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: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: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. The genome-wide microarray used was designed by NimbleGen. The genotyping chip was created by tiling all available probes to all known CNVs identified here and in previous studies.
Project description:Osteosarcoma in dogs is a spontaneously occurring disease with a global tumor gene expression signature indistinguishable from human pediatric tumors and clinical progression is remarkably similar. Unlike human OS, canine OS is a highly heritable disease with some large and giant dog breeds at >10x increased risk. We did a genome wide association study of osteosarcoma using the Illumina CanineHD genotyping array in three breeds: greyhound (mortality from OS = 26%), rottweiler (17%) and Irish wolfhound (IWH, 21%) and identified 33 inherited risk loci explaining 55 to 85% of phenotype variance in each breed.
Project description:Osteosarcoma in dogs is a spontaneously occurring disease with a global tumor gene expression signature indistinguishable from human pediatric tumors and clinical progression is remarkably similar. Unlike human OS, canine OS is a highly heritable disease with some large and giant dog breeds at >10x increased risk. We did a genome wide association study of osteosarcoma using the Illumina CanineHD genotyping array in three breeds: greyhound (mortality from OS = 26%), rottweiler (17%) and Irish wolfhound (IWH, 21%) and identified 33 inherited risk loci explaining 55 to 85% of phenotype variance in each breed.
Project description:Osteosarcoma in dogs is a spontaneously occurring disease with a global tumor gene expression signature indistinguishable from human pediatric tumors and clinical progression is remarkably similar. Unlike human OS, canine OS is a highly heritable disease with some large and giant dog breeds at >10x increased risk. We did a genome wide association study of osteosarcoma using the Illumina CanineHD genotyping array in three breeds: greyhound (mortality from OS = 26%), rottweiler (17%) and Irish wolfhound (IWH, 21%) and identified 33 inherited risk loci explaining 55 to 85% of phenotype variance in each breed.
Project description:Background: Dilated cardiomyopathy (DCM) is the most common acquired heart disease in large- and giant-breed dogs with Doberman Pinschers representing one of the most frequently affected breeds. MicroRNAs (miRNAs) are short non-coding RNAs which play important roles in gene regulation. Different miRNA expression patterns have been described for human DCM and might represent potential diagnostic markers. There are no studies to date investigating miRNA expression profiles in canine DCM. Goals: The goals of this study were to screen the miRNAs expression profile of canine serum by using a miRNA microarray platform and to compare the miRNA expression patterns of a group of Doberman Pinschers with DCM and healthy controls. Results: Although total RNA concentrations were very low in canine serum samples, 421 different miRNAs were detectable with sufficient signal intensity on the miRNA microarrays. About 30 miRNAs were differentially expressed in the two groups, but did not reach statistical significance. No significant differences were found using specific miRNA PCR assays. Conclusions: More than 400 miRNAs can be detected in canine serum samples. Changes in expression levels of various miRNAs between healthy and DCM dogs could be detected, but the results did not reach statistical significance most probably due to the small group size. miRNAs are potential new circulating biomarkers in veterinary medicine and should be investigated in larger patient groups and additional canine diseases
Project description:Canine gastric dilatation-volvulus (GDV) is a common life-threatening condition occurring primarily in large and giant breeds with a 3.9% to 36.7% lifetime risk. GDV is a complex disease with risk factors including age, diet, behavior, family history, and genetics. The genetic correlates of GDV have not previously been systematically explored. We undertook multiplatform genome-wide association analysis (GWAS) of 253 dogs including 106 healthy dogs and 147 dogs with at least one GDV episode. The study included ten dog breeds enriched for Borzoi, German Shepherd (GSD), Great Dane, and Standard Poodle. SNP array genotyping was performed on constitutional DNA from all 241 samples to identify GDV-associated SNPs and CNVs. To increase the coverage of our study we performed imputation analysis of the SNP data as well as additional whole genome sequencing (WGS) on a subset of 33 dogs (15 healthy dogs and 18 GDV patients from the three most represented breeds). Twenty-one patients were genotyped by both SNP and WGS platforms. The GWAS was conducted across breeds as well as on specific breeds using a mixed linear model adjusting for relatedness, population structure and sex. After genome-wide Bonferroni correction, we identified a significant protective GDV-associated SNP, rs851737064, occurring in an intergenic region, across all breeds. The signal was most significant in Collies, German Shorthaired Pointers, and Great Danes. Subsequent focused analysis across these three breeds identified 12 additional independent, protective and deleterious SNPs with significant GDV association. Additional GWAS conducted on Borzoi, GSD and Great Dane yielded significant genome-wide GDV associations in 11 independent SNPs, while that in Borzoi alone identified 2 independent GDV-associated SNPs. We then used WGS data to validate the imputation analysis. Notable significant SNPs included genes involved in gastric tone and motility including VHL, NALCN, and PRKCZ. From the WGS data we also detected two independent GDV-associated SNPs in Borzoi, GSD and Great Dane breeds on an intergenic region on chromosome 7 not covered by previous analyses. These data provide important new information regarding canine GDV risk factors and facilitate generation of hypotheses regarding the genetic and molecular underpinnings this syndrome.