Project description:This study used two different NimbleGen platforms to identify canine CNVs. The first identifies genome-wide CNVs while the second genotypes all known canine CNVs in a large panel of dogs from multiple breeds.
Project description:DNA structural variation (SV) comprises a major portion of genetic diversity, but its biological impact is unclear. We propose that the genetic history and extraordinary phenotypic variation of dogs make them an ideal mammal in which to study the effects of SV on biology and disease. The hundreds of existing dog breeds were created by selection of extreme morphological and behavioral traits. And along with those traits, each breed carries increased risk for different diseases. We used array CGH to create the first map of DNA copy number variation (CNV) or SV in dogs. The extent of this variation, and some of the gene classes affected, are similar to those of mice and humans. Most canine CNVs affect genes, including disease and candidate disease genes, and are thus likely to be functional. We identified many CNVs that may be breed or breed class specific. Cluster analysis of CNV regions showed that dog breeds tend to group according to breed classes. Our combined findings suggest many CNVs are (1) in linkage disequilibrium with flanking sequence, and (2) associated with breed specific traits. We discuss how a catalog of structural variation in dogs will accelerate the identification of the genetic basis of canine traits and diseases, beginning with the use of whole genome association and candidate CNV/gene approaches. Chen WK, Swartz JD, Rush LJ, Alvarez, CE. Mapping DNA structural variation in dogs. Genome Res. 2009. 19: 500 509 PMID: 19015322
Project description:DNA structural variation (SV) comprises a major portion of genetic diversity, but its biological impact is unclear. We propose that the genetic history and extraordinary phenotypic variation of dogs make them an ideal mammal in which to study the effects of SV on biology and disease. The hundreds of existing dog breeds were created by selection of extreme morphological and behavioral traits. And along with those traits, each breed carries increased risk for different diseases. We used array CGH to create the first map of DNA copy number variation (CNV) or SV in dogs. The extent of this variation, and some of the gene classes affected, are similar to those of mice and humans. Most canine CNVs affect genes, including disease and candidate disease genes, and are thus likely to be functional. We identified many CNVs that may be breed or breed class specific. Cluster analysis of CNV regions showed that dog breeds tend to group according to breed classes. Our combined findings suggest many CNVs are (1) in linkage disequilibrium with flanking sequence, and (2) associated with breed specific traits. We discuss how a catalog of structural variation in dogs will accelerate the identification of the genetic basis of canine traits and diseases, beginning with the use of whole genome association and candidate CNV/gene approaches. Chen WK, Swartz JD, Rush LJ, Alvarez, CE. Mapping DNA structural variation in dogs. Genome Res. 2009. 19: 500 509 PMID: 19015322 Array comparitive genomic hybridization analysis of structural variation in 9 dogs, and 1 lymphoma cell line.
Project description:Selective breeding of domestic dogs has generated diverse breeds often optimized for performing specialized tasks. Despite the heritability of breed-typical behavioral traits, identification of causal loci has proven challenging due to the complexity of canine population structure. We overcome longstanding difficulties in identifying genetic drivers of canine behavior by developing an innovative framework for understanding relationships between breeds and the behaviors that define them utilizing genetic data for over 4,000 domestic, semi-feral and wild canids and behavioral survey data for over 46,000 dogs. We identify ten major canine genetic lineages and their behavioral correlates and show that breed diversification is predominantly driven by non-coding regulatory variation. We determine that lineage-associated genes converge in neurodevelopmental co-expression networks, identifying a sheepdog-associated enrichment for interrelated axon guidance functions. This work presents a scaffold for canine diversification that positions the domestic dog as an unparalleled system for revealing the genetic origins of behavioral diversity.
Project description:Canine forms of osteoarthritis (OA) are very similar to those in humans and represent a welfare problem in the dog world population. In this study, we investigated the transcriptomic profile of peripheral blood in German Shepherd dogs with OA in order to identify diagnosis biomarkers. The bulk RNA-seq experiment was performed in a cohort of 12 adult dogs, 5 affected and 7 unaffected. Radiographs of the affected dogs revealed severe osteoarthritis in hip and elbow joints. The expression analysis showed 171 differentially expressed genes (DEGs), 113 were upregulated and 58 were downregulated compared to control dogs P (< 0.01). This pool of genes was functional annotated for signaling pathways using PANTHER tools. No overrepresented pathways were found. To gain further insights of the functional role of the DEGs in OA, we set a threshold of log2FoldChange value between -1.5 and 1.5. We ended up with 24 top up- and downregulated transcripts. Prioritization of these DEGs according to their known functional knowledge, revealed 5 possible candidates for OA biomarkers. The downregulated OSCAR gene encodes the osteoclast associated Ig-like receptor, which is involved in osteoclastogenesis regulation and bone homeostasis. In addition, the upregulated microRNA MIR339-1 and ncRNAs: LOC106559235 (downregulated), LOC102156762 (downregulated) and LOC111096460 (upregulated) are regulatory sequences, stable for gene profiling assessment in blood and related to OA pathogenesis regulation. We suggest OSCAR as the more likely candidate biomarker for OA diagnosis in dogs and, provide evidence of new circulating regulatory sequences differentially expressed in canine OA.