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Genome-wide array analysis of normal and malformed human hearts.

Circulation (2003-05-14)
Bogac Kaynak, Anja von Heydebreck, Siegrun Mebus, Dominik Seelow, Steffen Hennig, Jan Vogel, Hans-Peter Sperling, Reinhard Pregla, Vladimir Alexi-Meskishvili, Roland Hetzer, Peter E Lange, Martin Vingron, Hans Lehrach, Silke Sperling
ABSTRACT

We present the first genome-wide cDNA array analysis of human congenitally malformed hearts and attempted to partially elucidate these complex phenotypes. Most congenital heart defects, which account for the largest number of birth defects in humans, represent complex genetic disorders. As a consequence of the malformation, abnormal hemodynamic features occur and cause an adaptation process of the heart. The statistical analysis of our data suggests distinct gene expression profiles associated with tetralogy of Fallot, ventricular septal defect, and right ventricular hypertrophy. Applying correspondence analysis, we could associate specific gene functions to specific phenotypes. Furthermore, our study design allows the suggestion that alterations associated with primary genetic abnormalities can be distinguished from those associated with the adaptive response of the heart to the malformation (right ventricular pressure overload hypertrophy). We provide evidence for the molecular transition of the hypertrophic right ventricle to normal left ventricular characteristics. Furthermore, we present data on chamber-specific gene expression. Our findings propose that array analysis of malformed human hearts opens a new window to understand the complex genetic network of cardiac development and adaptation. For detailed access, see the online-only Data Supplement.

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ProbeQuant G-50 Micro Columns, Cytiva 28-9034-08, pack of 50 columns