Fig 1.
Genome-wide association for canine hip dysplasia: FASTA and QTSCORE, N(cases) = 132, N(controls) = 160.
For the upper two figure segments the red horizontal lines are the thresholds for Bonferroni correction for significance. The blue horizontal line is the threshold for significance for independent tests. In the undermost segment, where the permuted P-values are shown, the single red line represents the threshold for genome-wide significance level of 0.05.
Fig 2.
Genome-wide association for canine hip dysplasia: First meta-analysis, N(cases) = 132, N(controls) = 277.
For the upper two figure segments the red horizontal line is the threshold for Bonferroni correction for significance. The blue horizontal line is the threshold for significance for independent tests. In the undermost segment, where the permuted P-values are shown, the single red line represents the threshold for genome-wide significance level of 0.05.
Fig 3.
Genome-wide association for canine hip dysplasia: Second meta-analysis, N(cases) = 247, N(controls) = 277.
For the upper figure segment the red horizontal line is the threshold for Bonferroni correction for significance. The blue horizontal line is the threshold for significance for independent tests. In the undermost segment, where the permuted P-values are shown, the single red line represents the threshold for genome-wide significance level of 0.05.
Table 1.
Adjusted P-values, empirical genome-wide significance levels and odds ratios for the most significant SNPs from the original genome-wide association analyses.
Table 2.
Adjusted P-values, empirical genome-wide significance levels and odds ratios for the top SNPs after the meta-analysis in moderate-to-severe cases compared with controls.
Table 3.
Adjusted P-values, empirical genome-wide significance levels and odds ratios for the top SNPs after the meta-analysis of mild to severe cases compared with controls.
Table 4.
Protein coding genes near the top SNPs from the genome-wide association analyses.
Table 5.
Allelic and genotypic odds ratios between phenotype comparisons for the top markers on chromosomes 1 and 9.
Table 6.
Cross-tabulated frequencies and counts of the most common genotypes of the two top SNPs on chromosome 9 (BICF2S23027935, BICF2P742007) with the hip phenotypes.
Table 7.
Variants that segregated between cases and controls categorized by the associated gene and the predicted functional effect.
Fig 4.
Human NOG enhancer region compared to the related region in the dog genome.
At the top of the image there is a sequence comparison between human and dog. hs = human genomic (GRCh38.p7) region at chr17:56592775–56592815. cf = canine genomic (CanFam3.1) region at chr9:31453829–31453899. d1-d4 = the corresponding sequences of Dog1-Dog4. Below the sequence comparison is first the canine genomic region including the deletion (blue triangle), gap region marked with Ns, and the complete coding sequence for NOG from a Beagle (GenBank: AB544074.1). At the bottom of the image are the corresponding human genomic regions with a TF binding site (orange box) and TFs that can bind to this site as predicted by the ENCODE ChIP-seq experiments. Green boxes are H3K4Me1 histone mark (commonly associated with enhancers) peaks, and the blue box is a H3K4Me3 histone mark (commonly associated with active promoters) peak from the ENCODE data.
Table 8.
Number of upstream NOG deletion genotypes in cases and controls.
Table 9.
The odds ratios based on logistic regression modeling of the CHD phenotype using the NOG deletion allele and the GA top SNP combination genotype as independent variables.
Table 10.
Comparison of full (with NOG deletion) and reduced (without NOG deletion) generalized linear models on three subsets of dogs.
Fig 5.
The differential effects of three NOG regulatory alleles in a dual luciferase reporter assay.
Relative luminisence (NanoLuc/firefly luminisence expressed as median value ± standard deviation, three biological replicates with four technical replicates each per every construct). Left: HEK293 cells transfected with 50 ng plasmid DNA + 50 ng carrier DNA. Right: U-2 OS cells transfected with 10 ng plasmid DNA + 10 ng carrier DNA. pNL: empty control vector. A: construct A, B: construct B, C: construct C. *: P<0.05 relative to construct A. The difference between relative luminescence of the control plasmid and each of the constructs was always statistically significant.