Illustration of a Border Collie pedigree segregating PRA constructed by the Cyrillic 2

1 software. This pedigree is constituted of 80 dogs, 33 dogs are affected (30 males and 3 females).<p><b>Copyright information:</b></p><p>Taken from "Progressive Retinal Atrophy in the Border Collie: A new XLPRA"</p><p>http://www.biomedcentral.com/1746-6148/4/10</p><p>BMC Veterinary Research 2008;4():10-10.</p><p>Published online 3 Mar 2008</p><p>PMCID:PMC2324077.</p><p></p

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

Association of the <i>MKLN1</i>:c.400+3A>C genotype with the LAD phenotype.

<p>Association of the <i>MKLN1</i>:c.400+3A>C genotype with the LAD phenotype.</p

Sanger confirmation of the <i>MKLN1</i>:c.400+3A>C variant.

<p><b>(A)</b> Electropherograms from dogs with the three different genotypes. <b>(B)</b> Wildtype and mutant allele compared to the consensus sequence for the human U2 GT-AG type 5’-splice sites [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1007264#pgen.1007264.ref013" target="_blank">13</a>]. Subscript numbers in the consensus sequence indicate the percentage of the respective conserved nucleotide in 183,682 investigated human 5’-splice site motifs of the U2 GT-AG type. The additional difference to the optimal consensus in the U1 spliceosomal RNA recognition site in the mutant allele is highlighted in red. In human 5’-splice sites the most frequent base at position 3 is an A (60%). G is also common at this position (35%), while C and T are both rare (<3%) [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1007264#pgen.1007264.ref013" target="_blank">13</a>].</p

Experimental verification of the <i>MKLN1</i> splice defect.

<p><b>(A)</b> The genomic organization of the <i>MKLN1</i> gene. Exons 2–6 are enlarged and the position of the primers used for RT-PCR is indicated. <b>(B)</b> RT-PCR was performed using skin cDNA from a control and an LAD affected Bull Terrier. The picture shows a Fragment Analyzer gel image of the experiment. In the control animal, only the expected 366 bp product is visible. In the LAD affected dog, a 277 bp product representing a transcript lacking exon 4 is visible. The identity of the bands was verified by Sanger sequencing. Thus, the <i>MKLN1</i>:c.400+3A>C variant leads to complete skipping of exon 4 (<i>MKLN1</i>:r.312_400del89).</p

LAD phenotype.

<p><b>(A)</b> Inflammatory skin lesions in the face of an affected Bull Terrier. <b>(B)</b> Similar lesions in the inguinal region. <b>(C)</b> LAD affected puppy in the middle of two non-affected littermates. A pronounced growth delay and a subtle coat color dilution are visible. <b>(D, E)</b> Fore paws of an LAD affected Bull Terrier puppy at necropsy. Symmetrical scaling and crusting of the skin including interdigital areas and foot pads is visible <b>(F, G)</b> Histopathological micrographs of the junction of interdigital haired skin and digital pad from an affected Bull Terrier puppy <b>(F)</b> and a control dog <b>(G)</b>. Marked thickening of the epidermis, excessive layers of non-cornifying epithelium and a large pustule are evident in the affected dog. Hematoxylin-eosin, bar = 400 µm.</p

Association of the <i>MKLN1</i>:c.400+3A>C genotype with the LAD phenotype.

<p>Association of the <i>MKLN1</i>:c.400+3A>C genotype with the LAD phenotype.</p

Summary of the SNPs found in the targeted sequencing.

<p>Only variants that are homozygous for a rare allele in all affected dogs and not homozygous in controls were considered to perfectly segregate. Nb SNPs: Number of SNPs; Hom: Nb Homozygous variants; HTZ: Nb Heterozygous variants.</p