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      The population genetics of mutations: good, bad and indifferent

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          Abstract

          Population genetics is fundamental to our understanding of evolution, and mutations are essential raw materials for evolution. In this introduction to more detailed papers that follow, we aim to provide an oversight of the field. We review current knowledge on mutation rates and their harmful and beneficial effects on fitness and then consider theories that predict the fate of individual mutations or the consequences of mutation accumulation for quantitative traits. Many advances in the past built on models that treat the evolution of mutations at each DNA site independently, neglecting linkage of sites on chromosomes and interactions of effects between sites (epistasis). We review work that addresses these limitations, to predict how mutations interfere with each other. An understanding of the population genetics of mutations of individual loci and of traits affected by many loci helps in addressing many fundamental and applied questions: for example, how do organisms adapt to changing environments, how did sex evolve, which DNA sequences are medically important, why do we age, which genetic processes can generate new species or drive endangered species to extinction, and how should policy on levels of potentially harmful mutagens introduced into the environment by humans be determined?

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          The hitch-hiking effect of a favourable gene

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            Common polygenic variation contributes to risk of schizophrenia and bipolar disorder.

            Schizophrenia is a severe mental disorder with a lifetime risk of about 1%, characterized by hallucinations, delusions and cognitive deficits, with heritability estimated at up to 80%. We performed a genome-wide association study of 3,322 European individuals with schizophrenia and 3,587 controls. Here we show, using two analytic approaches, the extent to which common genetic variation underlies the risk of schizophrenia. First, we implicate the major histocompatibility complex. Second, we provide molecular genetic evidence for a substantial polygenic component to the risk of schizophrenia involving thousands of common alleles of very small effect. We show that this component also contributes to the risk of bipolar disorder, but not to several non-psychiatric diseases.
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              Epistasis--the essential role of gene interactions in the structure and evolution of genetic systems.

              Epistasis, or interactions between genes, has long been recognized as fundamentally important to understanding the structure and function of genetic pathways and the evolutionary dynamics of complex genetic systems. With the advent of high-throughput functional genomics and the emergence of systems approaches to biology, as well as a new-found ability to pursue the genetic basis of evolution down to specific molecular changes, there is a renewed appreciation both for the importance of studying gene interactions and for addressing these questions in a unified, quantitative manner.
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                Author and article information

                Journal
                Philosophical Transactions of the Royal Society B: Biological Sciences
                Phil. Trans. R. Soc. B
                The Royal Society
                0962-8436
                1471-2970
                April 27 2010
                April 27 2010
                April 27 2010
                : 365
                : 1544
                : 1153-1167
                Affiliations
                [1 ]Institute of Evolutionary Biology, University of Edinburgh, Edinburgh EH9 3JT, UK
                [2 ]Centre for Systems Biology at Edinburgh, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JT, UK
                Article
                10.1098/rstb.2009.0317
                2871823
                20308090
                8d203e01-3b39-4311-9383-4afceb43abb9
                © 2010

                https://royalsociety.org/journals/ethics-policies/data-sharing-mining/

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