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Author :
Publisher :
ISBN 13 : 9789462956155
Total Pages : 200 pages
Book Rating : 4.9/5 (561 download)
Download or read book Using Genetic Methods to Get Insights Into Human Complex Traits written by and published by . This book was released on 2017 with total page 200 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Author : D.C. Rao
Publisher : Academic Press
ISBN 13 : 0080569110
Total Pages : 788 pages
Book Rating : 4.0/5 (85 download)
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
Author : Liu Shu
Publisher :
ISBN 13 : 9789464891522
Total Pages : 0 pages
Book Rating : 4.8/5 (915 download)
Download or read book When Genes Meet the Brain written by Liu Shu and published by . This book was released on 2024 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: "While the investigation into complex human traits has extended for over a century, the mechanisms underlying many of them remain poorly understood. Imaging genetics is an interdisciplinary field that integrates genetic and neuroimaging techniques to explore the influence of genetic variations on brain structure and function, subsequently impacting complex traits. This thesis aims to identify the neural mechanisms underlying complex traits within the framework of imaging genetics. First, a systematic exploration of genetic relationships between the brain and various traits revealed distinct associations between brain structure/function and genetic predispositions to mental health and cognition. Second, we established links between gene expression and the neural correlates of major depressive disorder and risky behaviors, suggesting the intermediary processes bridging genes and their associated brain patterns. Addressing concerns about the replicability of neuroimaging analyses, the third objective of the thesis was to assess the replicability of brain-phenotype associations across various traits within different domains, emphasizing that large-scale neuroimaging data are required for replicable brain–phenotype associations. These findings have yielded valuable insights into the neural mechanisms underpinning complex traits, offering robust evidence for the pivotal roles of the brain in the pathways from genotype to phenotype."--
Author : D. C. Rao
Publisher : Academic Press
ISBN 13 :
Total Pages : 632 pages
Book Rating : 4.X/5 (4 download)
Download or read book Genetic Dissection of Complex Traits written by D. C. Rao and published by Academic Press. This book was released on 2001 with total page 632 pages. Available in PDF, EPUB and Kindle. Book excerpt: Genetic Dissection of Complex Traits will present the full range of methodologies that are essential for understanding the basis of human genetic disorders, the origin of such diseases, and theories on how to determine one's genetic predisposition to certain genetic diseases.
Author : Huwenbo Shi
Publisher :
ISBN 13 :
Total Pages : 163 pages
Book Rating : 4.:/5 (14 download)
Download or read book Computational Methods to Analyze Large-scale Genetic Studies of Complex Human Traits written by Huwenbo Shi and published by . This book was released on 2018 with total page 163 pages. Available in PDF, EPUB and Kindle. Book excerpt: Large-scale genome-wide association studies (GWAS) have produced a rich resource of genetic data over the past decade, urging the need to develop computational and statistical methods that analyze these data. This dissertation presents four statistical methods that model the correlation structure between genetic variants and its effect on GWAS summary association statistics to help understand the genetic basis of complex human traits and diseases. The first method employs the multivariate Bernoulli distribution to model haplotype data, allowing for higher-order interactions among genetic variants, and shows better accuracy in predicting DNase I hypersensitivity status. The second method partitions heritability into small regions on the genome using GWAS summary statistics data, while accounting for complex correlation structures among genetic variants, and uncovers the genetic architectures of complex human traits and diseases. Extending the second method into pairs of traits, the third method partitions genetic correlation into small genomic regions using GWAS summary statistics data, and provides insights into the shared genetic basis between pairs of traits. Finally, the fourth method dissects population-specific and shared causal genetic variants of complex traits in two continental populations, using GWAS summary statistics data obtained from samples of different ethnicities, and reveals differences in genetic architectures of two continental populations.
Author : National Research Council
Publisher : National Academies Press
ISBN 13 : 0309184746
Total Pages : 101 pages
Book Rating : 4.3/5 (91 download)
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.
Author : Institute of Medicine
Publisher : National Academies Press
ISBN 13 : 0309101964
Total Pages : 385 pages
Book Rating : 4.3/5 (91 download)
Download or read book Genes, Behavior, and the Social Environment written by Institute of Medicine and published by National Academies Press. This book was released on 2006-12-07 with total page 385 pages. Available in PDF, EPUB and Kindle. Book excerpt: Over the past century, we have made great strides in reducing rates of disease and enhancing people's general health. Public health measures such as sanitation, improved hygiene, and vaccines; reduced hazards in the workplace; new drugs and clinical procedures; and, more recently, a growing understanding of the human genome have each played a role in extending the duration and raising the quality of human life. But research conducted over the past few decades shows us that this progress, much of which was based on investigating one causative factor at a time—often, through a single discipline or by a narrow range of practitioners—can only go so far. Genes, Behavior, and the Social Environment examines a number of well-described gene-environment interactions, reviews the state of the science in researching such interactions, and recommends priorities not only for research itself but also for its workforce, resource, and infrastructural needs.
Author : Kunling Huang
Publisher :
ISBN 13 :
Total Pages : 0 pages
Book Rating : 4.:/5 (14 download)
Download or read book Statistical Methods for Integrating Quantitative Trait Loci Annotation in Post-gwas Analysis written by Kunling Huang and published by . This book was released on 2023 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Recent advances in large-scale genome-wide association studies (GWAS) have highlighted the involvement of common genetic variants in complex traits and diseases. Data integration efforts linking GWAS signals with functional annotation data have provided insights into the genetic architecture of numerous human complex traits. For example, expression quantitative trait loci (eQTL) studies in relevant biological tissues provide gene candidates for complex diseases, which can be tested as therapeutic targets. Integrating multi-omics annotation data with GWAS association data brings in orthogonal information and improves the understanding of complex trait etiology. In this dissertation, we present two approaches to link genomic annotations to genotype-phenotype associations identified through GWAS. The two approaches both associate complex traits with genetically imputed molecular traits (i.e., gene expression levels and metabolite levels), and identify regulatory and metabolic machineries underlying a variety of complex traits.We start with integrating eQTLs with autism spectrum disorder (ASD) in parent-offspring trios by quantifying the transmission disequilibrium of genetically regulated gene expression from parents to offspring and performing transcriptome-wide association studies (TWAS). We identify transcription factor POU3F2 in our analysis. POU3F2 mainly expresses in developmental brain and the gene targets regulated by POU3F2 are enriched for known risk genes for ASD and loss-of-function de novo mutations in ASD probands. TWAS suggests that ASD genes affected by very rare mutations may be regulated by an unlinked transcription factor affected by common genetic variations. Next, we extend our TWAS framework to study the regulatory roles of metabolite quantitative trait loci (mQTL). We introduce metabolome-wide association study (MWAS), which integrates metabolomics data with genetics data. We benchmarked and optimized genetic prediction models for a total of 703 metabolites from cerebrospinal fluid, plasma, and urine, and performed a biobank-wide association scan between imputed metabolite levels and 530 complex traits in UK Biobank. We found a total of 1,311 significant metabolite-trait associations after performing Bonferroni correction across all tested associations. The significant MWAS results explain the difference in human body fat mass and body fat-free mass. In summary, we perform joint analysis on eQTL/mQTL data and complex trait GWAS to identify genes or metabolites relevant to complex traits. Our approaches improve our understanding of the phenotypic outcomes of non-coding genetic variations and may contribute to novel biomarker discovery, clinical diagnosis improvement, and therapeutics development.
Author : National Research Council
Publisher : National Academies Press
ISBN 13 : 0309038405
Total Pages : 128 pages
Book Rating : 4.3/5 (9 download)
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.
Author : Tanya Ngoc Phung
Publisher :
ISBN 13 :
Total Pages : 213 pages
Book Rating : 4.:/5 (18 download)
Download or read book Methods and Models for the Analysis of Genetic Variation Across Species Using Large-scale Genomic Data written by Tanya Ngoc Phung and published by . This book was released on 2018 with total page 213 pages. Available in PDF, EPUB and Kindle. Book excerpt: Understanding how different evolutionary processes shape genetic variation within and between species is an important question in population genetics. The advent of next generation sequencing has allowed for many theories and hypotheses to be tested explicitly with data. However, questions such as what evolutionary processes affect neutral divergence (DNA differences between species) or genetic variation in different regions of the genome (such as on autosomes versus sex chromosomes) or how many genetic variants contribute to complex traits are still outstanding. In this dissertation, I utilized different large-scale genomic datasets and developed statistical methods to determine the role of natural selection on genetic variation between species, sex-biased evolutionary processes on shaping patterns of genetic variation on the X chromosome and autosomes, and how population history, mutation, and natural selection interact to control complex traits. First, I used genome-wide divergence data between multiple pairs of species ranging in divergence time to show that natural selection has reduced divergence at neutral sites that are linked to those under direct selection. To determine explicitly whether and to what extent linked selection and/or mutagenic recombination could account for the pattern of neutral divergence across the genome, I developed a statistical method and applied it to human-chimp neutral divergence dataset. I showed that a model including both linked selection and mutagenic recombination resulted in the best fit to the empirical data. However, the signal of mutagenic recombination could be coming from biased gene conversion. Comparing genetic diversity between the X chromosome and the autosomes could provide insights into whether and how sex-biased processes have affected genetic variation between different genomic regions. For example, X/A diversity ratio greater than neutral expectation could be due to more X chromosomes than expected and could be a result of mating practices such as polygamy where there are more reproducing females than males. I next utilized whole-genome sequences from dogs and wolves and found that X/A diversity is lower than neutral expectation in both dogs and wolves in ancient time-scales, arguing for evolutionary processes resulting in more males reproducing compared to females. However, within breed dogs, patterns of population differentiation suggest that there have been more reproducing females, highlighting effects from breeding practices such as popular sire effect where one male can father many offspring with multiple females. In medical genetics, a complete understanding of the genetic architecture is essential to unravel the genetic basis of complex traits. While genome wide association studies (GWAS) have discovered thousands of trait-associated variants and thus have furthered our understanding of the genetic architecture, key parameters such as the number of causal variants and the mutational target size are still under-studied. Further, the role of natural selection in shaping the genetic architecture is still not entirely understood. In the last chapter, I developed a computational method called InGeAr to infer the mutational target size and explore the role of natural selection on affecting the variant's effect on the trait. I found that the mutational target size differs from trait to trait and can be large, up to tens of megabases. In addition, purifying selection is coupled with the variant's effect on the trait. I discussed how these results support the omnigenic model of complex traits. In summary, in this dissertation, I utilized different types of large genomic dataset, from genome-wide divergence data to whole genome sequence data to GWAS data to develop models and statistical methods to study how different evolutionary processes have shaped patterns of genetic variation across the genome.
Download or read book Modelling Genetic and Genomic Interactions Underlying Gene Expression and Complex Traits written by and published by . This book was released on 2013 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Author : Yuan-Ming Zhang
Publisher : Frontiers Media SA
ISBN 13 : 2832543693
Total Pages : 278 pages
Book Rating : 4.8/5 (325 download)
Download or read book Advances in Statistical Methods for the Genetic Dissection of Complex Traits in Plants written by Yuan-Ming Zhang and published by Frontiers Media SA. This book was released on 2024-01-26 with total page 278 pages. Available in PDF, EPUB and Kindle. Book excerpt: Genome-wide association studies (GWAS) have been widely used in the genetic dissection of complex traits. However, there are still limits in current GWAS statistics. For example, (1) almost all the existing methods do not estimate additive and dominance effects in quantitative trait nucleotide (QTN) detection; (2) the methods for detecting QTN-by-environment interaction (QEI) are not straightforward and do not estimate additive and dominance effects as well as additive-by-environment and dominance-by-environment interaction effects, leading to unreliable results; and (3) no or too simple polygenic background controls have been employed in QTN-by-QTN interaction (QQI) detection. As a result, few studies of QEI and QQI for complex traits have been reported based on multiple-environment experiments. Recently, new statistical tools, including 3VmrMLM, have been developed to address these needs in GWAS. In 3VmrMLM, all the trait-associated effects, including QTN, QEI and QQI related effects, are compressed into a single effect-related vector, while all the polygenic backgrounds are compressed into a single polygenic effect matrix. These compressed parameters can be accurately and efficiently estimated through a unified mixed model analysis. To further validate these new GWAS methods, particularly 3VmrMLM, they should be rigorously tested in real data of various plants and a wide range of other species.
Author : Roger Detels
Publisher : Oxford University Press
ISBN 13 : 0198816804
Total Pages : 1777 pages
Book Rating : 4.1/5 (988 download)
Download or read book Oxford Textbook of Global Public Health written by Roger Detels and published by Oxford University Press. This book was released on 2022 with total page 1777 pages. Available in PDF, EPUB and Kindle. Book excerpt: "Public health is concerned with the process of mobilizing local, state/provincial, national, and international resources to assure the conditions in which all people can be healthy (Detels and Breslow 2002). To successfully implement this process and to make health for all achievable, public health must perform the functions listed in Box 1.1.1"--
Author :
Publisher :
ISBN 13 :
Total Pages : 440 pages
Book Rating : 4.:/5 (436 download)
Download or read book Statistical Methods for Genetic Association Analysis Involving Complex Longitudinal Data written by and published by . This book was released on 2009 with total page 440 pages. Available in PDF, EPUB and Kindle. Book excerpt: Most, if not all, human phenotypes exhibit a temporal, dosage-dependent, or age effect. In this work, I explore and showcase the use different analytical methods for assessing the genetic contribution to traits with temporal trends, or what I refer to as 'dynamic complex traits' (DCTs). The study of DCTs could offer insights into disease pathogenesis that are not achievable in other research settings. I describe the development and application of a method of DCT analysis termed `Curve-Based Multivariate Distance Matrix Regression' (CMDMR) using data from a structured longitudinal clinical study to demonstrate the approach in genetic association analysis (Chapter 2). The method was found to perform as well as or better than traditional statistical methods that might be applied to DCTs. I also applied the CMDMR method in conducting a genome wide association (GWA) study of height that essentially exploits dissimilarity among the longitudinal height profiles of individuals with different genotypes (Chapter 3). This framework is applied to height growth data from the Bogalusa Heart Study. I identified 7 novel variants in 6 loci (FAM19A1, FGF20, SCD5, MAP3K7, GLCCI1 and TJP2) associated with height profiles using parametric curves (all p-values
Author : Tim Bernard Bigdeli
Publisher :
ISBN 13 :
Total Pages : pages
Book Rating : 4.:/5 (784 download)
Download or read book Quantitative Genetic Methods to Dissect Heterogeneity in Complex Traits written by Tim Bernard Bigdeli and published by . This book was released on 2011 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Etiological models of complex disease are elusive[46, 33, 9], as are consistently replicable findings for major genetic susceptibility loci[54, 14, 15, 24]. Commonly-cited explanations invoke low-frequency genomic variation[41], allelic heterogeneity at susceptibility loci[33, 30], variable etiological trajectories[18, 17], and epistatic effects between multiple loci; these represent among the most methodologically-challenging issues in molecular genetic studies of complex traits. The response has been con- sistently reactionary -- hypotheses regarding the relative contributions of known functional elements, or emphasizing a greater role of rare variation[46, 33] have undergone periodic revision, driving increasingly collaborative efforts to ascertain greater numbers of participants and which assay a rapidly-expanding catalogue of human genetic variation. Major deep-sequencing initiatives, such as the 1,000 Genomes Project, are currently identifying human polymorphic sites at frequencies previously unassailable and, not ten years after publication of the first major genome-wide association findings, re-sequencing has already begun to displace GWAS as the standard for genetic analysis of complex traits. With studies of complex disease primed for an unprecedented survey of human genetic variation, it is essential that human geneticists address several prominent, problematic aspects of this research. Realizations regarding the boundaries of human traits previously considered to be effectively disparate in presentation[44, 39, 35, 27, 25, 12, 4, 13], as well as profound insight into the extent of human genetic diversity[23, 22] are not without consequence. Whereas the resolution of fine-mapping studies have undergone persistent refinement, recent polygenic findings suggest a less discriminant basis of genetic liability, raising the question of what a given, unitary association finding actually represents. Furthermore, realistic expectations regarding the pattern of findings for a particular genetic factor between or even within populations remain unclear. Of interest herein are methodologies which exploit the finite extent of genomic variability within human populations to distinguish single-point and cumulative group differences in liability to complex traits, the range of allele frequencies for which common association tests are appropriate, and the relevant dimensionality of common genetic variation within ethnically-concordant but differentially ascertained populations. Using high-density SNP genotype data, we consider both hypothesis-driven and agnostic (genome-wide) approaches to association analysis, and address specific issues pertaining to empirical significance and the statistical properties of commonly- applied tests. Lastly, we demonstrate a novel perspective of genome-wide genetic "background" through exhaustive evaluation of fundamental, stochastic genetic processes in a sample of matched affected and unaffected siblings selected from high- density schizophrenia families.
Author : Rany Mansour Salem
Publisher :
ISBN 13 :
Total Pages : 440 pages
Book Rating : 4.:/5 (436 download)
Download or read book Statistical Methods for Genetic Association Analysis Involving Complex Longitudinal Data written by Rany Mansour Salem and published by . This book was released on 2009 with total page 440 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Author : Nourollah Ahmadi
Publisher : Springer Nature
ISBN 13 : 1071622056
Total Pages : 651 pages
Book Rating : 4.0/5 (716 download)
Download or read book Genomic Prediction of Complex Traits written by Nourollah Ahmadi and published by Springer Nature. This book was released on 2022-04-22 with total page 651 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume explores the conceptual framework and the practical issues related to genomic prediction of complex traits in human medicine and in animal and plant breeding. The book is organized into five parts. Part One reminds molecular genetics approaches intending to predict phenotypic variations. Part Two presents the principles of genomic prediction of complex traits, and reviews factors that affect its reliability. Part Three describes genomic prediction methods, including machine-learning approaches, accounting for different degree of biological complexity, and reviews the associated computer-packages. Part Four reports on emerging trends such as phenomic prediction and incorporation into genomic prediction models of “omics” data and crop growth models. Part Five is dedicated to lessons learned from cases studies in the fields of human health and animal and plant breeding, and to methods for analysis of the economic effectiveness of genomic prediction. Written in the highly successful Methods in Molecular Biology series format, the book provides theoretical bases and practical guidelines for an informed decision making of practitioners and identifies pertinent routes for further methodological researches. Cutting-edge and thorough, Complex Trait Predictions: Methods and Protocols is a valuable resource for scientists and researchers who are interested in learning more about this important and developing field. Chapters 3, 9, 13, 14, and 21 are available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.
