In her study Elisabeth Salzer describes three novel monogenic diseases. For CD27 deficiency Elisabeth Salzer describes a large cohort of patients. Although all patients shared the same causative missense mutation, they displayed diverse clinical presentations. In another patient she was able to identify a mutation in PRKCD resulting in a primary immunodeficiency with severe Lupus-like autoimmunity. The patient exhibited increased mRNA levels of IL6. Therefore, treatment with Tocilizumab, a humanized anti-IL-6 receptor monoclonal antibody was suggested. In a family with a history of deaths due to inflammatory bowel disease she identified a missense mutation in IL21. She produced wild type and mutated IL-21 protein and demonstrated a loss of function phenotype. As IL-21 is in clinical trials, she proposed a potentially curative treatment option. These discoveries contributed to the understanding of the multifaceted regulatory mechanisms of the immune system and highlighted essential players in these complex signaling networks.

JIMD Reports publishes case and short research reports in the area of inherited metabolic disorders. Case reports highlight some unusual or previously unrecorded feature relevant to the disorder, or serve as an important reminder of clinical or biochemical features of a Mendelian disorder.

In Situ Hybridization Protocols, Fourth Edition contains 21 protocols that utilize the in situ hybridization technology to document or take advantage of the visualization of specific RNA molecules. 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 practical, In Situ Hybridization Protocols, Fourth Edition seeks to aid scientists in the further discovery of new RNA species and uncovering of their cellular functions.

With the detailed genomic information that is now becoming available, we have a plethora of data that allows researchers to address questions in a variety of areas. Genome-wide association studies (GWAS) have become a vital approach to identify candidate regions associated with complex diseases in human medicine, production traits in agriculture, and variation in wild populations. Genomic prediction goes a step further, attempting to predict phenotypic variation in these traits from genomic information. Genome-Wide Association Studies and Genomic Prediction pulls together expert contributions to address this important area of study. The volume begins with a section covering the phenotypes of interest as well as design issues for GWAS, then moves on to discuss efficient computational methods to store and handle large datasets, quality control measures, phasing, haplotype inference, and imputation. Later chapters deal with statistical approaches to data analysis where the experimental objective is either to confirm the biology by identifying genomic regions associated to a trait or to use the data to make genomic predictions about a future phenotypic outcome (e.g. predict onset of disease). As part of the Methods in Molecular Biology series, chapters provide helpful, real-world implementation advice.

In the past two decades we have seen a surge forward in understanding the genetics and biochemistry underlying many pediatric orthopaedic disorders. A few projects have even progressed into the realm of clinical trials that are primarily aimed at controlling progressive disease. Meanwhile, genomic technology development has outpaced expectations and is enabling gene discovery for disorders that were previously intractable with traditional genetic methods. Included in this latter category are common disorders that display multigenic inheritance, sporadic disorders, and very rare conditions that are difficult to ascertain. Simultaneously, the study of pediatric orthopaedic disorders has been continuously refined and updated, highlighting a number of likely genetic conditions that are as yet unsolved. Molecular Genetics of Pediatric Orthopaedic Disorders updates researchers and clinicians of new developments of pediatric orthopaedic genetics. The chapters inform the audience on the revolution in new genomic methods and the impact this is having on potential study designs and the potential to discover genetic causes of many unsolved orthopaedic conditions. Recent examples have been included of pediatric orthopaedic conditions, both rare and common, that are being solved with these new methods. The book also educates pediatric orthopedic clinicians and geneticists on our understanding of the biology of "classic" genetic diseases that were derived from prior genetic studies. Chapters include biobanks and strategies for studying very rare disorders, genes and pathways causing primordial dwarfism, and notch signaling in congenital scoliosis, and more.

In Nucleic Acid Chemistry: Methods and Protocols, expert researches in the field detail techniques and approaches for the detection of DNA and RNA. These techniques include the recovery of trace amounts of DNA for amplification and analysis, new qPCR chemistries, new application of isothermal amplification techniques, assays with visual or electric signals for point-of-care diagnostics, improvement of fluorescent in situ hybridization, and new signal amplification techniques. 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 key tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Nucleic Acid Chemistry: Methods and Protocols seeks to aid scientists in the further study of detection for DNA and RNA.

G protein-coupled receptors (GPCRs) are heptahelical transmembrane receptors that convert extra-cellular stimuli into intra-cellular signaling, and ultimately into biological responses. Since GPCRs are natural targets for approximately 40% of all modern medicines, it is not surprising that they have been the subject of intense research. Notwithstanding the amount of data generated over the years, discovering ligands of these receptors with optimal therapeutic properties is not straightforward and has certainly been hampered for years by the lack of high-resolution structural information about these receptors. Luckily, there has been a steady increase of high-resolution crystal structures of these receptors since 2007, and this information, integrated with dynamic inferences from computational and experimental methods, holds great potential for the discovery of new, improved drugs. This book, which provides, for the first time, state-of-the-art views on modeling and simulation of GPCRs, is divided into 4 parts. In the first part, the impact of currently available GPCR crystal structures on structural modeling is discussed extensively as are critical insights from simulations in the second part of the book. The third part reports recent progress in rational ligand discovery and mathematical modeling, whereas the fourth part provides an overview of bioinformatics tools and resources that are available for GPCRs.

This book addresses the differentiation control of skeletal muscle in different locations of the vertebrate body Particular attention is paid to novel regulatory molecules and signals as well as the heterogeneity of origin that have revealed a developmental overlap between skeletal and cardiac muscle. Different functional muscle groups are the product of the evolution of the vertebrate classes, making a phylogenetic comparison worthwhile for understanding the role of muscle stem cells and precursors in myogenesis. New insights into the hierarchy of transcription factors, particularly in the context of these different muscle groups have been gained from detailed investigations of the spatio-temporal and regulatory relationships derived from mouse and zebrafish genetics and avian microsurgery. Importantly, epigenetic mechanisms that have surfaced recently, in particular the role of MyomiRs, are also surveyed. With an eye to the human patient, encouraging results have been generated that identify parallels between embryonic myogenesis and regenerating myofibers due to common regulatory molecules. On the other hand, both processes differ considerably in quality and complexity of the processes employed. Interestingly, the heterogeneity in embryonic sources from which skeletal muscle groups in the vertebrate including the human body take origin is paralleled by differences in their susceptibility to particular muscle dystrophies as well as by the characteristics of the satellite cells involved in regeneration. The progress that has been made in the field of muscle stem cell biology, with special focus on the satellite cells, is outlined in this book by experts in the field. The authors review recent insights of the heterogeneous nature of these satellite cells regarding their gene signatures and regeneration potential. Furthermore, an improved understanding of muscle stem cells seems only possible when we study the impact of the cell environment on efficient stem cell replacement therapies for muscular dystrophies, putting embryological findings from different vertebrate classes and stem cell approaches into context.

The thymus is an evolutionarily ancient primary lymphoid organ common to all vertebrates in which T cell development takes place. Failing thymus function is associated with immunodeficiency and/or autoimmunity. In this volume, leading experts provide a comprehensive overview of recent advances in thymopoiesis research. The chapters cover the development of the thymic epithelial microenvironment, address the formation of a diverse and self-tolerant repertoire of T cell receptors as the basis for cellular immunity, discuss the mechanisms by which progenitor cells colonize the thymus and detail the molecular basis for T lineage decisions. The reviews illustrate the important role of the multifaceted process of thymopoiesis for adaptive immunity.

Regulatory Non-Coding RNAs: Methods and Protocols offers a collection of methods for those interested in the discovery, localization, and functional analysis of these non-coding transcripts that have the potential and ability to orchestrate and control gene expression. After a review of the field, this detailed volume continues with methods useful for the study of siRNAs, microRNAs and their targets, techniques concerned with long non-coding RNAs, as well as studies of the critical parameters of functional non-coding RNA protein-RNA interactions and the environment in which they act. Written for the highly successful Methods in Molecular Biology series, chapters include brief introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols and tips for troubleshooting and avoiding known pitfalls. Dependable and easy to use, Regulatory Non-Coding RNAs: Methods and Protocols provides a current, state-of-the-art collection of methods and approaches that will be of value to researchers in this expanding and fascinating field.

JIMD Reports publishes case and short research reports in the area of inherited metabolic disorders. Case reports highlight some unusual or previously unrecorded feature relevant to the disorder, or serve as an important reminder of clinical or biochemical features of a Mendelian disorder.

This is a short and self-contained introduction to the field of mathematical modeling of gene-networks in bacteria. As an entry point to the field, we focus on the analysis of simple gene-network dynamics. The notes commence with an introduction to the deterministic modeling of gene-networks, with extensive reference to applicable results coming from dynamical systems theory. The second part of the notes treats extensively several approaches to the study of gene-network dynamics in the presence of noise-either arising from low numbers of molecules involved, or due to noise external to the regulatory process. The third and final part of the notes gives a detailed treatment of three well studied and concrete examples of gene-network dynamics by considering the lactose operon, the tryptophan operon, and the lysis-lysogeny switch. The notes contain an index for easy location of particular topics as well as an extensive bibliography of the current literature. The target audience of these notes are mainly graduates students and young researchers with a solid mathematical background (calculus, ordinary differential equations, and probability theory at a minimum), as well as with basic notions of biochemistry, cell biology, and molecular biology. They are meant to serve as a readable and brief entry point into a field that is currently highly active, and will allow the reader to grasp the current state of research and so prepare them for defining and tackling new research problems.

This book examines the toxicological and health implications of environmental epigenetics and provides knowledge through an interdisciplinary approach. Included in this volume are chapters outlining various environmental risk factors such as phthalates and dietary components, life states such as pregnancy and ageing, hormonal and metabolic considerations and specific disease risks such as cancer cardiovascular diseases and other non-communicable diseases. Environmental Epigenetics imparts integrative knowledge of the science of epigenetics and the issues raised in environmental epidemiology. This book is intended to serve both as a reference compendium on environmental epigenetics for scientists in academia, industry and laboratories and as a textbook for graduate level environmental health courses. Environmental Epigenetics imparts integrative knowledge of the science of epigenetics and the issues raised in environmental epidemiology. This book is intended to serve both as a reference compendium on environmental epigenetics for scientists in academia, industry and laboratories and as a textbook for graduate level environmental health courses.

Motor dysfunction and cognitive impairment are major symptoms in both Huntington’s Disease (HD) and Parkinson’s Disease (PD). A breakthrough in HD research was the identification of the gene that causes this devastating monogenetic illness. Similarly, several genes were found to cause familial forms of PD. With their identification, a plethora of genetic animal models has been generated and has revolutionized the understanding of the pathobiology and pathophysiology of these disorders. The models allow us to study the earliest manifestations of the diseases behaviorally and neuropathologically and help us understand how they progress over time. Additionally, neurotoxic animal models are still of high interest to the PD field, as they are being used to study e.g. mitochondrial dysfunction in PD. This book focuses on animal models of both diseases and how they have helped and will continue to help understand the behavioral neurobiology in these disorders.

As imaging technologies and approaches have evolved, the scope of certain imaging techniques has moved far beyond the production of purely illustrative images or appealing time-lapse movies to providing the scientist with a rich range of ways to measure and quantify the biological process and outcome of gene expression. In Imaging Gene Expression: Methods and Protocols, expert authors offer up-to-date approaches and protocols that scientists in the field have developed, which would benefit the broader scientific community. Divided in three convenient parts, this detailed book covers the output of a gene, namely the RNA molecules that are transcribed from the gene and the way by which these molecules can be tracked or quantified in fixed or living cells, protocols that focus on the gene, DNA, or chromatin, as well as a variety of ways by which nuclear processes intertwined with gene expression can be followed and quantified in living cells as well as approaches for studying several sub-nuclear structures found in eukaryotic cells. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective subjects, lists of materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and up-to-date, Imaging Gene Expression: Methods and Protocols will serve researchers working toward imaging in the context of complete organisms.

Psychiatric genetics has become 'Big Biology'. This may come as a surprising development to those familiar with its controversial history. From eugenic origins and contentious twin studies to a global network of laboratories employing high-throughput genetic and genomic technologies, biological research on psychiatric disorders has become an international, multidisciplinary assemblage of massive data resources. How did psychiatric genetics achieve this scale? How is it socially and epistemically organized? And how do scientists experience this politics of scale? Psychiatric Genetics: From Hereditary Madness to Big Biology develops a sociological approach of exploring the origins of psychiatric genetics by tracing several distinct styles of scientific reasoning that coalesced at the beginning of the twentieth century. These styles of reasoning reveal, among other things, a range of practices that maintain an extraordinary stability in the face of radical criticism, internal tensions and scientific disappointments. The book draws on a variety of methods and materials to explore these claims. Combining genealogical analysis of historical literature, rhetorical analysis of scientific review articles, interviews with scientists, ethnographic observations of laboratory practices and international conferences, this book offers a comprehensive and detailed exploration of both local and global changes in the field of psychiatric genetics.

Genetics and its related technologies are revolutionising the world in which we live: The media is regularly dominated by the latest genetically modified (GM) food, human gene therapy or cancer chip technology; maverick scientists are in the process of cloning humans and the human genome sequence is available on the Internet. Fifty years ago we did not know what a gene was - today the awesome power of genetics is being released on an unsuspecting public, and with it a whole series of ethical dilemmas undreamth of even ten years ago. Does the question now become not 'can we?' but 'should we?'
By demystifying genetic engineering and exploring the basic biology underlying the living world, A Terrible Beauty is Born explains how clones and cloning technology are in many ways extensions of processes occurring constantly in nature. Used wisely these processes have the potential to bring enormous benefits; abused, they carry with them potential dangers which we ignore at our peril.

Hox Genes: Methods and Protocols explores techniques and methodologies which arose from or were successfully applied to the study of Hox genes and Hox proteins, at the intersection of experimental embryology, genetics, biochemistry, physiology, evolutionary biology and other life sciences. This detailed volume begins with a section on discovery and functional analysis of Hox genes and then it continues onward to discuss mode of action and biomedical applications of Hox proteins. 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. Expert and practical, Hox Genes: Methods and Protocols serves as an ideal guide to researchers striving to move forward in this dynamic and exciting area of study.

Are you considering to test your own DNA? Do you want to learn more about your health and ancestry? Understand your DNA - A Guide is about what you can use genetics for. For a few hundred dollars, you can now scan your own genes. Millions of people all over the world have already done so. Everyone wants to see what they can get to know about themselves, and the market growing rapidly. But what does it require from you? And what can you really use a DNA test for? Understand your DNA - A Guide helps you put the plots and charts of consumer genetics into perspective and enables you to figure out what's up and down in the media headlines. The book is also a key input for today's debate about what we as a society can and want to do with medical genetics. Genetics will play a growing role in the future. Understand your DNA - A Guide is an easy-to-read and necessary guide to that future. The book is provided with a foreword by Professor Sham Pak-Chung of Hong Kong University.While there are many books about genetics, they typically take the perspective of a scientist wanting to understand the molecular levels. At the same time, direct-to-consumer genetics is a booming market, with millions of people already tested. Very little has been published that will guide them for real, because the need here is more focused on medical and practical understanding, than focussed on molecules.This book therefore aims to hit that vacant spot in the market. It's a walk-through of all concepts that are necessary to understand in your own analysis. Meanwhile, it is also limited in scope to only those concepts - thus distinguishing it from broader works.The book is appropriate for the readerships in modern multi-ethnic metropolises because it mixes European and Asian examples, both from the collaboration between the author from Europe and the foreword-writer, Prof. Pak Sham of Hong Kong University. But also, because many of the examples in the book concerns differences and similarities between Asian and European ethnicities, something the author believes is a trend in time.Related Link(s)

The book serves as a comprehensive resource for scientists and clinicians studying the role of non-coding RNAs in inflammation (viral infections, wound inflammation), human inflammatory diseases (i.e. rheumatoid arthritis, Crohn’s disease, diabetes) and innate immunity. It provides a universal reference work comprising both basic and specialized information. Given that ncRNAs represent new therapeutic targets, this volume will also be of interest to industrial biomedical researchers and those involved in drug development.

Obesity is a multi-factorial disease, in which an excess of accumulated body fat can reach levels capable of affecting health. It results from an interplay between environmental factors, eating behavior, genes, epigenetics, and neuronal stimuli. The main aim of this book is to provide a state-of-the-art revision about the molecular mechanisms underpinning the development of obesity, reviewing the current knowledge in areas like monogenic and polygenic obesity forms, but also providing an updated view of the emerging knowledge about epigenetics, nutrigenomics, and neuronal aspects that also contribute to obesity.

This volume explores the myriad of techniques and methodological approaches that are being used in breast cancer research. The authors critically evaluate of the advantages and disadvantages of current methodologies, starting with the tools available for understanding the architecture of the human breast, including its tissue and cellular composition. The volume discusses the importance of functional studies in breast cancer research, especially with the help of laser capture microdissection, which allows the separation of small amounts of tissue, as well as specific cells, for biochemical analysis. In addition, the authors address methodologies including stem cell separation, which has helped in significantly understanding their role in normal breast development, but also further the understanding of breast cancer and its therapeutic management. The use of in vitro techniques and established cell lines for mechanistic studies in chemotherapeutic approaches have been invaluable will be discussed. Imaging techniques for evaluating in vitro and in vivo behavior of normal and cancerous breast tissue will be explored, as it provides a better understanding of the physiopathology of cancer. The volume will also discuss the molecular analysis of gene function in breast cancer through the transcriptomic and epigenomic profile. More importantly, the advancement of more refined techniques in sequencing will be covered. This monograph will be a comprehensive, authoritative and timely, as it addresses the emerging approaches used in breast cancer research.

This volume presents the most recent studies on mRNA polyadenylation in plants. Chapters are divided into three sections covering recent development of the use of bioinformatics tools in the field. numerous molecular, biochemical, and methods used to characterize polyadenylation sites on a genome-wide scale. 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 key tips on troubleshooting and avoiding known pitfalls. Some are specific for plant research, but most can be adopted for research in other organisms. Authoritative and practical, Polyadenylation in Plants: Methods and Protocols provides scientists with a wide range of methods to study mRNA 3'-end formation in plants.

Cancer Genomics and Proteomics: Methods and Protocols, Second Edition includes methods for the analyses of cancer genome and proteome that have illuminated us about the changes in cancer cells. 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 key tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Cancer Genomics and Proteomics: Methods and Protocols, Second Edition seeks to aid scientists in the further study into various aspects of tumor initiation and progression.

JIMD Reports publishes case and short research reports in the area of inherited metabolic disorders. Case reports highlight some unusual or previously unrecorded feature relevant to the disorder, or serve as an important reminder of clinical or biochemical features of a Mendelian disorder.