title: Canine population structure: assessment and impact of intra-breed stratification on SNP-based association studies.
abstract: BACKGROUND
  In 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.
  
  
  RESULTS
  In 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.
  
  
  CONCLUSIONS
  These data provide new guidelines for association studies using purebred dogs that take into account population structure.
authors: Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
authors: Pascale
authors: P
authors: Quignon
authors: Laetitia
authors: L
authors: Herbin
authors: Edouard
authors: E
authors: Cadieu
authors: Ewen F
authors: EF
authors: Kirkness
authors: Benoit
authors: B
authors: Hédan
authors: Dana S
authors: DS
authors: Mosher
authors: Francis
authors: F
authors: Galibert
authors: Catherine
authors: C
authors: André
authors: Elaine A
authors: EA
authors: Ostrander
authors: Christophe
authors: C
authors: Hitte
mesh_terms: D000818:Animals; D004285:Dogs; D005787:Gene Frequency; D006579:Heterozygote; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D013045:Species Specificity