This book is being planned as a tribute to Dr. Victor A. McKusick (1921-2008), who is well known as the "father of medical genetics". He was long associated with the Johns Hopkins University School of Medicine, first as a student in the 1940s, and later as a faculty member, becoming the Chairman of the Department of Medicine at Johns Hopkins. He was a co-founder of GENOMICS and founder and lifelong editor of Mendelian Inheritance in Man, a massive compendium of human syndromes and genetic variants. Dr. McKusick made distinguished contributions to all branches of medical genetics. He was a member of the U.S. National Academy of Sciences and many other academies in the world. He was awarded the National Medal of Science in 2002. He received many other honors including several honorary doctorates. The proposed book will reflect all the fields touched upon by Dr. McKusick's contributions. It will be a valuable source of the latest progress in medical genetics. The contributors are internationally distinguished in their chosen specialties. Besides professional distinction, they are being selected because of their past association with Dr. McKusick, as former students or colleagues who extended his research in some fashion. The proposed book will reflect all the fields touched upon by Dr. McKusick's contributions. It will be a valuable source of the latest progress in medical genetics. The contributors are internationally distinguished in their chosen specialties. Besides professional distinction, they are being selected because of their past association with Dr. McKusick, as former students or colleagues who extended his research in some fashion.

This innovative book provides a unique perspective on the biomedical and societal implications of personalized medicine and how it will help mitigate the healthcare crisis and rein in ever-growing expenditure. It introduces the reader to underlying concepts at the heart of personalized medicine - pharmacogenomics, targeted therapies and individualized diagnosis and treatment - and shows how, with the advent of genomic technologies, clinicians will have the capability to predict and diagnose disease more efficiently. Advocating a patient-centred approach at the heart of care, this introduction to personalized medicine, the science behind it, its economic effects, its effects upon patients and its overall implications for society will be invaluable to clinicians, to healthcare providers and to patients.

Genetics and Gene Therapy shows the wide range of the debate and the very real significance that genetics and its associated developments have for human beings, individually and collectively. Few areas of science and medicine have resulted in the volume of academic and popular literature as has genetics. The so-called revolution in understanding of the causes of disease states, and even behavioural traits, has focussed public attention on the influence of genes in making us what we are. Rapidly, however, the potential benefits of such understanding were overtaken, in the public mind at least, by the question of the possible (negative) implications of genetic knowledge and associated technologies. The chapters in this volume show just how wide-ranging concern has become, ranging from regulation to cloning, with the fear of discrimination in between. Part One begins with a range of general discussions of about the genetic enterprise itself, followed by consideration of some specific questions. Part Two then addresses cutting edge debates in genetics.

"Molecular Genetics of Inherited Eye Disorders" provides an authoritative and up-to-date account of molecular genetic advances in a wide spectrum of genetic eye disorders, and forms the second volume in the Modern Genetics book series. The field has produced some dramatic and often unexpected findings in recent years ranging from the elegant unravelling of the molecular basis of colour vision defects to the subtle complexity of the retinoblastoma gene. The role of crystallins in congenital cataract and of the rhodopsin molecule in retinitis pigmentosa are discussed, illustrating the importance of the "candidate gene" approach to genetic eye disease. "Reverse genetic" approaches to the cloning of genes responsible for aniridia and choroideremia exemplify the power of the new genetic techniques and signal the start of the next experimental phase, in which the functional characterization of identified genes begins. Sections on albinism, retinitis pigmentosa and collagen disorders deal w

This new edition explores current and emerging mutagenesis methods focusing specifically on mammalian systems and commonly used model organisms through comprehensive coverage and detailed protocols. Since the first edition, major advances and discoveries have made chromosomal mutagenesis a widely used technique and one that is available to any molecular biology laboratory, and this collection provides detailed protocols, case-studies, and reviews from thought-leaders in the field. 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 fully updated, Chromosomal Mutagenesis, Second Edition aims to help speed scientific discovery and aid in the next advances in the field.

To understand the ethical issues raised by genetic counselling, it is necessary for the practitioner, the detached observer and the student to be aware of different perspectives. This work includes contributions from health professionals engaged in genetic counselling, and also from observers and critics of genetic counselling who have backgrounds in law, philosophy, biology, social science, and in advocacy on behalf of those with mental handicap. This diversity is designed to assist health professionals in examining their activities with a fresh eye; it may also help the observer-critic to understand the ethical problems that arise in genetic counselling practice. It is natural for health professionals to focus their concern on the immediate questions raised by individual clients, and for detached observers to consider the broader social implications of the subject.

To understand the ethical issues raised by genetic counselling, it is necessary for the practitioner, the detached observer and the student to be aware of different perspectives. This work includes contributions from health professionals engaged in genetic counselling, and also from observers and critics of genetic counselling who have backgrounds in law, philosophy, biology, social science, and in advocacy on behalf of those with mental handicap. This diversity is designed to assist health professionals in examining their activities with a fresh eye; it may also help the observer-critic to understand the ethical problems that arise in genetic counselling practice. It is natural for health professionals to focus their concern on the immediate questions raised by individual clients, and for detached observers to consider the broader social implications of the subject.

This book provides a comprehensive compilation of the evidence available regarding the role of genetic differences in the etiology of human obesities and their health and metabolic implications. It also identifies the most promising research areas, methods, and strategies for use in future efforts to understand the genetic basis of obesities and their consequences on human health. Leading researchers in their respective fields present contributed chapters on such topics as etiology and the prevalence of obesities, nongenetic determinants of obesity and fat topography, and animal models and molecular biological technology used to delineate the genetic basis of human obesities. A major portion of the book is devoted to human genetic research and clinical observations encompassing adoption studies, twin studies, family studies, single gene effects, temporal trends and etiology heterogeneity, energy intake and food preference, energy expenditure, and susceptibility to metabolic derangements in the obese state. Future directions of research in the field are covered in the book as well.

This volume provides a comprehensive review of established and novel biomarkers across the continuum of breast cancer. The volume covers topics related to breast cancer risk and prevention, prediction of response to today's standard therapies, and markers capable of influencing treatment decisions in the near future. Chapter authors combine their wide-ranging expertise to review the current status of the biomarker and to offer their individual perspectives on how biomarkers may be used in future treatments and research. Breast cancer continues to be the most common malignancy diagnosed in women in the Western world. While there are multiple treatment approaches for breast cancer, today more than ever we recognize that each tumor is unique. The challenge ahead is to consider how to best use validated and novel biomarkers to select the most appropriate treatment(s) for individual patients.

This book focuses on histone mutations, especially those mutations closely related to cancer. Genetic mutations and epigenetic alterations contribute to the development of a variety of cancers: recent genetic studies have identified e.g. H3K27M and H3G34R/V mutation in over 75% of DIPG cases, H3.3K36M mutation in more than 90% of chondroblastoma cases, and H3G34W/L mutation in over 90% of giant cell tumors of bone. Given the high incidence and tumorigenesis effects of histone H3 mutations, they are also referred to as oncohistones. This book highlights the advances made in the area over the past 10 years, and offers a state-of-the-art summary of epigenetic alternation, gene expression, protein structure, drug discovery, immunotherapy, and mouse modeling of histone H3 mutations in various tumors. Chiefly intended to provide researchers and graduate students with an overall picture of these mutations, it will also be of interest to researchers in basic oncology, clinical oncology, and epigenetics, as well as academics and clinical oncology practitioners.

This collection of essays, with an extended commentary by the editor, is concerned with developments in reproductive technology and the possibilities of genetic engineering. The volume provides a forum for debate between science and society. Leading scientists in the field explain the nature and goals of "test tube" reproduction and genetic engineering, and their eugenic implications. Other papers draw out the legal and ethical problems raised by these developments. The ethical dilemmas are discussed both from the point of view of secular moral philosophy and from a theological perspective. The extended commentary attempts to place these questions in the context of a social ethic, rather than an individualist one, in contrast to the approach adopted by the Warnock Report.

Non-coding, inhibitory microRNAs have emerged as important modulators of cellular gene expression, through a process called RNA interference (RNAi). To date, hundreds of conserved and species-specific microRNAs have been identified in organisms ranging from single-celled algae to humans. Many of these tiny RNAs are now known to play fundamental roles in developmental biology and disease pathogenesis. In addition, RNAi has emerged as a technology useful for manipulating gene expression. In "RNA Interference Techniques," expert researchers present detailed methods for designing and delivering artificial inhibitory RNAs to neural tissue and for detecting or cloning endogenous microRNAs, all in order to aid investigators' attempts to ask basic biological questions or develop therapeutics for dominant neurogenetic disorders, cancer, or viral infection. As a volume in the successful "Neuromethods" series, the chapters provide authoritative accounts of the most commonly used approaches in the field today.

Cutting-edge and concise, "RNA Interference Techniques" promises to support the vital research in the field of RNAi and miRNAs, ever-continuing to grow rapidly and gain increasing importance in basic and translational biology.

Originally published in 1976, this volume reports research that will help us to understand the causes of psychogenic diseases. It deals both experimentally and theoretically with the question of symptom specificity in psychosomatic research - why some individuals respond to psychological stress with gastric disorders, others with sexual impotence, and still others with high blood pressure. As the author notes in summarizing his conclusions, "The repeated pairing of activation of a given organic system with intense nervous stress directs the pathological influence of the stressor primarily upon the system activated; subsequently the natural stimuli which would ordinarily activate the system in a normal manner sustain the pathological stressor's effect as a conditioned stimulus for the stressor effect." The translation of this work from the original Russian brings to the attention of Western investigators new and useful models of stress-induced disorders, and sheds new light on the pervasive problem of psychosomatic disease.

This book provides a comprehensive overview of the genetic basis underlying endocrine diseases. It covers both the molecular and clinical consequences of these genetic defects, as well as the relevance for clinical care, highlighting issues of genetic counseling. Several endocrine diseases have a genetic background, and contemporary research in the field plays a crucial role in the clinical care of endocrine diseases. In recent years, there have been major developments in our understanding of the genetic basis of endocrine diseases. Several novel genes and mutations predisposing individuals to monogenic endocrine diseases have been discovered, and with the advent of next generation sequencing, a huge amount of new data has become available. Further, novel molecular mechanisms, such as genomic imprinting, have been implicated in the pathogenesis of endocrine diseases. A better understanding of the genetic background of these diseases is relevant not only from the research perspective, but also in terms of clinical care. As such, this book is an essential read for both researchers and clinicians working in the field.

This book explains current strategies for mapping genomes of higher organisms and explores applications of gene mapping to agriculturally important species of plants and animals. It also explores the experimental techniques used for genetic and physical mapping of genes.

This second edition explores techniques involving pseudogenic DNA, RNA, and proteins. Chapters describe how to identify pseudogenes and how to study the functions and alterations of pseudogenic RNA and proteins, both in vitro, and in vivo. Written in the highly successful Methods in Molecular Biology series format, methodological 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 while avoiding known pitfalls. Authoritative and cutting-edge, Pseudogenes: Functions and Protocols, Second Edition aims to be a practical guide to researches, useful to help further their study in this field.

This book demonstrates that a pandemic of coronary heart disease occurred in North America, western and northern Europe, and Australia and New Zealand from the 1930s to about 2000. At its peak it caused more deaths than any other disease. The book examines and compares trends in coronary heart disease mortality rates for individual countries. The most detailed analyses are for the United States, where mortality rates are examined for race, sex, and age groups and for geographic regions. Popular explanations for the rise and fall of coronary heart disease mortality rates are examined.

Sickle cell and thalassaemia are among the world's most common genetic conditions. They are especially common in Africa, Brazil, the Caribbean, the Middle East and Asia. They affect all ethnic groups but they particularly impact on minority ethnic groups in North America, Europe and Australasia. Much research has focused on clinical, laboratory and genetic studies of these conditions. Through a wide-ranging selection of readings based on social scientific research into sickle cell and thalassaemia, this book seeks to redress this imbalance. This is important as, through an examination of the different social, economic and cultural contexts of the lives of people living with sickle cell or thalassaemia, the contributors demonstrate that people are more than the sum of their genes and that their life experiences are rarely derived solely from the clinical severity of their condition but depend on the social context of their lives. Genetics and Global Public Health presents a new concluding chapter which highlights the critical nature of social science research for sickle cell and thalassaemia communities, providing key insights into the social contexts of human behaviour and analysing how societal arrangements could change to assist people living with either condition. It will be of great interest to postgraduate and research students as well as professionals working in the field of public health. This book was originally published as a special issue of the journal Ethnicity and Health.

This book describes the identification and characterization of genetic loci that determine susceptibility to liver, mammary, or skin carcinogenesis in rodents. It focuses on protein kinases and phospholipases, and stress-related signal transduction.

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.

"Molecular Beacons" explains working principle of molecular beacons, discusses their design, synthesis, purification and characterization, explores their thermodynamic and kinetic properties, and more importantly, reviews their in vivo and in vitro applications with the emphasis on the design and modification of molecular beacons for in vivo mRNA imaging applications.

This book is designed to bring together in a single resource an organized and comprehensive view of molecular beacons and will be a valuable resource for academic, clinical and industrial scientists and graduate students who may consider exploring molecular beacons in their research or practice.

Chaoyong James Yang is the Lu Jiaxi Professor of Chemistry at Xiamen University, China.

Weihong Tan is a Distinguished Professor of Chemistry and Biomedical Engineering at Hunan University, China and also a University of Florida Distinguished Professor and V. T. and Louis Jackson Professor of Chemistry at the University of Florida, USA.

"

The existence of genes for RNA molecules not coding for proteins (ncRNAs) has been recognized since the 1950's, but until recently, aside from the critically important ribosomal and transfer RNA genes, most focus has been on protein coding genes. However, a long series of striking discoveries, from RNA's ability to carry out catalytic function, to discovery of riboswitches, microRNAs and other ribo-regulators performing critical tasks in essentially all living organisms, has created a burgeoning interest in this primordial component of the biosphere. However, the structural characteristics and evolutionary constraints on RNA molecules are very different from those of proteins, necessitating development of a completely new suite of informatic tools to address these challenges. In RNA Sequence, Structure, Function: Computational and Bioinformatic Methods, expert researchers in the field describe a substantial and relevant fraction of these methodologies from both practical and computational/algorithmic perspectives. Focusing on both of these directions addresses both the biologist interested in knowing more about RNA bioinformatics as well as the bioinformaticist interested in more detailed aspects of the algorithms. Written in the highly successful Methods in Molecular Biology series format, the chapters include the kind of detailed description and implementation advice that is crucial for getting optimal results. Thorough and intuitive, RNA Sequence, Structure, Function: Computational and Bioinformatic Methods aids scientists in continuing to study key methods and principles of RNA bioinformatics.

The postgenomic era presents a multitude of challenges for scientists in all areas of science. The information overload from new discoveries in genomics and proteomics highlight how little we really know about the functioning of a cell. The advent of Next-Generation Sequencing technologies promises to make our genetic blueprint available to the common man. The availability of the plethora of biological information has lead to the devel- ment of new areas of science and the coining of new "omics" terms including transcr- tomics, methylomics, toxicogenomics, pharmacogenomics, metabolomics, lipidomics, and so on. Remarkable research is being conducted to understand the various aspects of human health and how processes like histone modifcations, promoter usage, alternative splicing, posttranscriptional, and posttranslational modifcations contribute to disease. The advent of systems biology has unifed chemists and biochemists alike in the struggle to eradicate or treat human disease. Microarrays have blossomed into a fast developing and cutting-edge technology that promises to become a major component of personalized medicine. The 1990s witnessed a boom in many areas including genome sequencing, combinatorial chemistry, and c- puters, all of which have contributed to the development of microarray technology from its infancy into a mature tool. The growing potential of this tool is evident from the n- ber of publications since 1991 when Fodor et al. of Affymax (now Affymetrix) frst described the microarray prototype.

Velo-Cardio-Facial Syndrome (VCFS) is a genetic disorder caused by the deletion of part of chromosome 22. It occurs in approximately one in 4000 births and there are now more than 100 physical phenotypic features reported. VCFS affects every major system in the body and this 2005 book was the first to describe its full clinical impact. It has been authored by leading international VCFS clinicians/researchers. The focus is on clinical issues with chapters devoted to psychiatric disorders (with the sufferer showing very high levels of schizophrenia), neuroimaging, speech and language disorders, as well as cardiac, ENT, gastrointestinal, ophthalmic and urological manifestations. Molecular genetics, immunodeficiency and genetic counselling are also covered, and practical approaches to diagnosis and treatment described. As VCFS is seen as a paradigm for other microdeletion disorders, this book will not just appeal to clinicians seeing VCFS patients, but also to those interested in other genetic disorders.

Neuropsychiatric disorders such as schizophrenia, mood disorders, Alzheimer s disease, epilepsy, alcoholism, substance abuse and others are some of the most debilitating illnesses worldwide characterizing by the complexity of the causes, and lacking the laboratory tests that may promote diagnostic and prognostic procedures. Recent advances in neuroscience, genomic, genetic, proteomic and metabolomic knowledge and technologies have opened the way to searching biomarkers and endophenotypes, which may offer powerful and exciting opportunity to understand the etiology and the underlying pathophysiological mechanisms of neuropsychiatric disorders. The challenge now is to translate these advances into meaningful diagnostic and therapeutic advances.

This book offers a broad synthesis of the current knowledge about diverse topics of the biomarker and endophenotype strategies in neuropsychiatry. The book is organized into four interconnected volumes: Neuropsychological Endophenotypes and Biomarkers (with overview of methodological issues of the biomarker and endophenotype approaches in neuropsychiatry and some technological advances), Neuroanatomical and Neuroimaging Endophenotypes and Biomarkers, Metabolic and Peripheral Biomarkers and Molecular Genetic and Genomic Markers . The contributors are internationally and nationally recognized researchers and experts from 16 countries.

This four-volume handbook is intended for a broad spectrum of readers including neuroscientists, psychiatrists, neurologists, endocrinologists, pharmacologists, clinical psychologists, general practitioners, geriatricians, health care providers in the field of neurology and mental health interested in trends that have crystallized in the last decade, and trends that can be expected to further evolve in the coming years. It is hoped that this book will also be a useful resource for the teaching of psychiatry, neurology, psychology and mental health."