Abstract
BackgroundOur understanding of disease is increasingly informed by changes in gene expression between normal and abnormal tissues. The release of the canine genome sequence in 2005 provided an opportunity to better understand human health and disease using the dog as clinically relevant model. Accordingly, we now present the first genome-wide, canine normal tissue gene expression compendium with corresponding human cross-species analysis.Methodology/Principal FindingsThe Affymetrix platform was utilized to catalogue gene expression signatures of 10 normal canine tissues including: liver, kidney, heart, lung, cerebrum, lymph node, spleen, jejunum, pancreas and skeletal muscle. The quality of the database was assessed in several ways. Organ defining gene sets were identified for each tissue and functional enrichment analysis revealed themes consistent with known physio-anatomic functions for each organ. In addition, a comparison of orthologous gene expression between matched canine and human normal tissues uncovered remarkable similarity. To demonstrate the utility of this dataset, novel canine gene annotations were established based on comparative analysis of dog and human tissue selective gene expression and manual curation of canine probeset mapping. Public access, using infrastructure identical to that currently in use for human normal tissues, has been established and allows for additional comparisons across species.Conclusions/SignificanceThese data advance our understanding of the canine genome through a comprehensive analysis of gene expression in a diverse set of tissues, contributing to improved functional annotation that has been lacking. Importantly, it will be used to inform future studies of disease in the dog as a model for human translational research and provides a novel resource to the community at large.
Highlights
The opportunity to study health and disease in the dog (Canis lupus familiaris) has significantly expanded with the release of the first public draft of the canine genome. [1,2,3] This opportunity has been complemented by the development of high throughput technologies, such as expression and SNP microarrays, commercially available for the dog [4,5,6]
A comparison of gene expression profiles for ten normal canine organs was undertaken using an ANOVA model to assess the informative value of this data set
Consistent with previous studies in humans, .50% of all canine probesets (23,070) demonstrated differential expression based on tissue type and this corresponds to 10,878 unique gene symbols. [15,19,20] To further validate the utility of these data and to characterize relationships between biological replicates, samples were analyzed by principle component analysis (PCA) (Fig. 1A and Fig. S1) and hierarchical clustering (HC) (Fig. 1B) using those probesets differentially expressed in at least one tissue
Summary
The opportunity to study health and disease in the dog (Canis lupus familiaris) has significantly expanded with the release of the first public draft of the canine genome. [1,2,3] This opportunity has been complemented by the development of high throughput technologies, such as expression and SNP microarrays, commercially available for the dog [4,5,6]. Since the dog represents a model organism for human disease, the development of such a database would enable more rigorous comparative genomic analysis with gene expression data sets available for human, rat and murine tissues [2]. Such comparative studies would enable the identification of common gene regulatory regions as well as evolutionarily conserved gene expression networks providing a better understanding of organ functions in normal and diseased states. We present the first genome-wide, canine normal tissue gene expression compendium with corresponding human cross-species analysis
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