Method for Non-Invasive Prenatal Testing Using Parental Mosaicism Data

A method of enriching and characterizing nucleic acid derived from a nucleic acid sample comprising nucleic acid from the mother of the fetus and nucleic acid from the fetus, the method comprising the steps:

• preferentially enriching the nucleic acid from the mother and the fetus at a plurality of polymorphic loci of the chromosome, wherein the preferential enrichment preserves the allele frequencies that are present in each of the pre-enriched nucleic acid sample at each of the plurality of polymorphic loci locus of the plurality, wherein the enriching comprises multiplex targeted amplification of at least 100 polymorphic loci in a single reaction volume;
• sequencing the plurality of polymorphic loci in the enriched nucleic acid from the mother and the fetus and determining the single-nucleotide polymorphism (SNP) allele count at each polymorphic locus of the mother and the fetus;
• determining the degree of mosaicism of the chromosome in a tissue of the mother;
• creating a plurality of ploidy state hypotheses pertaining to different ploidy states of the chromosome in the fetus, wherein the ploidy state is selected from the group consisting of:
• nullsomy, monosomy, disomy, uniparental disomy, euploidy, trisomy, matching trisomy, unmatching trisomy, maternal trisomy, paternal trisomy, tetrasomy, balanced (2:2) tetrasomy, unbalanced (3:1) tetrasomy, pentasomy, hexasomy, other aneuploidy, and combinations thereof;
• determining the ploidy state of the chromosome of interest in the fetus according to a relative probability of each ploidy state hypothesis by comparing the SNP allele count from each polymorphic locus of the fetus to the SNP allele count from the same polymorphic locus of the mother and using the degree of mosaicism of the chromosome in a tissue of the mother.