Noninvasive Determination of the Fetal Genome

Researchers in Prof. Stephen Quake's laboratory have developed a method to measure the entire fetal genome noninvasively using materials from maternal blood. This technique involves knowing the whole-genome molecular haplotypes of either or both parents, followed by high-throughput shotgun sequencing of maternal cell-free DNA that contains a small portion of DNA from the fetus. To achieve whole-genome haplotyping of the parents, the researchers have also built a microfluidic device that can separate and analyze individual copies of each human chromosome from a few single blood cells.

The ability to determine fetal genotypes (including all SNPs and CNVs) across the entire genome enables testing for all inherited genetic disorders that currently require an invasive procedure to diagnose. The microfluidic device for haplotyping could also facilitate high-throughput, individualized haplotype analysis for personalized medicine, diagnostics and research applications.

Microfluidic device designed for the amplification of metaphase chromosomes from a single cell.

Stage of Research
The inventors have used the microfluidic device to analyze SNPs in a single human metaphase cell from four individuals. These assays determined alleles with 99.8% accuracy. They have applied the haplotyping technique on blood cells from two pregnant women and shotgun sequenced their cell-free plasma DNA and confirmed that the fetal genome could be revealed using their proposed technique.