Diagnosis of fetal abnormalities using polymorphisms including short tandem repeats
First Claim
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1. A method of analyzing a fetal blood cell in a maternal blood sample obtained from a pregnant human female, the method comprising:
- (a) obtaining the maternal blood sample;
(b) enriching the maternal blood sample for fetal blood cells to produce an enriched sample comprising fetal blood cells and maternal blood 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 blood cells and maternal blood cells from the enriched sample by serial dilution, wherein the binning results in at least one bin containing an individual fetal blood cell from the enriched sample;
(d) identifying bins that contain at least one fetal blood cell using one or more fetal blood cell biomarkers;
(e) lysing fetal blood cells in the identified bins;
(f) amplifying the genomes of the lysed fetal blood 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.
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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.
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Citations
17 Claims
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1. A method of analyzing a fetal blood cell in a maternal blood sample obtained from a pregnant human female, the method comprising:
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(a) obtaining the maternal blood sample; (b) enriching the maternal blood sample for fetal blood cells to produce an enriched sample comprising fetal blood cells and maternal blood 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 blood cells and maternal blood cells from the enriched sample by serial dilution, wherein the binning results in at least one bin containing an individual fetal blood cell from the enriched sample; (d) identifying bins that contain at least one fetal blood cell using one or more fetal blood cell biomarkers; (e) lysing fetal blood cells in the identified bins; (f) amplifying the genomes of the lysed fetal blood 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. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17)
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Specification