Introduction

While large fetal copy number aberrations can generally be detected through sequencing of DNA in maternal blood, the reliability of tests depends on the fraction of DNA that originates from the fetus. Existing methods to determine this fetal fraction require additional work or are limited to male fetuses. We aimed to create a sex-independent approach without additional work.DNA fragments used for noninvasive prenatal testing are cut only by natural processes; thus, influences on cutting by the packaging of DNA in nucleosomes will be preserved in sequencing. As cuts are expected to be made preferentially in linker regions, the shorter fetal fragments should be enriched for reads starting in nucleosome covered positions.We generated genome-wide nucleosome profiles based on single end sequencing of cell-free DNA. We found a difference between DNA digestion of fetal cell-free DNA and maternal cell-free DNA and used this to calculate the fraction of fetal DNA in maternal plasma for both male and female fetuses.Our method facilitates cost-effective noninvasive prenatal testing, as the fetal DNA fraction can be estimated without the need for expensive paired-end sequencing or additional tests. The methodology is implemented as a tool, which we called SANEFALCON (Single reAds Nucleosome-basEd FetAL fraCtiON). It is available for academic and non-profit purposes under Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International Public License. github.com/rstraver/sanefalcon. © 2016 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd.

Publications

  1. Calculating the fetal fraction for noninvasive prenatal testing based on genome-wide nucleosome profiles.
    Cite this
    Straver R, Oudejans CB, Sistermans EA, Reinders MJ, 2016-07-01 - Prenatal diagnosis

Credits

  1. Roy Straver
    Developer

    Department of Clinical Genetics, VU University Medical Center Amsterdam

  2. Cees B M Oudejans
    Developer

    Department of Clinical Chemistry, VU University Medical Center Amsterdam

  3. Erik A Sistermans
    Developer

    Department of Clinical Genetics, VU University Medical Center Amsterdam

  4. Marcel J T Reinders
    Investigator

    Delft Bioinformatics Lab, Delft University of Technology

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Summary
AccessionBT000444
Tool TypeApplication
Category
PlatformsLinux/Unix
Technologies
User InterfaceTerminal Command Line
Download Count0
Submitted ByMarcel J T Reinders