System and method for cleaning noisy genetic data from target individuals using genetic data from genetically related individuals
DCFirst Claim
1. A method for detecting aneuploidy in a fetus, the method comprising:
- (a) measuring the amounts of genetic material at multiple loci on a chromosome or chromosome segment of interest in a sample comprising cell-free DNA derived from the fetus and from the mother of the fetus, wherein the measuring comprises amplifying at least 70 loci in a single reaction and using microarray or sequencing to detect amplified reaction products, and wherein the amount of genetic material at a particular locus is determined irrespective of the identity of the alleles at that locus;
(b) determining, on a computer, the probability of aneuploidy in the fetus by comparing the measured amounts of genetic material to an expected amount for a particular copy number; and
(c) outputting the selected probability as an indication of whether the fetus has aneuploidy.
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Abstract
A system and method for determining the genetic data for one or a small set of cells, or from fragmentary DNA, where a limited quantity of genetic data is available, are disclosed. Genetic data for the target individual is acquired and amplified using known methods, and poorly measured base pairs, missing alleles and missing regions are reconstructed using expected similarities between the target genome and the genome of genetically related subjects. In accordance with one embodiment of the invention, incomplete genetic data is acquired from embryonic cells, fetal cells, or cell-free fetal DNA isolated from the mother'"'"'s blood, and the incomplete genetic data is reconstructed using the more complete genetic data from a larger sample diploid cells from one or both parents, with or without genetic data from haploid cells from one or both parents, and/or genetic data taken from other related individuals.
298 Citations
20 Claims
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1. A method for detecting aneuploidy in a fetus, the method comprising:
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(a) measuring the amounts of genetic material at multiple loci on a chromosome or chromosome segment of interest in a sample comprising cell-free DNA derived from the fetus and from the mother of the fetus, wherein the measuring comprises amplifying at least 70 loci in a single reaction and using microarray or sequencing to detect amplified reaction products, and wherein the amount of genetic material at a particular locus is determined irrespective of the identity of the alleles at that locus; (b) determining, on a computer, the probability of aneuploidy in the fetus by comparing the measured amounts of genetic material to an expected amount for a particular copy number; and (c) outputting the selected probability as an indication of whether the fetus has aneuploidy. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12)
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13. A method for detecting aneuploidy in a fetus, the method comprising:
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(a) measuring an amount of genetic material at multiple loci on a chromosome or chromosome segment of interest in a sample comprising cell-free DNA from the fetus and cell-free DNA from the mother of the fetus, wherein the measuring comprises amplifying at least 70 loci in a single reaction and using microarray or sequencing to detect amplified reaction products, and wherein the amount of genetic material at a particular locus is measured irrespective of the identity of the alleles at that locus; (b) determining, on a computer, the probability of aneuploidy in the fetus by comparing the measured amounts of genetic material to an expected amount for a particular copy number hypothesis, wherein the expected amount is determined using a mean value of genetic material at multiple loci for a reference chromosome or chromosome segment that is present in two copies; and (c) selecting a particular copy number with greatest probability, thereby detecting aneuploidy if present. - View Dependent Claims (14, 15, 16, 17, 18, 19, 20)
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Specification