Abstract

BackgroundIn canine genetics, the impact of population structure on whole genome association studies is typically addressed by sampling approximately equal numbers of cases and controls from dogs of a single breed, usually from the same country or geographic area. However one way to increase the power of genetic studies is to sample individuals of the same breed but from different geographic areas, with the expectation that independent meiotic events will have shortened the presumed ancestral haplotype around the mutation differently. Little is known, however, about genetic variation among dogs of the same breed collected from different geographic regions.Methodology/Principal FindingsIn this report, we address the magnitude and impact of genetic diversity among common breeds sampled in the U.S. and Europe. The breeds selected, including the Rottweiler, Bernese mountain dog, flat-coated retriever, and golden retriever, share susceptibility to a class of soft tissue cancers typified by malignant histiocytosis in the Bernese mountain dog. We genotyped 722 SNPs at four unlinked loci (between 95 and 271 per locus) on canine chromosome 1 (CFA1). We showed that each population is characterized by distinct genetic diversity that can be correlated with breed history. When the breed studied has a reduced intra-breed diversity, the combination of dogs from international locations does not increase the rate of false positives and potentially increases the power of association studies. However, over-sampling cases from one geographic location is more likely to lead to false positive results in breeds with significant genetic diversity.ConclusionsThese data provide new guidelines for association studies using purebred dogs that take into account population structure.

Highlights

  • The domestic dog species (Canis familiaris) is divided into over 300 pure breeding populations known as breeds

  • We have evaluated the genetic relatedness of independently bred lines of European and American dogs from the Bernese mountain dog (BMD), flat-coated retriever (FCR), golden retriever (GR) and Rottweiler (ROT) breeds

  • When the number of disease genotypes was unequal in the two populations, we found 7.1, 6.2, 7.2 and 4.3% for BMD, FCR, GR and ROT, respectively

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Summary

Introduction

The domestic dog species (Canis familiaris) is divided into over 300 pure breeding populations known as breeds. Relying on comparative maps generated between dog and human [8,9], the 1.56 poodle sequence [10], and, most recently, the whole genome assembly of the boxer [11], researchers have utilized families of dogs from one or a limited number of related breeds to identify loci responsible for variable phenotypes, typically associated with disease susceptibility (reviewed in [3,4,6]) and morphology[9,12,13]. The impact of population structure on whole genome association studies is typically addressed by sampling approximately equal numbers of cases and controls from dogs of a single breed, usually from the same country or geographic area. These data provide new guidelines for association studies using purebred dogs that take into account population structure

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