Genes associated with the phenotype.

<p>Genes associated with the phenotype.</p

Interconnected, statistically significant ROIs.

<p>Graphical representation of statistically significant ROIs and their overlapping. The direction of the arrow means that an element is included into another. Gene ROIs (light blue) can be part of pathway (green) or PPI (grey) ROIs, while domain ROIs (purple) can be part of gene ROIs.</p

Classification performance for each data set.

<p>Classification performance for each data set.</p

Examples of variants influencing more than one gene.

<p>Protein encoded by gene <i>A</i> interacts with proteins encoded by gene <i>B</i> and gene <i>C</i>. (a) Variant on gene <i>A</i>, <i>V</i>_<i>A</i> contributes to the score both for <i>A</i> and <i>B</i> due to their interaction. In the same way, variants on gene <i>B</i>, <i>V</i>_<i>B</i>, and on gene <i>C</i>, (<i>V</i>_<i>C</i>) both contribute to the scores of genes <i>A</i> <i>B</i> and <i>C</i>. (b) Resulting variant contributions on final PPIs scores.</p

Data fusion framework.

<p>Sequencing data are collapsed to calculate their mutational loads using four ROIs, namely genes, pathways, domains and PPIs. This allows studying ROI-phenotype associations along the four correspondent axes. Each element tested for association then becomes a feature for a prediction model. Single ROI types are combined to create data sets. Each data set is split into a training and test set. The training set is used to tune the learning parameters of a RF model and then select the best set of features, while the test set is used to measure the prediction performances.</p

Q-RT PCR results.

<p>Histograms represent the copy numbers ratio of a non-polymorphic probe within Sox9 gene in the two duplicated dogs (dog10 and dog44, red bars) relative to five normal control dogs (blue bars). The data have been normalized against two different reference sequences (Abs17, Bglr2).</p

List of CNVs identified with array-CGH in the seven cases with the indication of their code, type, location and size (CanFam2 assembly).

<p>CNVs were checked for occurrence in the Database of Genomic Copy Number Variants in the dog genome (<a href="http://dogs.genouest.org/LUPA.dir/CNV.html" target="_blank">http://dogs.genouest.org/LUPA.dir/CNV.html</a>) and in several papers <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0101244#pone.0101244-Chen1" target="_blank">[29]</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0101244#pone.0101244-Berglund1" target="_blank">[33]</a>.</p

Graphical representation of the SOX9 locus duplications discovered.

<p>The figure shows a 1,6(canFam2 assembly) and magnified views of the two SOX9 duplications detected, by array-CGH, in cases C10 (left) and C44 (right), respectively. The shaded areas indicate a gain in DNA copy number (duplication, average log2 ratios: +0, 5) detected by red dots. Asterisks indicate the 168 bp repeats.</p

Histological examination of the new cases reported.

<p>Case C61: Histologic section of the right (A) and left (B) gonad showing seminiferous tubules with diffuse atrophy of the seminal line. Case C64: Right Ovotestis (C): The gonads were surrounded by ovarian bursa and shown some follicular structures and corpora lutea (white arrow). In the medulla hypoplastic seminiferous tubules were present (black arrow). Case C65 (D): Dog ovotestis. In the gonad, follicular structures including oocytes (arrow) coexist with testicular tubuli lined by Setoli cells (asterisc) (Courtesy of Valeria Grieco, University of Milan).</p