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      Demographically-based evaluation of genomic regions under selection in domestic dogs

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      Author(s)
      Freedman, A. H.
      Schweizer, R. M.
      Vecchyo, D. Ortega-Del
      Han, E.
      Davis, B. W.
      Gronau, I.
      Silva, P. M.
      Galaverni, M.
      Fan, Z.
      Marx, P.
      Lorente-Galdos, B.
      Ramirez, O.
      Hormozdiari, F.
      Alkan C.
      Vilà, C.
      Squire K.
      Geffen, E.
      Kusak, J.
      Boyko, A. R.
      Parker, H. G.
      Lee C.
      Tadigotla, V.
      Siepel, A.
      Bustamante, C. D.
      Harkins, T. T.
      Nelson, S. F.
      Marques Bonet, T.
      Ostrander, E. A.
      Wayne, R. K.
      Novembre, J.
      Date
      2016
      Source Title
      PL o S Genetics
      Print ISSN
      1553-7390
      Publisher
      Public Library of Science
      Pages
      1 - 23
      Language
      English
      Type
      Article
      Item Usage Stats
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      157
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      Abstract
      Controlling for background demographic effects is important for accurately identifying loci that have recently undergone positive selection. To date, the effects of demography have not yet been explicitly considered when identifying loci under selection during dog domestication. To investigate positive selection on the dog lineage early in the domestication, we examined patterns of polymorphism in six canid genomes that were previously used to infer a demographic model of dog domestication. Using an inferred demographic model, we computed false discovery rates (FDR) and identified 349 outlier regions consistent with positive selection at a low FDR. The signals in the top 100 regions were frequently centered on candidate genes related to brain function and behavior, including LHFPL3, CADM2, GRIK3, SH3GL2, MBP, PDE7B, NTAN1, and GLRA1. These regions contained significant enrichments in behavioral ontology categories. The 3rdtop hit, CCRN4L, plays a major role in lipid metabolism, that is supported by additional metabolism related candidates revealed in our scan, including SCP2D1 and PDXC1. Comparing our method to an empirical outlier approach that does not directly account for demography, we found only modest overlaps between the two methods, with 60% of empirical outliers having no overlap with our demography-based outlier detection approach. Demography-aware approaches have lower-rates of false discovery. Our top candidates for selection, in addition to expanding the set of neurobehavioral candidate genes, include genes related to lipid metabolism, suggesting a dietary target of selection that was important during the period when proto-dogs hunted and fed alongside hunter-gatherers. © 2016, Public Library of Science. All Rights Reserved.
      Keywords
      Single nucleotide
      Behavior
      Brain function
      CADM2 gene
      CCRN4L gene
      Demography
      Diet
      Dog
      Domestic animal
      Domestication
      Gene
      Gene sequence
      Genetic polymorphism
      Genetic selection
      Genome
      Genomics
      Genotype
      GLRA1 gene
      GRIK3 gene
      LHFPL3 gene
      Lipid metabolism
      MBP gene
      Nonhuman
      NTAN1 gene
      PDE7B gene
      PDXC1 gene
      SCP2D1 gene
      Sequence alignment
      SH3GL2 gene
      Animal
      Genetics
      Population genetics
      Single nucleotide polymorphism
      Demography
      Dogs
      Population
      Lipid Metabolism
      Polymorphism
      Selection
      Permalink
      http://hdl.handle.net/11693/36809
      Published Version (Please cite this version)
      http://dx.doi.org/10.1371/journal.pgen.1005851
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      • Department of Computer Engineering 1561
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