title: Whole-genome sequence, SNP chips and pedigree structure: building demographic profiles in domestic dog breeds to optimize genetic-trait mapping.
abstract: In the decade following publication of the draft genome sequence of the domestic dog, extraordinary advances with application to several fields have been credited to the canine genetic system. Taking advantage of closed breeding populations and the subsequent selection for aesthetic and behavioral characteristics, researchers have leveraged the dog as an effective natural model for the study of complex traits, such as disease susceptibility, behavior and morphology, generating unique contributions to human health and biology. When designing genetic studies using purebred dogs, it is essential to consider the unique demography of each population, including estimation of effective population size and timing of population bottlenecks. The analytical design approach for genome-wide association studies (GWAS) and analysis of whole-genome sequence (WGS) experiments are inextricable from demographic data. We have performed a comprehensive study of genomic homozygosity, using high-depth WGS data for 90 individuals, and Illumina HD SNP data from 800 individuals representing 80 breeds. These data were coupled with extensive pedigree data analyses for 11 breeds that, together, allowed us to compute breed structure, demography, and molecular measures of genome diversity. Our comparative analyses characterize the extent, formation and implication of breed-specific diversity as it relates to population structure. These data demonstrate the relationship between breed-specific genome dynamics and population architecture, and provide important considerations influencing the technological and cohort design of association and other genomic studies.
authors.affiliation: Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Dayna L
authors.initials: DL
authors.lastname: Dreger
authors.affiliation: Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.|Institut de Génétique et Développement de Rennes, Rennes 35043, France.
authors.forename: Maud
authors.initials: M
authors.lastname: Rimbault
authors.affiliation: Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Brian W
authors.initials: BW
authors.lastname: Davis
authors.affiliation: Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.|PIC North America, Hendersonville, TN 37075, USA.
authors.forename: Adrienne
authors.initials: A
authors.lastname: Bhatnagar
authors.affiliation: Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Heidi G
authors.initials: HG
authors.lastname: Parker
authors.affiliation: Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA eostrand@mail.nih.gov.
authors.forename: Elaine A
authors.identifier: 0000-0001-6075-9738
authors.initials: EA
authors.lastname: Ostrander
mesh_terms: D000818:Animals; D000829:Animals, Domestic / Q000235:genetics; D001483:Base Sequence; D001947:Breeding; D002874:Chromosome Mapping / Q000379:methods*; D030541:Databases, Genetic; D003710:Demography; D004285:Dogs / Q000235:genetics*; D016678:Genome; D006720:Homozygote; D007178:Inbreeding; D020411:Oligonucleotide Array Sequence Analysis; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011156:Population Density; D011157:Population Dynamics; D019655:Quantitative Trait, Heritable
keywords: Canine; Homozygosity; Inbreeding; Population