Mass Spectrometric Detection of an SNP Panel as an Internal Positive Control for Fetal DNA Analysis in Maternal Plasma

Applications of fetal DNA detection in maternal plasma have been reported for the prenatal assessment of fetal RhD status, sex-linked disorders, and β-thalassemia. Because fetal DNA constitutes only 3% to 6% of the total DNA in maternal plasma (1), fetal sequences may occasionally go undetected because of low fetal DNA concentrations or fetal DNA loss during sample processing. Such false-negative results may lead to misinterpretation of the fetal genotype and consequently, false diagnoses. Thus the incorporation of analytical controls to confirm the presence of fetal DNA is recommended. Other investigators have developed a panel of insertion-deletion polymorphisms to serve this purpose(2). Single nucleotide polymorphisms (SNPs), however, are the most abundant class of polymorphisms in the human genome. We have recently developed a mass spectrometry based protocol, the s ingle a llele b ase e xtension r eaction (SABER), that allows the sensitive and specific detection of fetal SNPs in maternal plasma(3). We applied SABER to develop an SNP panel to serve as an …