Canine Population Structure: Assessment and Impact of Intra-Breed Stratification on SNP-Based Association Studies

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.

The genomic architecture of segmental duplications and associated copy number variants in dogs

“…We found extensive copy number variation in segmental duplications across 17 phenotypically diverse breeds that affect 429 genes. Our study provides the foundation for correlating structural variation with phenotypic variation observed within and between breeds, which we suspect will be an important complement to SNP centric genome-wide association studies Mosher et al 2007;Parker et al 2007;Quignon et al 2007;Salmon Hillbertz et al 2007;Sutter et al 2007). However, in order to perform more principled phenotypic studies with structural variation, it will be necessary to better delimit the Figure 4.…”

“…These resources have provided important foundations for delimiting patterns of population structure among breeds (Irion et al 2003;Parker et al 2004;Karlsson et al 2007;Quignon et al 2007), inferring targets of artificial selection (Pollinger et al 2005), and mapping traits such as Collie eye anomaly ), body size , and muscle mass .…”

A longitudinal study of ABC transporter expression in canine multicentric lymphoma

“…The results may serve as means to improve health of the breed as well as basis for comparative oncological research [12,16]. Furthermore, regional variation in genetic population structure may appear [28].…”

Genetic Variability inBracco ItalianoDog Breed Assessed by Pedigree Data

“…The genetic variability of a population can be estimated from genealogical data (Cecchi et al, 2009;Grazewska, 2007;Leroy et al, 2006;Leroy et al, 2009;Maki et al, 2001) or using the short tandem repeat (STR) molecular markers (Kim et al, 2001;Koskinen et al, 2000;Leroy et al, 2009). At the present several researches used SNPs ( Quignon et al, 2007;vonHoldt et al, 2010;Wayne and vonHoldt, 2012) because of the ease in genotyping a biallelic marker and the ability to multiplex thousands of markers in one reaction (Parker, 2012). The Bracco Italiano is one of the oldest pointing dog breed, used for hunting ever since the Renaissance time.…”