Microarray-based genetics of cardiac malformations

One of the most revolutionary approaches in human genomics is DNA microarray technology. Latest developments have brought this technology to a widespread use. In this paper we discuss its usefulness especially for the study of the genetic component in congenital heart disease as a model of multifactorial disease and the possible clinical applications in the near future. Malformations of the heart and blood vessels account for the largest number of human birth defects. The susceptibility of the heart to developmental anomalies reflects the complexity of the morphogenetic events responsible for the heart formation. The genetics of congenital heart disease points to the existence of powerful disease modifiers. Tissue analysis of gene expression with cDNA microarrays provides a measure of transcriptional or posttranscriptional regulation. Large-scale partial sequencing of cDNA libraries generating expressed sequence tags is an effective means of discovering novel genes and characterizing transcription patterns in different organs and tissues. The qualitative and quantitative analysis of genes expressed in cardiac tissue by means of comparison of expression patterns related to the normal and to the pathological tissue may be of great importance for the study of cardiac pathologies. The variation in phenotypic penetrance and severity suggests that if we can identify high-risk individuals, a reduction in infant morbidity might be possible by altering environmental or maternal factors.