Friedmann Advances in Genetics

1. Auflage 2014
ISBN: 978-0-12-800369-5
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: 6 - ePub Watermark

E-Book, Englisch, Band Volume 87, 312 Seiten

Reihe: Advances in Genetics

The field of genetics is rapidly evolving, and new medical breakthroughs are occurring as a result of advances in our knowledge of genetics. Advances in Genetics continually publishes important reviews of the broadest interest to geneticists and their colleagues in affiliated disciplines. Volume 87 presents an eclectic mix of articles of use to all human and molecular geneticists on topics including: gene transfer, fruiting body development and the genetics of Alzheimer's disease; and more. - Includes methods for testing with ethical, legal, and social implications - Critically analyzes future directions - Written and edited by recognized leaders in the field

Autoren/Hrsg.

Friedmann, Theodore

Inhaltsverzeichnis

1;Front Cover;1
2;Advances in Genetics;4
3;Copyright;5
4;CONTENTS;6
5;CONTRIBUTORS;8
6;1 - Opportunity for Selection in Human Health;10
6.1;1. INTRODUCTION;11
6.2;2. GENETIC VARIATION AND DEMOGRAPHIC SELECTION;17
6.3;3. EPISODES OF SELECTION;24
6.4;4. SELECTION SPECTRA;38
6.5;5. PLACE OF MULTILEVEL SELECTION IN MEDICAL PRACTICE AND PUBLIC HEALTH;52
6.6;6. DISCUSSION;60
6.7;ACKNOWLEDGMENTS;64
6.8;REFERENCES;64
7;2 - Clinical Applications Involving CNS Gene Transfer;80
7.1;1. INTRODUCTION;81
7.2;2. CNS CLINICAL TRIALS UTILIZING RETROVIRAL VECTORS;84
7.3;3. CNS CLINICAL TRIALS UTILIZING AAV VECTORS;101
7.4;4. LESSONS LEARNED FROM RELATED STUDIES;117
7.5;5. CONCLUSION;119
7.6;REFERENCES;120
8;3 - Methods for Gene Transfer to the Central Nervous System;134
8.1;1. INTRODUCTION;135
8.2;2. VECTORS FOR CNS GENE TRANSFER;136
8.3;3. GENOME DESIGNS FOR OPTIMAL EXPRESSIONS;177
8.4;4. CONCLUSIONS;186
8.5;REFERENCES;187
9;4 - The Filamentous Fungus Sordaria macrospora as a Genetic Model to Study Fruiting Body Development;208
9.1;1. INTRODUCTION;209
9.2;2. GENETIC AND GENOMIC TOOLS;211
9.3;3. THE STRIATIN-INTERACTING PHOSPHATASE AND KINASE COMPLEX, A MULTISUBUNIT PROTEIN COMPLEX GOVERNING FRUITING BODY DEVELOPMENT;219
9.4;4. CHROMATIN-RELATED PROCESSES;223
9.5;5. METABOLISM-RELATED DEVELOPMENTAL PROCESSES;227
9.6;6. AUTOPHAGY;236
9.7;7. CONCLUDING REMARKS AND OUTLOOK;242
9.8;ACKNOWLEDGMENTS;243
9.9;REFERENCES;243
10;5 - Genetics of Alzheimer’s Disease;254
10.1;1. INTRODUCTION;255
10.2;2. HERITABILITY OF ALZHEIMER’S DISEASE;257
10.3;3. GENETIC CAUSES OF EARLY-ONSET ALZHEIMER’S DISEASE;258
10.4;4. GENETIC RISK FACTORS FOR LATE-ONSET ALZHEIMER’S DISEASE;260
10.5;5. DISCUSSION;284
10.6;REFERENCES;287
11;INDEX;304

Leseproben

Chapter One Opportunity for Selection in Human Health
Diddahally R. Govindaraju email address: [e-mail]     National Evolutionary Synthesis Center, Durham, NC, USA Abstract
Natural selection defined by differential survival and reproduction of individuals in populations is influenced by genetic, developmental, and environmental factors operating at every age and stage in human life history: generation of gametes, conception, birth, maturation, reproduction, senescence, and death. Biological systems are built upon a hierarchical organization nesting subcellular organelles, cells, tissues, and organs within individuals, individuals within families, and families within populations, and the latter among other populations. Natural selection often acts simultaneously at more than one level of biological organization and on specific traits, which we define as multilevel selection. Under this model, the individual is a fundamental unit of biological organization and also of selection, imbedded in a larger evolutionary context, just as it is a unit of medical intervention imbedded in larger biological, cultural, and environmental contexts. Here, we view human health and life span as necessary consequences of natural selection, operating at all levels and phases of biological hierarchy in human life history as well as in sociological and environmental milieu. An understanding of the spectrum of opportunities for natural selection will help us develop novel approaches to improving healthy life span through specific and global interventions that simultaneously focus on multiple levels of biological organization. Indeed, many opportunities exist to apply multilevel selection models employed in evolutionary biology and biodemography to improving human health at all hierarchical levels. Multilevel selection perspective provides a rational theoretical foundation for a synthesis of medicine and evolution that could lead to discovering effective predictive, preventive, palliative, potentially curative, and individualized approaches in medicine and in global health programs. Keywords
Developmental demography; Evolution and medicine; Fitness; Genetic disease burden; Identity-by-context; Individualized medicine; Lansing range; Multilevel selection; Population structure; Units and targets of selection Natural selection acts only tentatively. Darwin (1871) …loss of fitness is the price paid by a species for its capacity for further evolution. Haldane (1937) Natural selection is multilevel: A phenotypic target can exist at any level of biological organization, from macromolecular to chromosomes to eukaryotic cells to multicellular organisms, and onto organized social groups, populations of organisms and groups, and finally, arguably, entire ecosystems. E. O. Wilson (2009) 1. Introduction
Disease is generally defined as any deviation from normal structure and function of an organ that is associated with a set of symptoms present in an individual due to known or unknown causes (Engel, 1977; Weatherall, 2011) including the ones attributable to genetic, developmental and environmental factors. Genetic bases of certain diseases associated with metabolism were first discovered by Garrod (1902, 1908) and later elaborated by others (Cushing, 1916). In recent years, several authors have emphasized, in accordance with Mayr’s model of proximate (immediate physiological and developmental) and ultimate (evolutionary) causes (Mayr, 1961), that diseases could be understood in terms of their proximate causation, the causal agent, and ultimate causation, as well as the evolutionary processes that gave rise to them (Childs, 1999, 2002; Nesse & Williams, 1996; Nesse, Stearns, & Omenn, 2006; Stearns, 2012; Stearns, Nesse, Govindaraju, & Ellison, 2010). As a corollary, because the origins and spread of human diseases may be traced to biological, physical, cultural, and social environments in which the human species has evolved, and is evolving, several medical scientists (Childs, 1999; Engel, 1977; Weatherall, 2011) have argued that it is logical to evaluate human diseases in those contexts. Diseases impose enormous health burden on human populations. These could arise due to congenital and other factors. Nearly 50% of all deaths among people under 65 years are due to either congenital factors (12%) or other noncommunicable disorders (38%) such as heart and liver disease, diabetes, osteoporosis, and asthma (Anonymous, 2012). Close to 8 million children are born each year with genetic defects, and 3 million children under age five die from these (Bittles, 2013; Weatherall, 2011). Roughly one in 15 or 400 million people worldwide, 25 million Americans, and 30 million Europeans are diagnosed with one or a few of the 7000 rare genetic disorders (van Weely & Leufkens, 2013, p. 46). Hence, it is conceivable that at least 50% of all diseases that cause human mortality may have genetic bases. Juvenile mortality (caused by genetic and nongenetic factors), in particular, is a significant contributor to natural selection (Haldane, 1957). Genetic disorders, including the rare ones, are the phenotypic manifestations of mutations and epimutations that often arise spontaneously among individuals within families, and spread among families nested within populations. Since all factors that influence inheritance and variation are governed by evolutionary laws, it may be reasonable to generalize that all biological components of human health and diseases spanning from gametogenesis, fertilization, birth, development, reproduction, maturity, and senescence are influenced by both proximate and evolutionary causes (Childs, 1999). Indeed, Garrod over a century ago wrote that, “As far as our present knowledge of them (inborn errors of metabolism/genetic disorders) enables us to judge they apparently result from failure of some step or other in the series of chemical changes which I call metabolism, and are in this respect most nearly analogous to what are known as malformation by defect” … “Upon chemical as upon structural variations, the factors which make for evolution have worked and are working” (Garrod, 1909). The foregoing clearly suggests that mortality due to genetic causes could potentially influence microevolutionary changes in human populations (Haldane, 1949). Currently, there is tremendous on-going effort in order to circumvent genetic disorders or to develop approaches for individual heath care on the bases of genetic architecture of diseases (e.g., “base pairs to bedside”; Green & Guyer, 2011). Since ultimately all genetic disorders are phenotypic manifestation of genetic and epigenetic variations, which also fuels all evolutionary changes, it helps to understand the origins and spread of these diseases from an evolutionary perspective, in order to develop effective medical interventions for improving human health. From a proximate view, diseases may be interpreted as perturbations in living systems caused by genetic, physiological, and environmental factors during the life history of organisms. These perturbations would differentially affect both viability and reproduction of individuals, families, populations, and to a limited extent large (meta) populations leading to changes in gene frequencies among populations over generations—a process broadly defined as natural selection (Haldane, 1957). Fitness, a function of differential viability and reproduction among individuals (also variance in fitness), represents natural selection, is the degree to which individuals in one generation contribute to the fitness of populations in subsequent generations. Indeed, the evolutionary potential and the associated properties or evolvability (Wagner, 2005) of any population are proportional to the amount of genetic variation it carries at that time (Fisher, 1930). The variance in fitness among individuals in a population is determined by among-individual differences in fitness traits (specifically number of individuals that contribute to future generations), and the degree of relationship between the variation in fitness and a trait defines the strength of natural selection on that trait. This original proposition on the direct relationship between variation in fitness among individuals and the degree of evolutionary changes in successive generations by Fisher (1930) has been further elaborated by others, primarily taking two related approaches: selection gradients, ß (Lande & Arnold, 1983; Price, 1970; Robertson, 1966), and opportunity for selection, I (Crow, 1958; O’Donald, 1970; Wade, 1979). Both indices have been employed to measure “the potential for selection to occur” among human populations in a relatively short term (Krakauer, Webster, Duval, Jones, & Shuster, 2011; Moorad, 2013; Stearns, Byars, Govindaraju, & Ewbank, 2010). Biological diversity is a nested hierarchy of nucleotides within genes, genes within chromosomes, chromosomes within cells, cells nested in individuals, and all of these organized into a multiscale hierarchy of families and populations within species (Rand, 2011). Since a majority of these components are hierarchically and developmentally...