Noninvasive prenatal exome sequencing diagnostic utility limited by sequencing depth and fetal fraction

Objective Sequencing cell-free DNA now allows detection of large chromosomal abnormalities and dominant Mendelian disorders in the prenatal period. Improving upon these methods would allow newborn screening programs to begin with prenatal genetics, ultimately improving the management of rare genetic disorders. Methods As a pilot study, we performed exome sequencing on the cell-free DNA from three mothers with singleton pregnancies to assess the viability of broad sequencing modalities in a noninvasive prenatal setting. Results We found poor resolution of maternal and fetal genotypes due to both sampling and technical issues. Conclusion We find broad sequencing modalities inefficient for noninvasive prenatal applications. Alternatively, we suggest a more targeted path forward for noninvasive prenatal genotyping.

Automated summary

Sequencing cell-free DNA can detect chromosomal abnormalities and Mendelian disorders in the prenatal period, but broad sequencing modalities are inefficient for noninvasive prenatal applications. A more targeted approach is recommended for noninvasive prenatal genotyping.