An Integrated Approach for the Genetic Dissection of Complex Traits in Yeast PDF Download
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Author: Gal-Hagit Romano
Publisher:
ISBN:
Category :
Languages : en
Pages : 244
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Author: Gal-Hagit Romano
Publisher:
ISBN:
Category :
Languages : en
Pages : 244
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Author: Alexander Kern
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
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Book Description
Understanding the genetic and evolutionary basis of complex traits is an outstanding question in genetics. In contrast to Mendelian traits which are usually affected by one or a few genes, complex traits are affected by variation in multiple genes, often hundreds to thousands. This complexity makes it difficult to determine which biological processes and genetic variants affect these traits. Furthermore, identifying natural selection affecting these traits can be difficult without knowledge of which variants are relevant. One method for identifying the genetic basis of complex traits is quantitative trait locus (QTL) mapping using offspring from genetic crosses of laboratory organisms. In Chapter 2, S. cerevisiae offspring from two parental strains between which polygenic selection on gene expression in the ergosterol pathway was identified are examined to see the effect of this selection on metabolite levels, a more downstream endophenotype. While metabolite QTL and expression QTL overlapped well, the selection on gene expression did not lead to the expected changes in metabolite levels. A new test was developed to identify selection on the metabolite levels, and while there was significant evidence of natural selection affecting metabolite levels, it was clear that the selection on gene expression did not predict the selection on metabolite levels, suggesting the need for studying pathways at multiple levels of endophenotypes to understand selection on complex traits. An additional complexity in understanding complex traits is the effects of environment. Not only can the environment in which an organism lives directly affect a complex trait, but some genetic variants will have different effects on fitness or other traits based on the environment. These effects are known as gene-by-environment interactions (GxE). In chapter 3, we develop an improved method for precisely measuring the effects of natural genetic variants in yeast using precision editing and growth competitions. We then use this technique to identify natural variants in S. cerevisiae which have GxE interactions, first within QTL regions and then within the ergosterol biosynthesis pathway. Together, these two chapters advance our understanding of complex traits at the pathway-level, first by looking between levels of endophenotypes, and then looking at complexity imparted by the environment through GxE interactions.
Author: D.C. Rao
Publisher: Academic Press
ISBN: 0080569110
Category : Medical
Languages : en
Pages : 788
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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
Author: Florian Markowetz
Publisher: Cambridge University Press
ISBN: 131638098X
Category : Science
Languages : en
Pages : 287
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Book Description
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.
Author: Rongling Wu
Publisher: Springer Science & Business Media
ISBN: 038768154X
Category : Science
Languages : en
Pages : 371
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Book Description
This book introduces the basic concepts and methods that are useful in the statistical analysis and modeling of the DNA-based marker and phenotypic data that arise in agriculture, forestry, experimental biology, and other fields. It concentrates on the linkage analysis of markers, map construction and quantitative trait locus (QTL) mapping, and assumes a background in regression analysis and maximum likelihood approaches. The strength of this book lies in the construction of general models and algorithms for linkage analysis, as well as in QTL mapping in any kind of crossed pedigrees initiated with inbred lines of crops.
Author: Andrew H. Paterson
Publisher: CRC Press
ISBN: 9781420049381
Category : Science
Languages : en
Pages : 328
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Book Description
In the past 10 years, contemporary geneticists using new molecular tools have been able to resolve complex traits into individual genetic components and describe each such component in detail. Molecular Dissection of Complex Traits summarizes the state of the art in molecular analysis of complex traits (QTL mapping), placing new developments in thi
Author: Yuan-Ming Zhang
Publisher: Frontiers Media SA
ISBN: 2832543693
Category : Science
Languages : en
Pages : 278
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Book Description
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: National Research Council
Publisher: National Academies Press
ISBN: 0309171806
Category : Nature
Languages : en
Pages : 347
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Book Description
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.
Author: National Research Council
Publisher: National Academies Press
ISBN: 0309038405
Category : Science
Languages : en
Pages : 128
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Book Description
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: Sudheer Doss
Publisher:
ISBN:
Category :
Languages : en
Pages : 252
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Book Description
