Professional Viewpoint: DNA Sequencing

PROFESSIONAL VIEWPOINT:   Journal Club

The SOFT Times Newsletter, Feb/Mar/Apr, 2013

By:  John C. Carey, MD, MPH, Medical Advisor, SOFT

Palomaki GE, Deciu C, Kloza EM, et al. 2012. DNA Sequencing of Maternal Plasma Reliably Identifies Trisomy 18 and Trisomy 13, as well as Down Syndrome: International Collaborative Study. Genetics in Medicine 14:296-305.

This article by Palomaki and co-authors is the third paper to address the issue of whether studying fetal cell-free DNA from maternal plasma can effectively identify trisomy 18 and 13 in the prenatal setting. This new technology, called noninvasive prenatal testing (NIPT), has emerged as a diagnostic test in recent years. NIPT involves drawing a blood sample from a pregnant mother and identifying fetal DNA material that is now known to be present in maternal blood. The use of maternal sample without the need for an invasive procedure (like amniocentesis) is an attractive approach. The sequencing of circulating cell-free DNA in maternal blood has been shown to reliably identify trisomy 21/Down syndrome in several studies in the last two years. The paper mentioned here applies the same DNA sequencing approach to the identification of trisomy 18 and 13 pregnancies.

The investigators examined almost 2,000 samples taken during pregnancy of known chromosome out- come. This study analyzes the samples that had been taken at 14 or 15 weeks of gestational age and using this technique detected 59 of 59 trisomy 18 pregnancies and 11 of 12 trisomy 13 pregnancies, demonstrating it was an effective test. Their false positive rates (that is, calling the result trisomy 18 or 13 when it was not) were less than 1% but showed an area that needs more investigation.

Currently there are four laboratory companies in North America that offer this new technology of DNA sequencing of maternal plasma for the detection of trisomy 13, 18, and 21 in high-risk pregnancies (mothers over age 35 and families with a previous history of trisomy). Application of this technology as a screening method to replace current programs is not occurring now but is likely to in the future.

The implications of this technology are far reaching: NIPT provides the availability of a reliable test with a noninvasive procedure, that is, a blood sample. It is likely that the application of this technology will replace the current first and second trimester screening programs that include blood sampling and ultra-sounds leading to the potential option of amniocentesis. It is also likely that the conditions to be identified will be broadened to more chromosome syndromes and other genetic conditions. I would anticipate more discussion of this topic in future columns.