Noninvasive fetal trisomy 21 detection using chromosome-selective sequencing: a variation of the molecular counting theme

Abstract

Evaluation of: Sparks A, Wang ET, Struble CA et al. Selective analysis of cell-free DNA in maternal blood for evaluation of fetal trisomy 21. Prenat. Diagn. 32, 3–9 (2012).

Fetal DNA is present in the plasma of pregnant women. A fetus with trisomy of a chromosome will release an increased amount of DNA from that chromosome into maternal plasma. Such an increase has previously been measured using methods that allow individual DNA molecules to be counted. One such method involves the use of random massively parallel sequencing of maternal plasma DNA. As the sequencing process is random, sequence tags from a potentially aneuploid chromosome only represent a fraction of the sequencing data. The performance of selective amplification and sequencing of specific genomic regions is a recently reported approach for focusing the sequencing power onto genomic regions of diagnostic interest. This article provides a critical analysis of this approach and puts this method in the perspective of other recent works in the field.

Keywords::

• fetal DNA
• massively parallel sequencing
• plasma DNA
• prenatal diagnosis

Financial & competing interests disclosure

The authors thank the University Grants Committee of the Government of the Hong Kong Special Administration Region, China – Areas of Excellence Scheme (AoE/M-04/06) for supporting their work. The authors hold or have filed patent applications on aspects of noninvasive prenatal diagnosis. Part of this patent portfolio has been licensed to Sequenom. YMD Lo and RWK Chiu are consultants to Sequenom. The authors hold equities in and receive research support from Sequenom. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.