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A compendium of canine normal tissue gene expression.

Briggs J, Paoloni M, Chen QR, Wen X, Khan J, Khanna C - PLoS ONE (2011)

Bottom Line: Public access, using infrastructure identical to that currently in use for human normal tissues, has been established and allows for additional comparisons across species.These 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.

View Article: PubMed Central - PubMed

Affiliation: Tumor and Metastasis Biology Section, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.

ABSTRACT

Background: 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 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 findings: The 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/significance: These 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.

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Use of canine-human comparative genomics and expression analysis to                            improve annotation of canine probesets.Canine brain had the greatest number of probesets without a gene symbol                            or gene name assigned. As proof-of-concept, these probesets within the                            top 50 canine brain selective list were re-mapped and underwent manual                            curation to link transcript information to expression data. Heatmap                            representing expression values for NetAffx™ unassigned canine                            probesets (NA) as well as LOC designated probesets in the top 50 brain                            selective expression list. Following manual curation the newly assigned                            gene symbols (curated gene symbol) are shown. Once these probesets were                            mapped to a known transcript, all other canine probesets for that                            transcript on the canine version 2.0 array were subsequently re-mapped                            and their relative expression is shown for comparison. In cases where                            the curated gene symbol is represented by (NA), this denotes that the                            probeset mapped unambiguously to an intronic region. Red represents                            increased and green decreased log-fold expression compared to the mean                            of all other tissues.
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pone-0017107-g004: Use of canine-human comparative genomics and expression analysis to improve annotation of canine probesets.Canine brain had the greatest number of probesets without a gene symbol or gene name assigned. As proof-of-concept, these probesets within the top 50 canine brain selective list were re-mapped and underwent manual curation to link transcript information to expression data. Heatmap representing expression values for NetAffx™ unassigned canine probesets (NA) as well as LOC designated probesets in the top 50 brain selective expression list. Following manual curation the newly assigned gene symbols (curated gene symbol) are shown. Once these probesets were mapped to a known transcript, all other canine probesets for that transcript on the canine version 2.0 array were subsequently re-mapped and their relative expression is shown for comparison. In cases where the curated gene symbol is represented by (NA), this denotes that the probeset mapped unambiguously to an intronic region. Red represents increased and green decreased log-fold expression compared to the mean of all other tissues.

Mentions: SV2B, synaptic vesicle glycoprotein 2B, is a known 1-to-1 canine/human ortholog listed in both the Ensembl and Homologene databases and shares 91.9% nucleotide sequence identity and 95.6% at the amino acid level for the predicted protein product [24]. Closer inspection of the gene structure, including intron/exon boundries and non-coding sequences, revealed the primary difference between the two gene annotations was the shorter predicted length of the 3′ untranslated region (UTR) in canine, even though this region is highly conserved. The automated gene annotation process currently employed by Ensembl uses a default UTR length, calculated as the highest of either the mean or the median of all annotated UTRs for a given species [22]. However, multiple lines of EST and ortholog expression evidence suggest the canine SV2B 3′ untranslated region may extend further than predicted. Through Bio-GPS/Novartis Symatlas (http://biogps.gnf.org) physical mapping of human SV2B exhibits a highly brain specific expression pattern. In addition, canine probeset, Cfa.11188.1.A1_at, physically aligns to the same orthologous region as the human Affymetrix U133A probeset 205551_at. Interestingly, NetAffx™ does list a different canine probeset for the SV2B gene, CfaAffx.17603.1.S1_at, which maps to the predicted protein coding sequence. However, only 10/11 probes match the CanFam 2.0 genome assembly and the individual probes are spread out over multiple exons (Fig. 3B). In addition, the expression values for this probeset in all canine samples, regardless of tissue, are extremely low (Fig. 4). One possibility is that one or more exons are alternatively spliced resulting in decreased sensitivity for this probeset.


A compendium of canine normal tissue gene expression.

Briggs J, Paoloni M, Chen QR, Wen X, Khan J, Khanna C - PLoS ONE (2011)

Use of canine-human comparative genomics and expression analysis to                            improve annotation of canine probesets.Canine brain had the greatest number of probesets without a gene symbol                            or gene name assigned. As proof-of-concept, these probesets within the                            top 50 canine brain selective list were re-mapped and underwent manual                            curation to link transcript information to expression data. Heatmap                            representing expression values for NetAffx™ unassigned canine                            probesets (NA) as well as LOC designated probesets in the top 50 brain                            selective expression list. Following manual curation the newly assigned                            gene symbols (curated gene symbol) are shown. Once these probesets were                            mapped to a known transcript, all other canine probesets for that                            transcript on the canine version 2.0 array were subsequently re-mapped                            and their relative expression is shown for comparison. In cases where                            the curated gene symbol is represented by (NA), this denotes that the                            probeset mapped unambiguously to an intronic region. Red represents                            increased and green decreased log-fold expression compared to the mean                            of all other tissues.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3104984&req=5

pone-0017107-g004: Use of canine-human comparative genomics and expression analysis to improve annotation of canine probesets.Canine brain had the greatest number of probesets without a gene symbol or gene name assigned. As proof-of-concept, these probesets within the top 50 canine brain selective list were re-mapped and underwent manual curation to link transcript information to expression data. Heatmap representing expression values for NetAffx™ unassigned canine probesets (NA) as well as LOC designated probesets in the top 50 brain selective expression list. Following manual curation the newly assigned gene symbols (curated gene symbol) are shown. Once these probesets were mapped to a known transcript, all other canine probesets for that transcript on the canine version 2.0 array were subsequently re-mapped and their relative expression is shown for comparison. In cases where the curated gene symbol is represented by (NA), this denotes that the probeset mapped unambiguously to an intronic region. Red represents increased and green decreased log-fold expression compared to the mean of all other tissues.
Mentions: SV2B, synaptic vesicle glycoprotein 2B, is a known 1-to-1 canine/human ortholog listed in both the Ensembl and Homologene databases and shares 91.9% nucleotide sequence identity and 95.6% at the amino acid level for the predicted protein product [24]. Closer inspection of the gene structure, including intron/exon boundries and non-coding sequences, revealed the primary difference between the two gene annotations was the shorter predicted length of the 3′ untranslated region (UTR) in canine, even though this region is highly conserved. The automated gene annotation process currently employed by Ensembl uses a default UTR length, calculated as the highest of either the mean or the median of all annotated UTRs for a given species [22]. However, multiple lines of EST and ortholog expression evidence suggest the canine SV2B 3′ untranslated region may extend further than predicted. Through Bio-GPS/Novartis Symatlas (http://biogps.gnf.org) physical mapping of human SV2B exhibits a highly brain specific expression pattern. In addition, canine probeset, Cfa.11188.1.A1_at, physically aligns to the same orthologous region as the human Affymetrix U133A probeset 205551_at. Interestingly, NetAffx™ does list a different canine probeset for the SV2B gene, CfaAffx.17603.1.S1_at, which maps to the predicted protein coding sequence. However, only 10/11 probes match the CanFam 2.0 genome assembly and the individual probes are spread out over multiple exons (Fig. 3B). In addition, the expression values for this probeset in all canine samples, regardless of tissue, are extremely low (Fig. 4). One possibility is that one or more exons are alternatively spliced resulting in decreased sensitivity for this probeset.

Bottom Line: Public access, using infrastructure identical to that currently in use for human normal tissues, has been established and allows for additional comparisons across species.These 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.

View Article: PubMed Central - PubMed

Affiliation: Tumor and Metastasis Biology Section, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.

ABSTRACT

Background: 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 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 findings: The 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/significance: These 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.

Show MeSH