Canine population structure: assessment and impact of intra-breed stratification on SNP-based association studies - PubMed (original) (raw)

Canine population structure: assessment and impact of intra-breed stratification on SNP-based association studies

Pascale Quignon et al. PLoS One. 2007.

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.

Methodology/principal findings: 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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1

Figure 1. Hierarchical clustering between the four breeds.

Clustering of the 119 dogs (k = 4) from the four different breeds. In the dendogram each vertical line represents a single dog and the color reflects the four clusters obtained by PLINK analysis. A grey dashed line indicates an outlier dog. Below the dendogram, dogs are named by their breed origin, and names are colored upon their cluster assignment. At the bottom of the figure, colored squares are drawn on four lines, each line representing the different breeds. The scale on the right axis represents the genetics distances calculated by PLINK software. Each breed separates from the others as the four colors correspond exactly to the four breeds, red for BMD, blue for FCR, black for GR and green for ROT.

Figure 2

Figure 2. Hierarchical clustering within breeds.

The figure shows the clustering analysis (k = 2) within each breed for BMD, FCR, ROT and GR (n = 30 for each breed). For each breed, a dendogram is drawn in which each vertical line represents a single dog. The two clusters are represented in blue and red, and grey dashed lines indicate outlier dogs. Below the dendogram, dogs are named by geographical origin (US or EU), and names are colored upon their cluster assignment. The scale on the right axis represents the genetics distances calculated by PLINK software.

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