Additional file 3: Table S2. of ADAM23 is a common risk gene for canine idiopathic epilepsy

Allelic association results of the ADAM23 variants. (XLSX 16 kb

Additional file 1: Table S1. of ADAM23 is a common risk gene for canine idiopathic epilepsy

Summary of the epilepsy questionnaires. (XLSX 13 kb

Additional file 2: Figure S1. of ADAM23 is a common risk gene for canine idiopathic epilepsy

Genome-wide association study results. The multidimensional scaling plots (i), quantile-quantile plots (ii) and Manhattan plots (iii) are presented for Finnish Lapphunds (A), Kromfohrländers (B), Miniature Pinschers (C) and Pyrenean Shepherds (D). In the multidimensional scaling plots, red circles denote cases and blue controls. (TIF 1000 kb

Genetic analyses in canine craniomandibular osteopathy identify a leaky splicing variant in exon 15 of <i>SLC37A2</i>, resulting in a frameshift that truncates the protein.

<p><b>A</b>. Laterolateral (left) and ventrodorsal (right) radiograph of the skull of two different WHWT affected with CMO. The typical palisade-like periosteal new bone formation is commonly located along the corpus mandibulae (left, white arrowheads) or around the Bulla tympanica (right, black arrowheads). <b>B.</b> Manhattan plot from GWAS indicates the associated region on chromosome 5 (p_genome = 0.02). <b>C.</b> A synonymous variant, c. 1332C>T, in exon 15 of <i>SLC37A2</i>. <b>D</b>. ESEfinder suggests that the synonymous variant affects a splicing enhancer site. The binding scores for the different splicing factors (colored blocks) for 79 nucleotides of exon 15 are shown for the wild-type and mutant allele. The c.1332C>T mutation eliminates a potential binding site for the SF2/ASF splicing factor (shown in purple). Binding scores for different splicing proteins (shown on the y-axis) are based on different weight matrices and cannot be compared directly to each other. <b>E</b>. A semi-quantitative RT-PCR in the wild-type (CC), carrier (CT) and affected (TT) WHWTs confirms the splicing defect (79 bp deletion) caused by the variant, and reveals a splicing leakage in the carrier and affected dogs. <i>B2M</i> was used as a loading control. <b>F</b>. A schematic 12-transmembrane secondary structure of SLC37A2 predicted by TMHMM. The truncated region in the mutated protein is indicated by a dashed line.</p

Genetic analyses in a developmental syndrome in Wire Fox Terriers reveal a deletion in exon 6 of <i>SCARF2</i>, resulting in an early truncation of the predicted protein.

<p><b>A</b>. A Manhattan plot from a GWAS indicates a locus on chromosome 26 (p_genome = 0.05). <b>B</b>. A 3.3-Mb disease-associated haplotype in the affected dogs. <b>C</b>. Targeted resequencing revealed a 2-bp deletion in exon 6 (c.865-866delTC), resulting in a severe truncation at Ser289 that removes the transmembrane and cytoplasmic domains of the predicted protein as indicated by a dashed line in the schematic structure. <b>D</b>. RT-PCR in the affected and control Wire Fox Terrier indicate expression of <i>SCARF2</i> mRNA and suggest that the mutated <i>SCARF2</i> transcript is not directed to nonsense-mediated RNA decay.</p