vasive assessment of chromosome 21 dosage in the fetus. STUDY DESIGN: 100 pregnant women were recruited to study. Cell free plasma RNA was extracted from maternal peripheral blood. Due to high heterozygosities, five SNP markers (rs8130833, rs4818219, rs59066201, rs7717, rs1044598) encoding the regions of PLAC4 and COL6A2 were studied. Fluoresceins labeled specific primers were used to amplify the markers. Digestion with restriction endonucleases was applied specifically to cut one allele while dumb to the other. PCR products were analyzed with capillary electrophoresis. Allelic ratios were calculated from the areas of the fluorescent peaks from each specific fragmental size. RESULTS: At least one of the five SNP markers exhibited heterozygous in 100% T21 cases. 95% cases showed multiple heterozygous alleles. Allelic ratios of the heterozygous SNP markers are 0.7-1.3 in non T21 fetus’s group vs 1.8-2.1 in T21 group. CONCLUSION: Trisomy 21 can be screening by noninvasive method using maternal blood. Five SNP markers encoding the regions of PLAC4 and COL6A2 can be accurately detected by fluorescent PCR and endonuclease digestion followed by capillary electrophoresis. The approach may be specifically useful for very fine mapping of the regions of chromosome 21 that are critical for Down syndrome.