Methods for non-invasive prenatal ploidy calling

A method for determining the number of copies of a chromosome or chromosome segment of interest in the genome of a gestating fetus, the method comprising:

• obtaining a plurality primers to a locus (i) that is known to be polymorphic in the human population and (i) that is likely to be informative based on the rate of SNP heterozygosity in the human population for the locus;
• wherein an informative polymorphic 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;
• amplifying at least 500 SNPs from DNA in a mixed sample comprising DNA derived from the fetus and DNA derived from the mother by using the plurality of primers to obtain amplified products comprising the plurality of polymorphic loci on the at least one chromosome that is expected to be disomic, wherein the mixed sample is prepared from a maternal blood or plasma sample that comprises free floating fetal and maternal DNA;
• 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;
• determining a ratio of DNA derived from the fetus to DNA derived from the mother 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;
• measuring genetic data at a plurality of loci on a chromosome or chromosome segment of interest in the mixed sample;
• creating one or more hypotheses specifying the number of copies of the chromosome or chromosome segment of interest in the genome of the fetus;
• determining, on a computer, the probability of each of the hypotheses using the measured genetic data for the chromosome or chromosome segment of interest and the ratio of DNA derived from the fetus to DNA derived from the mother;
• and
• selecting the hypothesis with the greatest probability, thereby determining the number of copies of the chromosome or chromosome segment of interest in the genome of the fetus.