When we worked on Down Syndrome brain in the past we have been focus ing on adult brain. This was a major step forwards as most work on Down Syndrome was carried out on fibroblasts or other tissues and, moreover, we introduced proteomics to identify and quantify brain protein expression. We considered evaluation of brain protein expression in Down Syndrome brain by and by more important than gene hunting at the nucleic acid level realiz ing the long unpredictable way from RNA to protein. The availability of fetal samples along with the proteomic appproach stimulated and reinforced studies on Down Syndrome brain. And indeed, it was found out that some observations on aberrant protein expression in adult Down Syndrome brain could not be verified in the fetal samples indi cating that neurodegeneration in adult Down Syndrome brain may have been responsible rather than trisomy 21. Using brains from the early second trimester of gestation led to the generation of a series of clues for the under standing of aberrant wiring of the brain in Down Syndrome and enabled the determination of altered key functions in early life; e. g. undetectably low drebrin was observed in Down Syndrome cortex, an integral constituent and marker for dendritic spines, main effectors of cross-talk between neurons. In addition, evaluation of the nature of the neuronal deficits in terms of neuro transmission markers could be established as well as neuronal density in fetal Down Syndrome cortex."

This book highlights key technologies and identifies areas for further development in proteogenomics. The utility and usefulness of very large Omics data sets (Next Gen Sequencing of DNA, RNA-seq, ribosome profiling, mass spectrometry- and antibody-based proteomics) is discussed and opportunities and challenges of related bioinformatics applications are outlined. The reader will be able to appreciate the interdisciplinary nature of the continuously evolving area of proteogenomics, which has already grown beyond its original concept of verifying gene annotations by proteomics. The chapters presented in this book are arranged to offer a general overview, rather than to provide detailed descriptions of technologies. The selected applications will provide useful insight into the level of detail that can be obtained in relation to certain diseases areas, including cancer biology and personalized medicine. The readers will find that each chapter delivers a comprehensive approach to proteogenomics, each from the point of view of a specific application. Research scientists interested in innovative processes that can offer a unique and at the same time a more complete access to technological developments and concepts that in turn can contribute to a better understand biological functions should read this book.

Metagenomics has proven to be a powerful tool for exploring the ecology, metabolic profiling, and comparison of complex microbial communities as well as its important applications in the mining of metagenomes for genes encoding novel biocatalysts and drug molecules for bioindustries. In Metagenomics: Methods and Protocols, expert researches provide an overview and introduction to basic methods commonly used in laboratories that have a strong background in microbial metagenomics. The book attempts to address all of the working steps involved in this crucial field, beginning with DNA isolation from soils and marine samples and continuing with the construction and screening of libraries, along with key advise involving bioinformatic tools available to analyze large metagenomic sequence data sets. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters include brief 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, Metagenomics: Methods and Protocols serves as a very complete guide to available screening protocols for all major biocatalysts in order to allow for the easy setup of these screens in any microbiology lab.

The evaluation of potential mutagenic activity is a critical step in the assessment of the safety of both new and pre-existing chemical types. In Genetic Toxicology: Principles and Methods, expert contributors help to satisfy the demand for education in this tremendously important area of study. The volume covers three basic areas: the scientific basis of the discipline, the methodologies of the main test assays, and the application of the methods, all aimed primarily at scientists in the safety departments of the industries working with both natural and synthetic chemicals. Written in the highly successful Methods in Molecular Biology (TM) 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. Intuitive and cutting-edge, Genetic Toxicology: Principles and Methods provides crucial support to both laboratory workers in providing quality information on the appropriate application of techniques and to study directors in their assay selection and protocol design in this vital field.

This book provides an overview of the role and function of regulatory RNAs that lack protein-coding potential in key reproductive tissues. This includes the role of small interfering RNAs (siRNAs), microRNAs (miRNAs), PIWI-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs) and long non-coding RNAs (lncRNAs). Through clear, detailed and comprehensive debate, international leading experts discuss the role these novel regulators in normal development of sexual dimorphisms, including the differentiation of ovaries and testes, the genital tract including prostate, epididymis and uterus, as well as mammary glands. In addition, particular attention is paid on their role in pathophysiological processes within the reproductive tract. The power of next generation sequencing has proved to be an invaluable tool to discover new non-coding RNAs. While the identification of non-coding RNA is relatively easy, analysing their function represents still a challenge today. In this book, authors present historical and conceptual background information, highlight the ways in which non-coding RNAs function is analysed and present their vision of the future research in their key research area.

Obesity is one of the most important contributing factors to disease throughout the world and is an area of great current interest among researchers and clinicians. The genetics of common obesity is complex, and an important thread through this labyrinth is the study of genetic syndromes in which obesity is a major component. By examining the genetic mechanisms of obesity in these syndromes, the authors will shed new light on the genetics of common obesity. This is the first book on this important and exciting new area and addreses both the molecular and clinical features of the obesity syndromes, providing hard-core information for researchers and practical guidelines for clinicians caring for obese patients.
The book is divided into three sections: the first covers approaches for assessing and investigating the obese individual; the second describes nondysmorphic, monogenic forms of obesity; and the third documents key, multisystem obesity syndromes with various genetic etiologies. It is as much a reference book as it is a manual and will appeal to clinical geneticists, obesity researchers, endocrinologists, nutritionists, and medical biologists.

This book, written by very well known opinion leaders in the field, covers all aspects of familial Mediterranean fever, the most common monogenic autoinflammatory disease. The opening chapters explain the genetic basis of the disease and provide insights into the pathogenesis derived from recent experimental studies. A large part of the book is then devoted to a detailed description of the typical and atypical clinical presentations, the disease course, and potential complications in both pediatric and adult patients. Guidance is provided on the measurement of disease severity and the management of patients in daily practice. The advice regarding treatment is based on the best currently available evidence and attention is also paid to important emerging treatments. The book is part of Springer's series Rare Diseases of the Immune System, which presents recently acquired knowledge on pathogenesis, diagnosis, and therapy with the aim of promoting a more holistic approach to these conditions. Monogenic autoinflammatory diseases are hereditary disorders that are caused by single-gene defects in innate immune regulatory pathways and are characterized by a clinical and biological inflammatory syndrome in which there is limited, if any, evidence of autoimmunity. Familial Mediterranean fever itself is due to a mutation in the MEFV gene, which codes for the protein pyrin; it is characterized by periodic fever and episodes of painful inflammation in the abdomen, chest, and joints. Familial Mediterranean Fever will be an invaluable source of up-to-date information for all practitioners involved in the care of patients with the disease.

This second edition expands upon the previous volume with new and updated chapters. Auditory and Vestibular Research: Methods and Protocols, Second Edition guides readers through protocols on cell culture, tissue engineering, nanotechnology, high-throughput screening, and physiology. Chapters on physiology cover techniques that include optical coherence tomography, patch clamping, and photostimulation of caged neurotransmitters. 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, Auditory and Vestibular Research: Methods and Protocols, Second Edition aims to ensure successful results in the further study of this vital field.

This important book proposes revising the current informed consent protocol for predictive genetic testing to reflect the trend toward patient-centered medicine. Emphasizing the predictive aspect of testing, the author analyzes the state of informed consent procedure in terms of three components: comprehension of risk assessment, disclosure to select appropriate treatment, and voluntariness. The book's revised model revisits these cornerstones, restructuring the consent process to allow for expanded comprehension time, enhanced patient safety, greater patient involvement and autonomy, and reduced chance of coercion by family or others. A comparison of the current and revised versions and case studies showing the new model in real-world applications add extra usefulness to this resource. Included in the coverage: The science behind PGT. Understanding genetic risks and probability. The history of informed consent. Revised model of informed consent: comprehension, disclosure, voluntariness, patient safety. Applications of the model in DTC and pleiotropic genetic testing. Implementation of the revised model, and assessing its effectiveness. A milestone in the bioethics literature, Informed Consent in Predictive Genetic Testing will be of considerable interest to genetic counselors, medical and bioethicists, and public health professionals.

The fourth edition of this well-known text provides students, researchers and technicians in the area of medicine, genetics and cell biology with a concise, understandable introduction to the structure and behavior of human chromosomes. It covers both basic and up-to-date material on normal and defective chromosomes, and this new edition is particularly enhanced by the complete revision of the material on the molecular genetics of chromosomes and chromosomal defects.

Despite the many milestones in cystic fibrosis (CF) research, progress toward curing the disease has been slow, and it is increasingly difficult to grasp and use the already wide and still growing range of diverse methods currently employed to study CF so as to understand it in its multidisciplinary nature. Cystic Fibrosis: Diagnosis and Protocols aims to provide the CF research community and related researchers with a very wide range of high-quality experimental tools, as an easy way to grasp and use classical and novel methods applied to cystic fibrosis. Volume II: Methods and Resources to Understand Cystic Fibrosis focuses on pathophysiology, Omics approaches, and a variety of key resources recently made available for CF research. Written in the highly successful Methods in Molecular Biology (TM) 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 practical, Cystic Fibrosis: Diagnosis and Protocols will provide readers with optimal working tools to address pressing questions in the best technical way, while helping all of us, as a research and clinical community, to move faster hand-in-hand toward unravelling the secrets of this challenging disorder and cure it.

The primary purpose of this volume is to demonstrate the range of applications of the Pyrosequencing technology in research and diagnostics and to provide detailed protocols. Beginning with an up-to-date overview of the biochemistry, the volume continues with quantitative analysis of genetic variation, ratio of expressed alleles at the RNA level, analysis of DNA methylation, global DNA methylation assays, specialized applications for DNA methylation analysis including loss of imprinting, single blastocyst analysis, allele-specific DNA methylation patterns, DNA methylation patterns associated with specific histone modifications. The volume further details tools and protocols for the detection of viruses and bacteria, and genetic and epigenetic analyses for forensics using Pyrosequencing. As a volume in the highly successful Methods in Molecular Biology series, chapters contain introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols and tips on troubleshooting and avoiding known pitfalls. Comprehensive and adaptable, Pyrosequencing: Methods and Protocols, Second Edition will greatly aid doctorial students, postdoctoral investigators and research scientists studying different aspects of genetics and cellular and molecular biology.

This volume focuses on apoptotic and non-apoptotic programmed cell death, including necroptosis, pyroptosis, and ferroptosis, and presents recent findings in the field. It discusses the crucial role that apoptotic and non-apoptotic cell death play in various pathological conditions, such as skin diseases, inflammatory bowel diseases, and virus infections. Further, it highlights the mechanisms underlying the recognition and clearance of dead cells, and the subsequent biological responses triggered by phagocytosed macrophages and factors released from dying cells. Offering insights into cell death, it is a valuable resource for researchers and clinicians developing novel strategies to treat various diseases that are closely associated with cell death.

This title develops from the 24th Stadler symposium. It explores the general theme "GENOME EXPLOITATION: Data Mining the Genomes." The idea behind the theme is to discuss and illustrate how scientists are going to characterize and make use of the massive amount of information being accumulated about plant and animal genomes. The book presents a state-of-the-art picture on mining the Genome databases. Its chapters are authored by key stars in the field.

High-throughput measurements of gene expression and genetic marker data facilitate systems biologic and systems genetic data analysis strategies. Gene co-expression networks have been used to study a variety of biological systems, bridging the gap from individual genes to biologically or clinically important emergent phenotypes.

The only monograph on cytogenetics for the pathologist, this up-to-the-minute reference/text contains the most up-to-date research findings on many important topics in medical genetics-notably FISH (fluorescent in situ hybridation)-based molecular cytogenetic technologies and spectral karyotyping. An excellent resource for cytogeneticists preparing for the certifying examination in Clinical Cytogenetics offered by the American Board of Medical Genetics (ABMG). Written by nearly 30 distinguished international contributors, Medical Cytogenetics -covers the history of the field, tissue culturing and staining techniques, and clinical applications of FISH, as well as other methods for genetic studies and chromosomal analysis -supplies numerous examples and case reports -examines reproductive dysfunctions such as in-utero abnormalities, male infertility, and failure to conceive -investigates chromosomal abnormalities associated with myeloid hematopoietic disorders, lymphoid neoplasms, and solid tumors such as those associated with breast cancer -reviews means of obtaining accreditation or licenses, use of external peer reviews and voluntary inspections, proficiency testing, and regulatory oversight -and more! Thoroughly referenced with over 1800 bibliographic citations, and supplemented with a useful glossary, a large number of practice questions, and over 40 color photographs, Medical Cytogenetics is a pragmatic, hands-on reference for pathologists, geneticists, cytogenetic technologists, molecular and cell biologists, clinical and medical oncologists, hematologists, neurologists, pediatricians, endocrinologists, obstetricians, gynecologists, and primary care physicians, and an exceptionaltext for upper-level undergraduate, graduate, and medical students in these disciplines.

"Mouse Genetics: Methods and Protocols" provide selected mouse genetic techniques and their application in modeling varieties of human diseases. The chapters are mainly focused on the generation of different transgenic mice to accomplish" "the manipulation of genes of interest, tracing cell lineages and modeling human diseases. Composed in the highly successful "Methods in Molecular Biology "series format, each chapter contains a brief introduction, a list of necessary materials, systematic, readily reproducible methods and a notes section, which shares tips on troubleshooting in order to avoid known pitfalls.

Comprehensive and authoritative, "Mouse Genetics: Methods and Protocols" promises to deliver fundamental techniques and protocols to geneticists, molecular biologists, cell and developmental biologists, students and postdoctoral fellows working in the various disciplines of mouse biology and modeling human disease.

After volume 33, this book series was replaced by the journal "Evolutionary Biology." Please visit www.springer.com/11692 for further information.

The nature of science is to work on the boundaries between the known and the unknown. These boundaries shift as new methods are developed and as new concepts are elaborated (e.g., the theory of the gene, or more recently, the coalescence framework in population genetics). These tools allow us to address questions that were previously outside the realm of science, and, as a consequence, the boundary between the knowable and unknowable has shifted. A study of limits should reveal and clarify the boundaries and make sharper the set of questions. This book examines and analyzes these new limits as they are applied to evolutionary biology and population genetics. It does this by framing the analysis within four major classes of problems - establishing the fact of evolution; understanding the evolutionary pathways that led to today's biological world; mechanisms of evolutionary change (e.g., models of social behavior, sexual selection, macro evolution); and, finally, prediction.

Despite the many milestones in cystic fibrosis (CF) research, progress towards curing the disease has been slow, and it is increasingly difficult to grasp and use the already wide and still growing range of diverse methods currently employed to study CF so as to understand it in its multidisciplinary nature. Cystic Fibrosis: Diagnosis and Protocols aims to provide the CF research community and related researchers with a very wide range of high-quality experimental tools, as an easy way to grasp and use classical and novel methods applied to cystic fibrosis. Volume I: Approaches to Study and Correct CFTR Defects focuses on the cystic fibrosis transmembrane conductance regulator (CFTR) and its expression, biogenesis, structure, and function in terms of the defects causing CF. Written in the highly successful Methods in Molecular Biology (TM) 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 practical, Cystic Fibrosis: Diagnosis and Protocols will provide readers with optimal working tools to address pressing questions in the best technical way, while helping all of us, as a research and clinical community, to move faster hand-in-hand toward unravelling the secrets of this challenging disorder and cure it.

Recent progress in high-throughput technologies and genome wide transcriptome studies have lead to a significant scientific milestone of discovering non-coding RNAs (ncRNAs) which spans through a major portion of the genome. These RNAs most often act as riboregulators, and actively participate in the regulation of important cellular functions at the transcriptional and/or post-transcriptional levels rather than simply being an intermediated messenger between DNA and proteins. As the appreciation for the importance of ncRNAs continues to emerge, it is also increasingly clear that these play critical roles in gene regulatory processes during development and differentiation. Further, regulatory RNAs are useful biomarkers for diagnosis of diseases. Hence these RNA regulators are essential to the development of therapeutics. This book on "Regulatory RNAs" offers a comprehensive view on our current understanding of these regulatory RNAs viz. siRNA, miRNA, piRNA, snoRNA, long non-coding RNA, small RNA etc. It addresses both the biogenesis and mechanism of action of regulatory RNAs with a primary focus on their annotation, experimental methodologies (microarray, next-gen sequencing etc.) for their discovery, computational tools for their prediction, and above all, applications of these revolutionary regulatory molecules in understanding biological systems and diseases, including therapeutics. This comprehensive volume is intended for readers with research or teaching interests in ncRNA biology and will provide a major information resource on current research in the fast-moving fields of RNA and gene expression regulation. Cutting-edge and concise, "Regulatory RNAs: Basics, Methods and Applications" promises to support vital research in the field of regulatory RNAs, ever-continuing to grow rapidly and gain increasing importance in basic and translational biology.

The field of epigenetics has played a major role at the forefront not only of molecular biology, but also of medical genetics and clinical medicine. Few disciplines have experienced growth comparable to that which we have witnessed for epigenetics in the past decade. The goal of "Epigenetics Protocols, Second Edition "is to highlight select techniques that have been mainstays in the field as well as to cover methods that are especially relevant to extant discoveries in epigenetics. This volume focuses on the two broad areas of epigenetics: DNA methylation and chromatin modifications, and also covers the complex topic of computational methods for epigenetic analyses which is essential to a complete understanding of the vast body of information that is being derived with the use of these newly-developed tools. Written in the highly successful "Methods in Molecular Biology " series format, chapters contain introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and notes on troubleshooting and avoiding known pitfalls.

Authoritative and accessible, "Epigenetics Protocols, Second Edition" serves as an ideal guide to advanced students, basic scientists and clinical researchers as well as clinicians and biotechnology investigators who wish to continue exploring this exciting and progressive research field."

This book explores mental disorders from a uniquely evolutionary perspective. Although there have been many attempts to mathematically model neural processes and, to some extent, their dysfunction, there is very little literature that models mental function within a sociocultural, socioeconomic, and environmental context. Addressing this gap in the extant literature, this book explores essential aspects of mental disorders, recognizing the ubiquitous role played by the exaptation of crosstalk between cognitive modules at many different scales and levels of organization, the missing heritability of complex diseases, and cultural epigenetics. Further, it introduces readers to valuable control theory tools that permit the exploration of the environmental induction of neurodevelopmental disorders, as well as the study of the synergism between culture, psychopathology and sleep disorders, offering a distinctively unique resource.

Genetic counselors translate the findings of scientific investigation into meaningful accounts that enable individuals and families to make decisions about their lives. This collection of original papers explores the history, values, and norms of that process, with some focus on the value of nondirectiveness in counseling practice. The contributors; examination of genetic counseling issues serves as a foundation from which to address other ethical, legal, and policy considerations in the expanding universe of clinical genetics.

Arising from firm foundations laid by mathematical population genetics, clinical genetics, and statistical epidemiology, genetic epidemiology attempts to identify the many components of risk

attributable to genes, environments, and interactions, and the course of its research can follow many diverse paths. In "Genetic Epidemiology," the success of genome-wide association studies in their identification of hundreds of disease susceptibility loci has inspired renowned experts to contribute thorough methodologies, which aim to bring together bioinformaticians, geneticists, clinicians, statisticians, and epidemiologists in the study of this vital field. The volume opens with chapters covering the basics; however, it quickly moves on to coverage of more specialist topics such as twin studies, Mendelian randomization, genetic association studies, more advanced areas, as well as case studies. As a part of the highly successful "Methods in Molecular Biology " series, this work provides the detailed description of the application and analysis of the most commonly employed methods that are necessary for a firm grounding in the field.

Authoritative and cutting-edge, "Genetic Epidemiology" aims to provide a basic framework for crucial interdisciplinary communication and understanding suited to newcomers to the field as well as experienced researchers and graduate level students."