A computer-implemented 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: receiving a plurality of sequence reads obtained from sequencing DNA from the biological sample; 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; identifying a plurality of second loci on one or more reference chromosomes, 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. receiving a plurality of sequence reads obtained from sequencing DNA from the biological sample; 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; identifying a plurality of second loci on one or more reference chromosomes, 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.