Research article

A Marfan syndrome gene expression phenotype in cultured skin fibroblasts

Zizhen Yao¹ , Jochen C Jaeger^1,7 , Walter L Ruzzo^1,2 , Cecile Z Morale^3,8 , Mary Emond⁴ , Uta Francke⁵ , Dianna M Milewicz⁶ , Stephen M Schwartz³ and Eileen R Mulvihill^3,9

¹Department of Computer Science and Engineering, University of Washington, Seattle, Washington 98195, USA

²Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA

³Department of Pathology, University of Washington, Seattle, Washington 98195, USA

⁴Department of Biostatistics, University of Washington, Seattle Washington 98195, USA

⁵Departments of Genetics and Pediatrics, Stanford University, Stanford, CA 94305-5323, USA

⁶University of Texas Medical School at Houston, 6431 Fannin, MSB 1.614, Houston, TX 77030, USA

⁷Hamilton Robotics, Via Crusch 8, Bonaduz, Switzerland

⁸Trubion Pharmaceuticals Inc., Seattle, Washington 98121, USA

⁹PO Box 33, Villanueva, NM 87583, USA

author email corresponding author email

BMC Genomics 2007, 8:319doi:10.1186/1471-2164-8-319

Published:	12 September 2007

Abstract

Background

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 × 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.