Download or read book Methods for the Quantitative Characterization of the Genetic Basis of Human Complex Traits written by Kathryn Burch and published by . This book was released on 2021 with total page 128 pages. Available in PDF, EPUB and Kindle. Book excerpt: A major finding from the last decade of genome-wide association studies (GWAS) is that variant-phenotype associations are significantly enriched in noncoding regulatory regions of the genome. This result suggests that GWAS associations localize variants that modulate phenotype via gene regulation as opposed to alterations in protein structure/function. However, for most complex traits, most aspects of genetic architecture-the number of causal variants/genes for a trait and the degree to which causal effect sizes are coupled with genomic features such as minor allele frequency (MAF) and linkage disequilibrium (LD)-remain actively debated. In this dissertation, I introduce three new methods to explore and quantitatively characterize complex-trait genetic architecture. First, I derive an unbiased estimator of genome-wide SNP-heritability under a very general random effects model that makes minimal assumptions on the underlying (unknown) genetic architecture of the trait. Second, I introduce a method for estimating the number of causal variants that are shared between two ancestral populations for a given trait, and I discuss the implications of the method and real-data results for improving polygenic risk prediction in ethnic minority populations. Third, I propose methods for partitioning the heritability of individual genes by MAF to identify disease-relevant genes, with the hypothesis that some disease-relevant genes may have relatively large heritability contributions from rare and low-frequency variants while still having low total gene-level heritability.
Download or read book Quantitative genetics and complex trait analysis in humans the genetic basis of complex diseases written by Christine Langhoff and published by GRIN Verlag. This book was released on 2003-06-07 with total page 12 pages. Available in PDF, EPUB and Kindle. Book excerpt: Essay from the year 2002 in the subject Biology - Genetics / Gene Technology, grade: 2.1 (B), Oxford University (New College), language: English, abstract: Ultimately, the goal of genetics is the analysis of the genotype of organisms. But the genotype can be identified – and therefore studied – only through its phenotypic effect. This means that two genotypes are recognised as different from each other because the phenotypes of their carriers are different. A problem can be seen with this approach as the actual variation between organisms is usually quantitative, not qualitative. Many different genotypes may have the same average phenotype. At the same time, because of environmental variation, two individuals of the same genotype may not have the same phenotype. This lack of a one-to-one correspondence between genotype and phenotype obscures underlying Mendelian genetics. I am going to explore the use of various statistical techniques for studying quantitative traits with application to behavioural traits. I am also going to examine whether there are behavioural traits with sufficiently high heritabilities to give hope for gene searches and I am going to discuss the difficulties that confront molecular geneticists regarding psychiatric genetics.
Download or read book Genetic Dissection of Complex Traits written by D.C. Rao and published by Academic Press. This book was released on 2008-04-23 with total page 788 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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
Download or read book Genetics and Analysis of Quantitative Traits written by Michael Lynch and published by Sinauer Associates Incorporated. This book was released on 1998-01 with total page 980 pages. Available in PDF, EPUB and Kindle. Book excerpt: Professors Lynch and Walsh bring together the diverse array of theoretical and empirical applications of quantitative genetics in a work that is comprehensive and accessible to anyone with a rudimentary understanding of statistics and genetics.
Download or read book Analysis and Simulation Methods for Artificial Selection Experiments in the Investigation of the Genetic Basis of Complex Traits written by Darren Kessner and published by . This book was released on 2014 with total page 151 pages. Available in PDF, EPUB and Kindle. Book excerpt: One of the fundamental goals of research in modern genetics is to determine the genetic basis for complex traits. One experimental approach to this problem is artificial selection, where individual organisms are selected each generation for extreme values of the trait under study. In these experiments, the investigator identifies putative trait loci based on genetic differentiation in evolved populations. Recently, researchers have combined artificial selection with genome- wide pooled massively parallel sequencing to identify quantitative trait loci. In this dissertation, I present analysis and simulation methods applicable to pooled sequencing and artificial selection experiments. In Chapter 1, I provide some background on artificial selection, massively parallel sequencing, and the use of simulations in population genetics. In Chapter 2, I present an expectation-maximization (EM) algorithm for estimating haplotype frequencies in a pooled sample directly from mapped sequence reads, in the case where the possible haplotypes are known. This method is relevant to the analysis of pooled sequencing data from selection experiments, in addition to the calculation of proportions of different species within a metagenomics sample. The method outperforms existing methods based on single-site allele frequencies, as well as simple approaches using sequence read data. I have implemented the method in a freely available open-source software tool called harp (Haplotype Analysis of Reads in Pools). In Appendix A, I present additional analyses to show that the method improves estimates of relative abundances and community diversity at higher taxon levels. In Chapter 3, I present a new forward-in-time simulator forqs (Forward-in-time simulation of Recombination, Quantitative traits, and Selection). forqs was designed to investigate haplotype patterns resulting from scenarios where substantial evolutionary change has taken place in a small number of generations due to recombination and/or selection on polygenic quantitative traits. The simulator uses a memory-efficient representation of chromosomes that allows the simulation of whole genomes. In addition, forqs explicitly models quantitative traits, and its modular design gives the user great flexibility in specifying trait architectures, selection and demography. In Chapter 4, I present a new analysis of the power of artificial selection experiments to detect and localize quantitative trait loci (QTLs), using the forqs simulator from Chapter 3. I show that modeling loci with constant selection coefficients does not fully capture the dynamics of QTLs under artificial selection. I also show that a substantial portion of the genetic variance of the trait (50-100%) can be explained by detected QTLs in as little as 20 generations of selection, depending on the trait architecture and experimental design. Furthermore, I show that the power to detect and localize QTLs depends crucially on the opportunity for recombination during the experiment. Finally, I show that an increase in power is obtained by leveraging founder haplotype information to obtain allele frequency estimates (using the harp method from Chapter 2).
Download or read book Scientific Frontiers in Developmental Toxicology and Risk Assessment written by National Research Council and published by National Academies Press. This book was released on 2000-12-21 with total page 348 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Integrative Statistical Methods to Understand the Genetic Basis of Complex Trait written by Gleb Kichaev and published by . This book was released on 2018 with total page 166 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Genome-wide Association study (GWAS) is one of the primary tools for understanding the genetic basis of complex traits. In this dissertation I introduce enhanced statistical methods to do integrative GWAS analysis with functional genomic data. First, I describe an integrative fine-mapping framework to prioritize causal variants at known GWAS risk loci. Next, I expand upon this framework to exploit genetic heterogeniety across human populations to improve statistical efficiency. I then consider a new inference strategy to reduce the computational burden of the methodology. Finally, I propose a new approach for GWAS discovery that leverages functional genomic data through polygenic modeling.
Download or read book Computational Genetic Approaches for Understanding the Genetic Basis of Complex Traits written by Eun Yong Kang and published by . This book was released on 2013 with total page 273 pages. Available in PDF, EPUB and Kindle. Book excerpt: Recent advances in genotyping and sequencing technology have enabled researchers to collect an enormous amount of high-dimensional genotype data. These large scale genomic data provide unprecedented opportunity for researchers to study and analyze the genetic factors of human complex traits. One of the major challenges in analyzing these high-throughput genomic data is requirements for effective and efficient computational methodologies. In this thesis, I introduce several methodologies for analyzing these genomic data which facilitates our understanding of the genetic basis of complex human traits. First, I introduce a method for inferring biological networks from high-throughput data containing both genetic variation information and gene expression profiles from genetically distinct strains of an organism. For this problem, I use causal inference techniques to infer the presence or absence of causal relationships between yeast gene expressions in the framework of graphical causal models. In particular, I utilize prior biological knowledge that genetic variations affect gene expressions, but not vice versa, which allow us to direct the subsequent edges between two gene expression levels. The prediction of a presence of causal relationship as well as the absence of causal relationship between gene expressions can facilitate distinguishing between direct and indirect effects of variation on gene expression levels. I demonstrate the utility of our approach by applying it to data set containing 112 yeast strains and the proposed method identifies the known "regulatory hotspot" in yeast. Second, I introduce efficient pairwise identity by descent (IBD) association mapping method, which utilizes importance sampling to improve efficiency and enables approximation of extremely small p-values. Two individuals are IBD at a locus if they have identical alleles inherited from a common ancestor. One popular approach to find the association between IBD status and disease phenotype is the pairwise method where one compares the IBD rate of case/case pairs to the background IBD rate to detect excessive IBD sharing between cases. One challenge of the pairwise method is computational efficiency. In the pairwise method, one uses permutation to approximate p-values because it is difficult to analytically obtain the asymptotic distribution of the statistic. Since the p-value threshold for genome-wide association studies (GWAS) is necessarily low due to multiple testing, one must perform a large number of permutations which can be computationally demanding. I present Fast-Pairwise to overcome the computational challenges of the traditional pairwise method by utilizing importance sampling to improve efficiency and enable approximation of extremely small p-values. Using the WTCCC type 1 diabetes data, I show that Fast-Pairwise can successfully pinpoint a gene known to be associated to the disease within the MHC region. Finally, I introduce a novel meta analytic approach to identify gene-by-environment interactions by aggregating the multiple studies with varying environmental conditions. Identifying environmentally specific genetic effects is a key challenge in understanding the structure of complex traits. Model organisms play a crucial role in the identification of such gene-by-environment interactions, as a result of the unique ability to observe genetically similar individuals across multiple distinct environments. Many model organism studies examine the same traits but, under varying environmental conditions. These studies when examined in aggregate provide an opportunity to identify genomic loci exhibiting environmentally-dependent effects. In this project, I jointly analyze multiple studies with varying environmental conditions using a meta-analytic approach based on a random effects model to identify loci involved in gene-by-environment interactions. Our approach is motivated by the observation that methods for discovering gene-by-environment interactions are closely related to random effects models for meta-analysis. We show that interactions can be interpreted as heterogeneity and can be detected without utilizing the traditional uni- or multi-variate approaches for discovery of gene-by-environment interactions. I apply our new method to combine 17 mouse studies containing in aggregate 4,965 distinct animals. We identify 26 significant loci involved in High-density lipoprotein (HDL) cholesterol, many of which show significant evidence of involvement in gene-by-environment interactions.
Download or read book Biosocial Surveys written by National Research Council and published by National Academies Press. This book was released on 2008-01-06 with total page 429 pages. Available in PDF, EPUB and Kindle. Book excerpt: Biosocial Surveys analyzes the latest research on the increasing number of multipurpose household surveys that collect biological data along with the more familiar interviewerâ€"respondent information. This book serves as a follow-up to the 2003 volume, Cells and Surveys: Should Biological Measures Be Included in Social Science Research? and asks these questions: What have the social sciences, especially demography, learned from those efforts and the greater interdisciplinary communication that has resulted from them? Which biological or genetic information has proven most useful to researchers? How can better models be developed to help integrate biological and social science information in ways that can broaden scientific understanding? This volume contains a collection of 17 papers by distinguished experts in demography, biology, economics, epidemiology, and survey methodology. It is an invaluable sourcebook for social and behavioral science researchers who are working with biosocial data.
Download or read book Analysis of Complex Disease Association Studies written by Eleftheria Zeggini and published by Academic Press. This book was released on 2010-11-17 with total page 353 pages. Available in PDF, EPUB and Kindle. Book excerpt: According to the National Institute of Health, a genome-wide association study is defined as any study of genetic variation across the entire human genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight), or the presence or absence of a disease or condition. Whole genome information, when combined with clinical and other phenotype data, offers the potential for increased understanding of basic biological processes affecting human health, improvement in the prediction of disease and patient care, and ultimately the realization of the promise of personalized medicine. In addition, rapid advances in understanding the patterns of human genetic variation and maturing high-throughput, cost-effective methods for genotyping are providing powerful research tools for identifying genetic variants that contribute to health and disease. This burgeoning science merges the principles of statistics and genetics studies to make sense of the vast amounts of information available with the mapping of genomes. In order to make the most of the information available, statistical tools must be tailored and translated for the analytical issues which are original to large-scale association studies. Analysis of Complex Disease Association Studies will provide researchers with advanced biological knowledge who are entering the field of genome-wide association studies with the groundwork to apply statistical analysis tools appropriately and effectively. With the use of consistent examples throughout the work, chapters will provide readers with best practice for getting started (design), analyzing, and interpreting data according to their research interests. Frequently used tests will be highlighted and a critical analysis of the advantages and disadvantage complimented by case studies for each will provide readers with the information they need to make the right choice for their research. Additional tools including links to analysis tools, tutorials, and references will be available electronically to ensure the latest information is available. Easy access to key information including advantages and disadvantage of tests for particular applications, identification of databases, languages and their capabilities, data management risks, frequently used tests Extensive list of references including links to tutorial websites Case studies and Tips and Tricks
Download or read book Evaluating Human Genetic Diversity written by National Research Council and published by National Academies Press. This book was released on 1998-01-19 with total page 101 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book assesses the scientific value and merit of research on human genetic differencesâ€"including a collection of DNA samples that represents the whole of human genetic diversityâ€"and the ethical, organizational, and policy issues surrounding such research. Evaluating Human Genetic Diversity discusses the potential uses of such collection, such as providing insight into human evolution and origins and serving as a springboard for important medical research. It also addresses issues of confidentiality and individual privacy for participants in genetic diversity research studies.
Download or read book Applications of Toxicogenomic Technologies to Predictive Toxicology and Risk Assessment written by National Research Council and published by National Academies Press. This book was released on 2007-12-19 with total page 300 pages. Available in PDF, EPUB and Kindle. Book excerpt: The new field of toxicogenomics presents a potentially powerful set of tools to better understand the health effects of exposures to toxicants in the environment. At the request of the National Institute of Environmental Health Sciences, the National Research Council assembled a committee to identify the benefits of toxicogenomics, the challenges to achieving them, and potential approaches to overcoming such challenges. The report concludes that realizing the potential of toxicogenomics to improve public health decisions will require a concerted effort to generate data, make use of existing data, and study data in new waysâ€"an effort requiring funding, interagency coordination, and data management strategies.
Download or read book Systems Genetics written by Florian Markowetz and published by Cambridge University Press. This book was released on 2015-07-02 with total page 287 pages. Available in PDF, EPUB and Kindle. Book excerpt: Whereas genetic studies have traditionally focused on explaining heritance of single traits and their phenotypes, recent technological advances have made it possible to comprehensively dissect the genetic architecture of complex traits and quantify how genes interact to shape phenotypes. This exciting new area has been termed systems genetics and is born out of a synthesis of multiple fields, integrating a range of approaches and exploiting our increased ability to obtain quantitative and detailed measurements on a broad spectrum of phenotypes. Gathering the contributions of leading scientists, both computational and experimental, this book shows how experimental perturbations can help us to understand the link between genotype and phenotype. A snapshot of current research activity and state-of-the-art approaches to systems genetics are provided, including work from model organisms such as Saccharomyces cerevisiae and Drosophila melanogaster, as well as from human studies.
Download or read book Theoretical Aspects of Pedigree Analysis written by Emil Ginsburg and published by RAMOT-TEL AVIV UNIVERSITY, ISRAEL. This book was released on 2006 with total page 94 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Mapping and Sequencing the Human Genome written by National Research Council and published by National Academies Press. This book was released on 1988-01-01 with total page 128 pages. Available in PDF, EPUB and Kindle. Book excerpt: There is growing enthusiasm in the scientific community about the prospect of mapping and sequencing the human genome, a monumental project that will have far-reaching consequences for medicine, biology, technology, and other fields. But how will such an effort be organized and funded? How will we develop the new technologies that are needed? What new legal, social, and ethical questions will be raised? Mapping and Sequencing the Human Genome is a blueprint for this proposed project. The authors offer a highly readable explanation of the technical aspects of genetic mapping and sequencing, and they recommend specific interim and long-range research goals, organizational strategies, and funding levels. They also outline some of the legal and social questions that might arise and urge their early consideration by policymakers.
Download or read book Understanding Racial and Ethnic Differences in Health in Late Life written by National Research Council and published by National Academies Press. This book was released on 2004-09-08 with total page 184 pages. Available in PDF, EPUB and Kindle. Book excerpt: As the population of older Americans grows, it is becoming more racially and ethnically diverse. Differences in health by racial and ethnic status could be increasingly consequential for health policy and programs. Such differences are not simply a matter of education or ability to pay for health care. For instance, Asian Americans and Hispanics appear to be in better health, on a number of indicators, than White Americans, despite, on average, lower socioeconomic status. The reasons are complex, including possible roles for such factors as selective migration, risk behaviors, exposure to various stressors, patient attitudes, and geographic variation in health care. This volume, produced by a multidisciplinary panel, considers such possible explanations for racial and ethnic health differentials within an integrated framework. It provides a concise summary of available research and lays out a research agenda to address the many uncertainties in current knowledge. It recommends, for instance, looking at health differentials across the life course and deciphering the links between factors presumably producing differentials and biopsychosocial mechanisms that lead to impaired health.
Download or read book Genomics in Aquaculture written by Simon A MacKenzie and published by Academic Press. This book was released on 2016-07-29 with total page 306 pages. Available in PDF, EPUB and Kindle. Book excerpt: Genomics in Aquaculture is a concise, must-have reference that describes current advances within the field of genomics and their applications to aquaculture. Written in an accessible manner for anyone—non-specialists to experts alike—this book provides in-depth coverage of genomics spanning from genome sequencing, to transcriptomics and proteomics. It provides, for ease of learning, examples from key species most relevant to current intensive aquaculture practice. Its coverage of minority species that have a specific biological interest (e.g., Pleuronectiformes) makes this book useful for countries that are developing such species. It is a robust, practical resource that covers foundational, functional, and applied aspects of genomics in aquaculture, presenting the most current information in a field of research that is rapidly growing. Provides the latest scientific methods and technologies to maximize efficiencies for healthy fish production, with summary tables for quick reference Offers an extended glossary of technical and methodological terms to help readers better understand key biological concepts Describes state-of-the-art technologies, such as transcriptomics and epigenomics, currently under development for future perspective of the field Covers minority species that have a specific biological interest (e.g., Pleuronectiformes), making the book useful to countries developing such species
