valuable resource for students and researchers in the fields of genetics, cell biology, molecular biology etc.

This detailed volume guides readers through strategic planning and user-friendly guidelines in order to select the most suitable CRISPR-Cas system and target sites with high activity and specificity. Methods covering CRISPR gRNA design, CRISPR delivery, CRISPR activity quantification (indel quantification), and examples of applying CRISPR gene editing in human pluripotent stem cells, primary cells, gene therapy, and genetic screening are included. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and invaluable, CRISPR Gene Editing: Methods and Protocols will assist undergraduates, graduates, and researchers with detailed guidelines and methods for the vitally important CRISPR gene editing field. Chapter 3 is available open access under a CC BY 4.0 license via link.springer.com.

Epigenetic mechanisms (DNA modifications, histone alterations and non-coding RNAs) are crucial for transcriptional regulation and alterations of the "physiological epigenome" are increasingly associated with human diseases. During the last decade the emerging field of neuroepigenomics have started to impact tremendously in areas such learning and memory, addiction or neurodegeneration. This expert volume covers the role of epigenetic molecular mechanism in regulation of central nervous system's function, one of the most exciting areas of contemporary molecular neuroscience. The book describes the current knowledge on the epigenetic basis of human disease covering the complete lifespan: from neurodevelopment/childhood (Rett Syndrome, Rubinstein-Taybi, autism), adolescence (eating disorders, drug addiction, anxiety), adulthood (depression, schizophrenia, amyotrophic lateral sclerosis, Huntington's disease) and elderly (Alzheimer's disease, Parkinson's disease). The book also covers the three major players on neuroepigenomic mechanisms: histones alterations, DNA modifications and non-coding RNAs, their roles at the molecular and cellular level and the impact of their alterations on neuronal function and behavior. Finally, a special chapter on state-of-the-art technologies helps the reader not only to understand epigenetic driven changes in human cognition and diseases but also the methodology that will help to generate paradigm shifts on our understanding of brain function and the role of the neuroepigenome in human diseases.

Provides clear summaries of Fluorescence in situ hybridization technologies and others. Comprehensively covers established and emerging methods. Chapters from an international team of leading researchers. Useful for students, researchers and clinicians.

The book recognizes that throughout the scientific, medical, and economic communities, new tests incorporating biomarkers are needed to improve the diagnosis of patients suffering from metabolic disorders. The early identification of those at risk of developing obesity will help to place these individuals on the best treatment course as early as possible for improved treatment outcomes. This will also help to cut costs incurred by the healthcare services. For all of this to occur, new research efforts are needed to identify novel biomarkers that can be used to predict the disease in the presymptomatic stage, for disease monitoring and for prediction of treatment response. It is also possible that new drug targets can be identified using these approaches which, in turn, can lead to the development of new treatment approaches. This volume also includes a series of reviews on biomarker discovery and usage in the study of diseases marked by perturbations in metabolism. It will describe the pros and cons of the various approaches and cover the successes and failures in this important research field.

This volume presents a series of protocols and methods, some of which are not widely used by researchers/practitioners, and will aid in the execution of different laboratory techniques. Forensic DNA Typing Protocols, Second Edition is arranged into a series of related chapters. Chapter 1-3 examines two different aspects of RNA analysis for body fluid identification. Chapters 4-7 focuses on the storage of biological materials and the extraction of DNA from hard tissues. Chapters 8-10 present methods for monitoring the quality of DNA extracts, and steps to aid in the purification of DNA. Chapters 11-16 talk about methods on non-standard markers, such as INDELs, Y chromosome STRs, and mitochondrial DNA. Detailed procedures and data analysis for phenotypes and ancestry are explored in Chapter 17-19. The last chapter (20) looks at the application of DNA typing to the identification of non-human material to species level. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Practical and thorough, Forensic DNA Typing Protocols, Second Edition, is a valuable resource for forensic specialists, researchers, and anyone interested in the field of forensic science.

This second edition explores up-to-date tools in various function-based technologies currently used in metagenomics. The chapters in this book discuss all of the working steps involved in these technologies, such as: DNA isolation from soils and marine samples followed by the construction and screening of libraries for diverse enzymes and biomolecules; current methods used to isolate DNA and construct large- and small-insert libraries from terrestrial and marine habitats; methods for establishing metagenome libraries in none-E.coli hosts; new molecular tools used for function-driven mining of metagenomic DNA; and screening protocols for a wide array of different genes encoding enzymes with relevance to biotechnology and ecology. Metagenomics: Methods and Protocols, Second Edition also provides detailed screening protocols for phosphatases, poly-hydroxyalkanoate, metabolism-related enzymes, stereoselective hydrolases, and microbial signals for the discovery of secondary metabolites. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Comprehensive and cutting-edge, Metagenomics: Methods and Protocols, Second Edition is a collection of up-to-date metagenome protocols and tools for the recovery of numerous major types of biocatalysts, and allows researchers to easily setup these screens in any microbiology laboratory.

Congenital malformations are worldwide occurrences striking in every condition of society. These severe physical abnormalities which are present at birth and affecting every part of the body happen more often than usually realized, once in every 33 births. The most common, after heart defects, are those of the neural tube (the brain and spinal cord) which happen in as many as one in every 350 births. They have been noted as curiousities in man and beast throughout recorded history and received great attention in our time by various fields of study, for example, their faulty prenatal development by embryologists, familial patterns by geneticists, causation by environmentalists and variability by population scientists.

Attention turned much in recent years to the relation of these malformations to deficiency of a particular dietary ingredient, folic acid, a subject this book analyzes in depth. The greatest conundrum of all, which this latest matter like so much else hinges on, is the amazing fact of the tremendous, almost universal decrease in the frequency of these anomalies since early in the 20th century. The puzzle is 'What can this downward trend possibly mean?' and at bottom 'Whether it is part of a long-term cyclical pattern'. This fascinating biological phenomenon is explored in the book together with various other topics.

The book focuses on the evolutionary impact of horizontal gene transfer processes on pathogenicity, environmental adaptation and biological speciation. Newly acquired genetic material has been considered as a driving force in evolution for prokaryotic genomes for many years, with recent technical developments advancing this field further. However, the extent and implications of gene transfer between prokaryotes and eukaryotes still raise controversies. This multi-authored volume introduces various means by which DNA can be exchanged, covers gene transfer between prokaryotes and their viruses as well as between bacteria and eukaryotes, such as fungi, plants and animals, and addresses the role of horizontal gene transfer in human diseases. Aspects discussed also include the relevance for virulence and drug resistance development on one hand, and for the occurrence of naturally derived antibiotics and other secondary metabolites on the other hand. This book offers new insights to anyone interested in genome evolution and the exchange of DNA between the different domains of life, the genetic toolkit for adaptation and the emergence of multidrug resistant bacteria.

This book brings together in one volume the current state of ageing research in the nematode Caenorhabditis elegans. The authors are leading researchers in the field, placing this topic in the context of human ageing, describing how and why basic discoveries in this simple organism have impacted our prospects for intervention in the ageing process. The authors cover a broad range of topics with regards to organismal and reproductive ageing including anatomical, physiological and biochemical changes, as well as genetic and environmental interventions that promote longevity and ameliorate age-related disease. Ageing is the single most important factor determining the onset of human disease in developed countries. With current worldwide demographic trends indicating that the number of individuals over the age of 65 will continue to rise, it is clear that an understanding of the processes that underpin ageing and age-related disease represents a key challenge in the biomedical sciences. In recent years there have been huge advances in our understanding of the ageing process and many of these have stemmed from genetic analysis of C. elegans. With no analogous book in this subject area this work will be of interest to a wide audience, ranging from academic researchers to the general public.

The growing knowledge about disturbances of epigenetic gene regulation in hematopoietic stem cell disorders is now being translated into treatment approaches that target the epigenetic defects pharmacologically. This book first presents the latest evidence regarding the epigenetic regulation of hematopoietic stem cell differentiation and hemoglobin production. The significance of DNA methylation abnormalities in hematopoietic disorders and of epigenetic disturbances in lung cancer and other solid tumors is then discussed. A major part of the book, however, relates specifically to the translation of basic research and drug development to clinical applications, and in this context both present and future clinical strategies are considered. Individual chapters are devoted to the use of DNA hypomethylating agents and chromatin-modifying agents, and the treatment of hematologic malignancies and solid tumors by means of epigenetic agents is discussed in detail.

This volume explores and challenges the assumption that behavioral proclivities and pathologies are directly traceable to experience-an assumption that still widely dominates folk psychology as well as the perspective of many mental health practitioners. This tendency continues despite powerful evidence from the field of behavioral genetics that genetic endowment dwarfs other discrete influences on development and psychopathology when extrinsic conditions are not extreme. An interdisciplinary collection, the book uses historical, cultural and clinical perspectives to challenge the longstanding notion of identity as the product of a life-narrative. Although the nativist-empiricist debate has been revivified by recent advances in molecular biology, such ideas date back to the Socratic dialogue on the innate mathematical sense possessed by an illiterate slave. The author takes a philosophical and historical approach in revisiting the writings of select figures from science, medicine, and literature whose insights into the potency of inherited factors in behavior were particularly prescient, and ran contrary to the modern declivity toward the self as narrative. The final part of the volume uses historical and clinical perspectives to help illuminate the elusive concept of innateness, and highlights important ramifications of the revolution in behavioral genetics. Seeking to challenge the clinical utility of the therapeutic narrative rather than the importance of experience per se, the book will ultimately appeal to psychiatrists, psychologists, and academics from various disciplines working across the fields of behavioral genetics, evolutionary biology, philosophy of science, and the history of science.

This volume explores methods and protocols for detecting epistasis from genetic data. Chapters provide methods and protocols demonstrating approaches to identify epistasis, genetic epistasis testing, genome-wide epistatic SNP networks, epistasis detection through machine learning, and complex interaction analysis using trigenic synthetic genetic array ( -SGA). Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, application details for both the expert and non-expert reader, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Epistasis: Methods and Protocols aims to ensure successful results in the further study of this vital field. "Simulating Evolution in Asexual Populations with Epistasis" is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.

This book presents protocols for identification of genetic drivers of cancer. Chapters guide readers through a brief history of cancer gene discovery, in silico approaches, in vitro approaches, and in vivo approaches using forward genetic screens in mice. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Cancer Driver Genes: Methods and Protocols aims to provide protocols that will be used and adapted by cancer researchers to expand the knowledge base of molecular mechanisms contributing to initiation, progression, and metastasis of cancer.

It is now almost a decade since the identification of the Huntington's Disease gene and its mutation, during which time, major advances in our understanding of this disorder have been achieved. Since publication of the first two editions of this book, there have been considerable insights into how the mutation leads to the molecular pathology, neuropathology and clinical symptoms of Huntington's Disease, and experimental tools are now in place to take this research further towards new therapeutic approaches. As a result of these major advances, this well-established series of books has required radical updating. An international group of researchers and clinicians with specialist interests in HD has been commissioned to document the recent advances in our understanding of this disease. Developments in the fields of structural biology, cell biology, neurochemistry and neuropathology, with full coverage of transgenic animal models, are discussed in detail. The clinical sections cover genetic, neurological and psychiatric aspects as well as new developments in therapy. This book will continue to provide an invaluable source of information for clinicians and scientists involved with Huntington's Disease, including geneticists, psychiatrists and neurologists, and basic science research workers in genetics and neurobiology.