TitleA Marfan syndrome gene expression phenotype in cultured skin fibroblasts.
Publication TypeJournal Article
Year of Publication2007
AuthorsYao Z, Jaeger JC, Ruzzo WL, Morale CZ, Emond M, Francke U, Milewicz DM, Schwartz SM, Mulvihill ER
JournalBMC genomics
Date or Month Published2007
KeywordsCells, Cultured, Fibroblasts, Gene Expression Profiling, Gene Expression Regulation, Genetic Variation, Humans, Marfan Syndrome, Models, Biological, Oligonucleotide Array Sequence Analysis, Phenotype, Skin
AbstractBACKGROUND: Marfan syndrome (MFS) is a heritable connective tissue disorder caused by mutations in the fibrillin-1 gene. This syndrome constitutes a significant identifiable subtype of aortic aneurysmal disease, accounting for over 5% of ascending and thoracic aortic aneurysms. RESULTS: We used spotted membrane DNA macroarrays to identify genes whose altered expression levels may contribute to the phenotype of the disease. Our analysis of 4132 genes identified a subset with significant expression differences between skin fibroblast cultures from unaffected controls versus cultures from affected individuals with known fibrillin-1 mutations. Subsequently, 10 genes were chosen for validation by quantitative RT-PCR. CONCLUSION: Differential expression of many of the validated genes was associated with MFS samples when an additional group of unaffected and MFS affected subjects were analyzed (p-value < 3 x 10-6 under the null hypothesis that expression levels in cultured fibroblasts are unaffected by MFS status). An unexpected observation was the range of individual gene expression. In unaffected control subjects, expression ranges exceeding 10 fold were seen in many of the genes selected for qRT-PCR validation. The variation in expression in the MFS affected subjects was even greater.
Downloadshttp://www.ncbi.nlm.nih.gov/pubmed/17850668?dopt=Abstract Abstract
Alternate JournalBMC Genomics
Citation Key1875
PubMed ID17850668