Breed History and Structure Predict the Utility of Canine Genome Studies

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 traits, researchers have leveraged the dog system as an effective natural model for the study of complex traits, such as disease susceptibility, behavior, and morphology, providing 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 bottleneck. 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 for 800 individuals from 80 breeds. These data were coupled with extensive pedigree data analyses for 11 breeds, which allowed us to compute breed structure, demography, and molecular measures of genome diversity that should be acknowledged in order to accurately design canine genomic studies. 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 essential considerations influencing the technological and sampling design of association and other genomic studies.