MS analysis of single-nucleotide differences in circulating nucleic acids: Application to noninvasive prenatal diagnosis.

摘要: The analysis of circulating nucleic acids has revealed applications in the noninvasive diagnosis, monitoring, and prognostication many clinical conditions. Circulating fetal-specific sequences have been detected constitute a fraction total DNA maternal plasma. diagnostic reliability depends on fractional concentration targeted sequence, analytical sensitivity, specificity. robust discrimination single-nucleotide differences between species is technically challenging demands adoption highly sensitive specific systems. We developed method based single-allele base extension reaction MS, which allows for reliable detection alleles, including point mutations polymorphisms, approach was applied to exclude fetal inheritance four most common Southeast Asian β-thalassemia at-risk pregnancies weeks 7 21 gestation. Fetal genotypes were correctly predicted all cases studied. haplotype polymorphism linked β-globin locus, HBB, plasma also achieved. Consequently, prenatal diagnosis mother father carrying identical accomplished. These advances will help catalyzing This implications other areas such as oncology transplantation.