Cellular And Animal Models In Human Genomics Research

Cellular and Animal Models in Human Genomics Research provides an indispensable resource for applying comparative genomics in the annotation of disease-gene associated variants that are identified by human genomic sequencing. The book presents a thorough overview of effective protocols for the use of cellular and animal modeling methods to turn lists of plausible genes into causative biomarkers. With chapters written by international experts, the book first addresses the fundamental aspects of using cellular and animal models in genetic and genomic studies, including in-depth examples of specific models and their utility, i.e., yeast, worms, flies, fish, mice and large animals. Protocols for properly conducting model studies, genomic technology, modeling candidate genes vs. genetic variants, integrative modeling, utilizing induced pluripotent stem cells, and employing CRISPR-Cas9 are also discussed in-depth. Provides a thorough, accessible resource that helps researchers and students employ cellular and animal models in their own genetic and genomic studies Offers guidance on how to effectively interpret the results and significance of genetic and genomic model studies for human health Features chapters from international experts in the use of specific cellular and animal models, including yeast, worms, flies, fish, mice, and large animals, among other organisms

Animal Models for the Study of Human Disease, Second Edition, provides needed information on model sharing, animal alternatives, animal ethics and access to databanks of models, bringing together common descriptions of models for busy researchers across biomedical and biological sciences. Offering easily searchable advantages and disadvantages for each animal model and organized by disease topics, this resource aids researchers in finding the best animal model for research in human disease. Organized by disease orientation for ease of searchability Provides information on locating resources, animal alternatives, and animal ethics Covers a broad range of animal models used in research for human disease Contributed by leading experts across the globe Expanded coverage of diabetes and neurological diseases

To create and establish mutant mice as models for human diseases and traits, various forward and reverse genetics tools are currently available. Newly developed tools of high-throughput identification of novel mutations and site-directed mutagenesis, or gene targeting, in the mouse genome have caused forward and reverse genetics, respectively, to rapidly expand during the last two decades. Worldwide efforts including a variety of international consortiums have been producing many useful mutant mouse strains for functional genomics to elucidate the mechanisms behind diseases and traits. Resource centers and public databases have also been built to enhance their utilities. The modeling has started from Mendelian monogenic traits and has expanded to more complex quantitative traits as well. Multidisciplinary integration among, for example, molecular, cellular, and developmental biology; genetics; genomics; medicine; statistics; and informatics must be orchestrated to fully utilize the resources and knowledge of model mice.

Scientific Frontiers in Developmental Toxicology and Risk Assessment reviews advances made during the last 10-15 years in fields such as developmental biology, molecular biology, and genetics. It describes a novel approach for how these advances might be used in combination with existing methodologies to further the understanding of mechanisms of developmental toxicity, to improve the assessment of chemicals for their ability to cause developmental toxicity, and to improve risk assessment for developmental defects. For example, based on the recent advances, even the smallest, simplest laboratory animals such as the fruit fly, roundworm, and zebrafish might be able to serve as developmental toxicological models for human biological systems. Use of such organisms might allow for rapid and inexpensive testing of large numbers of chemicals for their potential to cause developmental toxicity; presently, there are little or no developmental toxicity data available for the majority of natural and manufactured chemicals in use. This new approach to developmental toxicology and risk assessment will require simultaneous research on several fronts by experts from multiple scientific disciplines, including developmental toxicologists, developmental biologists, geneticists, epidemiologists, and biostatisticians.

Genome-wide association (GWA) studies and tumor-specific epigenome, transcriptome and genome sequencing projects are generating an ever-growing list of susceptibility alleles, as well as putative gain- and loss-of-function gene mutations associated with cancer. These genetic changes ultimately need to be validated to determine their contribution to the initiation, progression and likelihood of treatment response for various cancers. The bottle-neck is no longer obtaining sequence data or completion of the GWA studies, but rather the ability efficiently to validate candidate genes identified by these projects. In vivo studies in animal models are the “gold standard” for validation of these candidate drivers and modifiers of cancer. Furthermore, once a gene product or molecular pathway has been validated as playing an important role in the development or progression of cancer, animal models provide the necessary preclinical data for evaluation of the efficacy and toxicity of new therapeutics targeting that gene or pathway. As such, animal models play an essential role in cancer research by facilitating the translation of genomic discoveries into preclinical studies that precede new targeted therapies for cancer. In this chapter, we will discuss vertebrate and invertebrate animal models as they apply to cancer genomics, as well as key technologies employed. In particular, we will focus on the use of murine and zebrafish human tumor xenografts and transgenic models.

Animal experiments have contributed much to our understanding of mechanisms of disease and are important for determining new therapies. Animal Models of Human Disease reviews the latest research and developments in this field. Discusses new discoveries, approaches, and ideas Contributions from leading scholars and industry experts Reference guide for researchers involved in molecular biology and related fields

Genomics research on animals has generated huge databases and several new concepts and strategies, which are used to elucidate origin, evolution and phylogeny of species. Genetic and physical maps of genomes give details on chromosomal location, function, expression and regulation of genes. The series Genome Mapping and Genomics in Animals provides comprehensive and up-to-date reviews on genomic research on selected animal systems contributed by leading scientists from around the world. This volume offers information on gene mapping and genomics research in domesticated and farmed animals including cattle, water buffalo, sheep, deer, poultry, turkeys, rabbits, dogs and pigs. While the genome maps for some species are very limited, full genome sequences are available for cattle, chickens and dogs. Genomic research contributes to the identification of genetic regions that control the functionality and well-being of animals. Several farmed species are also used as models for biomedical studies.

Genetically modified animals were created about 30 years ago, and are considered good models of human diseases. In this chapter, the types of genetically engineered mice, such as transgenic, knockout conditional knockout, and knockin animals, and the general techniques on how to obtain them are described. In addition, the available genetically modified models for genetic diseases, multifactorial and polygenic (complex) disorders, neurodegenerative, inflammatory diseases, besides cancer models, are presented. The aim of the chapter is to help investigators to find out the best models for their studies.