Harmony Test is not influenced by guanine-cytosine content of a sample

The Harmony® Test specifically analyses pre-defined and carefully selected sequences of the chromosomes in question by means of the DANSR (Digital Analysis of Selected Regions) technology1. Other NIPT methods based on the rMPS (random massively parallel sequencing) method (e.g. PraenaTest®, Praenatalis-Test®), sequence randomly selected sequences of free DNA.

The random sequencing employed in rMPS methods is susceptible to a shift of the so-called GC distribution. This is caused, amongst other things, by treatment with low-molecular weight heparin 2, 3. This is why an LMWH treatment in conjunction with the rMPS method can lead to increased test failures and to a higher number of false positive and false negative results 4.

The DANSR method used in the Harmony® Test thus has three advantages:

  1. the sequences that are examined and thus their GC distribution are pre-defined and hence are not affected by the pregnant woman’s heparin treatment,
  2. the fetal DNA fraction is analysed independent of the GC content5 and
  3. the greater sequencing depth in the chromosomes in question ensures greater security and a lower susceptibility to interference.


  1. Sparks AB, Wang ET, Struble CA, Barrett W, Stokowski R, McBride C, Zahn J, Lee K, Shen N, Doshi J, Sun M, Garrison J, Sandler J, Hollemon D, Pattee P, Tomita-Mitchell A, Mitchell M, Stuelpnagel J, Song K, Oliphant A. Selective analysis of cell-free DNA in maternal blood for evaluation of fetal trisomy. Prenat Diagn. 2012 Jan;32(1):3-9. doi: 10.1002/pd.2922.
  2. Chiu RW, Sun H, Akolekar R, Clouser C, Lee C, McKernan K, Zhou D, Nicolaides KH, Lo YM. Maternal plasma DNA analysis with massively parallel sequencing by ligation for noninvasive prenatal diagnosis of trisomy 21. Clin Chem. 2010 Mar;56(3):459-63. doi: 10.1373/clinchem.2009.136507.
  3. Fan HC, Quake SR. Sensitivity of noninvasive prenatal detection of fetal aneuploidy from maternal plasma using shotgun sequencing is limited only by counting statistics. PLoS One. 2010 May 3;5(5):e10439. doi:10.1371/journal.pone.0010439.
  4. Lutz M, Lifecodexx Newsletter March 2015
  5. Sparks AB, Struble CA, Wang ET, Song K, Oliphant A. Noninvasive prenatal detection and selective analysis of cell-free DNA obtained from maternal blood: evaluation for trisomy 21 and trisomy 18. Am J Obstet Gynecol. 2012 Apr;206(4):319.e1-9. doi: 10.1016/j.ajog.2012.01.030.