Multiple breeds have increased risk of SCCD.

<p>Photos of three at-risk breeds evaluated in this study are shown. A) Giant Schnauzer. B) Briard. C) Standard Poodle.</p

A significant association on CFA5 was identified in a GWAS comparing black and light colored STPOs.

<p>The GWAS compared 24 black and 24 light colored STPOs at 126,697 SNPs. Chromosome position is listed on the X-axis, and the negative log of the uncorrected P value of association of each SNP with the phenotype, as taken from EMMAX is indicated on the Y-axis.</p

Association between SCCD risk and the peak GWAS SNP, CFA15:32,383,555, in STPO cases and controls.

a<p>100,000 permutations using PLINK Max(T).</p

Association between SCCD risk and the LD block A risk-associated haplotype in the STPO, Briard, and Giant Schnauzer cases and controls.

a<p>P values comparing original STPO cases and control, Briard cases and control or Giant Schnauzer cases and controls.</p>b<p>Odds ratio (OR) and 95% confidence interval (CI) for SCCD in the breeds <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003409#pgen.1003409-Goldschmidt3" target="_blank">[25]</a>.</p

Frequency of the 5.7-Kb element CNV in light colored, black, and young STPOs.

a<p>Risk alleles are four or five copies of the CNV.</p

Association between SCCD risk and the 5.7-Kb element CNV in the STPO cases and controls.

a<p>Risk alleles are four or five copies of the CNV.</p

Interbreed haplotype analysis refines the SCCD locus to 144.9 Kb.

<p>The black bar represents the STPO one recombination region. The blue bars indicate the results of the interbreed haplotype analyses comparing STPOs with Giant Schnauzers (top blue bar) and Briards (bottom blue bar). The red box outlines the 144.9 Kb consensus region. The triangle plot displays the LD patterns in STPO cases (n = 38) and controls (n = 30) for the 186 variants within the region. The black vertical lines within the triangle plot indicate the locations of the tagging SNPs or in/dels within each block.</p

STPO cases narrow the region to 28.3 Kb.

<p>The red bars represent the four LD blocks in the 144.9 Kb region, termed A through D. The haplotype mapping results derived from 84 STPO cases are indicated by the blue bars, with the number of cases indicated on the right. The majority of STPO cases (n = 64) share at least one copy of the same haplotype within blocks A, B, C and D. Eight cases share in LD blocks A and B, six cases share in LD blocks A, B and C, and another six cases share in LD blocks B, C and D. The conservation and repeat elements in the reference genome for the 28.3 Kb from the end of block A to the beginning of block C are shown. The red boxes indicate the two copies of the 5.7 Kb element. Within the RefSeq Genes track, the blue lines are the PstI sites surrounding the CNV and the orange boxes are the locations of the probe used for the Southern blot.</p

GWAS for SCCD in STPOs identifies a significant locus on CFA15.

<p>The GWAS compared 31 cases versus 34 controls at 36,897 SNPs. Values on the Y-axis represent the negative log of the uncorrected P value for association of each SNP with the disease phenotype from PLINK. The X-axis indicates the chromosome position in order from the top of CFA1 to the end of CFAX, which is labeled CFA39.</p

Recombination and association analyses resolve the region to the <i>KITLG</i> locus.

<p>The association analysis results for the 658 SNPs with minor allele frequencies >10% are plotted as the negative log of the uncorrected P value. The X-axis is the base position along CFA15. The results of the recombination analysis are shown as the red brackets with the inner and outer red brackets indicating the one and three recombination intervals respectively. The orange boxes are the known or predicted genes in the region, as labeled.</p