As researchers continue to make enormous progress in mapping disease genes, exciting, novel, and complex analyses have emerged. In this book, scientists from around the world, who are leaders in this field, contribute their vast experience and expertise to produce a comprehensive and fascinating text for researchers and clinicians alike. They provide cutting-edge analysis of the most up-to-date and preeminent information available.

This volume describes high-throughput approaches to a series of robust, established methodologies in molecular genetic studies of population samples. Such developments have been essential not only to linkage and association studies of single-gene and complex traits in humans, animals and plants, but also to the characterisation of clone banks, for example in mapping of genomes. Chapters have been written by developers or highly experienced end-users concerned with a diverse array of biological applications. The book should appeal to any researcher for whom costs and throughput in their genetics laboratory have become an issue.

This second edition volume discusses the revolutionary development of faster and less expensive DNA sequencing technologies from the past 10 years and focuses on general technologies that can be utilized by a wide array of plant biologists to address specific questions in their favorite model systems. This book is organized into five parts. Part I examines the tools and methods required for identifying epigenetic and conformational changes at the whole-genome level. Part II presents approaches used to determine key aspects of a gene's function, such as techniques used to identify and characterize gene regulatory networks. This is followed by a discussion of tools used to analyze the levels of mRNA, mRNA translation rates and metabolites. Part III features a compilation of forward and reverse genetic approaches that include recent implementation of high-throughput sequencing in classical methodologies such as QTL mapping. The final two parts explore strategies to facilitate and accelerate the generation and testing of functional DNA elements and basic computational tools used to facilitate the use of systems biology approached by a broad spectrum of plant researchers. Written in the highly successful Methods of 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. Practical and timely, Plant Functional Genomics: Methods and Protocols, Second Edition highlights the latest developments in DNA sequencing technologies that are likely to continue shaping the future of functional genomics.

As microarray technology has matured, data analysis methods have advanced as well. Methods Of Microarray Data Analysis III is the third book in this pioneering series dedicated to the existing new field of microarrays. While initial techniques focused on classification exercises (volume I of this series), and later on pattern extraction (volume II of this series), this volume focuses on data quality issues. Problems such as background noise determination, analysis of variance, and errors in data handling are highlighted.

Three tutorial papers are presented to assist with a basic understanding of underlying principles in microarray data analysis, and twelve new papers are highlighted analyzing the same CAMDA'02 datasets: the Project Normal data set or the Affymetrix Latin Square data set. A comparative study of these analytical methodologies brings to light problems, solutions and new ideas. This book is an excellent reference for academic and industrial researchers who want to keep abreast of the state of art of microarray data analysis.

The field of DNA computation has flourished since the publication of Adleman's seminal article, in which he demonstrated for the first time how a computation may be performed at a molecular level by performing standard operations on a tube of DNA strands. Since Adleman's original experiment, interest in DNA computing has increased dramatically. This book provides a broad overview of the entire field of DNA computation, tracing its history and development. It contains detailed descripions of all major theoretical models and experimental results to date, which are lacking in existing texts. Potential future developments are also discussed. The book is a useful reference source for researchers and students, as well as an accessible introduction for people new to the field.

Epigenetics refers to heritable patterns of gene expression which do not depend on alterations of genomic DNA sequence.

This book provides a state-of-the-art account of a few selected hot spots by scientists at the edge in this extremely active field. It puts special emphasis on two main streams of research. One is the role of post-translational modifications of proteins, mostly histones, on chromatin structure and accessibility. The other one deals with parental genomic imprinting, a process which allows to express a few selected genes from only one of the parental allele while extinguishing the other.

At present, there is growing interest in high pressure bioscience and biotechnology. The activities are nearly equally distributed between fundamental research and applications. With original work on marine and terrestrial microbiology, biochemistry, molecular biology, deep-sea diving, food science and other industrial applications, this book covers the whole range of current high pressure bioscience. Advances in High Pressure Bioscience and Biotechnology will be welcomed by all industrial and academic researchers who are working in this field.

This book presents practical approaches for the analysis of data from gene expression microarrays. Each chapter describes the conceptual and methodological underpinning for a statistical tool and its implementation in software. Methods cover all aspects of statistical analysis of microarrays, from annotation and filtering to clustering and classification. Chapters are written by the developers of the software. All software packages described are free to academic users. The book includes coverage of various packages that are part of the Bioconductor project and several related R tools. The materials presented cover a range of software tools designed for varied audiences. Some chapters describe simple menu-driven software in a user-friendly fashion, and are designed to be accessible to microarray data analysts without formal quantitative training. Most chapters are directed at microarray data analysts with master-level training in computer science, biostatistics or bioinformatics. A minority of more advanced chapters are intended for doctoral students and researchers. The team of editors is from the Johns Hopkins Schools of Medicine and Public Health and has been involved with developing methods and software for microarray data analysis since the inception of this technology. Giovanni Parmigiani is Associate Professor of Oncology, Pathology and Biostatistics. He is the author of the book on "Modeling in Medical decision Making," a fellow of the ASA, and a recipient of the Savage Awards for Bayesian statistics. Elizabeth S. Garrett is Assistant Professor of Oncology and Biostatistics, and recipient of the Abbey Award for statistical education. Rafael A Irizarry is Assistant Professor of Biostatistics, and recipient of the Noether Award for non-parametric statistics. Scott L. Zeger is Professor and chair of Biostatistics. He is co-author of the book "Longitudinal Data Analysis," a fellow of the ASA and recipient of the Spiegelman Award for public health statistics.

As studies using microarray technology have evolved, so have the data analysis methods used to analyze these experiments. The CAMDA conference plays a role in this evolving field by providing a forum in which investors can analyze the same data sets using different methods. Methods of Microarray Data Analysis IV is the fourth book in this series, and focuses on the important issue of associating array data with a survival endpoint. Previous books in this series focused on classification (Volume I), pattern recognition (Volume II), and quality control issues (Volume III).

In this volume, four lung cancer data sets are the focus of analysis. We highlight three tutorial papers, including one to assist with a basic understanding of lung cancer, a review of survival analysis in the gene expression literature, and a paper on replication. In addition, 14 papers presented at the conference are included. This book is an excellent reference for academic and industrial researchers who want to keep abreast of the state of the art of microarray data analysis.

Jennifer Shoemaker is a faculty member in the Department of Biostatistics and Bioinformatics and the Director of the Bioinformatics Unit for the Cancer and Leukemia Group B Statistical Center, Duke University Medical Center. Simon Lin is a faculty member in the Department of Biostatistics and Bioinformatics and the Manager of the Duke Bioinformatics Shared Resource, Duke University Medical Center.

The field of DNA repair is vast and advancing rapidly. Recent investigations have begun to focus on the involvement of chromatin in the repair of broken DNA. Although I have no doubt that many breakthroughs in our understanding of chromatin, chromatin regulation, and DNA repair lie in our future, presently this is a new line in inquiry. As such there are many, many unanswered questions. Indeed, most of the correct questions have probably not even been asked yet. Here I have attempted to present a review of some of the current body of knowledge that may prove relevant to understanding the role of chromatin in DNA repair. Because the volume of research, and the relevant findings, come from a staggering array of labs, systems, and ideas I have focused primarily on findings developed from the study of the budding yeast Saccharomyces cerevisiae. Unfortunately, this means that I have left out a great deal of information. It is my hope, however, that the information I do detail, particularly in Chapter 1, will give a flavor for the scope of the problem and perhaps highlight some of the interesting directions this field is taking, or may one day take. I would also point out that the primary research that is presented herein is not in any way meant to represent the comprehensive scope of research being performed. To understand DNA repair will require investigation from innumerable labs, performed by innumerable researchers, moving in unexpected directions.

MicroRNA research and development is the billion-dollar baby and most lucrative option for drug discovery in gene therapy industries worldwide. Personalized microRNA treatments are in many cases the only remedy for viral diseases that have no cure in conventional drugs and offer to bring us closer than ever to "personalized medicine." They also counteract cancer and other infectious and neuro-diseases. Early diagnosis, prognosis, staging, and sub-classification of various cancers can easily be facilitated by microRNA-based biomarkers. MicroRNA surveys recent advances in RNA and RNA-protein components that highlight RNA delivery, its stability, and applications of RNA-based drugs for the modulation of gene/protein expression and gene editing. The book not only focuses on the modern medicines of microRNA-based early diagnostic and therapy development, but also works as a hidden treasure for drug discovery of multiple rare diseases worldwide. It offers indispensable learning materials for academic researchers, graduate, and medical students, and offers a powerful practical guide for RNA-Pharma and gene therapy industries.

A comprehensive account of genomic rearrangement, focusing on the mechanisms of inversion, translocation, gene and genome duplication and gene transfer and on the patterns that result from them in comparative maps. Includes analyses of genomic sequences in organelles, prokaryotes and eukaryotes as well as comparative maps of the nuclear genomes in higher plants and animals. The book showcases a variety of algorithmic and statistical approaches to rearrangement and map data.

In 1957 two young scientists, Matthew Meselson and Frank Stahl, produced a landmark experiment confirming that DNA replicates as predicted by the double helix structure Watson and Crick had recently proposed. It also gained immediate renown as a "most beautiful" experiment whose beauty was tied to its simplicity. Yet the investigative path that led to the experiment was anything but simple, Frederic L. Holmes shows in this masterful account of Meselson and Stahl's quest. This book vividly reconstructs the complex route that led to the Meselson-Stahl experiment and provides an inside view of day-to-day scientific research--its unpredictability, excitement, intellectual challenge, and serendipitous windfalls, as well as its frustrations, unexpected diversions away from original plans, and chronic uncertainty. Holmes uses research logs, experimental films, correspondence, and interviews with the participants to record the history of Meselson and Stahl's research, from their first thinking about the problem through the publication of their dramatic results. Holmes also reviews the scientific community's reception of the experiment, the experiment's influence on later investigations, and the reasons for its reputation as an exceptionally beautiful experiment.

Since the advent of the Human Genome Project, an increasing number of disease-causing genes have been discovered and, in some cases, genetic tests developed. However, this is only the first step. The second, much larger phase is the analysis of the total sequence. What does the rest of the DNA do? The answer to this question will be determined by computer prediction, expression profiling, and comparative genome analysis. Comparative Genomics covers such topics as identifying novel genes, determining gene function, control sequences, and developmental switches. The book aims to demonstrate how different approaches taken with model organisms, such as mutation studies, expression profiling of cDNAs, in situ localization of message and comparative genome analysis (both at the gene and nucleotide level) will aid in our understanding of the results coming out of the Human Genome Project and contribute significantly to our understanding of how genes function.

A Beginner's Guide to Microarrays addresses two audiences - the core facility manager who produces, hybridizes, and scans arrays, and the basic research scientist who will be performing the analysis and interpreting the results. User friendly coverage and detailed protocols are provided for the technical steps and procedures involved in many facets of microarray technology, including:

-Cleaning and coating glass slides,
-Designing oligonucleotide probes,
-Constructing arrays for the detection and quantification of different bacterial species,
-Preparing spotting solutions,
-Troubleshooting spotting problems,
-Setting up and running a core facility,
-Normalizing background signal and controlling for systematic variance,
-Designing experiments for maximum effect,
-Analyzing data with statistical procedures,
-Clustering data with machine-learning protocols.

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.

The fungus fusarium is a major plant pathogen that causes disease in nearly every agriculturally important plant. In addition, some strains produce mycotoxins that can cause serious illness in humans and livestock. The enormous economic importance of and health hazards posed by fusarium have fuelled research into its biochemistry, genetics, genomics, proteomics and metabolomics by scientists worldwide. In this book, an international group of researchers critically review the most important research on the genomics and molecular and cellular biology of fusarium.

An outstanding panel of hands-on experts and developers of CE equipment describe in step-by-step fashion their best cutting-edge methods for the detection and analysis of DNA mutations and modifications, ranging from precise DNA loci to entire genomes of organisms. This first volume of the set, Introduction to the Capillary Electrophoresis of Nucleic Acids, covers the practical and theoretical considerations behind the use of capillary electrophoresis for the analysis of small oligonucleotides and modified nucleotides. Along with detailed instructions ensuring ready reproducibility, these protocols offer time-tested advice on instrumentation, signal detection, the capillary environment, and the integration of mass spectrometry with CE. Several chapters are devoted to the analysis of small therapeutic oligonucleotides, nucleosides, and ribonucleotides by CE. The companion volume, Practical Applications of Capillary Electrophoresis, addresses techniques for high-throughput analysis of DNA fragments using SNP detection, mutation detection, DNA sequencing methods, and DNA-ligand interactions. Comprehensive and up-to-date, the paired volumes of Capillary Electrophoresis of Nucleic Acids offer an authoritative guide with easy access to fast, versatile, reliable, and powerful technologies for all those basic and clinical investigators analyzing DNA variation today.

Recent work has revealed that stabilizing G-quadruplexes in telomeric DNA inhibits telomerase activity, providing impetus for the development of G-quartet-interacting drugs, while G-quartet-containing oligonucleotides have been recognized as a potent class of aptamers effective against STAT3 and other transcription factors implicated in oncogenesis, proving these guanine-quartets to be a vital and rich area for future study. In "G-Quadruplex DNA: Methods and Protocols", experts in the field present a collection of detailed techniques for studying G-quartet formation, dynamics, and molecular recognition. 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 notes on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, "G-Quadruplex DNA: Methods and Protocols "promises to be a useful resource for those familiar with G-quartets as well as an easy entry point for those researchers from diverse fields who are just developing an interest in the exciting implications of G-quadruplex DNA.

The current explosive progress in molecular biological research can be definitively traced to the development of molecular cloning technology. The ability to insert specific gene sequences into cloning vectors and their subse quent expansion is the cornerstone of modem molecular biology. A direct practical outcome of molecular cloning technology is its application to ex press specific recombinant genes. Currently, recombinant gene products are used in a wide spectrum of applications, including gene therapy, production of bioactive pharmaceuticals, synthesis of novel biopolymers, in agriculture and animal husbandry, and so on. A fundamental requirement for successful recombinant gene expression is the design of the cloning vector and the choice of the host organism for expression. Recombinant Gene Expression Protocols grows out of the need for a laboratory manual that provides the reader the background and rationale, as well as the practical protocols for the preparation of "expression constructs" and their introduction into appropriate host cells and/or organisms. The chap ters in this book are grouped by their expression hosts, including E. coli, yeast, mammalian cells, nonmammalian eukaryotes such as plants, Xenopus, and insects, as well as in transgenic organisms. In-depth information is presented on the important characteristics of expression cloning vectors and the various methods for efficiently introducing expression constructs into target cells and/ or organisms. Throughout Recombinant Gene Expression Protocols, the authors have consistently striven for a balanced presentation of both background informa tion and actual laboratory details.

Transposable elements are short lengths of DNA with the capacity to move between different points within a genome. This process can affect the function of genes at or near the insertion site. The present book gives an overview of the impact of transposable elements on plant genomes and explains how to recognize and study transposable elements, e.g. by using state-of-the-art strategies like "new generation sequencing." Moreover, the impact of transposable elements on plant genome structure and function is reviewed in detail, and also illustrated in examples and case studies. The book is intended both for readers familiar with the field and for newcomers. With large-scale sequencing becoming increasingly available, more and more people will come across transposable element sequences in their data, and this volume will hopefully help to convince them that they are not just "junk DNA."

Since newly created beings are often perceived as either wholly good or bad, the genetic alteration of living cells impacts directly on a symbolic meaning deeply imbedded in every culture. During the earlier years of gene expression research, te- nological applications were confined mainly to academic and industrial laboratories, and were perceived as highly beneficial since molecules that were previously unable to be separated or synthesized became accessible as therapeutic agents. Such were the success stories of hormones, antibodies, and vaccines produced in the bacterium Escherichia coli. Originally this bacterium gained fame among humans for being an unwanted host in the intestine, or worse yet, for being occasionally dangerous and pathogenic. H- ever, it was easily identified in contaminated waters during the 19th century, thus becoming a clear indicator of water pollution by human feces. Tamed, cultivated, and easily maintained in laboratories, its fast growth rate and metabolic capacity to adjust to changing environments fascinated the minds of scientists who studied and modeled such complex phenomena as growth, evolution, genetic exchange, infection, survival, adaptation, and further on-gene expression. Although at the lower end of the complexity scale, this microbe became a very successful model system and a key player in the fantastic revolution kindled by the birth of recombinant DNA technology.

With the predicted increase of the human population and the subsequent need for larger food supplies, root health in crop plants could play a major role in providing sustainable highly productive crops that can cope with global climate changes. While the essentiality of roots and their relation to plant performance is broadly recognized, less is known about their role in plant growth and development. Root Genomics examines how various new genomic technologies are rapidly being applied to the study of roots, including high-throughput sequencing and genotyping, TILLING, transcription factor analysis, comparative genomics, gene discovery and transcriptional profiling, post-transcriptional events regulating microRNAs, proteome profiling and the use of molecular markers such as SSRs, DArTs, and SNPs for QTL analyses and the identification of superior genes/alleles. The book also covers topics such as the molecular breeding of crops in problematic soils and the responses of roots to a variety of stresses.

The development of PCR, which enables extremely small amounts of DNA to be amplified, led to the rapid development of a multiplicity of a- lytical procedures to utilize this new resource for analysis of genetic variation and for the detection of disease causing mutations. The advent of capillary electrophoresis (CE), with its power to separate and analyze very small amounts of DNA, has also stimulated researchers to develop analytical procedures for the CE format. The advantages of CE in terms of speed and reproducibility of analysis are manifold. Further, the high sensitivity of detection, and the ab- ity to increase sample throughput with parallel analysis, has led to the creation of a full range of analysis of DNA molecules, from modified DNA-adducts and single-strand oligonucleotides through to PCR-amplified DNA fragments and whole chromosomes. Capillary Electrophoresis of Nucleic Acids focuses on such analytical protocols, which can be used for detection and analysis of mutations and modification, from precise DNA loci through to entire genomes of organisms. Important practical considerations for CE, such as the choice of separation media, electrophoresis conditions, and the influence of buffer additives and dyes on DNA mobility, are discussed in several key chapters and within particular applications.

This book contains a broad survey on the peroxiredoxins. It involves almost all groups that contributed significant insights into the emerging field. Coverage discusses the diverse biological roles of the new protein family in the context of other antioxidant systems like those based on heme or selenium catalysis. In addition, the book highlights related future perspectives.