Two Trisomies Detected by Digital Assay Plus Algorithm

A biochemical assay combined with an algorithm accurately identified the risk of fetal trisomy 21 and 18 from maternal-blood cell-free DNA (cfDNS).

The noninvasive test enables scientists to detect the risk that a fetus has the chromosomal abnormalities that cause Down syndrome and a genetic disorder known as Edwards' syndrome. The new approach is more scalable than other recently developed genetic screening tests and has the potential to reduce unnecessary amniocentesis or chorionic villus sampling (CVS).

The digital analysis of selected regions (DASR) combined with the algorithm, fetal-fraction optimized risk of trisomy evaluation (FORTE), was studied by Andrew B. Sparks, PhD, from Aria Diagnostics (San Jose, CA, USA) and colleagues.

Using cfDNA obtained from maternal blood in a training set (163 subjects) and a blinded validation set (167 subjects) Dr. Sparks' group produced an individualized trisomy risk score for each subject, which correctly discriminated all cases of trisomy 21 and 18 from disomic cases. All subjects in the validation set passed quality control, and FORTE performance discriminated 36 of 36 cases of trisomy 21 and 8 of 8 cases of trisomy 18 from 123 of 123 disomic cases.

The DANSR assay and the FORTE algorithm were also validated for detection of the two trisomies by Ghalia Ashoor, MD, and colleagues from the University of London (London, United Kingdom). They assessed the prenatal detection of trisomies 21 and 18 using maternal-plasma cfDNA obtained at 11 to 13 weeks of gestation. Risk scores for trisomy 21 and 18 were given for 397 samples. The sensitivity for detecting trisomy 21 and 18 was 100 and 98 %, respectively, and the specificity was 100 %.

These two studies appeared online January 27, 2012, in the American Journal of Obstetrics & Gynecology. Dr. Ashoor and her colleagues wrote, "This nested case-control study has demonstrated that the DANSR assay with FORTE algorithm represent a promising method for accurate detection of fetal trisomy 21 and trisomy 18."

Currently, diagnosis of fetal chromosomal abnormalities, or aneuploidies, relies on invasive testing in pregnancies identified as high-risk. A technique known as massively parallel shotgun sequencing (MPSS) analyzes cell-free DNA (cfDNA) from the mother’s plasma and has been used to detect trisomy 21 (T21) pregnancies, those with an extra copy of chromosome 21 that leads to Down syndrome, and trisomy 18 (T18), the chromosomal defect underlying Edwards' syndrome. MPSS accurately identifies the conditions by analyzing the entire genome, but it requires a large amount of DNA sequencing, limiting its clinical usefulness.

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