In recent studies, Roche Nimblegen comparative genomic hybridisation (CGH) microarrays were used to perform systematic and genome-wide analysis of DNA copy number variation (CNV) across dog breeds.
Results from these studies revealed that the extent of CNVs in the dog genome and their association with known and candidate disease genes is similar to mice and humans.
In the first study, Chen et al analysed seven pedigree (purebred) dog breeds using a standard Nimblegen Dog CGH whole-genome tiling array consisting of 385,000 long oligonucleotide probes with a median probe spacing of 4,675bp.
This analysis identified many CNVs in linkage disequilibrium with flanking sequence.
Cluster analysis showed that CNV regions in dog breeds tend to group according to breed classes and may be associated with breed-specific traits.
In the second study, Nicholas et al designed a custom Nimblegen CGH array targeting all predicted segmental duplication regions, which are now recognised as 'hotspots' for genome copy number variation in humans and other model organisms.
Analysis of the public canine genome reference sequence revealed an estimated 4.21 per cent of the genome is comprised of segmental duplications, which overlap 841 genes and are enriched for certain biological functions and transcription factors.
Analysis of a panel of 17 genetically and phenotypically diverse dog breeds and a gray wolf, identified extensive copy number variation (3,583 CNVs mapping to 678 unique regions) that span 429 genes involved in a wide range of biological processes including gene regulation, sensory perception and immune responses.
In total, CNVs were shown to comprise 24Mb of polymorphic sequence and 20 per cent of the predicted segmental duplications exhibit CNVs.
To date, research on genetic variation in dogs has been largely limited to either single nucleotide polymorphism (SNP) or microsatellite studies.
However, the studies described above indicate that DNA copy number variation is a significant source of genetic and phenotypic variation in dogs.
The availability of high-resolution maps of CNVs across dog breeds will allow researchers to evaluate the biological significance of breed-specific CNVs and associated candidate disease genes.
According to the researchers, results from these studies illustrate how canine CNV discovery can impact the rapidly growing use of dog models, uncover and answer basic genetic mechanisms, and address diseases in both dogs and humans.
Dogs share over 350 inherited diseases that are similar to those of humans.
Therefore, continued studies of dog genome variation and its impact on disease will hopefully lead to translational research and improved healthcare for humans as well as canines.
