Figure 4

Connectivity and enrichment analysis identifies pathways linked to OS in multiple breeds. (a) Most of the associated regions in each breed contain one or more genes (black text). Genic regions are shown for the greyhounds (blue), IWH (purple), and Rottweilers (red), with hue alternating between light and dark to distinguish regions, numbered as in Table 1. GRAIL [37] analysis identified non-random connectivity (P<0.05) between associated genes (bold text), both within breeds (blue, purple, and red arched lines for greyhounds, IWH, and Rottweilers) and between breeds (grey arched lines). Twelve regions contain genes (blue dots) connected to the key word ‘bone’, one of the top terms identified by GRAIL (Table S4). (b, c, d) When gene set enrichment P values for the associated regions and regions of reduced variability are combined, most sets shows no inflation compared to background (grey circles; RRV P values from 28 other breeds). However a small number are inflated, including (b) five from the NCI pathway interaction database [47], (c) two from the Molecular Signatures database of shared cis-regulatory motif based sets [48], and (d) 0 from the Gene Ontology database. (e) Of the seven gene sets (colors match discovery breed), five are significantly enriched (bold numbers) in regions that are aberrant in all greyhound (blue), all Rottweiler (red), or all dogs (black) for which we compared normal and tumor DNA using comparative genomic hybridization. Boxed numbers show number of genes in gene set overlapping CGH regions; ‘up’ and ‘down’ indicates gain or loss in all samples; ‘any’ indicates all samples are either amplified or deleted.