Genome-Wide Association Studies and Genomic Prediction


Book Description

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.




Genetic Dissection of Complex Traits


Book Description

The field of genetics is rapidly evolving and new medical breakthroughs are occuring as a result of advances in knowledge of genetics. This series continually publishes important reviews of the broadest interest to geneticists and their colleagues in affiliated disciplines. Five sections on the latest advances in complex traits Methods for testing with ethical, legal, and social implications Hot topics include discussions on systems biology approach to drug discovery; using comparative genomics for detecting human disease genes; computationally intensive challenges, and more




Genome-Wide Association Studies


Book Description

This book examines the utility of genome-wide association studies (GWAS) in the era of next-generation sequencing and big data, identifies limitations and potential means of overcoming them, and looks to the future of GWAS and what may lay beyond. GWAS are among the most powerful tools for elucidating the genetic aspects of human and disease diversity. In Genome-Wide Association Studies, experts in the field explore in depth the impacts of GWAS on genomic research into a variety of common diseases, including cardiovascular, autoimmune, diabetic, cancer, and infectious diseases. The book will equip readers with a sound understanding both of the types of disease and phenotypes that are suited for GWAS and of the ways in which a road map resulting from GWAS can lead to the realization of personalized/precision medicine: functional analysis, drug seeds, pathway analysis, disease mechanism, risk prediction, and diagnosis.




Design, Analysis, and Interpretation of Genome-Wide Association Scans


Book Description

This book presents the statistical aspects of designing, analyzing and interpreting the results of genome-wide association scans (GWAS studies) for genetic causes of disease using unrelated subjects. Particular detail is given to the practical aspects of employing the bioinformatics and data handling methods necessary to prepare data for statistical analysis. The goal in writing this book is to give statisticians, epidemiologists, and students in these fields the tools to design a powerful genome-wide study based on current technology. The other part of this is showing readers how to conduct analysis of the created study. Design and Analysis of Genome-Wide Association Studies provides a compendium of well-established statistical methods based upon single SNP associations. It also provides an introduction to more advanced statistical methods and issues. Knowing that technology, for instance large scale SNP arrays, is quickly changing, this text has significant lessons for future use with sequencing data. Emphasis on statistical concepts that apply to the problem of finding disease associations irrespective of the technology ensures its future applications. The author includes current bioinformatics tools while outlining the tools that will be required for use with extensive databases from future large scale sequencing projects. The author includes current bioinformatics tools while outlining additional issues and needs arising from the extensive databases from future large scale sequencing projects.




Quantitative Genetics in Maize Breeding


Book Description

Maize is used in an endless list of products that are directly or indirectly related to human nutrition and food security. Maize is grown in producer farms, farmers depend on genetically improved cultivars, and maize breeders develop improved maize cultivars for farmers. Nikolai I. Vavilov defined plant breeding as plant evolution directed by man. Among crops, maize is one of the most successful examples for breeder-directed evolution. Maize is a cross-pollinated species with unique and separate male and female organs allowing techniques from both self and cross-pollinated crops to be utilized. As a consequence, a diverse set of breeding methods can be utilized for the development of various maize cultivar types for all economic conditions (e.g., improved populations, inbred lines, and their hybrids for different types of markets). Maize breeding is the science of maize cultivar development. Public investment in maize breeding from 1865 to 1996 was $3 billion (Crosbie et al., 2004) and the return on investment was $260 billion as a consequence of applied maize breeding, even without full understanding of the genetic basis of heterosis. The principles of quantitative genetics have been successfully applied by maize breeders worldwide to adapt and improve germplasm sources of cultivars for very simple traits (e.g. maize flowering) and very complex ones (e.g., grain yield). For instance, genomic efforts have isolated early-maturing genes and QTL for potential MAS but very simple and low cost phenotypic efforts have caused significant and fast genetic progress across genotypes moving elite tropical and late temperate maize northward with minimal investment. Quantitative genetics has allowed the integration of pre-breeding with cultivar development by characterizing populations genetically, adapting them to places never thought of (e.g., tropical to short-seasons), improving them by all sorts of intra- and inter-population recurrent selection methods, extracting lines with more probability of success, and exploiting inbreeding and heterosis. Quantitative genetics in maize breeding has improved the odds of developing outstanding maize cultivars from genetically broad based improved populations such as B73. The inbred-hybrid concept in maize was a public sector invention 100 years ago and it is still considered one of the greatest achievements in plant breeding. Maize hybrids grown by farmers today are still produced following this methodology and there is still no limit to genetic improvement when most genes are targeted in the breeding process. Heterotic effects are unique for each hybrid and exotic genetic materials (e.g., tropical, early maturing) carry useful alleles for complex traits not present in the B73 genome just sequenced while increasing the genetic diversity of U.S. hybrids. Breeding programs based on classical quantitative genetics and selection methods will be the basis for proving theoretical approaches on breeding plans based on molecular markers. Mating designs still offer large sample sizes when compared to QTL approaches and there is still a need to successful integration of these methods. There is a need to increase the genetic diversity of maize hybrids available in the market (e.g., there is a need to increase the number of early maturing testers in the northern U.S.). Public programs can still develop new and genetically diverse products not available in industry. However, public U.S. maize breeding programs have either been discontinued or are eroding because of decreasing state and federal funding toward basic science. Future significant genetic gains in maize are dependent on the incorporation of useful and unique genetic diversity not available in industry (e.g., NDSU EarlyGEM lines). The integration of pre-breeding methods with cultivar development should enhance future breeding efforts to maintain active public breeding programs not only adapting and improving genetically broad-based germplasm but also developing unique products and training the next generation of maize breeders producing research dissertations directly linked to breeding programs. This is especially important in areas where commercial hybrids are not locally bred. More than ever public and private institutions are encouraged to cooperate in order to share breeding rights, research goals, winter nurseries, managed stress environments, and latest technology for the benefit of producing the best possible hybrids for farmers with the least cost. We have the opportunity to link both classical and modern technology for the benefit of breeding in close cooperation with industry without the need for investing in academic labs and time (e.g., industry labs take a week vs months/years in academic labs for the same work). This volume, as part of the Handbook of Plant Breeding series, aims to increase awareness of the relative value and impact of maize breeding for food, feed, and fuel security. Without breeding programs continuously developing improved germplasm, no technology can develop improved cultivars. Quantitative Genetics in Maize Breeding presents principles and data that can be applied to maximize genetic improvement of germplasm and develop superior genotypes in different crops. The topics included should be of interest of graduate students and breeders conducting research not only on breeding and selection methods but also developing pure lines and hybrid cultivars in crop species. This volume is a unique and permanent contribution to breeders, geneticists, students, policy makers, and land-grant institutions still promoting quality research in applied plant breeding as opposed to promoting grant monies and indirect costs at any short-term cost. The book is dedicated to those who envision the development of the next generation of cultivars with less need of water and inputs, with better nutrition; and with higher percentages of exotic germplasm as well as those that pursue independent research goals before searching for funding. Scientists are encouraged to use all possible breeding methodologies available (e.g., transgenics, classical breeding, MAS, and all possible combinations could be used with specific sound long and short-term goals on mind) once germplasm is chosen making wise decisions with proven and scientifically sound technologies for assisting current breeding efforts depending on the particular trait under selection. Arnel R. Hallauer is C. F. Curtiss Distinguished Professor in Agriculture (Emeritus) at Iowa State University (ISU). Dr. Hallauer has led maize-breeding research for mid-season maturity at ISU since 1958. His work has had a worldwide impact on plant-breeding programs, industry, and students and was named a member of the National Academy of Sciences. Hallauer is a native of Kansas, USA. José B. Miranda Filho is full-professor in the Department of Genetics, Escola Superior de Agricultura Luiz de Queiroz - University of São Paulo located at Piracicaba, Brazil. His research interests have emphasized development of quantitative genetic theory and its application to maize breeding. Miranda Filho is native of Pirassununga, São Paulo, Brazil. M.J. Carena is professor of plant sciences at North Dakota State University (NDSU). Dr. Carena has led maize-breeding research for short-season maturity at NDSU since 1999. This program is currently one the of the few public U.S. programs left integrating pre-breeding with cultivar development and training in applied maize breeding. He teaches Quantitative Genetics and Crop Breeding Techniques at NDSU. Carena is a native of Buenos Aires, Argentina. http://www.ag.ndsu.nodak.edu/plantsci/faculty/Carena.htm




Genetics, Genomics and Breeding of Poplar


Book Description

Written by researchers representing six countries and 28 institutions, this book highlights the development of the genus Populus as a model organism for tree genomics. Reflecting an impressive depth of coverage, the contributors' thorough reviews and analyses of Populus genomics provide insight into future discoveries about the basic biology of thi




The Applications of New Multi-Locus GWAS Methodologies in the Genetic Dissection of Complex Traits


Book Description

Genome-Wide Association Studies (GWAS) are widely used in the genetic dissection of complex traits. Most existing methods are based on single-marker association in genome-wide scans with population structure and polygenic background controls. To control the false positive rate, the Bonferroni correction for multiple tests is frequently adopted. This stringent correction results in the exclusion of important loci, especially for GWAS in crop genetics. To address this issue, multi-locus GWAS methodologies have been recommended, i.e., FASTmrEMMA, ISIS EM-BLASSO, mrMLM, FASTmrMLM, pLARmEB, pKWmEB and FarmCPU. In this Research Topic, our purpose is to clarify some important issues in the application of multi-locus GWAS methods. Here we discuss the following subjects: First, we discuss the advantages of new multi-locus GWAS methods over the widely-used single-locus GWAS methods in the genetic dissection of complex traits, metabolites and gene expression levels. Secondly, large experiment error in the field measurement of phenotypic values for complex traits in crop genetics results in relatively large P-values in GWAS, indicating the existence of small number of significantly associated SNPs. To solve this issue, a less stringent P-value critical value is often adopted, i.e., 0.001, 0.0001 and 1/m (m is the number of markers). Although lowering the stringency with which an association is made could identify more hits, confidence in these hits would significantly drop. In this Research Topic we propose a new threshold of significant QTN (LOD=3.0 or P-value=2.0e-4) in multi-locus GWAS to balance high power and low false positive rate. Thirdly, heritability missing in GWAS is a common phenomenon, and a series of scientists have explained the reasons why the heritability is missing. In this Research Topic, we also add one additional reason and propose the joint use of several GWAS methodologies to capture more QTNs. Thus, overall estimated heritability would be increased. Finally, we discuss how to select and use these multi-locus GWAS methods.




Handbook of Statistical Genomics


Book Description

A timely update of a highly popular handbook on statistical genomics This new, two-volume edition of a classic text provides a thorough introduction to statistical genomics, a vital resource for advanced graduate students, early-career researchers and new entrants to the field. It introduces new and updated information on developments that have occurred since the 3rd edition. Widely regarded as the reference work in the field, it features new chapters focusing on statistical aspects of data generated by new sequencing technologies, including sequence-based functional assays. It expands on previous coverage of the many processes between genotype and phenotype, including gene expression and epigenetics, as well as metabolomics. It also examines population genetics and evolutionary models and inference, with new chapters on the multi-species coalescent, admixture and ancient DNA, as well as genetic association studies including causal analyses and variant interpretation. The Handbook of Statistical Genomics focuses on explaining the main ideas, analysis methods and algorithms, citing key recent and historic literature for further details and references. It also includes a glossary of terms, acronyms and abbreviations, and features extensive cross-referencing between chapters, tying the different areas together. With heavy use of up-to-date examples and references to web-based resources, this continues to be a must-have reference in a vital area of research. Provides much-needed, timely coverage of new developments in this expanding area of study Numerous, brand new chapters, for example covering bacterial genomics, microbiome and metagenomics Detailed coverage of application areas, with chapters on plant breeding, conservation and forensic genetics Extensive coverage of human genetic epidemiology, including ethical aspects Edited by one of the leading experts in the field along with rising stars as his co-editors Chapter authors are world-renowned experts in the field, and newly emerging leaders. The Handbook of Statistical Genomics is an excellent introductory text for advanced graduate students and early-career researchers involved in statistical genetics.




Association Mapping in Plants


Book Description

For the past decade, there has been success in using conventional map-based strategies in identification and cloning of quantitative trait loci (QTL) in model plant species including tomato and Arabidopsis. These quantitative traits are generally the products of many loci with varying degrees of effect upon the observed phenotypes. Recently, a new approach to genetic mapping has emerged called association mapping. This new technique takes into account the thousands of genes to evaluate for QTL effect and is a more efficient approach that does not require generation of segregating populations/large numbers of progeny. As it can utilize all of the historic recombination events in a diverse population of individuals it can generate higher resolution genetic maps and, is needed to complement current map based cloning methods. Association Mapping in Plants provides both basic and advanced understanding of association mapping and an awareness of population genomics tools to facilitate mapping and identification of the underlying causes of quantitative trait variation in plants. It acts as a useful review of the marker technology, the statistical methodology, and the progress to date. It also offers guides to the use of single nucleotide polymorphisms (SNPs) in association studies. This book will appeal to all those with an interest in plant genetics, plant breeding, and plant genomics. About the Editors: Dr. Nnadozie C. Oraguzie is a Senior Scientist in Genetics at the Horticulture and Food Research Institute of New Zealand Ltd (HortResearch). Dr. Erik H. A. Rikkerink is a Science Leader at HortResearch, New Zealand. Dr. Susan E. Gardiner is a Principal Scientist and leader of the Gene Mapping research team at HortResearch, New Zealand. Dr. H. Nihal De Silva/STRONG is a Senior Scientist of Biometrics at HortResearch, New Zealand.




Forest Genomics and Biotechnology


Book Description

This Research Topic addresses research in genomics and biotechnology to improve the growth and quality of forest trees for wood, pulp, biorefineries and carbon capture. Forests are the world’s greatest repository of terrestrial biomass and biodiversity. Forests serve critical ecological services, supporting the preservation of fauna and flora, and water resources. Planted forests also offer a renewable source of timber, for pulp and paper production, and the biorefinery. Despite their fundamental role for society, thousands of hectares of forests are lost annually due to deforestation, pests, pathogens and urban development. As a consequence, there is an increasing need to develop trees that are more productive under lower inputs, while understanding how they adapt to the environment and respond to biotic and abiotic stress. Forest genomics and biotechnology, disciplines that study the genetic composition of trees and the methods required to modify them, began over a quarter of a century ago with the development of the first genetic maps and establishment of early methods of genetic transformation. Since then, genomics and biotechnology have impacted all research areas of forestry. Genome analyses of tree populations have uncovered genes involved in adaptation and response to biotic and abiotic stress. Genes that regulate growth and development have been identified, and in many cases their mechanisms of action have been described. Genetic transformation is now widely used to understand the roles of genes and to develop germplasm that is more suitable for commercial tree plantations. However, in contrast to many annual crops that have benefited from centuries of domestication and extensive genomic and biotechnology research, in forestry the field is still in its infancy. Thus, tremendous opportunities remain unexplored. This Research Topic aims to briefly summarize recent findings, to discuss long-term goals and to think ahead about future developments and how this can be applied to improve growth and quality of forest trees.