Patent ID: 8877442

Claim:
A method of non-invasively determining parental haplotypes which are inherited by a fetus, comprising: a. obtaining a maternal sample from a female pregnant with at least one fetus, wherein said sample contains DNA from both the pregnant female and the fetus; b. determining a paternally inherited haplotype by the steps of: i. simultaneously isolating all of the chromosomes from a single metaphase cell of the fetus's father by partitioning said chromosomes into a plurality of channels of a microfluidic device and analyzing each of said chromosomes to determine a set of paternal single nucleotide polymorphisms (SNPs); ii. simultaneously isolating all of the chromosomes from a single metaphase cell of the fetus's mother by partitioning said chromosomes into a plurality of channels of a microfluidic device and analyzing each of said chromosomes to determine a set of maternal single nucleotide polymorphisms (SNPs); iii. determining all SNPs that are heterozygous in the father and homozygous in the mother to identify at various loci alleles present in the father and absent in the mother, thereby defining each of the father's haplotypes; and iv. counting a number of representative alleles on each paternal haplotype to determine a representation of the two paternal haplotypes in the maternal sample containing DNA from the pregnant female and the fetus; v. comparing the representation of the two paternal haplotypes to obtain a relative representation in the maternal sample containing DNA from the pregnant female and the fetus; vi. determining an over-representation ε of one of the two paternal haplotypes in the maternal sample containing DNA from the pregnant female and the fetus; and vii. correlating said over-representation ε with a paternally inherited haplotype; and c. determining a maternally inherited haplotype by the steps of: i. determining all SNPs that are heterozygous in the fetus's mother; and ii. identifying alleles present in the mother but absent in the paternally inherited haplotype at each SNP locus to define the mother's haplotypes; iii. counting a number of representative alleles on each maternal haplotype to determine a representation of the two maternal haplotypes; iv. comparing the representation of the two maternal haplotypes to obtain a relative representation; v. determining an over-representation ε of one of the two maternal haplotypes in the maternal sample containing DNA from the pregnant female and the fetus; and vi. correlating said over-representation ε with a maternally inherited haplotype.