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15-01-2012 | Genetics | Article

Prenatal assay of maternal blood shows promise for diagnosis of fetal trisomy


Free abstract

MedWire News: A novel assay that selectively analyzes cell-free DNA in maternal blood is highly accurate and cost-effective for assessing fetal aneuploidy, say US researchers.

"Diagnostic testing [during pregnancy] includes invasive procedures such as chorionic villus sampling (CVS) or amniocentesis, and although these tests are highly accurate, they come at significant health risks to the fetus and mother, including the potential loss of a healthy fetus," say Ken Song (Aria Diagnostics, San Jose, California) and colleagues.

To try and combat the risks for CVS or amniocentesis, a novel form of assay - known as digital analysis of selected regions (DANSR; Aria Diagnostics, San Jose, California) - has been developed to test for Trisomy 21 (T21; associated with Down's syndrome) and Trisomy 18 (T18; associated with Edward's syndrome). The assay corresponds to 384 locations on chromosomes 18 and 21.

DANSR selectively analyzes cell-free DNA from maternal blood samples. In the current study, Song and team assessed the accuracy of DANSR to diagnose T21 and T18 using blood samples from 298 pregnant women. In total, the cohort included 39 confirmed cases of T21 and seven confirmed cases of T18.

As reported in the journal Prenatal Diagnosis, the DANSR assay correctly identified all cases of aneuploidy in the cohort.

The assay uses a standard Z-test of chromosomal proportions to distinguish samples from women carrying babies with T21 or T18 aneuploidy from average risk women.

At the lowest sequencing depth of 204,000 sequencing counts per sample, average risk samples were mostly correctly distinguished from aneuploid samples, but 0.4% of average risk samples were classified as aneuploid. However, increasing the sequencing depth to 410,000 counts per sample eliminated this small discrepancy, with all average risk samples being classified correctly.

"This depth of sequencing represents less than 5% of that required by massively parallel shotgun sequencing approaches," which suggests that this technique is both cost-efficient and scalable as a method of fetal aneuploidy assessment, say the researchers.

"These findings demonstrate that our technology can deliver on the promise of making molecular diagnostics more affordable and accessible to a broad population," explained Song in a press statement.

"We are very excited about this first publication that demonstrates the potential for a non-invasive test that is highly accurate, cost efficient and scalable," he said.

The investigators hope that the DANSR technology can eventually be developed to allow diagnosis of other genetic conditions, such as subchromosomal copy number variations, which cannot be analysed using massively parallel DNA shotgun sequencing.

By Helen Albert

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