Newborn screening by sequence and the road ahead.

Newborn screening (NBS) programs are an anomaly in medicine—a universally applied, state-mandated evaluation of healthy individuals. The program had its origin in the presymptomatic diagnosis of phenylketonuria (1 ), but as technologies for the use of dried blood spots (DBS) have improved, there has been a rapid expansion of the number of disorders evaluated, as well as an increase in the governmental mandates for testing (2 ). DNA-based diagnosis is already a feature of NBS. The first integrated use of genetic testing was for the confirmation of hemoglobinopathies (3 ). Genetic testing is now used as a primary or confirmatory technique in nearly every NBS system in the US. In addition to the analysis of sequence, DNA-based testing can also be used to detect the normal maturation of cell-mediated immunity through the detection of T-cell receptor excision circles (TRECs) (4 ). Clearly, additional tests will be added over time. The expanded use of DNA-based testing in NBS requires a reliable extraction method that delivers genomic DNA of sufficient quality and quantity for downstream applications.