Abstract
Birth defects affect 3-5% of live births and are a major cause of fetal, neonatal and infant morbidity and mortality in all industrialized countries. Some 40-60% of congenital physical anomalies in humans have no cause, 20% that seem to be multifactorial, 10-13% environmental and 12-25% genetic.
Classical cytogenetic or common comparative genomic hybridization (CGH) methods have limited use in investigation of the whole genome because of their low resolution (5-10 Mb). Fluorescence in situ hybridization (FISH) and quantitative fluorescence polymerase chain reaction (QF-PCR) have higher resolution but do not allow genome-wide screening and require some prior knowledge regarding the suspected chromosomal abnormality and its genomic location.
Because of these limitations, the impact of genetic micro imbalances as etiological factors for the development of congenital malformations (CM) is underestimated. Array-based techniques have enabled higher resolution screens for genomic imbalances in CM as they permit identification of micro aberrations with a size between 60 bp and several hundred kilobases. They make possible screening of the whole genome and detection of novel unbalanced micro structural rearrangements in a single reaction and also effective screening of new dose-dependent genes. In addition, the application of the aCGH technology has the potential to improve our understanding of the normal quantitative variants of the human genome.