A method of analyzing a biological sample from a female subject pregnant with a fetus to determine whether the fetus has an aneuploidy associated with a first chromosome, the biological sample containing a mixture of DNA molecules from the fetus and the female subject, the method comprising: enriching the biological sample for DNA molecules from a plurality of target regions; sequencing DNA molecules from the biological sample to obtain a plurality of sequence reads; analyzing the plurality of sequence reads, wherein analyzing a sequence read includes: identifying a location of the sequence read in a reference genome by aligning the sequence read to the reference genome; and determining a respective allele of the sequence read; identifying a plurality of first loci on the first chromosome, the plurality of first loci corresponding to a portion of the target regions; identifying a plurality of second loci on one or more reference chromosomes, the plurality of second loci corresponding to a portion of the target regions, wherein the pregnant female is homozygous for a respective maternal allele at each of the first and second loci, and wherein the fetus is heterozygous for the respective maternal allele and a respective paternal allele at each of the first and second loci, the respective paternal alleles being different from the respective maternal alleles; determining a first maternal amount of the respective maternal alleles at the plurality of first loci; determining a first paternal amount of the respective paternal alleles at the plurality of first loci; calculating a first ratio of the first maternal amount and the first paternal amount; determining a second maternal amount of the respective maternal alleles at the plurality of second loci; determining a second paternal amount of the respective paternal alleles at the plurality of second loci; calculating a second ratio of the second maternal amount and the second paternal amount; calculating a third ratio of the first ratio and the second ratio; and comparing the third ratio to one or more cutoff values to determine whether the fetus has an aneuploidy associated with the first chromosome. enriching the biological sample for DNA molecules from a plurality of target regions; sequencing DNA molecules from the biological sample to obtain a plurality of sequence reads; analyzing the plurality of sequence reads, wherein analyzing a sequence read includes: identifying a location of the sequence read in a reference genome by aligning the sequence read to the reference genome; and determining a respective allele of the sequence read; identifying a location of the sequence read in a reference genome by aligning the sequence read to the reference genome; and determining a respective allele of the sequence read; identifying a plurality of first loci on the first chromosome, the plurality of first loci corresponding to a portion of the target regions; identifying a plurality of second loci on one or more reference chromosomes, the plurality of second loci corresponding to a portion of the target regions, wherein the pregnant female is homozygous for a respective maternal allele at each of the first and second loci, and wherein the fetus is heterozygous for the respective maternal allele and a respective paternal allele at each of the first and second loci, the respective paternal alleles being different from the respective maternal alleles; determining a first maternal amount of the respective maternal alleles at the plurality of first loci; determining a first paternal amount of the respective paternal alleles at the plurality of first loci; calculating a first ratio of the first maternal amount and the first paternal amount; determining a second maternal amount of the respective maternal alleles at the plurality of second loci; determining a second paternal amount of the respective paternal alleles at the plurality of second loci; calculating a second ratio of the second maternal amount and the second paternal amount; calculating a third ratio of the first ratio and the second ratio; and comparing the third ratio to one or more cutoff values to determine whether the fetus has an aneuploidy associated with the first chromosome.