Diagnosis of fetal abnormalities using polymorphisms including short tandem repeats
AssigneesVerinata Health, Inc., The General Hospital Corporation, GPR Scientific, LLC
InventorsRoland Stoughton, Ravi Kapur, Barb Ariel Cohen, Daniel Shoemaker, Ronald W. Davis, Mehmet Toner
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Abstract
The present invention provides systems, apparatuses, and methods to detect the presence of fetal cells when mixed with a population of maternal cells in a sample and to test fetal abnormalities, i.e. aneuploidy. In addition, the present invention provides methods to determine when there are insufficient fetal cells for a determination and report a non-informative case. The present invention involves quantifying regions of genomic DNA from a mixed sample. More particularly the invention involves quantifying DNA polymorphisms from the mixed sample.
Claims20
A method of analyzing a fetal cell in a mixed sample obtained from a pregnant human female, the method comprising:
- (a) obtaining the mixed sample comprising fetal and maternal cells;
- (b) enriching the mixed sample for fetal cells to produce an enriched sample comprising fetal cells and maternal cells, wherein the enrichment increases the ratio of fetal cells to maternal cells to about 1/10,000 to about 1/10;
- (c) binning fetal cells and maternal cells from the enriched sample by serial dilution, wherein the binning results in at least one bin containing an individual fetal cell from the enriched sample;
- (d) identifying bins that contain at least one fetal cell using one or more fetal cell biomarkers;
- (e) lysing fetal cells in the identified bins;
- (f) amplifying genomes of the lysed fetal cells in the identified bins to produce amplified nucleic acids;
- and
- (g) analyzing the amplified nucleic acids in bins that contain at least one fetal cell for aneuploidy using ultra-deep sequencing.
Dependencies are inferred from the claim text.