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Review

Noninvasive prenatal chromosomal aneuploidy detection using plasma cell-free nucleic acid

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Pages 581-590 | Published online: 10 Jan 2014
 

Abstract

It has been shown that by the end of the first trimester of pregnancy, a small but significant portion of DNA extracted from maternal plasma is of fetal origin. This knowledge has been utilized for the development of clinical diagnostic assays that are widely used outside the USA for the minimally invasive prenatal determination of, for example, fetal Rhesus antigen status. Such assays that enable the detection of paternally inherited fetal alleles are relatively straightforward, because the fetal sequence of interest is unique to the father and is therefore not masked by any identical maternal alleles. By contrast, maternally inherited traits, including the majority of common human aneuploidies such as trisomy 21, are much harder to detect in plasma because of the overwhelming background of endogenous maternal sequences that are identical to the fetal target alleles. One way to ‘see’ fetal DNA past the veil of maternal genomic DNA is to utilize methods that can selectively amplify or enrich fetal alleles from maternal plasma. Such enrichment can be achieved by taking advantage of either differential DNA methylation or transcription patterns that exist between the first-trimester placenta at its maternal interface and maternal nucleated blood cells. These are the primary sources of fetal and maternal nucleic acids, respectively, in maternal plasma. Methods have recently emerged that combine such targeted strategies with digital genotyping assays using massively parallel nanofluidic devices. More recently, unbiased approaches that utilize high-throughput DNA sequencing have been developed that do not require prior knowledge of the placental or maternal leukocyte transcriptome or DNA methylome. Such methods have the potential to revolutionize the clinical standard of care for noninvasive prenatal diagnosis of fetal genetic disease. Recent developments in the field are discussed herein.

Financial & competing interests disclosure

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

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

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