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


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.
Department of Vertebrate Genetics, Max-Planck-Institute for Molecular Genetics, Berlin, Germany.
Bogac
B
Kaynak
Anja
A
von Heydebreck
Siegrun
S
Mebus
Dominik
D
Seelow
Steffen
S
Hennig
Jan
J
Vogel
Hans-Peter
HP
Sperling
Reinhard
R
Pregla
Vladimir
V
Alexi-Meskishvili
Roland
R
Hetzer
Peter E
PE
Lange
Martin
M
Vingron
Hans
H
Lehrach
Silke
S
Sperling
D000222:Adaptation, Physiological; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D016678:Genome; D006330:Heart Defects, Congenital / Q000235:genetics*; D006345:Heart Septal Defects, Ventricular / Q000235:genetics; D006801:Humans; D017380:Hypertrophy, Right Ventricular / Q000235:genetics; D015999:Multivariate Analysis; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D012016:Reference Values; D018401:Sample Size; D013771:Tetralogy of Fallot / Q000235:genetics