Next-generation sequencing and the impact on prenatal diagnosis

ABSTRACT

Introduction: The advent of affordable and rapid next-generation sequencing has been transformative for prenatal diagnosis. Sequencing of cell-free DNA in maternal plasma has enabled the development of not only a highly sensitive screening test for fetal aneuploidies, but now definitive noninvasive prenatal diagnosis for monogenic disorders at an early gestation. Sequencing of fetal exomes offers broad diagnostic capability for pregnancies with unexpected fetal anomalies, improving the yield and accuracy of diagnoses and allowing better counseling for parents. The challenge now is to translate these approaches into mainstream use in the clinic.

Areas covered: Here, the authors review the current literature to describe the technologies available and how these have evolved. The opportunities and challenges at hand, including considerations for service delivery, counseling, and development of ethical guidelines, are discussed.

Expert commentary: As technology continues to advance, future developments may be toward noninvasive fetal whole exome or whole genome sequencing and a universal method for noninvasive prenatal diagnosis without the need to sequence both parents or an affected proband. Expansion of cell-free fetal DNA analysis to include the transcriptome and the methylome is likely to yield clinical benefits for monitoring other pregnancy-related pathologies such as preeclampsia and intrauterine growth restriction.

KEYWORDS:

• Prenatal diagnosis
• next-generation sequencing
• noninvasive prenatal diagnosis
• monogenic disorders
• cell-free fetal DNA
• single gene disorders
• exome sequencing
• fetal abnormalities

Declaration of interest

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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

LS Chitty is partially funded by the NIHR Biomedical Research Centre at Great Ormond Street Hospital. The views expressed are those of the author and not necessarily those of the NHS, the NIHR or the Department of Health.