Table 1. Current approaches to interrogation of fetal cfDNA.

A variety of commercial and proof-of-concept methods use cfDNA in the maternal plasma to determine fetal genetic makeup in a targeted or holistic manner. Closed circles denote information explicitly obtained with each method. Open circles denote information that can be obtained with each method, but not explicitly addressed in the referenced publication. “Common SNPs” and “Rare SNVs” refer to genome-wide determination of common single-nucleotide polymorphisms and rare single-nucleotide variants. Relative cost estimates are denoted by dollar signs. “MPS”: massively parallel sequencing. “CNV”: copy-number variant.

Study	Method overview	Trisomy / Monosomy	Sub-chrom. CNVs	Common SNPs	Rare SNVs	Single gene target	Gene panel / exome	De novo point mutations	Cost
Fan et al. (2008); Chiu et al. (2008)	MPS to determine relative over- or under-abundance of specific chromosomes using maternal plasma. Statistical models to infer gain or loss of entire chromosomes.	●							$$
Tynan et al. (2011)	Multiplex PCR to detect fetal sex and RHD status in RhD-negative pregnant women.					●			$
Lo et al. (2007)	Digital PCR to identify overrepresentation of specific allele in maternal plasma, and to assess chromosomal imbalance to infer trisomy 21.	●				○			$
Srinivasan et al. (2013)	High-coverage MPS of DNA from plasma to identify over- or under- abundance of reads from 1 Mb genomic bins. Statistical model to infer CNVs.	●	●						$$
Fan et al. (2012)	DNA from maternal blood and plasma. Haplotype-based predictions of fetal inheritance using cfDNA at common genomic SNPs and exome.	●	●	●		○	●		$$$
Kitzman et al. (2012)	DNA from blood (mom), saliva (dad), and plasma. Haplotype- based predictions of fetal inheritance using cfDNA and statistical modeling.	●	○	●	●	○	●	●	$$$$