The canine genome has been sequenced and is available for studies identifying and associating genetically caused diseases, which are of relevance for both animal and human health. Bioinformatic analyses determined that around 94% of the dog genome belongs to regions of conserved synteny between the dog, human, mouse and rat genomes [
20]. The euchromatic part of the canine genome is only about 18% smaller than the human genome [
21], but the human and dog genomes differ largely in the chromosome number (46 and 78, respectively). With respect to the common ancestor of eutherian mammals (CAE, 2n = 42), their genome is substantially rearranged. However, mouse and rat genomes are also severely altered with respect to the CAE genome, as they are highly rearranged and have accumulated large numbers of nucleotide substitutions in neutral sites [
22]. Nonetheless, the canine gene products seem to be more closely related to their human homologs than those of mice. This suggests potentially higher functional similarity between canine and human proteins, as well as indicates possibly better crossreactivity of human antibodies with canine proteins than with murine ones, especially with respect to DDR proteins ([
23]; own observations). The antibody crossreactivity would be especially beneficial in case of functional studies. Humans and dogs share an ancestrally related pathogenic basis for cancer, with pathognomonic genetic changes being conserved in both species [
24]. As an example, the
BCR-ABL fusion gene could be detected with fluorescence in situ hybridization (FISH) in canine chronic myelogenous leukemia (CML) and chronic monocytic leukemia, which is equivalent to the Philadelphia chromosome (with the
BCR-ABL fusion) in human CML showing equal genomic break sites [
24,
25]. Besides similarities in protein-coding regions, it is important to keep in mind that the slight differences in the total amount of canine and human genetic material could result in different levels and regulations of the micro (mi) RNAs, which are becoming increasingly relevant. Apart from genetic alterations of proteins, alterations in the miRNA coding regions were shown to affect the regulation of DNA repair [
26,
27]. Nevertheless, as it is well established that the canine gene products are very similar to the human ones, the
functional read-outs of canine studies based on the protein-coding regions do exhibit a high potential to result in deeper understanding and more accurate predicting of the treatment-response. Involvement of proteomic screens could provide additional insight in this matter.