Rare cell analysis using sample splitting and DNA tags
First Claim
1. A method of determining a presence or absence of a fetal aneuploidy in a fetus by analysis of a maternal blood sample obtained from a pregnant woman comprising a mixture of fetal and maternal cells, the method comprising:
- (a) enriching a mixture of fetal and maternal cells of a maternal blood sample for fetal cells to obtain a mixed cell preparation enriched for fetal cells;
(b) splitting the mixed cell preparation of step (a) into at least 100 discrete portions and directing the discrete portions to different locations;
(c) identifying at least one location that contains a single fetal cell and obtaining genomic DNA from the single fetal cell at the at least one identified location;
(d) amplifying fetal genomic DNA obtained from the single fetal cell at the at least one identified location;
(e) sequencing the fetal genomic DNA of step (d) to generate sequence data; and
(f) determining the presence or absence of a fetal aneuploidy from the sequence data of step (e), wherein said determining comprises analyzing the sequence data using computer executable logic recorded on a computer readable medium.
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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, e.g. aneuploidy. The present invention involves labeling regions of genomic DNA in each cell in said mixed sample with different labels wherein each label is specific to each cell and quantifying the labeled regions of genomic DNA from each cell in the mixed sample. More particularly the invention involves quantifying labeled DNA polymorphisms from each cell in the mixed sample.
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Citations
21 Claims
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1. A method of determining a presence or absence of a fetal aneuploidy in a fetus by analysis of a maternal blood sample obtained from a pregnant woman comprising a mixture of fetal and maternal cells, the method comprising:
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(a) enriching a mixture of fetal and maternal cells of a maternal blood sample for fetal cells to obtain a mixed cell preparation enriched for fetal cells; (b) splitting the mixed cell preparation of step (a) into at least 100 discrete portions and directing the discrete portions to different locations; (c) identifying at least one location that contains a single fetal cell and obtaining genomic DNA from the single fetal cell at the at least one identified location; (d) amplifying fetal genomic DNA obtained from the single fetal cell at the at least one identified location; (e) sequencing the fetal genomic DNA of step (d) to generate sequence data; and (f) determining the presence or absence of a fetal aneuploidy from the sequence data of step (e), wherein said determining comprises analyzing the sequence data using computer executable logic recorded on a computer readable medium. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21)
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Specification