DNA microarray technology for neonatal screening

Modern molecular biology, owing much to the Human Genome initiative, has elucidated many of the genetic mechanisms underlying heritable metabolic disease. While the use of molecular methods has flourished in research laboratories, complexity and cost have limited their utility in newborn screening. Newborn blood cards provide high quality DNA samples able to provide reliable support to highly multiplexed polymerase chain reactions (PCR). New manufacturing processes have reduced the cost of DNA microarray technology to the point where it is a practical tool for population screening. In a single assay, a DNA microarray facilitates the co-detection of amplification products diagnostic for several genetic diseases. High throughput is achieved with automation at every step, from DNA extraction to detection of hybrids. We suggest that it is both feasible and practical to develop a first-tier newborn screening protocol based upon multiplex PCR and analysis of amplification products using DNA microarrays. Initial data utilizing the model systems of sickle cell disease, alpha-1-antitrypsin deficiency and Factor V Leiden will be reported.