With a little help from your family: advances in non-invasive prenatal diagnosis

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Accurate prenatal diagnosis is important to guide pregnancy and birth management, therapeutic strategies, and future family planning, but invasive diagnostic techniques are associated with a risk of miscarriage. Advances in next-generation sequencing have allowed the development of methodologies for non-invasive prenatal diagnosis (NIPD) from cell-free fetal DNA circulating in maternal blood.

There has been much discussion recently regarding moving NIPD to the clinic, and so far this technology has been mainly applied to detection of sex-linked, single gene and chromosomal abnormality disorders. A successful example is the detection of aneuploidies, as discussed in a Review and Open debate previously published in Genome Medicine. By contrast, using NIPD to diagnose complex diseases or those caused by de novo mutations remains very challenging due to the complexity and cost of the approaches proposed.

A novel approach that could solve part of this problem has been published in the February issue of Genome Medicine by Shengpei Chen and colleagues. The authors describe a simple and effective methodology for inference of the fetal genome. This strategy is based on whole genome sequencing of cell-free fetal DNA from maternal plasma guided by both parental haplotypes, which allows for fetal genotype and haplotype determination in one step.

This approach is an important advance in NIPD, as discussed by Philippos Patsalis and Elisavet Papageorgiou in a Commentary published in BMC Medicine. It overcomes limitations of previous methodologies, such as the low level of fetal DNA concentrations found in maternal plasma and the lack of robustness and accuracy in the characterization of both maternal and paternal alleles.