We describe an amplification-free method for sequencing of cell-free DNA, even from low levels of starting material.

We evaluated this method in the context of prenatal diagnosis of fetal aneuploidy and compared it with a PCR-based library preparation method as well as a recently described method using unique molecular identifiers (UMI). All methods performed well, however coverage was increased by the amplification-free method and GC-induced bias was reduced by both the amplification-free method and the UMI method. Future diagnostic applications including whole genome sequencing of cell-free DNA will benefit from amplification-free sequencing.

Amplification-free sequencing of cell-free DNA for prenatal non-invasive diagnosis of chromosomal aberrations Published in Genomics (PDF)