"Your genome is an email attachment" What a difference a few years can make? In 2001, to a global fanfare, the completion of the frst draft sequence of the human genome was announced. This had been a Herculean effort, involving thousands of researchers and millions of dollars. Today, a project to re-sequence 1,000 genomes is well underway, and within a year or two, your own "personal genome" is likely to be available for a few thousand pounds, a price that will undoubtedly decrease further. We are fast approaching the day when your genome will be available as an email attachment (about 4 Mb). The key to this feat is the fact that any two human genomes are more than 99% identical, so rather than representing every base, there is really only a requirement to store the 1% of variable sequence judged against a common reference genome. This brings us directly to the focus of this edition of Methods in Molecular Biology, Genetic Variation. The human genome was once the focus of biology, but now individual genome var- tion is taking the center stage. This new focus on individual variation ultimately democ- tizes biology, offering individuals insight into their own phenotype. But these advances also raise huge concerns of data misuse, misinterpretation, and misunderstanding. The immediacy of individual genomes also serves to highlight our relative ignorance of human genetic variation, underlining the need for more studies of the nature and impact of genetic variation on human phenotypes.

MicroRNA Protocols provides diverse, novel, and useful descriptions of miRNAs in several species, including plants, worms, flies, fish, chicks, mice, and humans. These include some useful adaptations and applications that could be relevant to the wider research community who are already familiar with the identification of miRNAs. This volume will stimulate the reader to explore diverse ways to understanding the mechanism in which miRNAs facilitate the molecular aspects of the biomedical research.

Eukaryotic DNA Damage Surveillance and Repair contains chapters from experts in the field of DNA damage detection, repair, and cell cycle control. The work reviews current understanding of how different types of DNA damage are detected and focuses on how these surveillance mechanisms are coupled to processes of DNA repair, cell cycle control, and apoptosis.
The title will be of interest to undergraduate/postgraduate students and academics alike.

This volume summarizes recent advances in research on mesenchymal cell populations in the bone marrow. It explores how mesenchymal cells create niches for immune cells in extramedullary organs and it discusses new concepts of lympho-hematopoietic microenvironments. Readers are introduced to the fundamentals of hematopoietic stem cells (HSCs) differentiation to all types of blood cells, including immune cells, in the bone marrow. The book highlights how this process is supported and regulated by the individual microenvironments of stem cells, termed niches. The identity of HSC niches has been subject to longstanding debates. Recent studies identified the population of mesenchymal stem cells as the major cellular component of niches, for hematopoietic stem and progenitor cells (HSPCs) and their candidate developmental origin. Furthermore, candidate cellular niches for immune cells in lymph nodes and adipose and connective tissues were identified. The authors of this volume focus on shared features between those and HSPC niche cells in the bone marrow. Covering latest research results, this book serves as fascinating read for researchers and clinicians in hematology and immunology.

RNA interference (RNAi), in which RNA silences RNA, is the most recent discovery to revolutionize the study of biology. In RNAi: Design and Applications, leaders in the field contribute state-of-the-art, easy to follow methods and bench protocols designed for practical, everyday use of RNAi in biological research. Divided into two parts, this comprehensive volume covers fundamentals including designs of RNAi, biochemical assay protocols for the major components of RNAi, and study of potential off-target effects, followed by an extensive section covering various applications of RNAi in diverse model organisms and systems, from antiviral and anticancer applications to altering flower color in plants. Cutting edge and clearly written, RNAi: Design and Applications enables a researcher with standard molecular biological training to perform major RNAi-related experiments and contribute to this revolutionary, growing field.

Haldane, Mayr, and Beanbag Genetics presents a summary of the classic exchange between two great biologists - J.B.S. Haldane and Ernst Mayr - regarding the value of the contributions of the mathematical school represented by J.B.S. Haldane, R.A. Fisher and S. Wright to the theory of evolution. Their pioneering contributions from 1918 to the 1960s dominated and shaped the field of population genetics, unique in the annals of science. In 1959, Mayr questioned what he regarded as the beanbag genetic approach of these pioneers to evolutionary theory, "an input or output of genes, as the adding of certain beans to a beanbag and the withdrawing of others." In 1964, Mayr's contention was refuted by Haldane in a remarkably witty, vigorous and pungent essay, "A defense of beanbag genetics" which compared the mathematical theory to a scaffolding within which a reasonably secure theory expressible in words may be built up. Correspondence between Haldane and Mayr is included.
Beanbag genetics has come a long way since 1964. Mayr's (1959) critique of simple uncomplicated population genetics is no longer valid. Population genetics today includes much more than Mayr's beanbag genetics. Population genetics models now include multiple factors, linkage, dominance and epistasis. These may be regarded as the advanced beanbag models. Furthermore, population genetics and developmental genetics have become interdependent. Contemporary beanbag genetics includes molecular clocks, nucleotide diversity, coalescence and DNA-based phylogenetic trees, along with the four major holdovers from classical genetics, mutation, selection, migration and random drift. Molecular genetics has made it possible to study evolution rates at the nucleotide level. It is also possible today to compare DNA similarities and divergence in diverse species of animals and plants, which were not previously crossable.

Advances in computers and biotechnology have had a profound impact on biomedical research, and as a result complex data sets can now be generated to address extremely complex biological questions. Correspondingly, advances in the statistical methods necessary to analyze such data are following closely behind the advances in data generation methods. The statistical methods required by bioinformatics present many new and difficult problems for the research community.

This book provides an introduction to some of these new methods. The main biological topics treated include sequence analysis, BLAST, microarray analysis, gene finding, and the analysis of evolutionary processes. The main statistical techniques covered include hypothesis testing and estimation, Poisson processes, Markov models and Hidden Markov models, and multiple testing methods.

The second edition features new chapters on microarray analysis and on statistical inference, including a discussion of ANOVA, and discussions of the statistical theory of motifs and methods based on the hypergeometric distribution. Much material has been clarified and reorganized.

The book is written so as to appeal to biologists and computer scientists who wish to know more about the statistical methods of the field, as well as to trained statisticians who wish to become involved with bioinformatics. The earlier chapters introduce the concepts of probability and statistics at an elementary level, but with an emphasis on material relevant to later chapters and often not covered in standard introductory texts. Later chapters should be immediately accessible to the trained statistician. Sufficient mathematical background consistsof introductory courses in calculus and linear algebra. The basic biological concepts that are used are explained, or can be understood from the context, and standard mathematical concepts are summarized in an Appendix. Problems are provided at the end of each chapter allowing the reader to develop aspects of the theory outlined in the main text.

Warren J. Ewens holds the Christopher H. Brown Distinguished Professorship at the University of Pennsylvania. He is the author of two books, Population Genetics and Mathematical Population Genetics. He is a senior editor of Annals of Human Genetics and has served on the editorial boards of Theoretical Population Biology, GENETICS, Proceedings of the Royal Society B and SIAM Journal in Mathematical Biology. He is a fellow of the Royal Society and the Australian Academy of Science.

Gregory R. Grant is a senior bioinformatics researcher in the University of Pennsylvania Computational Biology and Informatics Laboratory. He obtained his Ph.D. in number theory from the University of Maryland in 1995 and his Masters in Computer Science from the University of Pennsylvania in 1999.

Comments on the First Edition. "This book would be an ideal text for a postgraduate coursea ][and] is equally well suited to individual studya ]. I would recommend the book highly" (Biometrics). "Ewens and Grant have given us a very welcome introduction to what is behind those pretty [graphical user] interfaces" (Naturwissenschaften.). "The authors do an excellent job of presenting the essence of the material without getting bogged down in mathematical details" (Journal. American Staistical. Association). "The authors have restructured classical materialto a great extent and the new organization of the different topics is one of the outstanding services of the book" (Metrika).

That molecular neurobiology has become a dominant part of neuroscience research can be credited to the discovery of inducible gene expression in the brain and spinal cord. This volume deals with genes, whose expression patterns in the vertebrate central nervous system were the first to be revealed and then the most extensively investigated over the last 15 years. Immediate early genes (IEG) and their protein products, especially those acting as regulators of transcription (inducible transcription factors, ITF) have proven to be very valuable tools in functional neuroanatomy and neurophysiology, as they are rapidly and transiently induced in specific neurons in response to various modes of stimulation. Thus, they have been used to map neuronal populations selectively responsive to a variety of conditions, such as sensory and learning experience, electrical stimulation of specific circuits, seizures, and neurodegeneration.

This single volume, written by the most prominent authors in the field, brings together for the first time information about the most widely studied IEG/ITF in a whole variety of phenomena of neuronal activation. It starts with a critical appraisal of the technologies employed for the studies on gene, protein, and transcription factor activity in the nervous system. Several chapters present exhaustive examples of expression patterns of the ITF in "vocal" avian brain, mammalian brain sensory regions, areas involved in regulation of circadian rhythms, and the spinal cord. The next parts cover functional and regular aspects of individual IEG/ITF expression: c-fos in learning and memory, c-jun and others in neuropathology and neuronal stress responses, Elk-1, egr family, and CREB in neuronal plasticity and learning.

This volume will be useful as a major reference on this topic. Furthermore, it attempts to unravel the seemingly overwhelming complexity of the phenomena of gene expression in the central nervous system.

After genomic sequencing, microarray technology has emerged as a widely used platform for genomic studies in the life sciences. Microarray technology provides a systematic way to survey DNA and RNA variation. With the abundance of data produced from microarray studies, however, the ultimate impact of the studies on biology will depend heavily on data mining and statistical analysis. The contribution of this book is to provide readers with an integrated presentation of various topics on analyzing microarray data.

This book facilitates the introduction of SAGE into the laboratory and provides a framework for interpreting and comparing data derived from SAGE experiments. SAGE studies encompass 50,000 tags and can provide detailed knowledge of the 2000 most highly expressed genes in the tissue sample. The SAGE protocols presented are detailed, fully annotated, and tested, and are all written by experienced SAGE researchers from around the world.

Carbon Dots in Agricultural Systems integrates and crystallizes the emerging knowledge and application strategies of carbon dots as a powerful tool in agriculture systems. The book includes practical insights into the synthesis of carbon dots from indigenous raw materials and how to employ them in agriculture systems to increase crop productivity and provide renewable and cost-effective strategies that meet agricultural needs. Presented by an international team of experts, this resource updates on the latest in synthesis, physical, chemical and optical properties, along with the effects and mechanisms of carbon dots, all further explained in real-world studies. Finally, the book highlights emerging innovative topics which are of great relevance to scientists, academicians and innovators in agriculture (soil science, agricultural chemistry and agronomy) and biotechnology for further research and development.

Fluorescent nucleic acid probes, which use energy transfer, include such constructs as molecular beacons, molecular break lights, Scorpion primers, TaqMan probes, and others. These probes signal detection of their targets by changing either the intensity or the color of their fluorescence. Not surpr- ingly, these luminous, multicolored probes carry more flashy names than their counterparts in the other fields of molecular biology. In recent years, fluor- cent probes and assays, which make use of energy transfer, have multiplied at a high rate and have found numerous applications. However, in spite of this explosive growth in the field, there are no manuals summarizing different p- tocols and fluorescent probe designs. In view of this, the main objective of Fluorescent Energy Transfer Nucleic Acid Probes: Designs and Protocols is to provide such a collection. Oligonucleotides with one or several chromophore tags can form fluor- cent probes capable of energy transfer. Energy transport within the probe can occur via the resonance energy transfer mechanism, also called Foerster tra- fer, or by non-Foerster transfer mechanisms. Although the probes using Foerster transfer were developed and used first, the later non-Foerster-based probes, such as molecular beacons, now represent an attractive and widely used option. The term "fluorescent energy transfer probes" in the title of this book covers both Foerster-based fluorescence resonance energy transfer (FRET) probes and probes using non-FRET mechanisms. Energy transfer probes serve as molecule-size sensors, changing their fluorescence upon detection of various DNA reactions.

Insect pests remain one of the main constraints to food and fiber production worldwide despite farmers deploying a range of techniques to protect their crops. Modern pest control is guided by the principles of integrated pest management (IPM) with pest resistant germplasm being an important part of the foundation. Since 1996, when the first genetically modified (GM) insect-resistant maize variety was commercialized in the USA, the area planted to insect-resistant GM varieties has grown dramatically, representing the fastest adoption rate of any agricultural technology in human history. The goal of our book is to provide an overview on the role insect-resistant GM plants play in different crop systems worldwide. We hope that the book will contribute to a more rational debate about the role GM crops can play in IPM for food and fiber production.

The book covers various biotechnological research efforts and their applications in fisheries and aquaculture, especially in the area of fish breeding, health management, nutrition and culture. Application of the recent biotechnological tools, like Transcriptomics, Transgenesis, Nanotechnology, Metabolomics, RNAi and CRISPRi Technologies in the field of fisheries research are included in the book. Topics like conservation genetics for management of fishery resources are also covered in the book. It aims at addressing the growing need of the biotechnology in advancing the cause of aquaculture with a view to provide food and nutritional security to the world. This book will be of immense use to teachers, researchers, academicians, development officials and policymakers, involved in R&D of fisheries and aquaculture sectors. Also, the book serves as an additional reading material for undergraduate and graduate students of fisheries, marine sciences, ecology, aquaculture, and environmental sciences. The research in aquaculture biotechnology is likely to have significant impact on aquaculture and fisheries by way of supporting nutritional food security to the growing population.

Advances in Genetics increases its focus on modern human genetics and its relation to medicine with the merger of this long-standing serial with Molecular Genetic Medicine. This merger affirms the Academic Press commitment to publish important reviews of the broadest interest to geneticists and their colleagues in affiliated disciplines.
Genetics, the science of heredity, lies at the heart of biology, and many diseases are impacted by an individuals genetic make-up. The field of genetics is rapidly evolving and new medical break-throughs are occurring as a result of advances in knowledge of genetics. Advances in Genetics continually publishes important reviews of the broadest interest to geneticists and their colleagues in affiliated disciplines. This volume of Advances in Genetics contains the following articles: Targeted Expression of Tetanus Toxin; Germ-line Transformants Spreading Out to Many Insect Species; Genes Mediating Sex-Specific Behaviors in "Drosophila"; and Evolutionary Analyses of Genes and Their Functional Implications.

Fungal comparative genomics started in 2000 by the genome sequencing of several yeast species. Since then, over 30 fungal genome sequences have become available. This set represents a huge evolutionary divergence, but also contains closely related genomes. This volume describes how to use this set of genomes to trace events in genome evolution, to extract information about highly conserved and less conserved sequence elements, and to develop novel methods in genomics.

"Homology Effects" offers contributions from an international panel of researchers whose aim has been both to introduce newcomers to the field of homology effects, and to bring colleagues up to date. Topic coverage includes dosage compensation, X-inactivation, imprinting, paramutation, homology-dependent gene silencing, transvection, pairing-sensitive silencing, nuclear organization of chromosomes, DNA repair, quelling, RIP, RNAi and antisense biology, homology effects in ciliates, prion biology, and a discourse on the evolution of gene duplications.
Advances in Genetics presents an eclectic mix of articles of use to all human and molecular geneticists. They are written and edited by recognized leaders in the field and make this an essential series of books for anyone in the genetics field.
Homology, the examination of similarity due to shared common ancestry, encompasses a fascinating class of phenomena in mammals, plants, insects, ciliates, nematodes, fungi, and bacteria. Homology effects concern processes that recognize homology at the level of DNA and/or RNA, as well as at the level of protein. Their collective history begins at the turn of the century and includes some of the most puzzling and extraordinary observations in biology. The volume covers phenomena that have often been considered unusual, exceptional to the rule, and "out of the ordinary" and, therefore, not for general study. However, it is now becoming clear that taken together, these phenomena represent a class of regulatory mechanisms that are widespread, as well as exceptionally powerful.

Chromosomes Today, Volume 13 includes the plenary lectures presented at the 13th International Chromosome Conference, covering the most recent advances in the studies on chromosomes. The contributions in this volume were presented by some of the world's leaders in cytogenetic and molecular research and outline the present status of knowledge on the composition, structure, function and evolution of chromosomes, including, among others, the advancement of the human genome project. The use of cytogenetic studies has greatly increased in the last few years, resulting in a progressive improvement in the available methods that has consequently allowed a more detailed analysis of the molecular organization of eukaryotic chromosomes and a precise in situ localisation of specific gene sequences. This volume of Chromosomes Today provides up-to-date information regarding the topics at the forefront of chromosome research: genetic regulation, imprinting, DNA duplication, meiotic pairing, and the regulation of the...

During the past decade, geneticists have cloned scores of Mendelian disease genes and constructed a rough draft of the entire human genome. The unprecedented insights into human disease and evolution offered by mapping, cloning, and sequencing will transform medicine and agriculture. This revolution depends vitally on the contributions of applied mathematicians, statisticians, and computer scientists. Mathematical and Statistical Methods for Genetic Analysis is written to equip students in the mathematical sciences to understand and model the epidemiological and experimental data encountered in genetics research. Mathematical, statistical, and computational principles relevant to this task are developed hand in hand with applications to population genetics, gene mapping, risk prediction, testing of epidemiological hypotheses, molecular evolution, and DNA sequence analysis. Many specialized topics are covered that are currently accessible only in journal articles. This second edition expands the original edition by over 100 pages and includes new material on DNA sequence analysis, diffusion processes, binding domain identification, Bayesian estimation of haplotype frequencies, case-control association studies, the gamete competition model, QTL mapping and factor analysis, the Lander-Green-Kruglyak algorithm of pedigree analysis, and codon and rate variation models in molecular phylogeny. Sprinkled throughout the chapters are many new problems. Kenneth Lange is Professor of Biomathematics and Human Genetics at the UCLA School of Medicine. At various times during his career, he has held appointments at the University of New Hampshire, MIT, Harvard, and the University of Michigan. While at the University of Michigan, he was the Pharmacia & Upjohn Foundation Professor of Biostatistics. His research interests include human genetics, population modeling, biomedical imaging, computational statistics, and applied stochastic processes. Springer-Verlag published his book Numerical Analysis for Statisticians in 1999.

This book is intended to not only provide a broad perspective of recent progress in the field, but also to draw attention to some of the major questions that are currently under investigation, and also what we can anticipate learning from continued developments in the next several years of research. An important goal in splicing research is to understand the role of nuclear organization in the control of alternative splicing. The nucleus is divided into several subnuclear compartments and splicing occurs in only a subset of these locations. Moreover, nuclear organization can change in response to the activity of factors that are required to transcribe and splice a particular pre-mRNAs. Alternative Splicing in the Postgenomic Era serves as a valuable resource for both experts and non-experts alike. Research in the burgeoning field of alternative splicing in the postgenomic era is poised to uncover new and important aspects of gene regulation, as well as functions of the proteome.

As the emerging field of proteomics continues to expand at an extremely rapid rate, the relative quantification of proteins, targeted by their function, becomes its greatest challenge. Complex analytical strategies have been designed that allow comparative analysis of large proteomes, as well as in depth detection of the core proteome or the interaction network of a given protein of interest. In Functional Proteomics: Methods and Protocols, expert researchers describe the latest protocols being developed to address the problems encountered in high-throughput proteomics projects, with emphasis on the factors governing the technical choices for given applications. The case studies within the volume focus on the following three crucial aspects of the experimental design: 1) the strategy used for the selection, purification and preparation of the sample to be analyzed by mass spectrometry, 2) the type of mass spectrometer used and the type of data to be obtained from it, and 3) the method used for the interpretation of the mass spectrometry data and the search engine used for the identification of the proteins in the different types of sequence data banks available. As a part of the highly successful Methods in Molecular Biology (TM) series, the chapters compile step-by-step, readily reproducible laboratory protocols, lists of the necessary materials and reagents, and tips on troubleshooting and avoiding known pitfalls. Comprehensive and cutting-edge, Functional Proteomics: Methods and Protocols is an ideal resource for all scientists pursuing this developing field and its multitudinous data.

Eminent scientists have contributed comprehensive reviews on all aspects of the genomics of Rhodococcus, Mycobacteria, Streptomyces and other organisms. The authors provide an insight into the many facets of large scale functional investigation in a variety of bacteria with the explicit goal to find common rules in the dynamic and structural organization of these organisms. This volume is the definitive guide to current research in this increasingly important area and is essential reading for all microbiologists, biotechnologists, and genome scientists.

This volume contains state-of-the-art methods tackling all aspects of small non-coding RNAs biology. Small Non-Coding RNAs: Methods and Protocols guides readers through customized dedicated protocols and technologies that will be of valuable help to all those willing to contribute deciphering the numerous functions of small non-coding RNAs. 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 troubles troubleshooting and avoiding known pitfalls. Instructive and practical, Small Non-Coding RNAs: Methods and Protocols reaches out to biochemists, cellular and molecular biologists already working in the field of RNA biology and to those just starting to study small non-coding RNAs.

Heterogeneity, or mixtures, are ubiquitous in genetics. Even for data as simple as mono-genic diseases, populations are a mixture of affected and unaffected individuals. Still, most statistical genetic association analyses, designed to map genes for diseases and other genetic traits, ignore this phenomenon. In this book, we document methods that incorporate heterogeneity into the design and analysis of genetic and genomic association data. Among the key qualities of our developed statistics is that they include mixture parameters as part of the statistic, a unique component for tests of association. A critical feature of this work is the inclusion of at least one heterogeneity parameter when performing statistical power and sample size calculations for tests of genetic association. We anticipate that this book will be useful to researchers who want to estimate heterogeneity in their data, develop or apply genetic association statistics where heterogeneity exists, and accurately evaluate statistical power and sample size for genetic association through the application of robust experimental design.