BACKGROUND AND PURPOSE: 

• There are potentially thousands of genes where loss of function could impact health 
• There have been limited studies using high coverage whole genome sequencing (WGS) on fetal cells and cell free DNA obtained through amniocentesis  
• Mao et al. (Clinical Chemistry, 2018) aimed to acquire whole-genome sequence of a fetus from either cellular or cell-free DNA (cfDNA) of an amniotic sample 

METHODS: 

• There were 31 amniocentesis samples  
• DNA was obtained from two sources 
  • cfDNA (DNA freely circulating in the amniotic fluid) outside of cells 
  • Whole cells in the amniotic fluid  
• DNA was sequenced to approximately 50x genome coverage 

RESULTS: 

• Up to 97% of the fetal genome could be confidently called from freely circulating DNA in the amniotic fluid or the cell pellet after spinning down the amniotic fluid  
  • WGS could be added to leftover amniotic fluid specimens without disturbing current standard of care  
• Two fetal genomes were found to harbor potentially detrimental variants in two genes 
  • Chromodomain helicase DNA binding protein 8 (CHD8) 
  • LDL receptor-related protein 1 (LRP1) 
• CHD8 and LRP1 are associated with higher risk for autism spectrum disorder and keratosis pilaris atrophicans, respectively 
• Drug sensitivities and carrier information of fetuses was also collected 

CONCLUSION: 

• Whole genome sequences of 31 fetuses demonstrated that the cfDNA or DNA from the cell pellet can be analyzed with little difference in quality 
• This authors suggest that accurate and complex fetal analyses could soon become available 

Note: ACOG and other professional associations consider WGS appropriate in research settings only (see ‘Related ObG Topics’ below)

Learn More – Primary Sources: 

Advanced Whole-Genome Sequencing and Analysis of Fetal Genomes from Amniotic Fluid 

Related ObG Topics:

ISPD, SMFM and PQF Release a Joint Position Statement on Fetal Genome-Wide Sequencing

The Genome and Whole Genome Sequencing

The Exome and Whole Exome Sequencing