| 摘要 |
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. |
| 主权项 |
1. A method for determining the risk of aneuploidy of at least one chromosome or chromosome segment of interest in the genome of a gestating fetus, the method comprising:
a) obtaining a plurality of probes to each of a plurality of loci (i) that are known to be polymorphic in the human population and (ii) that are likely to be informative based on the rate of SNP heterozygosity in the human population for the locus; wherein each of the plurality of loci is a SNP locus on at least one chromosome that is expected to be disomic in both the mother and the fetus where the mother is homozygous for a first allele at that locus, and the father is (i) heterozygous for the first allele and a second allele or (ii) homozygous for a second allele at that locus; b) amplifying free floating maternal and fetal DNA from a blood, serum, or plasma sample from the mother of the gestating fetus, using the plurality of probes to obtain amplified products comprising the plurality of polymorphic loci on the at least one chromosome that is expected to be disomic; c) measuring an amount of the amplified products to obtain a measured quantity of each allele at the plurality of polymorphic loci on the at least one chromosome that is expected to be disomic; d) determining a ratio of fetal to maternal DNA in the blood, serum, or plasma sample using (i) the measured quantity of the second allele or (ii) the measured quantity of the first and second alleles for each of the polymorphic loci on the at least one chromosome that is expected to be disomic; e) measuring genetic data at a plurality of loci on at least one chromosome or chromosome segment of interest in the blood, serum, or plasma sample; f) 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; and g) determining, on a computer, the probability of each of the hypotheses using the measured genetic data for the at least one chromosome or chromosome segment of interest and the ratio of fetal to maternal DNA, and thereby the risk of aneuploidy of the at least one chromosome or chromosome segment of interest in the genome of the fetus. |
