Methods for non-invasive prenatal ploidy calling
First Claim
1. A method for determining the risk of aneuploidy of at least one chromosome or chromosome segment of interest in the genome of a fetus, the method comprising:
- performing a multiplex amplification to amplify at least 100 non-polymorphic loci per chromosome targeted and at least 100 SNP loci of free floating maternal and fetal DNA in a maternal blood, plasma, or serum sample using a plurality of probes to obtain amplified products;
performing microarray analysis to measure the genetic data at a plurality of amplified SNP loci on at least one chromosome that is expected to be disomic in both the mother of the fetus and the fetus;
performing microarray analysis to measure the genetic data at a plurality of amplified non-polymorphic loci;
creating one or more hypotheses specifying the number of copies of the at least one chromosome or chromosome segment of interest in the genome of the fetus;
determining the probability of each of the hypotheses of the number of copies of the at least one chromosome or chromosome segment of interest using the measured genetic data from the plurality of amplified SNP loci and the measured genetic data from the plurality of amplified non-polymorphic loci; and
determining the risk of aneuploidy of the at least one chromosome or chromosome segment of interest using the determined probabilities of each of the hypotheses.
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Abstract
Disclosed herein are methods for determining the copy number of a chromosome in a fetus in the context of non-invasive prenatal diagnosis. In an embodiment, the measured genetic data from a sample of genetic material that contains both fetal DNA and maternal DNA is analyzed, along with the genetic data from the biological parents of the fetus, and the copy number of the chromosome of interest is determined. In an embodiment, the maternal serum is measured using a single-nucleotide polymorphism (SNP) microarray, along with parental genomic data, and the determination of the chromosome copy number is used to make clinical decisions pertaining to the fetus.
273 Citations
20 Claims
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1. A method for determining the risk of aneuploidy of at least one chromosome or chromosome segment of interest in the genome of a fetus, the method comprising:
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performing a multiplex amplification to amplify at least 100 non-polymorphic loci per chromosome targeted and at least 100 SNP loci of free floating maternal and fetal DNA in a maternal blood, plasma, or serum sample using a plurality of probes to obtain amplified products; performing microarray analysis to measure the genetic data at a plurality of amplified SNP loci on at least one chromosome that is expected to be disomic in both the mother of the fetus and the fetus; performing microarray analysis to measure the genetic data at a plurality of amplified non-polymorphic loci; creating one or more hypotheses specifying the number of copies of the at least one chromosome or chromosome segment of interest in the genome of the fetus; determining the probability of each of the hypotheses of the number of copies of the at least one chromosome or chromosome segment of interest using the measured genetic data from the plurality of amplified SNP loci and the measured genetic data from the plurality of amplified non-polymorphic loci; and determining the risk of aneuploidy of the at least one chromosome or chromosome segment of interest using the determined probabilities of each of the hypotheses. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13)
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14. A method for determining the risk of aneuploidy of at least one chromosome or chromosome segment of interest in the genome of a fetus, the method comprising:
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performing a multiplex amplification to amplify at least 100 non-polymorphic loci per chromosome targeted and at least 100 SNP loci from DNA from a maternal blood, serum, or plasma sample comprising free floating maternal and fetal DNA, in a single amplification reaction; performing microarray analysis to measure in the same reaction the genetic data at a plurality of amplified SNP loci and amplified non-polymorphic loci on at least one chromosome that is expected to be disomic and at least one chromosome or chromosome segment of interest in both the mother of the fetus and the fetus; creating one or more hypotheses specifying the number of copies of the at least one chromosome or chromosome segment of interest in the genome of the fetus; determining the probability of each of the hypotheses of the number of copies of the at least one chromosome or chromosome segment of interest using the measured genetic data from the plurality of amplified SNP loci and amplified non-polymorphic loci; and determining the risk of aneuploidy of the at least one chromosome or chromosome segment of interest using the determined probabilities of each of the hypotheses. - View Dependent Claims (15, 16, 17, 18)
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19. A method for determining the risk of aneuploidy of at least one chromosome or chromosome segment of interest in the genome of a fetus, the method comprising:
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performing a multiplex amplification to amplify at least 100 non-polymorphic loci per chromosome targeted and at least 100 SNP loci from DNA from a maternal blood, serum, or plasma sample comprising free floating maternal and fetal DNA, in a single amplification reaction; performing microarray analysis to measure in the same reaction the genetic data at a plurality of amplified SNP loci and amplified non-polymorphic loci on at least one chromosome that is expected to be disomic and at least one chromosome or chromosome segment of interest in both the mother of the fetus and the fetus, wherein the fetal DNA in the sample is not preferentially enriched over the maternal DNA before performing the amplifying or the measuring; performing microarray analysis to measure the amount of amplified SNP loci and amplified non-polymorphic loci; creating one or more hypotheses specifying the number of copies of the at least one chromosome or chromosome segment of interest in the genome of the fetus; determining the probability of each of the hypotheses of the number of copies of the at least one chromosome or chromosome segment of interest using the measured genetic data from the plurality of amplified SNP loci and amplified non-polymorphic loci; and determining the risk of aneuploidy of the at least one chromosome or chromosome segment of interest using the determined probabilities of each of the hypotheses. - View Dependent Claims (20)
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Specification