title: Linked genetic variants on chromosome 10 control ear morphology and body mass among dog breeds.
abstract: BACKGROUND
  The domestic dog is a rich resource for mapping the genetic components of phenotypic variation due to its unique population history involving strong artificial selection. Genome-wide association studies have revealed a number of chromosomal regions where genetic variation associates with morphological characters that typify dog breeds. A region on chromosome 10 is among those with the highest levels of genetic differentiation between dog breeds and is associated with body mass and ear morphology, a common motif of animal domestication. We characterised variation in this region to uncover haplotype structure and identify candidate functional variants.
  
  
  RESULTS
  We first identified SNPs that strongly associate with body mass and ear type by comparing sequence variation in a 3 Mb region between 19 breeds with a variety of phenotypes. We next genotyped a subset of 123 candidate SNPs in 288 samples from 46 breeds to identify the variants most highly associated with phenotype and infer haplotype structure. A cluster of SNPs that associate strongly with the drop ear phenotype is located within a narrow interval downstream of the gene MSRB3, which is involved in human hearing. These SNPs are in strong genetic linkage with another set of variants that correlate with body mass within the gene HMGA2, which affects human height. In addition we find evidence that this region has been under selection during dog domestication, and identify a cluster of SNPs within MSRB3 that are highly differentiated between dogs and wolves.
  
  
  CONCLUSIONS
  We characterise genetically linked variants that potentially influence ear type and body mass in dog breeds, both key traits that have been modified by selective breeding that may also be important for domestication. The finding that variants on long haplotypes have effects on more than one trait suggests that genetic linkage can be an important determinant of the phenotypic response to selection in domestic animals.
authors.affiliation: Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden. matthew.webster@imbim.uu.se.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Webster
authors.affiliation: Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden. nkamgari@yahoo.com.
authors.forename: Nona
authors.initials: N
authors.lastname: Kamgari
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, MA, USA. perloski@broadinstitute.org.
authors.forename: Michele
authors.initials: M
authors.lastname: Perloski
authors.affiliation: Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden. marc.hoeppner@imbim.uu.se.|Bioinformatics Infrastructure for Life Sciences, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden. marc.hoeppner@imbim.uu.se.
authors.forename: Marc P
authors.initials: MP
authors.lastname: Hoeppner
authors.affiliation: Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden. erik.axelsson@imbim.uu.se.
authors.forename: Erik
authors.initials: E
authors.lastname: Axelsson
authors.affiliation: Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden. ake.hedhammar@slu.se.
authors.forename: Åke
authors.initials: Å
authors.lastname: Hedhammar
authors.affiliation: Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden. gerli.pielberg@imbim.uu.se.
authors.forename: Gerli
authors.initials: G
authors.lastname: Pielberg
authors.affiliation: Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden. kersli@broadinstitute.org.|Broad Institute of MIT and Harvard, Cambridge, MA, USA. kersli@broadinstitute.org.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Lindblad-Toh
mesh_terms: D000818:Animals; D000829:Animals, Domestic / Q000235:genetics; D015992:Body Mass Index; D001947:Breeding; D002875:Chromosomes / Q000235:genetics*; D004285:Dogs / Q000033:anatomy & histology / Q000235:genetics*; D004423:Ear / Q000033:anatomy & histology*; D055106:Genome-Wide Association Study; D025743:HMGA2 Protein / Q000235:genetics; D051150:Methionine Sulfoxide Reductases / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide
chemical_list: D025743:HMGA2 Protein; D051150:Methionine Sulfoxide Reductases