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      A High Resolution Genome-Wide Scan for Significant Selective Sweeps: An Application to Pooled Sequence Data in Laying Chickens

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          In most studies aimed at localizing footprints of past selection, outliers at tails of the empirical distribution of a given test statistic are assumed to reflect locus-specific selective forces. Significance cutoffs are subjectively determined, rather than being related to a clear set of hypotheses. Here, we define an empirical p-value for the summary statistic by means of a permutation method that uses the observed SNP structure in the real data. To illustrate the methodology, we applied our approach to a panel of 2.9 million autosomal SNPs identified from re-sequencing a pool of 15 individuals from a brown egg layer line. We scanned the genome for local reductions in heterozygosity, suggestive of selective sweeps. We also employed a modified sliding window approach that accounts for gaps in the sequence and increases scanning resolution by moving the overlapping windows by steps of one SNP only, and suggest to call this a “creeping window” strategy. The approach confirmed selective sweeps in the region of previously described candidate genes, i.e. TSHR, PRL, PRLHR, INSR, LEPR, IGF1, and NRAMP1 when used as positive controls. The genome scan revealed 82 distinct regions with strong evidence of selection (genome-wide p-value<0.001), including genes known to be associated with eggshell structure and immune system such as CALB1 and GAL cluster, respectively. A substantial proportion of signals was found in poor gene content regions including the most extreme signal on chromosome 1. The observation of multiple signals in a highly selected layer line of chicken is consistent with the hypothesis that egg production is a complex trait controlled by many genes.

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          Most cited references 44

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          The Sequence Alignment/Map format and SAMtools

          Summary: The Sequence Alignment/Map (SAM) format is a generic alignment format for storing read alignments against reference sequences, supporting short and long reads (up to 128 Mbp) produced by different sequencing platforms. It is flexible in style, compact in size, efficient in random access and is the format in which alignments from the 1000 Genomes Project are released. SAMtools implements various utilities for post-processing alignments in the SAM format, such as indexing, variant caller and alignment viewer, and thus provides universal tools for processing read alignments. Availability: Contact:
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            Empirical threshold values for quantitative trait mapping.

            The detection of genes that control quantitative characters is a problem of great interest to the genetic mapping community. Methods for locating these quantitative trait loci (QTL) relative to maps of genetic markers are now widely used. This paper addresses an issue common to all QTL mapping methods, that of determining an appropriate threshold value for declaring significant QTL effects. An empirical method is described, based on the concept of a permutation test, for estimating threshold values that are tailored to the experimental data at hand. The method is demonstrated using two real data sets derived from F(2) and recombinant inbred plant populations. An example using simulated data from a backcross design illustrates the effect of marker density on threshold values.
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              Genome-wide detection and characterization of positive selection in human populations.

              With the advent of dense maps of human genetic variation, it is now possible to detect positive natural selection across the human genome. Here we report an analysis of over 3 million polymorphisms from the International HapMap Project Phase 2 (HapMap2). We used 'long-range haplotype' methods, which were developed to identify alleles segregating in a population that have undergone recent selection, and we also developed new methods that are based on cross-population comparisons to discover alleles that have swept to near-fixation within a population. The analysis reveals more than 300 strong candidate regions. Focusing on the strongest 22 regions, we develop a heuristic for scrutinizing these regions to identify candidate targets of selection. In a complementary analysis, we identify 26 non-synonymous, coding, single nucleotide polymorphisms showing regional evidence of positive selection. Examination of these candidates highlights three cases in which two genes in a common biological process have apparently undergone positive selection in the same population:LARGE and DMD, both related to infection by the Lassa virus, in West Africa;SLC24A5 and SLC45A2, both involved in skin pigmentation, in Europe; and EDAR and EDA2R, both involved in development of hair follicles, in Asia.

                Author and article information

                Role: Editor
                PLoS One
                PLoS ONE
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                29 November 2012
                : 7
                : 11
                [1 ]Animal Breeding and Genetics Group, Department of Animal Sciences, Georg-August University, Göttingen, Germany
                [2 ]Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany
                [3 ]Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum Müchen, Neuherberg, Germany
                [4 ]Institute of Farm Animal Genetics, Friedrich Loeffler Institut, Neustadt-Mariensee, Germany
                [5 ]The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, United Kingdom
                [6 ]Lohmann Tierzucht GmbH, Cuxhaven, Germany
                [7 ]Department of Animal Sciences, University of Wisconsin-Madison, Madison, Wisconsin, United States of America
                North Carolina State University, United States of America
                Author notes

                Competing Interests: Author RP is employed by Lohmann Tierzucht GmbH. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

                Conceived and designed the experiments: SQ HS DWB DG. Performed the experiments: TMS RP SW. Analyzed the data: SQ DG HS FT AAG DWB GH. Contributed reagents/materials/analysis tools: TMS RP FT AAG DWB. Wrote the paper: SQ HS DG.


                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                Page count
                Pages: 12
                This research was funded by the German Federal Ministry of Education and Research (BMBF) within the AgroClustEr “Synbreed - Synergistic plant and animal breeding” (FKZ 0315528). The authors acknowledge support by the German Research Foundation and the Open Access Publication Funds of the Göttingen University. DWB, AAG and FT acknowledge the BBSRC/DEFRA LINK grant project for its role in SNP discovery and data handling. Part of this work was carried out while DG was visiting Georg-August-University Goettingen as Alexander von Humboldt Foundation Senior Researcher Awardee. SQ thanks the European Science Foundation (ESF) for financial support of the sabbatical stay at the Roslin Institute (grant No: 3276). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Research Article
                Animal Management
                Animal Genetics
                Anatomy and Physiology
                Reproductive System
                Developmental Biology
                Evolutionary Biology
                Evolutionary Processes
                Evolutionary Selection
                Complex Traits
                Genome-Wide Association Studies
                Population Genetics
                Model Organisms
                Animal Models



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