Functional annotations of diabetes nephropathy susceptibility loci through analysis of genome-wide renal gene expression in rat models of diabetes mellitus
<p>Abstract</p> <p>Background</p> <p>Hyperglycaemia in diabetes mellitus (DM) alters gene expression regulation in various organs and contributes to long term vascular and renal complications. We aimed to generate novel renal genome-wide gene transcription data in rat m...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2009-07-01
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| Series: | BMC Medical Genomics |
| Online Access: | http://www.biomedcentral.com/1755-8794/2/41 |
| _version_ | 1811189308510437376 |
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| author | Farrall Martin Parving Hans-Henrik Marre Michel Hadjadj Samy Groop Per-Henrik Tarnow Lise Blancher Christine Woon Peng Y Wallace Karin J Wilder Steven P Argoud Karène Kaisaki Pamela J Hu Yaomin Cox Roger D Lathrop Mark Vionnet Nathalie Bihoreau Marie-Thérèse Gauguier Dominique |
| author_facet | Farrall Martin Parving Hans-Henrik Marre Michel Hadjadj Samy Groop Per-Henrik Tarnow Lise Blancher Christine Woon Peng Y Wallace Karin J Wilder Steven P Argoud Karène Kaisaki Pamela J Hu Yaomin Cox Roger D Lathrop Mark Vionnet Nathalie Bihoreau Marie-Thérèse Gauguier Dominique |
| author_sort | Farrall Martin |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Hyperglycaemia in diabetes mellitus (DM) alters gene expression regulation in various organs and contributes to long term vascular and renal complications. We aimed to generate novel renal genome-wide gene transcription data in rat models of diabetes in order to test the responsiveness to hyperglycaemia and renal structural changes of positional candidate genes at selected diabetic nephropathy (DN) susceptibility loci.</p> <p>Methods</p> <p>Both Affymetrix and Illumina technologies were used to identify significant quantitative changes in the abundance of over 15,000 transcripts in kidney of models of spontaneous (genetically determined) mild hyperglycaemia and insulin resistance (Goto-Kakizaki-GK) and experimentally induced severe hyperglycaemia (Wistar-Kyoto-WKY rats injected with streptozotocin [STZ]).</p> <p>Results</p> <p>Different patterns of transcription regulation in the two rat models of diabetes likely underlie the roles of genetic variants and hyperglycaemia severity. The impact of prolonged hyperglycaemia on gene expression changes was more profound in STZ-WKY rats than in GK rats and involved largely different sets of genes. These included genes already tested in genetic studies of DN and a large number of protein coding sequences of unknown function which can be considered as functional and, when they map to DN loci, positional candidates for DN. Further expression analysis of rat orthologs of human DN positional candidate genes provided functional annotations of known and novel genes that are responsive to hyperglycaemia and may contribute to renal functional and/or structural alterations.</p> <p>Conclusion</p> <p>Combining transcriptomics in animal models and comparative genomics provides important information to improve functional annotations of disease susceptibility loci in humans and experimental support for testing candidate genes in human genetics.</p> |
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| institution | Directory Open Access Journal |
| issn | 1755-8794 |
| language | English |
| last_indexed | 2024-04-11T14:33:50Z |
| publishDate | 2009-07-01 |
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| series | BMC Medical Genomics |
| spelling | doaj.art-21e95a36f2b44a5db0b99fe4cf2bca8c2022-12-22T04:18:26ZengBMCBMC Medical Genomics1755-87942009-07-01214110.1186/1755-8794-2-41Functional annotations of diabetes nephropathy susceptibility loci through analysis of genome-wide renal gene expression in rat models of diabetes mellitusFarrall MartinParving Hans-HenrikMarre MichelHadjadj SamyGroop Per-HenrikTarnow LiseBlancher ChristineWoon Peng YWallace Karin JWilder Steven PArgoud KarèneKaisaki Pamela JHu YaominCox Roger DLathrop MarkVionnet NathalieBihoreau Marie-ThérèseGauguier Dominique<p>Abstract</p> <p>Background</p> <p>Hyperglycaemia in diabetes mellitus (DM) alters gene expression regulation in various organs and contributes to long term vascular and renal complications. We aimed to generate novel renal genome-wide gene transcription data in rat models of diabetes in order to test the responsiveness to hyperglycaemia and renal structural changes of positional candidate genes at selected diabetic nephropathy (DN) susceptibility loci.</p> <p>Methods</p> <p>Both Affymetrix and Illumina technologies were used to identify significant quantitative changes in the abundance of over 15,000 transcripts in kidney of models of spontaneous (genetically determined) mild hyperglycaemia and insulin resistance (Goto-Kakizaki-GK) and experimentally induced severe hyperglycaemia (Wistar-Kyoto-WKY rats injected with streptozotocin [STZ]).</p> <p>Results</p> <p>Different patterns of transcription regulation in the two rat models of diabetes likely underlie the roles of genetic variants and hyperglycaemia severity. The impact of prolonged hyperglycaemia on gene expression changes was more profound in STZ-WKY rats than in GK rats and involved largely different sets of genes. These included genes already tested in genetic studies of DN and a large number of protein coding sequences of unknown function which can be considered as functional and, when they map to DN loci, positional candidates for DN. Further expression analysis of rat orthologs of human DN positional candidate genes provided functional annotations of known and novel genes that are responsive to hyperglycaemia and may contribute to renal functional and/or structural alterations.</p> <p>Conclusion</p> <p>Combining transcriptomics in animal models and comparative genomics provides important information to improve functional annotations of disease susceptibility loci in humans and experimental support for testing candidate genes in human genetics.</p>http://www.biomedcentral.com/1755-8794/2/41 |
| spellingShingle | Farrall Martin Parving Hans-Henrik Marre Michel Hadjadj Samy Groop Per-Henrik Tarnow Lise Blancher Christine Woon Peng Y Wallace Karin J Wilder Steven P Argoud Karène Kaisaki Pamela J Hu Yaomin Cox Roger D Lathrop Mark Vionnet Nathalie Bihoreau Marie-Thérèse Gauguier Dominique Functional annotations of diabetes nephropathy susceptibility loci through analysis of genome-wide renal gene expression in rat models of diabetes mellitus BMC Medical Genomics |
| title | Functional annotations of diabetes nephropathy susceptibility loci through analysis of genome-wide renal gene expression in rat models of diabetes mellitus |
| title_full | Functional annotations of diabetes nephropathy susceptibility loci through analysis of genome-wide renal gene expression in rat models of diabetes mellitus |
| title_fullStr | Functional annotations of diabetes nephropathy susceptibility loci through analysis of genome-wide renal gene expression in rat models of diabetes mellitus |
| title_full_unstemmed | Functional annotations of diabetes nephropathy susceptibility loci through analysis of genome-wide renal gene expression in rat models of diabetes mellitus |
| title_short | Functional annotations of diabetes nephropathy susceptibility loci through analysis of genome-wide renal gene expression in rat models of diabetes mellitus |
| title_sort | functional annotations of diabetes nephropathy susceptibility loci through analysis of genome wide renal gene expression in rat models of diabetes mellitus |
| url | http://www.biomedcentral.com/1755-8794/2/41 |
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