Published Online
on May 12, 2003

A more recent version of this article appeared on May 20, 2003

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Submitted on December 9, 2002
Revised on February 26, 2003
Accepted on February 27, 2003

Genome-Wide Array Analysis of Normal and Malformed Human Hearts

Bogac Kaynak MSc, Anja von Heydebreck PhD, Siegrun Mebus MD, Dominik Seelow MSc, Steffen Hennig PhD, Jan Vogel BSc, Hans-Peter Sperling MD, Reinhard Pregla MD, Vladimir Alexi-Meskishvili MD, PhD, Roland Hetzer MD, PhD, Peter E. Lange MD, PhD, Martin Vingron PhD, Hans Lehrach PhD, and Silke Sperling MD^*

From the Departments of Vertebrate Genetics (B.K., D.S., S.H., J.V., H.L., S.S.) and Computational Molecular Biology (A.v.H., M.V.), Max-Planck-Institute for Molecular Genetics, Berlin; and the Departments of Pediatric Cardiology (S.M., H.-P.S., P.E.L.) and Cardiovascular Surgery (R.P., V.A.-M., R.H.), German Heart Center Berlin, Germany.

^* To whom correspondence should be addressed. E-mail: sperling{at}molgen.mpg.de.

Background--We present the first genome-wide cDNA array analysis of human congenitally malformed hearts and attempted to partially elucidate these complex phenotypes. Most congential 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.

Methods and Results--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.

Conclusions--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.

Key words: heart defects, congenital • hypertrophy • atrium • ventricle • molecular biology

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