Identification of Hypertension-Related Genes Through an Integrated Genomic-Transcriptomic Approach
| العنوان: | Identification of Hypertension-Related Genes Through an Integrated Genomic-Transcriptomic Approach |
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| المؤلفون: | Yoram Yagil, Detlev Ganten, Norbert Hubner, Friedrich C. Luft, Herbert Schulz, Jan Monti, Marina Sapojnikov, Chana Yagil |
| المصدر: | Circulation Research. 96:617-625 |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2005. |
| سنة النشر: | 2005 |
| مصطلحات موضوعية: | Candidate gene, Transcription, Genetic, Microarray, Hydrolases, Physiology, Quantitative Trait Loci, Biology, Kidney, Genome, Transcriptome, Animals, Genetic Predisposition to Disease, RNA, Messenger, Sodium Chloride, Dietary, Desoxycorticosterone, HSP47 Heat-Shock Proteins, Gene, Heat-Shock Proteins, Serpins, Oligonucleotide Array Sequence Analysis, t-Complex Genome Region, Drug Implants, Genetics, Reverse Transcriptase Polymerase Chain Reaction, Gene Expression Profiling, Myelin and Lymphocyte-Associated Proteolipid Proteins, Chromosome Mapping, Dyneins, Nuclear Proteins, Chromosome, Rats, Inbred Strains, Genomics, Antigens, Differentiation, Rats, Phenotype, Receptors, LDL, Hypertension, Gene chip analysis, DNA microarray, Cardiology and Cardiovascular Medicine, Microtubule-Associated Proteins, Algorithms, Transcription Factors |
| الوصف: | In search for the genetic basis of hypertension, we applied an integrated genomic-transcriptomic approach to identify genes involved in the pathogenesis of hypertension in the Sabra rat model of salt-susceptibility. In the genomic arm of the project, we previously detected in male rats two salt-susceptibility QTLs on chromosome 1, SS1a ( D1Mgh2-D1Mit11 ; span 43.1 cM) and SS1b ( D1Mit11-D1Mit4 ; span 18 cM). In the transcriptomic arm, we studied differential gene expression in kidneys of SBH/y and SBN/y rats that had been fed regular diet or salt-loaded. We used the Affymetrix Rat Genome RAE230 GeneChip and probed >30 000 transcripts. The research algorithm called for an initial genome-wide screen for differentially expressed transcripts between the study groups. This step was followed by cluster analysis based on 2×2 ANOVA to identify transcripts that were of relevance specifically to salt-sensitivity and hypertension and to salt-resistance. The two arms of the project were integrated by identifying those differentially expressed transcripts that showed an allele-specific hypertensive effect on salt-loading and that mapped within the defined boundaries of the salt-susceptibility QTLs on chromosome 1. The differentially expressed transcripts were confirmed by RT-PCR. Of the 2933 genes annotated to rat chromosome 1, 1102 genes were identified within the boundaries of the two blood pressure QTLs. The microarray identified 2470 transcripts that were differentially expressed between the study groups. Cluster analysis identified genome-wide 192 genes that were relevant to salt-susceptibility and/or hypertension, 19 of which mapped to chromosome 1. Eight of these genes mapped within the boundaries of QTLs SS1a and SS1b . RT-PCR confirmed 7 genes, leaving TcTex1, Myadm, Lisch7, Axl-like, Fah, PRC1-like, and Serpinh1 . None of these genes has been implicated in hypertension before. These genes become henceforth targets for our continuing search for the genetic basis of hypertension. |
| تدمد: | 1524-4571 0009-7330 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3958317ad60acad8c14c90828a4dfec0 https://doi.org/10.1161/01.res.0000160556.52369.61 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....3958317ad60acad8c14c90828a4dfec0 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15244571 00097330 |
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