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Canine normal tissue gene expression profiles

ABSTRACT: Our 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 understand health and disease in the dog using investigative techniques including gene expression profiling. Accordingly, we now present a publicly accessible canine normal tissue gene expression database that will streamline the study of canine tissues and facilitate comparative genomic analysis with other mammals. The Affymetrix platform was utilized to catalogue the genetic signatures of 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. Public access and use of this data, using infrastructure identical to that currently in use for human normal tissues, has been established and allows for additional cross-species comparisons. 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. It is expected that this dataset will contribute to more advanced study of disease in the dog and biologically robust biomedical studies that utilize the dog as a model for translational research.

ORGANISM(S): Canis lupus familiaris

PROVIDER: GSE20113 | GEO | 2010/12/31

SECONDARY ACCESSION(S): PRJNA124245

REPOSITORIES: GEO

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Project description:Background: The determination of altered expression of genes in specific tumor types and their effect upon cellular processes may create insight in tumorigenesis and help to design better treatments. The Flatcoated retriever is a dog breed with an exceptionally high incidence of histiocytic sarcomas. The breed develops two distinct entities of histiocytic neoplasia, a soft tissue form and a visceral form. Gene expression studies of these tumors has value for comparable human diseases such as histiocytic/dendritic cell sarcoma for which knowledge is difficult to accrue due to their rare occurrence. In addition, such studies may help in the search for genetic aberrations underlying the genetic predisposition in this dog breed. Methods: Microarray analysis and pathway analyses were performed on fresh-frozen tissues obtained from Flatcoated retrievers with localized, soft tissue histiocytic sarcomas (STHS) and disseminated, visceral histiocytic sarcomas (VHS) and on normal canine spleens from various breeds. Expression differences of nine genes were validated with quantitative real-time PCR (qPCR) analyses. Results: QPCR analyses identified the significantly altered expression of nine genes; PPBP, SpiC, VCAM1, ENPEP, ITGAD (down-regulated), and GTSF1, Col3a1, CD90 and LUM (up-regulated) in the comparison of both the soft tissue and the visceral form with healthy spleen. DAVID pathway analyses revealed 24 pathways that were significantly involved in the development of HS in general, most of which were involved in the DNA repair and replication process. Conclusions: This study identified altered expression of nine genes not yet implicated in histiocytic sarcoma manifestations in the dog nor in comparable human histiocytic/dendritic sarcomas. Extraploration of this downside effect of canine inbreeding strategies for the study of similar sarcomas in humans might also lead to the identification of genes related to these rare malignancies in the human. Microarray expression dataset including STHS: Soft Tissue (localized) Histiocytic Sarcoma; VHS: Visceral (disseminated)Histiocytic Sarcoma; together with normal spleen (NS) samples. Comparisons were analysed in dyeswap on a 2-color platform against a common reference sample, consisting of a multitude of canine organs, including liver, spleen, kidney, lung, hart, intestine and bone.

Project description:Dogs are commonly used models of human inherited retinal disorders. Because the dog retina contains a macula-like region, dogs are susceptible to maculopathies with many shared genetic etiologies with humans. Human macular gene expression has been characterized and provides insight into the underlying basis of macular disease. We sought to compare macular gene expression profiles in dogs and humans and interrogate macular disease-associated genes for differential expression between macula and periphery. RNA sequencing was performed on 8mm samples of the dog macular region and superior peripheral region, sampling retina and retinal pigmented epithelium/choroid separately. Read sequences were mapped to CanFam3.1 and raw read counts were analyzed to determine significantly differentially expressed genes between macula and periphery within each tissue. A similar analytic pipeline was used with a published dataset of human samples to allow direct dog/human comparisons. Pathways and processes involved in significantly DEGs were identified using the Database for Annotation, Visualization and Integrated Discovery. Dogs and humans shared the extent and direction of macular retinal differential gene expression, with multiple shared biological pathways implicated in differential expression. There were fewer similarities between dog and human in the supporting tissues of the retina (the RPE, choroid, sclera). Many genes implicated in heritable retinal and macular disorders in both dogs and humans were differentially expressed between macula and periphery. Approximately 2/3 of genes associated with human age-related macular degeneration were differentially expressed in at least one human tissue, whereas approximately half were differentially expressed in at least one dog tissue. This work underpins the dog macular retinal region as analogous to the human macula in terms of differential gene expression. Whilst age-related maculopathy has not been described in dogs, evidence supports the study of aging of the macula and susceptibility to age-associated pathology in dogs.

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Canine normal tissue gene expression profiles

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